Commentary

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).

Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?

Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.

Dr. Aftab: What do you see as some of the strengths of our profession?


Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.



Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?


Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.



Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.


Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?



Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).

Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?

Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.

Dr. Aftab: What do you see as some of the strengths of our profession?


Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.



Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?


Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.



Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.


Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?



Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).

Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?

Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.

Dr. Aftab: What do you see as some of the strengths of our profession?


Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.



Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?


Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.



Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.


Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?



Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.

A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.¹ To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.

Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.¹ Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.

Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.¹

Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.¹

When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.

The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.

If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.

If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.²

Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.

Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at obnews@mdedge.com.
 

References

1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.

2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.

A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.¹ To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.

Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.¹ Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.

Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.¹

Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.¹

When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.

The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.

If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.

If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.²

Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.

Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at obnews@mdedge.com.
 

References

1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.

2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.

A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.¹ To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.

Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.¹ Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.

Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.¹

Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.¹

When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.

The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.

If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.

If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.²

Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.

Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at obnews@mdedge.com.
 

References

1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.

2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.

In this modern age of health care where telemedicine rules, conversational agents (CAs) that use text messaging systems are becoming a major mode of communication.

Many people are familiar with voice-enabled agents, such as Apple’s Siri, Google Now, and Microsoft’s Cortana. However, CAs come in different forms of complexity, ranging from a short message service–based texting platform to an embodied conversational agent (ECA).

ECAs allow participants to interact with a physical or graphical figure that simulates a person in appearance, behavior, and dialect. These are essentially virtual humans, or avatars, who talk with participants. By taking greater advantage of these automated agents, some have projected there may be $11 billion in combined cost savings across a variety of business sectors by 2023.¹ The health care field is one sector in which CAs can play an important role. Because of their accessibility, CAs have the potential to improve mental health by combating health care inequities and stigma, encouraging disclosure from participants, and serving as companions during the COVID-19 pandemic.

CAs provide accessible health care for rural, low socioeconomic status (SES), and minority communities in a variety of advantageous ways. For example, one study found that long-term use of a text-based agent that combines motivational interviewing and cognitive-behavioral therapy (CBT) can support smoking cessation in adolescents of low SES.²

CAs can help vulnerable participants advocate for themselves and proactively maintain their mental health through access to health care resources. In specific cases, these agents equalize health care treatment for different populations. Even though some participants live in secluded areas or are blocked by barriers, these text-based agents can still provide self-help intervention for them at any time on an individual basis, regardless of their location or socioeconomic status. Furthermore, they serve as highly cost-effective mental health promotion tools for large populations, some of which might not otherwise be reached by mental health care.

In combating mental illnesses such as depression and anxiety, studies have found that CAs are great treatment tools. For example, participants in an experimental group who received a self-help program based on CBT from a text-based CA named Woebot experienced significantly reduced depression symptoms when compared to the control group of participants, who received only information from a self-help electronic book.³ As a result, CAs might prove successful in treating younger populations who find online tools more feasible and accessible. Often, this population self-identifies depressive and anxiety symptoms without consulting a health care professional. Thus, this tool would prove useful to those who are bothered by the stigma of seeing a mental health professional.

Virtual human–based CAs also encourage participants to disclose more information in a nonjudgmental manner, especially among people with diseases with stigma. CAs use neutral languages, which may be helpful when dealing with stigmatized issues such as HIV, family planning, and abortion care because this heightens confidentiality and privacy. When participants believe that the agent does not “judge” or evaluate their capabilities, this elicits more sensitive information from them. For example, one study found that military service members who believed that they were interacting with a computer rather than a human operator reported lower fear of self-disclosure, displayed more sadness, and were rated by observers as more willing to disclose posttraumatic stress disorder symptoms.⁴ Additional findings show that participants prefer CAs when topics are highly sensitive and more likely to evoke negative self-admissions.

In what we hope will soon be a post–COVID-19 landscape of medicine, CAs are fast being used on the front lines of health care technology. Empathetic CAs can combat adverse effects of social exclusion during these pressing times. Etsuko Ishii, a researcher affiliated with the Hong Kong University of Science and Technology, and associates demonstrated that a virtual CA was as effective as a COVID-19 companion because it uses natural language processing (NLP) and nonverbal facial expressions to give users the feeling that they are being treated with empathy.⁵ While minimizing the number of in-person interactions that could potentially spread COVID-19, these agents promote virtual companionship that mirrors natural conversations and provide emotional support with psychological safety as participants express their pent-up thoughts. Not only do these agents help recover mood quickly, but they also have the power to overcome geographic barriers, be constantly available, and alleviate the high demand for mental health care. As a result, CAs have the potential to facilitate better communication and sustain social interactions within the isolated environment the pandemic has created.

CAs can predict, detect, and determine treatment solutions for mental health conditions based on behavioral insights. These agents’ natural language processing also allows them to be powerful therapeutic agents that can serve different communities, particularly for populations with limited access to medical resources. As the use of CAs becomes more integrated into telemedicine, their utility will continue to grow as their proven versatility in many situations expands the boundaries of health care technology.
 

Ms. Wong, a medical student at New York Institute of Technology College of Osteopathic Medicine in Old Westbury, conducts research related to mental health care services. She disclosed writing a telemental health software platform called Orchid. Dr. Vo, a board-certified psychiatrist, is the medical director of telehealth for the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia. She is a faculty member of the University of Pennsylvania, also in Philadelphia. Dr. Vo conducts digital health research focused on using automation and artificial intelligence for suicide risk screening and connecting patients to mental health care services. She disclosed serving as cofounder of Orchid.

References

1. Chatbots: Vendor opportunities & market forecasts 2020-2024. Juniper Research, 2020.

2. Simon P et al. On using chatbots to promote smoking cessation among adolescents of low socioeconomic status, Artificial Intelligence and Work: Association for the Advancement of Artificial Intelligence (AAAI) 2019 Fall Symposium, 2019.

3. Fitzpatrick KK et al. JMIR Mental Health. 2017;4(2):e19.

4. Lucas GM et al. Front Robot AI. 2017 Oct 12. doi: 10.3389/frobt.2017.00051.

5. Ishii E et al. ERICA: An empathetic android companion for COVID-19 quarantine. arXiv preprint arXiv:2106.02325.

In this modern age of health care where telemedicine rules, conversational agents (CAs) that use text messaging systems are becoming a major mode of communication.

Many people are familiar with voice-enabled agents, such as Apple’s Siri, Google Now, and Microsoft’s Cortana. However, CAs come in different forms of complexity, ranging from a short message service–based texting platform to an embodied conversational agent (ECA).

ECAs allow participants to interact with a physical or graphical figure that simulates a person in appearance, behavior, and dialect. These are essentially virtual humans, or avatars, who talk with participants. By taking greater advantage of these automated agents, some have projected there may be $11 billion in combined cost savings across a variety of business sectors by 2023.¹ The health care field is one sector in which CAs can play an important role. Because of their accessibility, CAs have the potential to improve mental health by combating health care inequities and stigma, encouraging disclosure from participants, and serving as companions during the COVID-19 pandemic.

CAs provide accessible health care for rural, low socioeconomic status (SES), and minority communities in a variety of advantageous ways. For example, one study found that long-term use of a text-based agent that combines motivational interviewing and cognitive-behavioral therapy (CBT) can support smoking cessation in adolescents of low SES.²

CAs can help vulnerable participants advocate for themselves and proactively maintain their mental health through access to health care resources. In specific cases, these agents equalize health care treatment for different populations. Even though some participants live in secluded areas or are blocked by barriers, these text-based agents can still provide self-help intervention for them at any time on an individual basis, regardless of their location or socioeconomic status. Furthermore, they serve as highly cost-effective mental health promotion tools for large populations, some of which might not otherwise be reached by mental health care.

In combating mental illnesses such as depression and anxiety, studies have found that CAs are great treatment tools. For example, participants in an experimental group who received a self-help program based on CBT from a text-based CA named Woebot experienced significantly reduced depression symptoms when compared to the control group of participants, who received only information from a self-help electronic book.³ As a result, CAs might prove successful in treating younger populations who find online tools more feasible and accessible. Often, this population self-identifies depressive and anxiety symptoms without consulting a health care professional. Thus, this tool would prove useful to those who are bothered by the stigma of seeing a mental health professional.

Virtual human–based CAs also encourage participants to disclose more information in a nonjudgmental manner, especially among people with diseases with stigma. CAs use neutral languages, which may be helpful when dealing with stigmatized issues such as HIV, family planning, and abortion care because this heightens confidentiality and privacy. When participants believe that the agent does not “judge” or evaluate their capabilities, this elicits more sensitive information from them. For example, one study found that military service members who believed that they were interacting with a computer rather than a human operator reported lower fear of self-disclosure, displayed more sadness, and were rated by observers as more willing to disclose posttraumatic stress disorder symptoms.⁴ Additional findings show that participants prefer CAs when topics are highly sensitive and more likely to evoke negative self-admissions.

In what we hope will soon be a post–COVID-19 landscape of medicine, CAs are fast being used on the front lines of health care technology. Empathetic CAs can combat adverse effects of social exclusion during these pressing times. Etsuko Ishii, a researcher affiliated with the Hong Kong University of Science and Technology, and associates demonstrated that a virtual CA was as effective as a COVID-19 companion because it uses natural language processing (NLP) and nonverbal facial expressions to give users the feeling that they are being treated with empathy.⁵ While minimizing the number of in-person interactions that could potentially spread COVID-19, these agents promote virtual companionship that mirrors natural conversations and provide emotional support with psychological safety as participants express their pent-up thoughts. Not only do these agents help recover mood quickly, but they also have the power to overcome geographic barriers, be constantly available, and alleviate the high demand for mental health care. As a result, CAs have the potential to facilitate better communication and sustain social interactions within the isolated environment the pandemic has created.

CAs can predict, detect, and determine treatment solutions for mental health conditions based on behavioral insights. These agents’ natural language processing also allows them to be powerful therapeutic agents that can serve different communities, particularly for populations with limited access to medical resources. As the use of CAs becomes more integrated into telemedicine, their utility will continue to grow as their proven versatility in many situations expands the boundaries of health care technology.
 

Ms. Wong, a medical student at New York Institute of Technology College of Osteopathic Medicine in Old Westbury, conducts research related to mental health care services. She disclosed writing a telemental health software platform called Orchid. Dr. Vo, a board-certified psychiatrist, is the medical director of telehealth for the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia. She is a faculty member of the University of Pennsylvania, also in Philadelphia. Dr. Vo conducts digital health research focused on using automation and artificial intelligence for suicide risk screening and connecting patients to mental health care services. She disclosed serving as cofounder of Orchid.

References

1. Chatbots: Vendor opportunities & market forecasts 2020-2024. Juniper Research, 2020.

2. Simon P et al. On using chatbots to promote smoking cessation among adolescents of low socioeconomic status, Artificial Intelligence and Work: Association for the Advancement of Artificial Intelligence (AAAI) 2019 Fall Symposium, 2019.

3. Fitzpatrick KK et al. JMIR Mental Health. 2017;4(2):e19.

4. Lucas GM et al. Front Robot AI. 2017 Oct 12. doi: 10.3389/frobt.2017.00051.

5. Ishii E et al. ERICA: An empathetic android companion for COVID-19 quarantine. arXiv preprint arXiv:2106.02325.

In this modern age of health care where telemedicine rules, conversational agents (CAs) that use text messaging systems are becoming a major mode of communication.

Many people are familiar with voice-enabled agents, such as Apple’s Siri, Google Now, and Microsoft’s Cortana. However, CAs come in different forms of complexity, ranging from a short message service–based texting platform to an embodied conversational agent (ECA).

ECAs allow participants to interact with a physical or graphical figure that simulates a person in appearance, behavior, and dialect. These are essentially virtual humans, or avatars, who talk with participants. By taking greater advantage of these automated agents, some have projected there may be $11 billion in combined cost savings across a variety of business sectors by 2023.¹ The health care field is one sector in which CAs can play an important role. Because of their accessibility, CAs have the potential to improve mental health by combating health care inequities and stigma, encouraging disclosure from participants, and serving as companions during the COVID-19 pandemic.

CAs provide accessible health care for rural, low socioeconomic status (SES), and minority communities in a variety of advantageous ways. For example, one study found that long-term use of a text-based agent that combines motivational interviewing and cognitive-behavioral therapy (CBT) can support smoking cessation in adolescents of low SES.²

CAs can help vulnerable participants advocate for themselves and proactively maintain their mental health through access to health care resources. In specific cases, these agents equalize health care treatment for different populations. Even though some participants live in secluded areas or are blocked by barriers, these text-based agents can still provide self-help intervention for them at any time on an individual basis, regardless of their location or socioeconomic status. Furthermore, they serve as highly cost-effective mental health promotion tools for large populations, some of which might not otherwise be reached by mental health care.

In combating mental illnesses such as depression and anxiety, studies have found that CAs are great treatment tools. For example, participants in an experimental group who received a self-help program based on CBT from a text-based CA named Woebot experienced significantly reduced depression symptoms when compared to the control group of participants, who received only information from a self-help electronic book.³ As a result, CAs might prove successful in treating younger populations who find online tools more feasible and accessible. Often, this population self-identifies depressive and anxiety symptoms without consulting a health care professional. Thus, this tool would prove useful to those who are bothered by the stigma of seeing a mental health professional.

Virtual human–based CAs also encourage participants to disclose more information in a nonjudgmental manner, especially among people with diseases with stigma. CAs use neutral languages, which may be helpful when dealing with stigmatized issues such as HIV, family planning, and abortion care because this heightens confidentiality and privacy. When participants believe that the agent does not “judge” or evaluate their capabilities, this elicits more sensitive information from them. For example, one study found that military service members who believed that they were interacting with a computer rather than a human operator reported lower fear of self-disclosure, displayed more sadness, and were rated by observers as more willing to disclose posttraumatic stress disorder symptoms.⁴ Additional findings show that participants prefer CAs when topics are highly sensitive and more likely to evoke negative self-admissions.

In what we hope will soon be a post–COVID-19 landscape of medicine, CAs are fast being used on the front lines of health care technology. Empathetic CAs can combat adverse effects of social exclusion during these pressing times. Etsuko Ishii, a researcher affiliated with the Hong Kong University of Science and Technology, and associates demonstrated that a virtual CA was as effective as a COVID-19 companion because it uses natural language processing (NLP) and nonverbal facial expressions to give users the feeling that they are being treated with empathy.⁵ While minimizing the number of in-person interactions that could potentially spread COVID-19, these agents promote virtual companionship that mirrors natural conversations and provide emotional support with psychological safety as participants express their pent-up thoughts. Not only do these agents help recover mood quickly, but they also have the power to overcome geographic barriers, be constantly available, and alleviate the high demand for mental health care. As a result, CAs have the potential to facilitate better communication and sustain social interactions within the isolated environment the pandemic has created.

CAs can predict, detect, and determine treatment solutions for mental health conditions based on behavioral insights. These agents’ natural language processing also allows them to be powerful therapeutic agents that can serve different communities, particularly for populations with limited access to medical resources. As the use of CAs becomes more integrated into telemedicine, their utility will continue to grow as their proven versatility in many situations expands the boundaries of health care technology.
 

Ms. Wong, a medical student at New York Institute of Technology College of Osteopathic Medicine in Old Westbury, conducts research related to mental health care services. She disclosed writing a telemental health software platform called Orchid. Dr. Vo, a board-certified psychiatrist, is the medical director of telehealth for the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia. She is a faculty member of the University of Pennsylvania, also in Philadelphia. Dr. Vo conducts digital health research focused on using automation and artificial intelligence for suicide risk screening and connecting patients to mental health care services. She disclosed serving as cofounder of Orchid.

References

1. Chatbots: Vendor opportunities & market forecasts 2020-2024. Juniper Research, 2020.

2. Simon P et al. On using chatbots to promote smoking cessation among adolescents of low socioeconomic status, Artificial Intelligence and Work: Association for the Advancement of Artificial Intelligence (AAAI) 2019 Fall Symposium, 2019.

3. Fitzpatrick KK et al. JMIR Mental Health. 2017;4(2):e19.

4. Lucas GM et al. Front Robot AI. 2017 Oct 12. doi: 10.3389/frobt.2017.00051.

5. Ishii E et al. ERICA: An empathetic android companion for COVID-19 quarantine. arXiv preprint arXiv:2106.02325.

Nearly 9 in 10 U.S. women take a medication at some point in their pregnancy, with approximately 50% of women taking at least one prescription medication.¹ These medications may be prescribed without the benefit of knowledge gained through clinical trials. Knowledge is gained after market, often after multiple years, and potentially following widespread use. The situation is similar for vaccines, as was recently seen with the SARS-CoV2 pandemic. Early in the pandemic, evidence emerged that pregnancy increased the risk for severe illness from COVID-19, yet pregnant people and their providers were forced to make a difficult decision of risk/benefit with little data to guide them.

The FDA product label provides a summary and narrative of animal and human safety studies relating to pregnancy. But what if that label contains little to no information, or reports studies with conflicting results? Perhaps the product is new on the market or is infrequently used during pregnancy. Regardless, health care providers and pregnant patients still need to make decisions about medication use. The following list outlines information that can be found, and strategies to support providers and patients in making informed choices for a treatment plan.


Taking stock of the available information:

• If possible, connect with the specialist who prescribed the patient’s medication in question. They may have already assembled information regarding use of that medication in pregnancy.
• The sponsor may have published useful information from the phase 3 trials, including the outcomes of enrolled patients who inadvertently became pregnant.
• Review the animal data in the product label. Regulators require the careful selection of animal models, and this data can present a source of adjunct information regarding the medication’s effects on pregnancy, reproduction, and development. Negative results can be as revealing as positive results.
• Pharmacologic data in the label can also be informative. Although most labels have pharmacologic data based on trials in healthy nonpregnant individuals, understanding pregnancy physiology and the patient’s preexisting or pregnancy-specific condition(s) can provide insights.² Close patient monitoring and follow-up are of key importance.
• Consider viable alternatives that may address the patient’s needs. There may be effective alternatives that have been better studied and shown to have low reproductive toxicity.
• Consider the risks to the patient as well as the developing fetus if the preexisting or pregnancy-specific condition is uncontrolled.
• Consult a teratogen specialist who can provide information to both patients and health care providers on the reproductive hazards or safety of many exposures, even those with limited data regarding use in pregnancy. For example, MotherToBaby provides a network of teratogen specialists.

Understanding perceptions of risk, decision-making, and strategies to support informed choices:

• Perceptions of risk: Each person perceives risk and benefit differently. The few studies that have attempted to investigate perception of teratogenic risk have found that many pregnant people overestimate the magnitude of teratogenic risk associated with a particular exposure.³ Alternatively, a medication’s benefit in controlling the maternal condition is often not considered sufficiently. Health care providers may have their own distorted perceptions of risk, even in the presence of evidence.
• Decision-making: Most teratogen data inherently involve uncertainty; it is rare to have completely nonconflicting data with which to make a decision. This makes decisions about whether or not to utilize a particular medication or other agent in pregnancy very difficult. For example, a patient would prefer to be told a black and white answer such as vaccines are either 100% safe or 100% harmful. However, no medical treatment is held to that standard of certainty. Even though it may be more comfortable to avoid an action and “just let things happen,” the lack of a decision is still a decision. The decision to not take medication may have risks inherent in not treating a condition and may result in adverse outcomes in the developing fetus. Lastly, presenting teratogen information often involves challenges in portraying and interpreting numerical risk. For example, when considering data presented in fraction format, patients and some health care providers may focus on the numerator or count of adverse events, while ignoring the magnitude of the denominator.
• Strategies: Health literacy “best practice” strategies are useful whether there is a lot of data or very little. These include the of use plain language and messages delivered in a clear and respectful voice, the use of visual aids, and the use effective teaching methods such as asking open-ended questions to assess understanding. Other strategies include using caution in framing information: for example, discussing a 1% increase in risk for a baby to have a medication-associated birth defect should also be presented as a 99% chance the medication will not cause a birth defect. Numeracy challenges can also be addressed by using natural numbers rather than fractions or percentages: for example, if there were 100 women in this room, one would have a baby with a birth defect after taking this medication in pregnancy, but 99 of these women would not.

In today’s medical world, shared decision-making is the preferred approach to choices. Communicating and appropriately utilizing information to make choices about medication safety in pregnancy are vital undertakings. An important provider responsibility is helping patients understand that science is built on evidence that amasses and changes over time and that it represents rich shades of gray rather than “black and white” options.

Dr. Hardy is executive director, head of pharmacoepidemiology, Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention (BDRP), represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Conover is the director of Nebraska MotherToBaby. She is assistant professor at the Munroe Meyer Institute, University of Nebraska Medical Center.

References

1. Mitchell AA et al. Am J Obstet Gynecol. 2011;205(1):51:e1-e8.

2. Feghali M et al. Semin Perinatol 2015;39:512-9.

3. Conover EA, Polifka JE. Am J Med Genet Part C Semin Med Genet 2011;157:227-33.

Nearly 9 in 10 U.S. women take a medication at some point in their pregnancy, with approximately 50% of women taking at least one prescription medication.¹ These medications may be prescribed without the benefit of knowledge gained through clinical trials. Knowledge is gained after market, often after multiple years, and potentially following widespread use. The situation is similar for vaccines, as was recently seen with the SARS-CoV2 pandemic. Early in the pandemic, evidence emerged that pregnancy increased the risk for severe illness from COVID-19, yet pregnant people and their providers were forced to make a difficult decision of risk/benefit with little data to guide them.

The FDA product label provides a summary and narrative of animal and human safety studies relating to pregnancy. But what if that label contains little to no information, or reports studies with conflicting results? Perhaps the product is new on the market or is infrequently used during pregnancy. Regardless, health care providers and pregnant patients still need to make decisions about medication use. The following list outlines information that can be found, and strategies to support providers and patients in making informed choices for a treatment plan.


Taking stock of the available information:

• If possible, connect with the specialist who prescribed the patient’s medication in question. They may have already assembled information regarding use of that medication in pregnancy.
• The sponsor may have published useful information from the phase 3 trials, including the outcomes of enrolled patients who inadvertently became pregnant.
• Review the animal data in the product label. Regulators require the careful selection of animal models, and this data can present a source of adjunct information regarding the medication’s effects on pregnancy, reproduction, and development. Negative results can be as revealing as positive results.
• Pharmacologic data in the label can also be informative. Although most labels have pharmacologic data based on trials in healthy nonpregnant individuals, understanding pregnancy physiology and the patient’s preexisting or pregnancy-specific condition(s) can provide insights.² Close patient monitoring and follow-up are of key importance.
• Consider viable alternatives that may address the patient’s needs. There may be effective alternatives that have been better studied and shown to have low reproductive toxicity.
• Consider the risks to the patient as well as the developing fetus if the preexisting or pregnancy-specific condition is uncontrolled.
• Consult a teratogen specialist who can provide information to both patients and health care providers on the reproductive hazards or safety of many exposures, even those with limited data regarding use in pregnancy. For example, MotherToBaby provides a network of teratogen specialists.

Understanding perceptions of risk, decision-making, and strategies to support informed choices:

• Perceptions of risk: Each person perceives risk and benefit differently. The few studies that have attempted to investigate perception of teratogenic risk have found that many pregnant people overestimate the magnitude of teratogenic risk associated with a particular exposure.³ Alternatively, a medication’s benefit in controlling the maternal condition is often not considered sufficiently. Health care providers may have their own distorted perceptions of risk, even in the presence of evidence.
• Decision-making: Most teratogen data inherently involve uncertainty; it is rare to have completely nonconflicting data with which to make a decision. This makes decisions about whether or not to utilize a particular medication or other agent in pregnancy very difficult. For example, a patient would prefer to be told a black and white answer such as vaccines are either 100% safe or 100% harmful. However, no medical treatment is held to that standard of certainty. Even though it may be more comfortable to avoid an action and “just let things happen,” the lack of a decision is still a decision. The decision to not take medication may have risks inherent in not treating a condition and may result in adverse outcomes in the developing fetus. Lastly, presenting teratogen information often involves challenges in portraying and interpreting numerical risk. For example, when considering data presented in fraction format, patients and some health care providers may focus on the numerator or count of adverse events, while ignoring the magnitude of the denominator.
• Strategies: Health literacy “best practice” strategies are useful whether there is a lot of data or very little. These include the of use plain language and messages delivered in a clear and respectful voice, the use of visual aids, and the use effective teaching methods such as asking open-ended questions to assess understanding. Other strategies include using caution in framing information: for example, discussing a 1% increase in risk for a baby to have a medication-associated birth defect should also be presented as a 99% chance the medication will not cause a birth defect. Numeracy challenges can also be addressed by using natural numbers rather than fractions or percentages: for example, if there were 100 women in this room, one would have a baby with a birth defect after taking this medication in pregnancy, but 99 of these women would not.

In today’s medical world, shared decision-making is the preferred approach to choices. Communicating and appropriately utilizing information to make choices about medication safety in pregnancy are vital undertakings. An important provider responsibility is helping patients understand that science is built on evidence that amasses and changes over time and that it represents rich shades of gray rather than “black and white” options.

Dr. Hardy is executive director, head of pharmacoepidemiology, Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention (BDRP), represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Conover is the director of Nebraska MotherToBaby. She is assistant professor at the Munroe Meyer Institute, University of Nebraska Medical Center.

References

1. Mitchell AA et al. Am J Obstet Gynecol. 2011;205(1):51:e1-e8.

2. Feghali M et al. Semin Perinatol 2015;39:512-9.

3. Conover EA, Polifka JE. Am J Med Genet Part C Semin Med Genet 2011;157:227-33.

Nearly 9 in 10 U.S. women take a medication at some point in their pregnancy, with approximately 50% of women taking at least one prescription medication.¹ These medications may be prescribed without the benefit of knowledge gained through clinical trials. Knowledge is gained after market, often after multiple years, and potentially following widespread use. The situation is similar for vaccines, as was recently seen with the SARS-CoV2 pandemic. Early in the pandemic, evidence emerged that pregnancy increased the risk for severe illness from COVID-19, yet pregnant people and their providers were forced to make a difficult decision of risk/benefit with little data to guide them.

The FDA product label provides a summary and narrative of animal and human safety studies relating to pregnancy. But what if that label contains little to no information, or reports studies with conflicting results? Perhaps the product is new on the market or is infrequently used during pregnancy. Regardless, health care providers and pregnant patients still need to make decisions about medication use. The following list outlines information that can be found, and strategies to support providers and patients in making informed choices for a treatment plan.


Taking stock of the available information:

• If possible, connect with the specialist who prescribed the patient’s medication in question. They may have already assembled information regarding use of that medication in pregnancy.
• The sponsor may have published useful information from the phase 3 trials, including the outcomes of enrolled patients who inadvertently became pregnant.
• Review the animal data in the product label. Regulators require the careful selection of animal models, and this data can present a source of adjunct information regarding the medication’s effects on pregnancy, reproduction, and development. Negative results can be as revealing as positive results.
• Pharmacologic data in the label can also be informative. Although most labels have pharmacologic data based on trials in healthy nonpregnant individuals, understanding pregnancy physiology and the patient’s preexisting or pregnancy-specific condition(s) can provide insights.² Close patient monitoring and follow-up are of key importance.
• Consider viable alternatives that may address the patient’s needs. There may be effective alternatives that have been better studied and shown to have low reproductive toxicity.
• Consider the risks to the patient as well as the developing fetus if the preexisting or pregnancy-specific condition is uncontrolled.
• Consult a teratogen specialist who can provide information to both patients and health care providers on the reproductive hazards or safety of many exposures, even those with limited data regarding use in pregnancy. For example, MotherToBaby provides a network of teratogen specialists.

Understanding perceptions of risk, decision-making, and strategies to support informed choices:

• Perceptions of risk: Each person perceives risk and benefit differently. The few studies that have attempted to investigate perception of teratogenic risk have found that many pregnant people overestimate the magnitude of teratogenic risk associated with a particular exposure.³ Alternatively, a medication’s benefit in controlling the maternal condition is often not considered sufficiently. Health care providers may have their own distorted perceptions of risk, even in the presence of evidence.
• Decision-making: Most teratogen data inherently involve uncertainty; it is rare to have completely nonconflicting data with which to make a decision. This makes decisions about whether or not to utilize a particular medication or other agent in pregnancy very difficult. For example, a patient would prefer to be told a black and white answer such as vaccines are either 100% safe or 100% harmful. However, no medical treatment is held to that standard of certainty. Even though it may be more comfortable to avoid an action and “just let things happen,” the lack of a decision is still a decision. The decision to not take medication may have risks inherent in not treating a condition and may result in adverse outcomes in the developing fetus. Lastly, presenting teratogen information often involves challenges in portraying and interpreting numerical risk. For example, when considering data presented in fraction format, patients and some health care providers may focus on the numerator or count of adverse events, while ignoring the magnitude of the denominator.
• Strategies: Health literacy “best practice” strategies are useful whether there is a lot of data or very little. These include the of use plain language and messages delivered in a clear and respectful voice, the use of visual aids, and the use effective teaching methods such as asking open-ended questions to assess understanding. Other strategies include using caution in framing information: for example, discussing a 1% increase in risk for a baby to have a medication-associated birth defect should also be presented as a 99% chance the medication will not cause a birth defect. Numeracy challenges can also be addressed by using natural numbers rather than fractions or percentages: for example, if there were 100 women in this room, one would have a baby with a birth defect after taking this medication in pregnancy, but 99 of these women would not.

In today’s medical world, shared decision-making is the preferred approach to choices. Communicating and appropriately utilizing information to make choices about medication safety in pregnancy are vital undertakings. An important provider responsibility is helping patients understand that science is built on evidence that amasses and changes over time and that it represents rich shades of gray rather than “black and white” options.

Dr. Hardy is executive director, head of pharmacoepidemiology, Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention (BDRP), represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Conover is the director of Nebraska MotherToBaby. She is assistant professor at the Munroe Meyer Institute, University of Nebraska Medical Center.

References

1. Mitchell AA et al. Am J Obstet Gynecol. 2011;205(1):51:e1-e8.

2. Feghali M et al. Semin Perinatol 2015;39:512-9.

3. Conover EA, Polifka JE. Am J Med Genet Part C Semin Med Genet 2011;157:227-33.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at obnews@mdedge.com.

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at obnews@mdedge.com.

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at obnews@mdedge.com.

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at victoria.persampiere@jefferson.edu or via fpnews@mdedge.com.

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at victoria.persampiere@jefferson.edu or via fpnews@mdedge.com.

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at victoria.persampiere@jefferson.edu or via fpnews@mdedge.com.

For decades, we have recognized the age-related natural decline in female fecundity (the ability to reproduce) after the age of 30 (Maturitas 1988;[Suppl]1:15-22). Advanced maternal age (AMA) has also been demonstrated to increase miscarriage and pregnancies with chromosomal abnormalities, presumably from the increased rate of oocyte aneuploidy. There has been a sixfold increase in the rate of first birth in women aged 35-39 years (NCHS Data Brief 2014;152:1-8). Consequently, over the last decade, women, often before they reach AMA, have turned to elective oocyte cryopreservation for fertility preservation.

Ovarian aging

Ovarian aging occurs through the decline in quality and quantity of oocytes. The former is a reflection of the woman’s chronologic age. Markers of female ovarian aging have been utilized, for the past 3 decades, most commonly by basal follicle stimulating hormone. Currently, to assess the quantity of ovarian follicles, antimüllerian hormone (AMH) and transvaginal ultrasound for ovarian antral follicle count (AFC) are the most accurate indicators (J Clin Endocrinol Metab 2004:89:2977-81). While ovarian age testing, particularly AMH, has been widely used to assess a woman’s “fertility potential,” it does not reflect her natural fecundity. In a prospective cohort study, AMH levels (ng/mL) divided into < 0.7, 0.7-8.4, and > 8.4, did not affect natural conception in women aged 30-44 who were divided into the categories of <35, 35-37, or 38-44 years (JAMA 2017;318:1367-76). Although AMH does reduce success with IVF, its main value is the inverse correlation when prescribing gonadotropin dosage for controlled ovarian stimulation.

Despite the familiarity with ovarian aging effects on fertility, the male biological clock remains less studied and understood. Over the last 4 decades, paternal age has increased an average of 3.5 years presumably due to delayed child rearing from professional or personal reasons, improved contraception as well as increased divorce, remarriage, and life expectancy (Hum Reprod. 2017;32:2110-6). Nevertheless, we have little data to definitively counsel men on the effects of advanced paternal age (APA) and no consensus on an actual defined age of designation. This month’s article will summarize the current literature on male age and its impact on fertility.
 

Testicular aging

Men older than 45 years require approximately five times longer to achieve a pregnancy as men less than 25 after adjustment for female age (Fertil Steril. 2003;79:1520-7). The most likely parameter to assess male fertility, other than pregnancy rates, would be the sperm. Sperm counts, beginning at age 41, may decline but concentrations have been shown to increase in older men apparently because of declining semen volume (Ageing Res Rev. 2015;19:22-33). Sperm motility, but not morphology, also declines while genetic alterations of sperm increase with age. The issue of chromosomal abnormalities in sperm from men of advanced age appears to be similar to that in the oocytes of women with AMA. Consequently, both sexes may contribute to embryo aneuploidy resulting in declining fertility and increasing miscarriage.

For all ages, studies have suggested that elevated male body mass index as well as alcohol consumption and cigarette smoking, including e-cigarettes, can lead to impaired sperm production (Hum Reprod Update 2013;19:221-31).
 

Fertility treatment outcomes

A mainstay of fertility treatment, particularly in men with mild to moderate impairments in semen parameters, is ovulation induction with intrauterine insemination. Male age has been shown to be a significant indicator for pregnancy rates, including those with normal semen parameters (J Obstet Gynaecol. 2011;31:420-3). Men above age 45 contributed to lower pregnancy rates and higher miscarriages during IUI treatment cycles (Reprod BioMed Online 2008;17:392-7).

During IVF cycles, the sperm of men with APA often undergo ICSI (intracytoplasmic sperm injection) due to higher fertilization rates compared with standard insemination. However, APA sperm appear to have lower fertilization rates and decreased embryo development to the blastocyst stage during cycles using donor oocytes, although pregnancy outcomes are inconsistent (Trans Androl Urol. 2019;8[Suppl 1]:S22-S30; Fertil Steril. 2008;90:97-103).
 

Perinatal and children’s health

The offspring from APA men appear to have higher rates of stillbirth, low birth weight, and preterm birth, as well as birth defects. Men older than 40-45 years have twice the risk of an autistic child and three times the risk of schizophrenia in their offspring (Transl Psychiatry 2017;7:e1019; Am J Psychiatry 2002;159:1528-33).

Conclusions

Most of the literature supports negative effects on sperm and reproduction from men with APA. The challenge in deciphering the true role of APA on fertility is that the partner is often of AMA. A consideration to avoid this effect would be sperm cryopreservation at a younger age, similar to the common trend among women. Preimplantation genetic testing of embryos from men with APA is also a potential option to reduce miscarriage and avoid a chromosomally abnormal pregnancy. Ethicists have pondered the impact of APA on parenthood and the detrimental effect of early paternal death on the child. Nevertheless, the effect of APA in reproduction is a vital area to study with the same fervor as AMA (Fertil Steril 2009;92:1772-5).

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts. Email him at obnews@mdedge.com.

For decades, we have recognized the age-related natural decline in female fecundity (the ability to reproduce) after the age of 30 (Maturitas 1988;[Suppl]1:15-22). Advanced maternal age (AMA) has also been demonstrated to increase miscarriage and pregnancies with chromosomal abnormalities, presumably from the increased rate of oocyte aneuploidy. There has been a sixfold increase in the rate of first birth in women aged 35-39 years (NCHS Data Brief 2014;152:1-8). Consequently, over the last decade, women, often before they reach AMA, have turned to elective oocyte cryopreservation for fertility preservation.

Ovarian aging

Ovarian aging occurs through the decline in quality and quantity of oocytes. The former is a reflection of the woman’s chronologic age. Markers of female ovarian aging have been utilized, for the past 3 decades, most commonly by basal follicle stimulating hormone. Currently, to assess the quantity of ovarian follicles, antimüllerian hormone (AMH) and transvaginal ultrasound for ovarian antral follicle count (AFC) are the most accurate indicators (J Clin Endocrinol Metab 2004:89:2977-81). While ovarian age testing, particularly AMH, has been widely used to assess a woman’s “fertility potential,” it does not reflect her natural fecundity. In a prospective cohort study, AMH levels (ng/mL) divided into < 0.7, 0.7-8.4, and > 8.4, did not affect natural conception in women aged 30-44 who were divided into the categories of <35, 35-37, or 38-44 years (JAMA 2017;318:1367-76). Although AMH does reduce success with IVF, its main value is the inverse correlation when prescribing gonadotropin dosage for controlled ovarian stimulation.

Despite the familiarity with ovarian aging effects on fertility, the male biological clock remains less studied and understood. Over the last 4 decades, paternal age has increased an average of 3.5 years presumably due to delayed child rearing from professional or personal reasons, improved contraception as well as increased divorce, remarriage, and life expectancy (Hum Reprod. 2017;32:2110-6). Nevertheless, we have little data to definitively counsel men on the effects of advanced paternal age (APA) and no consensus on an actual defined age of designation. This month’s article will summarize the current literature on male age and its impact on fertility.
 

Testicular aging

Men older than 45 years require approximately five times longer to achieve a pregnancy as men less than 25 after adjustment for female age (Fertil Steril. 2003;79:1520-7). The most likely parameter to assess male fertility, other than pregnancy rates, would be the sperm. Sperm counts, beginning at age 41, may decline but concentrations have been shown to increase in older men apparently because of declining semen volume (Ageing Res Rev. 2015;19:22-33). Sperm motility, but not morphology, also declines while genetic alterations of sperm increase with age. The issue of chromosomal abnormalities in sperm from men of advanced age appears to be similar to that in the oocytes of women with AMA. Consequently, both sexes may contribute to embryo aneuploidy resulting in declining fertility and increasing miscarriage.

For all ages, studies have suggested that elevated male body mass index as well as alcohol consumption and cigarette smoking, including e-cigarettes, can lead to impaired sperm production (Hum Reprod Update 2013;19:221-31).
 

Fertility treatment outcomes

A mainstay of fertility treatment, particularly in men with mild to moderate impairments in semen parameters, is ovulation induction with intrauterine insemination. Male age has been shown to be a significant indicator for pregnancy rates, including those with normal semen parameters (J Obstet Gynaecol. 2011;31:420-3). Men above age 45 contributed to lower pregnancy rates and higher miscarriages during IUI treatment cycles (Reprod BioMed Online 2008;17:392-7).

During IVF cycles, the sperm of men with APA often undergo ICSI (intracytoplasmic sperm injection) due to higher fertilization rates compared with standard insemination. However, APA sperm appear to have lower fertilization rates and decreased embryo development to the blastocyst stage during cycles using donor oocytes, although pregnancy outcomes are inconsistent (Trans Androl Urol. 2019;8[Suppl 1]:S22-S30; Fertil Steril. 2008;90:97-103).
 

Perinatal and children’s health

The offspring from APA men appear to have higher rates of stillbirth, low birth weight, and preterm birth, as well as birth defects. Men older than 40-45 years have twice the risk of an autistic child and three times the risk of schizophrenia in their offspring (Transl Psychiatry 2017;7:e1019; Am J Psychiatry 2002;159:1528-33).

Conclusions

Most of the literature supports negative effects on sperm and reproduction from men with APA. The challenge in deciphering the true role of APA on fertility is that the partner is often of AMA. A consideration to avoid this effect would be sperm cryopreservation at a younger age, similar to the common trend among women. Preimplantation genetic testing of embryos from men with APA is also a potential option to reduce miscarriage and avoid a chromosomally abnormal pregnancy. Ethicists have pondered the impact of APA on parenthood and the detrimental effect of early paternal death on the child. Nevertheless, the effect of APA in reproduction is a vital area to study with the same fervor as AMA (Fertil Steril 2009;92:1772-5).

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts. Email him at obnews@mdedge.com.

For decades, we have recognized the age-related natural decline in female fecundity (the ability to reproduce) after the age of 30 (Maturitas 1988;[Suppl]1:15-22). Advanced maternal age (AMA) has also been demonstrated to increase miscarriage and pregnancies with chromosomal abnormalities, presumably from the increased rate of oocyte aneuploidy. There has been a sixfold increase in the rate of first birth in women aged 35-39 years (NCHS Data Brief 2014;152:1-8). Consequently, over the last decade, women, often before they reach AMA, have turned to elective oocyte cryopreservation for fertility preservation.

Ovarian aging

Ovarian aging occurs through the decline in quality and quantity of oocytes. The former is a reflection of the woman’s chronologic age. Markers of female ovarian aging have been utilized, for the past 3 decades, most commonly by basal follicle stimulating hormone. Currently, to assess the quantity of ovarian follicles, antimüllerian hormone (AMH) and transvaginal ultrasound for ovarian antral follicle count (AFC) are the most accurate indicators (J Clin Endocrinol Metab 2004:89:2977-81). While ovarian age testing, particularly AMH, has been widely used to assess a woman’s “fertility potential,” it does not reflect her natural fecundity. In a prospective cohort study, AMH levels (ng/mL) divided into < 0.7, 0.7-8.4, and > 8.4, did not affect natural conception in women aged 30-44 who were divided into the categories of <35, 35-37, or 38-44 years (JAMA 2017;318:1367-76). Although AMH does reduce success with IVF, its main value is the inverse correlation when prescribing gonadotropin dosage for controlled ovarian stimulation.

Despite the familiarity with ovarian aging effects on fertility, the male biological clock remains less studied and understood. Over the last 4 decades, paternal age has increased an average of 3.5 years presumably due to delayed child rearing from professional or personal reasons, improved contraception as well as increased divorce, remarriage, and life expectancy (Hum Reprod. 2017;32:2110-6). Nevertheless, we have little data to definitively counsel men on the effects of advanced paternal age (APA) and no consensus on an actual defined age of designation. This month’s article will summarize the current literature on male age and its impact on fertility.
 

Testicular aging

Men older than 45 years require approximately five times longer to achieve a pregnancy as men less than 25 after adjustment for female age (Fertil Steril. 2003;79:1520-7). The most likely parameter to assess male fertility, other than pregnancy rates, would be the sperm. Sperm counts, beginning at age 41, may decline but concentrations have been shown to increase in older men apparently because of declining semen volume (Ageing Res Rev. 2015;19:22-33). Sperm motility, but not morphology, also declines while genetic alterations of sperm increase with age. The issue of chromosomal abnormalities in sperm from men of advanced age appears to be similar to that in the oocytes of women with AMA. Consequently, both sexes may contribute to embryo aneuploidy resulting in declining fertility and increasing miscarriage.

For all ages, studies have suggested that elevated male body mass index as well as alcohol consumption and cigarette smoking, including e-cigarettes, can lead to impaired sperm production (Hum Reprod Update 2013;19:221-31).
 

Fertility treatment outcomes

A mainstay of fertility treatment, particularly in men with mild to moderate impairments in semen parameters, is ovulation induction with intrauterine insemination. Male age has been shown to be a significant indicator for pregnancy rates, including those with normal semen parameters (J Obstet Gynaecol. 2011;31:420-3). Men above age 45 contributed to lower pregnancy rates and higher miscarriages during IUI treatment cycles (Reprod BioMed Online 2008;17:392-7).

During IVF cycles, the sperm of men with APA often undergo ICSI (intracytoplasmic sperm injection) due to higher fertilization rates compared with standard insemination. However, APA sperm appear to have lower fertilization rates and decreased embryo development to the blastocyst stage during cycles using donor oocytes, although pregnancy outcomes are inconsistent (Trans Androl Urol. 2019;8[Suppl 1]:S22-S30; Fertil Steril. 2008;90:97-103).
 

Perinatal and children’s health

The offspring from APA men appear to have higher rates of stillbirth, low birth weight, and preterm birth, as well as birth defects. Men older than 40-45 years have twice the risk of an autistic child and three times the risk of schizophrenia in their offspring (Transl Psychiatry 2017;7:e1019; Am J Psychiatry 2002;159:1528-33).

Conclusions

Most of the literature supports negative effects on sperm and reproduction from men with APA. The challenge in deciphering the true role of APA on fertility is that the partner is often of AMA. A consideration to avoid this effect would be sperm cryopreservation at a younger age, similar to the common trend among women. Preimplantation genetic testing of embryos from men with APA is also a potential option to reduce miscarriage and avoid a chromosomally abnormal pregnancy. Ethicists have pondered the impact of APA on parenthood and the detrimental effect of early paternal death on the child. Nevertheless, the effect of APA in reproduction is a vital area to study with the same fervor as AMA (Fertil Steril 2009;92:1772-5).

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts. Email him at obnews@mdedge.com.

The recent U.S. Preventive Services Task Force (USPSTF) draft statement on aspirin use is concerning: “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit.” I take no issue with the data and appreciate the efforts of the researchers, but at a minimum the public statement is incomplete. At most, it’s dangerously poor messaging.

As physicians, we understand how best to apply this information, but most laypeople, some at significant cardiovascular risk, closed their medicine cabinets this morning and left their aspirin bottle unopened on the shelf. Some of these patients have never spent an hour in the hospital for cardiac-related issues, but they have mitigated their risk for myocardial infarction by purposely poisoning their platelets daily with 81 mg of aspirin. And they should continue to do so.
 

Don’t forget the calcium score

Take, for instance, my patient Jack, who is typical of many patients I’ve seen throughout the years. Jack is 68 years old and has never had a cardiac event or a gastrointestinal bleed. His daily routine includes a walk, a statin, and a baby aspirin because his CT coronary artery calcium (CAC) score was 10,000 at age 58.

He first visited me 10 years ago because his father died of a myocardial infarction in his late 50s. Jack’s left ventricular ejection fraction is normal and his stress ECG shows 1-mm ST-segment depression at 8 minutes on a Bruce protocol stress test, without angina. Because Jack is well-educated and keeps up with the latest cardiology recommendations, he is precisely the type of patient who may be harmed by this new USPSTF statement by stopping his aspirin.

In October 2020, an analysis from the DALLAS Heart Study showed that persons with a CAC score greater than 100 had a higher cumulative incidence of bleeding and of atherosclerotic cardiovascular disease (ASCVD) events compared with those with no coronary calcium. After adjustment for clinical risk factors, the association between CAC and bleeding was attenuated and no longer statistically significant, whereas the relationship between CAC and ASCVD remained.

I asked one of the investigators, Amit Khera, MD, MSc, from UT Southwestern Medical Center, about the latest recommendations. He emphasized that both the American College of Cardiology/American Heart Association prevention guidelines and the USPSTF statement say that aspirin could still be considered among patients who are at higher risk for cardiovascular events. The USPSTF delineated this as a 10-year ASCVD risk greater than 10%.

Dr. Khera, who was an author of the 2019 guidelines, explained that the guideline committee purposely did not make specific recommendations as to what demarcated higher risk because the data were not clear at that time. Since then, a couple of papers, including the Dallas Heart Study analysis published in JAMA Cardiology, showed that patients at low bleeding risk with a calcium score above 100 may get a net benefit from aspirin. “Thus, in my patients who have a high calcium score and low bleeding risk, I do discuss the option to start or continue aspirin,” he said.
 

One size does not fit all

I watched ABC World News Tonight on Tuesday, October 12, and was immediately troubled about the coverage of the USPSTF statement. With viewership for the “Big Three” networks in the millions, the message to discontinue aspirin may have unintended consequences for many at-risk patients. The blood-thinning effects of a single dose of aspirin last about 10 days; it will be interesting to see if the rates of myocardial infarction increase over time. This could have been avoided with a better-worded statement – I’m concerned that the lack of nuance could spell big trouble for some.

In JAMA Cardiology, Dr. Khera and colleagues wrote that, “Aspirin use is not a one-size-fits-all therapy.” All physicians likely agree with that opinion. The USPSTF statement should have included the point that if you have a high CT coronary artery calcium score and a low bleeding risk, aspirin still fits very well even if you haven’t experienced a cardiac event. At a minimum, the USPSTF statement should have included the suggestion for patients to consult their physician for advice before discontinuing aspirin therapy.

I hope patients like Jack get the right message.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology.

A version of this article first appeared on Medscape.com.

The recent U.S. Preventive Services Task Force (USPSTF) draft statement on aspirin use is concerning: “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit.” I take no issue with the data and appreciate the efforts of the researchers, but at a minimum the public statement is incomplete. At most, it’s dangerously poor messaging.

As physicians, we understand how best to apply this information, but most laypeople, some at significant cardiovascular risk, closed their medicine cabinets this morning and left their aspirin bottle unopened on the shelf. Some of these patients have never spent an hour in the hospital for cardiac-related issues, but they have mitigated their risk for myocardial infarction by purposely poisoning their platelets daily with 81 mg of aspirin. And they should continue to do so.
 

Don’t forget the calcium score

Take, for instance, my patient Jack, who is typical of many patients I’ve seen throughout the years. Jack is 68 years old and has never had a cardiac event or a gastrointestinal bleed. His daily routine includes a walk, a statin, and a baby aspirin because his CT coronary artery calcium (CAC) score was 10,000 at age 58.

He first visited me 10 years ago because his father died of a myocardial infarction in his late 50s. Jack’s left ventricular ejection fraction is normal and his stress ECG shows 1-mm ST-segment depression at 8 minutes on a Bruce protocol stress test, without angina. Because Jack is well-educated and keeps up with the latest cardiology recommendations, he is precisely the type of patient who may be harmed by this new USPSTF statement by stopping his aspirin.

In October 2020, an analysis from the DALLAS Heart Study showed that persons with a CAC score greater than 100 had a higher cumulative incidence of bleeding and of atherosclerotic cardiovascular disease (ASCVD) events compared with those with no coronary calcium. After adjustment for clinical risk factors, the association between CAC and bleeding was attenuated and no longer statistically significant, whereas the relationship between CAC and ASCVD remained.

I asked one of the investigators, Amit Khera, MD, MSc, from UT Southwestern Medical Center, about the latest recommendations. He emphasized that both the American College of Cardiology/American Heart Association prevention guidelines and the USPSTF statement say that aspirin could still be considered among patients who are at higher risk for cardiovascular events. The USPSTF delineated this as a 10-year ASCVD risk greater than 10%.

Dr. Khera, who was an author of the 2019 guidelines, explained that the guideline committee purposely did not make specific recommendations as to what demarcated higher risk because the data were not clear at that time. Since then, a couple of papers, including the Dallas Heart Study analysis published in JAMA Cardiology, showed that patients at low bleeding risk with a calcium score above 100 may get a net benefit from aspirin. “Thus, in my patients who have a high calcium score and low bleeding risk, I do discuss the option to start or continue aspirin,” he said.
 

One size does not fit all

I watched ABC World News Tonight on Tuesday, October 12, and was immediately troubled about the coverage of the USPSTF statement. With viewership for the “Big Three” networks in the millions, the message to discontinue aspirin may have unintended consequences for many at-risk patients. The blood-thinning effects of a single dose of aspirin last about 10 days; it will be interesting to see if the rates of myocardial infarction increase over time. This could have been avoided with a better-worded statement – I’m concerned that the lack of nuance could spell big trouble for some.

In JAMA Cardiology, Dr. Khera and colleagues wrote that, “Aspirin use is not a one-size-fits-all therapy.” All physicians likely agree with that opinion. The USPSTF statement should have included the point that if you have a high CT coronary artery calcium score and a low bleeding risk, aspirin still fits very well even if you haven’t experienced a cardiac event. At a minimum, the USPSTF statement should have included the suggestion for patients to consult their physician for advice before discontinuing aspirin therapy.

I hope patients like Jack get the right message.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology.

A version of this article first appeared on Medscape.com.

The recent U.S. Preventive Services Task Force (USPSTF) draft statement on aspirin use is concerning: “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit.” I take no issue with the data and appreciate the efforts of the researchers, but at a minimum the public statement is incomplete. At most, it’s dangerously poor messaging.

As physicians, we understand how best to apply this information, but most laypeople, some at significant cardiovascular risk, closed their medicine cabinets this morning and left their aspirin bottle unopened on the shelf. Some of these patients have never spent an hour in the hospital for cardiac-related issues, but they have mitigated their risk for myocardial infarction by purposely poisoning their platelets daily with 81 mg of aspirin. And they should continue to do so.
 

Don’t forget the calcium score

Take, for instance, my patient Jack, who is typical of many patients I’ve seen throughout the years. Jack is 68 years old and has never had a cardiac event or a gastrointestinal bleed. His daily routine includes a walk, a statin, and a baby aspirin because his CT coronary artery calcium (CAC) score was 10,000 at age 58.

He first visited me 10 years ago because his father died of a myocardial infarction in his late 50s. Jack’s left ventricular ejection fraction is normal and his stress ECG shows 1-mm ST-segment depression at 8 minutes on a Bruce protocol stress test, without angina. Because Jack is well-educated and keeps up with the latest cardiology recommendations, he is precisely the type of patient who may be harmed by this new USPSTF statement by stopping his aspirin.

In October 2020, an analysis from the DALLAS Heart Study showed that persons with a CAC score greater than 100 had a higher cumulative incidence of bleeding and of atherosclerotic cardiovascular disease (ASCVD) events compared with those with no coronary calcium. After adjustment for clinical risk factors, the association between CAC and bleeding was attenuated and no longer statistically significant, whereas the relationship between CAC and ASCVD remained.

I asked one of the investigators, Amit Khera, MD, MSc, from UT Southwestern Medical Center, about the latest recommendations. He emphasized that both the American College of Cardiology/American Heart Association prevention guidelines and the USPSTF statement say that aspirin could still be considered among patients who are at higher risk for cardiovascular events. The USPSTF delineated this as a 10-year ASCVD risk greater than 10%.

Dr. Khera, who was an author of the 2019 guidelines, explained that the guideline committee purposely did not make specific recommendations as to what demarcated higher risk because the data were not clear at that time. Since then, a couple of papers, including the Dallas Heart Study analysis published in JAMA Cardiology, showed that patients at low bleeding risk with a calcium score above 100 may get a net benefit from aspirin. “Thus, in my patients who have a high calcium score and low bleeding risk, I do discuss the option to start or continue aspirin,” he said.
 

One size does not fit all

I watched ABC World News Tonight on Tuesday, October 12, and was immediately troubled about the coverage of the USPSTF statement. With viewership for the “Big Three” networks in the millions, the message to discontinue aspirin may have unintended consequences for many at-risk patients. The blood-thinning effects of a single dose of aspirin last about 10 days; it will be interesting to see if the rates of myocardial infarction increase over time. This could have been avoided with a better-worded statement – I’m concerned that the lack of nuance could spell big trouble for some.

In JAMA Cardiology, Dr. Khera and colleagues wrote that, “Aspirin use is not a one-size-fits-all therapy.” All physicians likely agree with that opinion. The USPSTF statement should have included the point that if you have a high CT coronary artery calcium score and a low bleeding risk, aspirin still fits very well even if you haven’t experienced a cardiac event. At a minimum, the USPSTF statement should have included the suggestion for patients to consult their physician for advice before discontinuing aspirin therapy.

I hope patients like Jack get the right message.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology.

A version of this article first appeared on Medscape.com.

As the famous saying goes, “laughter is the best medicine.”

So it’s no surprise that humor is a great way to connect with different people and across various groups.

Memes are usually conveyed as images and texts that communicate ideas or thoughts. A meme, or “imitated thing” (translation from the Greek mimeme), was reappropriated from Richard Dawkins in his book The Selfish Gene; we can characterize “meme” with the word “gene” insofar as both self-replicate and are translated from person to person.

I am a big fan of memes. In fact, I can confidently say that one-third of my camera roll is dedicated to saved memes from Facebook, Instagram, and friends. Shameless to say, I’m also part of a few online groups dedicated to memes. They are relatable, as well as quick and fun ways to make light of an otherwise dull or upsetting situation.

Memes are contagious. From the moment they are created, they can be shared from one person to another, be edited or changed to adapt to the current situation, and become viral. They can be used to augment a conversation or replace the need for text communication entirely – in a sense, they are an entire language in and of themselves. They are constantly undergoing selection, repacking, and filtration. As a result, the most popular, successful, and, usually, relatable meme comes out on top, whereas the others fall behind and become “extinct.”

Memes generally adopt a form of word- or image-play that resonates well with people. The type of content varies from general lighthearted harmless animal humor to wry political and/or social commentary. They can be nearly universal or target specific groups (for example, students).

The popularity of memes depends on two factors: likability and “viralability.” Likability refers to how stimulating or engaging the content is, whereas “viralability” refers to the ability of the content to create a similar effect of user engagement across multiple people. Both factors are dynamic and can be quantified on the basis of the number of likes, shares, and/or comments.

In a content analysis of 1,000 memes on Facebook, researchers found that affiliative and aggressive humor styles were the most prevalent. Affiliative humor refers to a style of banter or joke that portrays others in a positive light, whereas aggressive humor achieves the opposite (that is, portrays others in a negative light). Interestingly, the type of humor that achieved the average most likes and shares was self-defeating humor (that is, disparaging one’s own situation in a negative perspective).

Self-defeating memes are suggested to have higher meme fitness. Meme fitness refers to the replicability of a meme. In this context, self-defeating memes have a unique ability to resonate with peoples’ thoughts and feelings in a sarcastic way and create laughter in contexts of general hardships (for example, failed relationships, academic hardships, or general life weaknesses). In a way, I’ve found that self-defeating memes offer a branch of support; to know that I am not going through certain problems alone, and that others can understand these difficulties, is comforting.

Memes can target emotional pain, neutralize the threat, and turn discomfort into a discourse of playfulness and warmth. Especially during times of great uncertainty, a bit of banter and wry humor may be just what we need to make light of difficult situations.

Leanna M.W. Lui, HBSc, completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc student.

A version of this article first appeared on Medscape.com.

As the famous saying goes, “laughter is the best medicine.”

So it’s no surprise that humor is a great way to connect with different people and across various groups.

Memes are usually conveyed as images and texts that communicate ideas or thoughts. A meme, or “imitated thing” (translation from the Greek mimeme), was reappropriated from Richard Dawkins in his book The Selfish Gene; we can characterize “meme” with the word “gene” insofar as both self-replicate and are translated from person to person.

I am a big fan of memes. In fact, I can confidently say that one-third of my camera roll is dedicated to saved memes from Facebook, Instagram, and friends. Shameless to say, I’m also part of a few online groups dedicated to memes. They are relatable, as well as quick and fun ways to make light of an otherwise dull or upsetting situation.

Memes are contagious. From the moment they are created, they can be shared from one person to another, be edited or changed to adapt to the current situation, and become viral. They can be used to augment a conversation or replace the need for text communication entirely – in a sense, they are an entire language in and of themselves. They are constantly undergoing selection, repacking, and filtration. As a result, the most popular, successful, and, usually, relatable meme comes out on top, whereas the others fall behind and become “extinct.”

Memes generally adopt a form of word- or image-play that resonates well with people. The type of content varies from general lighthearted harmless animal humor to wry political and/or social commentary. They can be nearly universal or target specific groups (for example, students).

The popularity of memes depends on two factors: likability and “viralability.” Likability refers to how stimulating or engaging the content is, whereas “viralability” refers to the ability of the content to create a similar effect of user engagement across multiple people. Both factors are dynamic and can be quantified on the basis of the number of likes, shares, and/or comments.

In a content analysis of 1,000 memes on Facebook, researchers found that affiliative and aggressive humor styles were the most prevalent. Affiliative humor refers to a style of banter or joke that portrays others in a positive light, whereas aggressive humor achieves the opposite (that is, portrays others in a negative light). Interestingly, the type of humor that achieved the average most likes and shares was self-defeating humor (that is, disparaging one’s own situation in a negative perspective).

Self-defeating memes are suggested to have higher meme fitness. Meme fitness refers to the replicability of a meme. In this context, self-defeating memes have a unique ability to resonate with peoples’ thoughts and feelings in a sarcastic way and create laughter in contexts of general hardships (for example, failed relationships, academic hardships, or general life weaknesses). In a way, I’ve found that self-defeating memes offer a branch of support; to know that I am not going through certain problems alone, and that others can understand these difficulties, is comforting.

Memes can target emotional pain, neutralize the threat, and turn discomfort into a discourse of playfulness and warmth. Especially during times of great uncertainty, a bit of banter and wry humor may be just what we need to make light of difficult situations.

Leanna M.W. Lui, HBSc, completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc student.

A version of this article first appeared on Medscape.com.

As the famous saying goes, “laughter is the best medicine.”

So it’s no surprise that humor is a great way to connect with different people and across various groups.

Memes are usually conveyed as images and texts that communicate ideas or thoughts. A meme, or “imitated thing” (translation from the Greek mimeme), was reappropriated from Richard Dawkins in his book The Selfish Gene; we can characterize “meme” with the word “gene” insofar as both self-replicate and are translated from person to person.

I am a big fan of memes. In fact, I can confidently say that one-third of my camera roll is dedicated to saved memes from Facebook, Instagram, and friends. Shameless to say, I’m also part of a few online groups dedicated to memes. They are relatable, as well as quick and fun ways to make light of an otherwise dull or upsetting situation.

Memes are contagious. From the moment they are created, they can be shared from one person to another, be edited or changed to adapt to the current situation, and become viral. They can be used to augment a conversation or replace the need for text communication entirely – in a sense, they are an entire language in and of themselves. They are constantly undergoing selection, repacking, and filtration. As a result, the most popular, successful, and, usually, relatable meme comes out on top, whereas the others fall behind and become “extinct.”

Memes generally adopt a form of word- or image-play that resonates well with people. The type of content varies from general lighthearted harmless animal humor to wry political and/or social commentary. They can be nearly universal or target specific groups (for example, students).

The popularity of memes depends on two factors: likability and “viralability.” Likability refers to how stimulating or engaging the content is, whereas “viralability” refers to the ability of the content to create a similar effect of user engagement across multiple people. Both factors are dynamic and can be quantified on the basis of the number of likes, shares, and/or comments.

In a content analysis of 1,000 memes on Facebook, researchers found that affiliative and aggressive humor styles were the most prevalent. Affiliative humor refers to a style of banter or joke that portrays others in a positive light, whereas aggressive humor achieves the opposite (that is, portrays others in a negative light). Interestingly, the type of humor that achieved the average most likes and shares was self-defeating humor (that is, disparaging one’s own situation in a negative perspective).

Self-defeating memes are suggested to have higher meme fitness. Meme fitness refers to the replicability of a meme. In this context, self-defeating memes have a unique ability to resonate with peoples’ thoughts and feelings in a sarcastic way and create laughter in contexts of general hardships (for example, failed relationships, academic hardships, or general life weaknesses). In a way, I’ve found that self-defeating memes offer a branch of support; to know that I am not going through certain problems alone, and that others can understand these difficulties, is comforting.

Memes can target emotional pain, neutralize the threat, and turn discomfort into a discourse of playfulness and warmth. Especially during times of great uncertainty, a bit of banter and wry humor may be just what we need to make light of difficult situations.

Leanna M.W. Lui, HBSc, completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc student.

A version of this article first appeared on Medscape.com.

Dementia remains a major cause of disability in older adults. In addition, it places a strain on family members and other caregivers taking care of these patients.

It is estimated that by the year 2060, 13.9 million Americans over the age of 65 will be diagnosed with dementia. Few good treatments are currently available.

Earlier this year, the American Psychological Association (APA) Task Force issued clinical guidelines “for the Evaluation of Dementia and Age-Related Cognitive Change.” While these 16 guidelines are aimed at psychologists, primary care doctors are often the first ones to evaluate a patient who may have dementia. As a family physician, I find having these guidelines especially helpful.
 

Neuropsychiatric testing and defining severity and type

This new guidance places emphasis on neuropsychiatric testing and defining the severity and type of dementia present.

Over the past 2 decades, diagnoses of mild neurocognitive disorders have increased, and this, in part, is due to diagnosing these problems earlier and with greater precision. It is also important to know that biomarkers are being increasingly researched, and it is imperative that we stay current with this research.

Cognitive decline may also occur with the coexistence of other mental health disorders, such as depression, so it is important that we screen for these as well. This is often difficult given the behavioral changes that can arise in dementia, but, as primary care doctors, we must differentiate these to treat our patients appropriately.
 

Informed consent

Informed consent can become an issue with patients with dementia. It must be assessed whether the patient has the capacity to make an informed decision and can competently communicate that decision.

The diagnosis of dementia alone does not preclude a patient from giving informed consent. A patient’s mental capacity must be determined, and if they are not capable of making an informed decision, the person legally responsible for giving informed consent on behalf of the patient must be identified.

Patients with dementia often have other medical comorbidities and take several medications. It is imperative to keep accurate medical records and medication lists. Sometimes, patients with dementia cannot provide this information. If that is the case, every attempt should be made to obtain records from every possible source.
 

Cultural competence

The guidelines also stress that there may be cultural differences when applying neuropsychiatric tests. It is our duty to maintain cultural competence and understand these differences. We all need to work to ensure we control our biases, and it is suggested that we review relevant evidence-based literature.

While ageism is common in our society, it shouldn’t be in our practices. For these reasons, outreach in at-risk populations is very important.
 

Pertinent data

The guidelines also suggest obtaining all possible information in our evaluation, especially when the patient is unable to give it to us.

Often, as primary care physicians, we refer these patients to other providers, and we should be providing all pertinent data to those we are referring these patients to. If all information is not available at the time of evaluation, follow-up visits should be scheduled.

If possible, family members should be present at the time of visit. They often provide valuable information regarding the extent and progression of the decline. Also, they know how the patient is functioning in the home setting and how much assistance they need with activities of daily living.
 

Caretaker support

Another important factor to consider is caretaker burnout. Caretakers are often under a lot of stress and have high rates of depression. It is important to provide them with education and support, as well as resources that may be available to them. For some, accepting the diagnosis that their loved one has dementia may be a struggle.

As doctors treating dementia patients, we need to know the resources that are available to assist dementia patients and their families. There are many local organizations that can help.

Also, research into dementia is ongoing and we need to stay current. The diagnosis of dementia should be made as early as possible using appropriate screening tools. The sooner the diagnosis is made, the quicker interventions can be started and the family members, as well as the patient, can come to accept the diagnosis.

As the population ages, we can expect the demands of dementia to rise as well. Primary care doctors are in a unique position to diagnose dementia once it starts to appear.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.

Dementia remains a major cause of disability in older adults. In addition, it places a strain on family members and other caregivers taking care of these patients.

It is estimated that by the year 2060, 13.9 million Americans over the age of 65 will be diagnosed with dementia. Few good treatments are currently available.

Earlier this year, the American Psychological Association (APA) Task Force issued clinical guidelines “for the Evaluation of Dementia and Age-Related Cognitive Change.” While these 16 guidelines are aimed at psychologists, primary care doctors are often the first ones to evaluate a patient who may have dementia. As a family physician, I find having these guidelines especially helpful.
 

Neuropsychiatric testing and defining severity and type

This new guidance places emphasis on neuropsychiatric testing and defining the severity and type of dementia present.

Over the past 2 decades, diagnoses of mild neurocognitive disorders have increased, and this, in part, is due to diagnosing these problems earlier and with greater precision. It is also important to know that biomarkers are being increasingly researched, and it is imperative that we stay current with this research.

Cognitive decline may also occur with the coexistence of other mental health disorders, such as depression, so it is important that we screen for these as well. This is often difficult given the behavioral changes that can arise in dementia, but, as primary care doctors, we must differentiate these to treat our patients appropriately.
 

Informed consent

Informed consent can become an issue with patients with dementia. It must be assessed whether the patient has the capacity to make an informed decision and can competently communicate that decision.

The diagnosis of dementia alone does not preclude a patient from giving informed consent. A patient’s mental capacity must be determined, and if they are not capable of making an informed decision, the person legally responsible for giving informed consent on behalf of the patient must be identified.

Patients with dementia often have other medical comorbidities and take several medications. It is imperative to keep accurate medical records and medication lists. Sometimes, patients with dementia cannot provide this information. If that is the case, every attempt should be made to obtain records from every possible source.
 

Cultural competence

The guidelines also stress that there may be cultural differences when applying neuropsychiatric tests. It is our duty to maintain cultural competence and understand these differences. We all need to work to ensure we control our biases, and it is suggested that we review relevant evidence-based literature.

While ageism is common in our society, it shouldn’t be in our practices. For these reasons, outreach in at-risk populations is very important.
 

Pertinent data

The guidelines also suggest obtaining all possible information in our evaluation, especially when the patient is unable to give it to us.

Often, as primary care physicians, we refer these patients to other providers, and we should be providing all pertinent data to those we are referring these patients to. If all information is not available at the time of evaluation, follow-up visits should be scheduled.

If possible, family members should be present at the time of visit. They often provide valuable information regarding the extent and progression of the decline. Also, they know how the patient is functioning in the home setting and how much assistance they need with activities of daily living.
 

Caretaker support

Another important factor to consider is caretaker burnout. Caretakers are often under a lot of stress and have high rates of depression. It is important to provide them with education and support, as well as resources that may be available to them. For some, accepting the diagnosis that their loved one has dementia may be a struggle.

As doctors treating dementia patients, we need to know the resources that are available to assist dementia patients and their families. There are many local organizations that can help.

Also, research into dementia is ongoing and we need to stay current. The diagnosis of dementia should be made as early as possible using appropriate screening tools. The sooner the diagnosis is made, the quicker interventions can be started and the family members, as well as the patient, can come to accept the diagnosis.

As the population ages, we can expect the demands of dementia to rise as well. Primary care doctors are in a unique position to diagnose dementia once it starts to appear.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.

Dementia remains a major cause of disability in older adults. In addition, it places a strain on family members and other caregivers taking care of these patients.

It is estimated that by the year 2060, 13.9 million Americans over the age of 65 will be diagnosed with dementia. Few good treatments are currently available.

Earlier this year, the American Psychological Association (APA) Task Force issued clinical guidelines “for the Evaluation of Dementia and Age-Related Cognitive Change.” While these 16 guidelines are aimed at psychologists, primary care doctors are often the first ones to evaluate a patient who may have dementia. As a family physician, I find having these guidelines especially helpful.
 

Neuropsychiatric testing and defining severity and type

This new guidance places emphasis on neuropsychiatric testing and defining the severity and type of dementia present.

Over the past 2 decades, diagnoses of mild neurocognitive disorders have increased, and this, in part, is due to diagnosing these problems earlier and with greater precision. It is also important to know that biomarkers are being increasingly researched, and it is imperative that we stay current with this research.

Cognitive decline may also occur with the coexistence of other mental health disorders, such as depression, so it is important that we screen for these as well. This is often difficult given the behavioral changes that can arise in dementia, but, as primary care doctors, we must differentiate these to treat our patients appropriately.
 

Informed consent

Informed consent can become an issue with patients with dementia. It must be assessed whether the patient has the capacity to make an informed decision and can competently communicate that decision.

The diagnosis of dementia alone does not preclude a patient from giving informed consent. A patient’s mental capacity must be determined, and if they are not capable of making an informed decision, the person legally responsible for giving informed consent on behalf of the patient must be identified.

Patients with dementia often have other medical comorbidities and take several medications. It is imperative to keep accurate medical records and medication lists. Sometimes, patients with dementia cannot provide this information. If that is the case, every attempt should be made to obtain records from every possible source.
 

Cultural competence

The guidelines also stress that there may be cultural differences when applying neuropsychiatric tests. It is our duty to maintain cultural competence and understand these differences. We all need to work to ensure we control our biases, and it is suggested that we review relevant evidence-based literature.

While ageism is common in our society, it shouldn’t be in our practices. For these reasons, outreach in at-risk populations is very important.
 

Pertinent data

The guidelines also suggest obtaining all possible information in our evaluation, especially when the patient is unable to give it to us.

Often, as primary care physicians, we refer these patients to other providers, and we should be providing all pertinent data to those we are referring these patients to. If all information is not available at the time of evaluation, follow-up visits should be scheduled.

If possible, family members should be present at the time of visit. They often provide valuable information regarding the extent and progression of the decline. Also, they know how the patient is functioning in the home setting and how much assistance they need with activities of daily living.
 

Caretaker support

Another important factor to consider is caretaker burnout. Caretakers are often under a lot of stress and have high rates of depression. It is important to provide them with education and support, as well as resources that may be available to them. For some, accepting the diagnosis that their loved one has dementia may be a struggle.

As doctors treating dementia patients, we need to know the resources that are available to assist dementia patients and their families. There are many local organizations that can help.

Also, research into dementia is ongoing and we need to stay current. The diagnosis of dementia should be made as early as possible using appropriate screening tools. The sooner the diagnosis is made, the quicker interventions can be started and the family members, as well as the patient, can come to accept the diagnosis.

As the population ages, we can expect the demands of dementia to rise as well. Primary care doctors are in a unique position to diagnose dementia once it starts to appear.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.