Expert Commentary

Yland JJ, Bresnick KA, Hatch EE, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966.

EXPERT COMMENTARY

Most US women aged 15 to 49 currently use contraception, with long-acting reversible contraception (LARC)—IUDs and the contraceptive implant—increasing in popularity over the last decade.¹ Oral contraceptive pills, male condoms, and LARC are the most common reversible methods used.¹ While the efficacy and safety of contraception have been established, few studies have examined the effect of recent contraceptive use on fertility.

Fecundability is the probability of pregnancy during a single menstrual cycle for a couple engaging in regular intercourse and not using contraception.² Small studies have found short-term reductions in fecundability after discontinuing combined oral contraceptives and larger reductions after stopping injectable contraceptives, with no long-term differences among methods.^3,4

Data are limited regarding the effects of other forms of contraception on fecundability, particularly LARC methods. A recent study was designed to evaluate the association between the last contraceptive method used and subsequent fecundability.²

Details of the study

Yland and colleagues pooled data from 3 prospective cohort studies of 17,954 women planning pregnancies in Denmark, Canada, and the United States. Participants reported the contraceptive method used most recently before trying to conceive. They completed questionnaires every 2 months for 12 months or until they reported a pregnancy. Women were excluded if they tried to conceive for more than 6 menstrual cycles at study entry.

The authors calculated the fecundability ratio—the average probability of conception per cycle for a specific contraceptive method compared with a reference method—using proportional probability models adjusted for potential confounders. They also calculated pregnancy attempt time using participant-reported menstrual cycle length and date of last menstrual period during follow-up questionnaires.

Continue to: Injectable contraceptives associated with longest delayed fertility return...

After adjusting for personal factors, medical history, lifestyle characteristics, and indicators of underlying fertility, the authors found that injectable contraceptive use was associated with decreased fecundability compared with barrier method use (fecundability ratio [FR], 0.65; 95% confidence interval [CI], 0.47–0.89). Hormonal IUD use was associated with slight increases in fecundability compared with barrier method use (FR, 1.14; 95% CI, 1.07–1.22) and copper IUD use (FR, 1.18; 95% CI, 1.05–1.33). All other contraceptive methods were not significantly different from barrier methods.

LARC method use was associated with the shortest delay in return of normal fertility (2 cycles), followed by oral and ring contraceptives (3 cycles) and patch (4 cycles). Women using injectable contraceptives experienced the longest delay (5–8 menstrual cycles). Lifetime duration of contraceptive use did not impact fecundability in the North American cohort.

Study strengths and limitations

This large, prospective study contributes useful information about fecundability after stopping contraceptive methods. It confirms earlier studies’ findings that showed decreased fecundability after stopping injectable contraceptives. Study participants’ most recent method used was similar to overall US method distribution.¹

Study limitations include online recruitment of self-selecting participants, which introduces selection bias. The study population was overwhelmingly white (92%) and highly educated (70% with college degrees), quite different from the US population. These findings may therefore have limited generalizability. Additionally, injectable contraceptive users had higher body mass index and were more likely to smoke and have diabetes, infertility, or irregular menstrual cycles. IUD users were more likely to be parous and have a history of unplanned pregnancy, indicating possible higher baseline fertility. Even after adjusting, possible unmeasured factors could impact study results. ●

Yland JJ, Bresnick KA, Hatch EE, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966.

EXPERT COMMENTARY

Most US women aged 15 to 49 currently use contraception, with long-acting reversible contraception (LARC)—IUDs and the contraceptive implant—increasing in popularity over the last decade.¹ Oral contraceptive pills, male condoms, and LARC are the most common reversible methods used.¹ While the efficacy and safety of contraception have been established, few studies have examined the effect of recent contraceptive use on fertility.

Fecundability is the probability of pregnancy during a single menstrual cycle for a couple engaging in regular intercourse and not using contraception.² Small studies have found short-term reductions in fecundability after discontinuing combined oral contraceptives and larger reductions after stopping injectable contraceptives, with no long-term differences among methods.^3,4

Data are limited regarding the effects of other forms of contraception on fecundability, particularly LARC methods. A recent study was designed to evaluate the association between the last contraceptive method used and subsequent fecundability.²

Details of the study

Yland and colleagues pooled data from 3 prospective cohort studies of 17,954 women planning pregnancies in Denmark, Canada, and the United States. Participants reported the contraceptive method used most recently before trying to conceive. They completed questionnaires every 2 months for 12 months or until they reported a pregnancy. Women were excluded if they tried to conceive for more than 6 menstrual cycles at study entry.

The authors calculated the fecundability ratio—the average probability of conception per cycle for a specific contraceptive method compared with a reference method—using proportional probability models adjusted for potential confounders. They also calculated pregnancy attempt time using participant-reported menstrual cycle length and date of last menstrual period during follow-up questionnaires.

Continue to: Injectable contraceptives associated with longest delayed fertility return...

After adjusting for personal factors, medical history, lifestyle characteristics, and indicators of underlying fertility, the authors found that injectable contraceptive use was associated with decreased fecundability compared with barrier method use (fecundability ratio [FR], 0.65; 95% confidence interval [CI], 0.47–0.89). Hormonal IUD use was associated with slight increases in fecundability compared with barrier method use (FR, 1.14; 95% CI, 1.07–1.22) and copper IUD use (FR, 1.18; 95% CI, 1.05–1.33). All other contraceptive methods were not significantly different from barrier methods.

LARC method use was associated with the shortest delay in return of normal fertility (2 cycles), followed by oral and ring contraceptives (3 cycles) and patch (4 cycles). Women using injectable contraceptives experienced the longest delay (5–8 menstrual cycles). Lifetime duration of contraceptive use did not impact fecundability in the North American cohort.

Study strengths and limitations

This large, prospective study contributes useful information about fecundability after stopping contraceptive methods. It confirms earlier studies’ findings that showed decreased fecundability after stopping injectable contraceptives. Study participants’ most recent method used was similar to overall US method distribution.¹

Study limitations include online recruitment of self-selecting participants, which introduces selection bias. The study population was overwhelmingly white (92%) and highly educated (70% with college degrees), quite different from the US population. These findings may therefore have limited generalizability. Additionally, injectable contraceptive users had higher body mass index and were more likely to smoke and have diabetes, infertility, or irregular menstrual cycles. IUD users were more likely to be parous and have a history of unplanned pregnancy, indicating possible higher baseline fertility. Even after adjusting, possible unmeasured factors could impact study results. ●

Yland JJ, Bresnick KA, Hatch EE, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966.

EXPERT COMMENTARY

Most US women aged 15 to 49 currently use contraception, with long-acting reversible contraception (LARC)—IUDs and the contraceptive implant—increasing in popularity over the last decade.¹ Oral contraceptive pills, male condoms, and LARC are the most common reversible methods used.¹ While the efficacy and safety of contraception have been established, few studies have examined the effect of recent contraceptive use on fertility.

Fecundability is the probability of pregnancy during a single menstrual cycle for a couple engaging in regular intercourse and not using contraception.² Small studies have found short-term reductions in fecundability after discontinuing combined oral contraceptives and larger reductions after stopping injectable contraceptives, with no long-term differences among methods.^3,4

Data are limited regarding the effects of other forms of contraception on fecundability, particularly LARC methods. A recent study was designed to evaluate the association between the last contraceptive method used and subsequent fecundability.²

Details of the study

Yland and colleagues pooled data from 3 prospective cohort studies of 17,954 women planning pregnancies in Denmark, Canada, and the United States. Participants reported the contraceptive method used most recently before trying to conceive. They completed questionnaires every 2 months for 12 months or until they reported a pregnancy. Women were excluded if they tried to conceive for more than 6 menstrual cycles at study entry.

The authors calculated the fecundability ratio—the average probability of conception per cycle for a specific contraceptive method compared with a reference method—using proportional probability models adjusted for potential confounders. They also calculated pregnancy attempt time using participant-reported menstrual cycle length and date of last menstrual period during follow-up questionnaires.

Continue to: Injectable contraceptives associated with longest delayed fertility return...

After adjusting for personal factors, medical history, lifestyle characteristics, and indicators of underlying fertility, the authors found that injectable contraceptive use was associated with decreased fecundability compared with barrier method use (fecundability ratio [FR], 0.65; 95% confidence interval [CI], 0.47–0.89). Hormonal IUD use was associated with slight increases in fecundability compared with barrier method use (FR, 1.14; 95% CI, 1.07–1.22) and copper IUD use (FR, 1.18; 95% CI, 1.05–1.33). All other contraceptive methods were not significantly different from barrier methods.

LARC method use was associated with the shortest delay in return of normal fertility (2 cycles), followed by oral and ring contraceptives (3 cycles) and patch (4 cycles). Women using injectable contraceptives experienced the longest delay (5–8 menstrual cycles). Lifetime duration of contraceptive use did not impact fecundability in the North American cohort.

Study strengths and limitations

This large, prospective study contributes useful information about fecundability after stopping contraceptive methods. It confirms earlier studies’ findings that showed decreased fecundability after stopping injectable contraceptives. Study participants’ most recent method used was similar to overall US method distribution.¹

Study limitations include online recruitment of self-selecting participants, which introduces selection bias. The study population was overwhelmingly white (92%) and highly educated (70% with college degrees), quite different from the US population. These findings may therefore have limited generalizability. Additionally, injectable contraceptive users had higher body mass index and were more likely to smoke and have diabetes, infertility, or irregular menstrual cycles. IUD users were more likely to be parous and have a history of unplanned pregnancy, indicating possible higher baseline fertility. Even after adjusting, possible unmeasured factors could impact study results. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.

Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).

Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.

Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
 

What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?

All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.

In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
 

Which psychedelic agents are under investigation in the United States, and for which indications?

Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.

Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.

A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.

Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.

LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.

Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.

Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.
 

What is the typical treatment regimen for psychedelic agents?

It is hard to speak of a “treatment regimen” in agents that are not used in clinical practice. Ongoing clinical trials with psilocybin generally involve one or two 6- to 8-hour sessions involving the oral administration of a moderately high dose under psychologically supported conditions.

Based on the current evidence base, which agents show the most promise?

Psilocybin is currently the most promising classic psychedelic undergoing clinical trials.

Do psychedelics have to be administered in a controlled setting in order to be effective?

Although many people have had meaningful experiences whether inside or outside of a controlled setting, there are serious potential risks associated with use of psilocybin and other classic psychedelics. The safety of psilocybin has been established in clinical studies in which participants have been carefully screened physically and psychologically, are psychologically prepared before their first session, and are psychologically supported during and after sessions. In vulnerable individuals, psilocybin has been associated with enduring psychiatric problems and sometimes persisting visual perceptual conditions. When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others – including life-threatening risk. Thus, for safety reasons, the optimal environment for using these agents is in a controlled setting.

Do results differ between patients who have used psychedelic agents previously and those who have not?

We have not found any difference between psychedelic-naive volunteers and those who have used psychedelics in the past.

Do you provide patient education prior to treatment initiation?

All of our study participants are thoroughly screened for medical concerns or mental health history such as psychosis, which would preclude their participation. They are educated about the effects of these agents and what they might expect and typically receive several hours of psychological preparation before the first session. They are also provided with psychological support after sessions. Additionally, we spend time developing trust and rapport prior to the first session.

How durable are the effects of psychedelic treatment?

Studies in patients and healthy participants suggest that the positive effects of psilocybin are long lasting, with most individuals reporting positive changes in moods, attitudes, and behavior that they attribute to psilocybin and which endure months or years after the session. The qualities of the acute session experience can vary widely ranging from experiences of transcendence or psychological insight to experiences of intense anxiety or fear.

An enduring shift in worldview and sense of self, as well as psychological insight, may increase psychological flexibility, thereby allowing individuals to subsequently avoid maladaptive patterns of behavior or thought and to make more healthy choices.

Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experience of their lives.
 

Do participants experience any adverse effects? If so, how are they managed?

Sometimes, despite all the preparation, screening, and support we provide, some participants can have frightening experiences, such as fear and anxiety during the session. When that occurs, it is often shorted lived. The psychological preparation we provide before the session and the psychological support we provide during the session are important for managing such effects.

We provide support and encourage participants to stay with that experience, which may open to experiences of deep meaning or insight. A number of people report that these psychologically challenging states are a valuable part of the overall experience.

We conducted a survey of roughly 2,000 people who took high doses of psilocybin mushrooms and then had a challenging experience. About 10% reported they put themselves or others at risk of physical harm. Of more concern, of those whose experience occurred more than 1 year before, 8% sought treatment for enduring psychological symptoms. These findings underscore potential risks of psilocybin use but do not provide an estimate of the actual incidence of such effects.

Importantly, in our research at Johns Hopkins, we have not observed such effects in over 700 sessions that we have conducted with almost 400 participants, likely because we thoroughly screen and prepare participants and support them after they have completed the study. The potential for serious lasting harm represents a concern and points to the importance of adequate screening and aftercare.
 

What are the implications for future therapeutics?

We are living in exciting times, in terms of psychedelic research. The potential for a single treatment with a classic psychedelic to produce rapid and sustained therapeutic effects, possibly across a range of psychiatric conditions, is unprecedented in psychiatry. The effect appears to be an “inverse PTSD effect.”

In PTSD, a single exposure to a traumatic event can rewire the nervous system to the point that it produces enduring harm and toxicity. In the case of psychedelics, a single exposure appears to have enduring positive effects in worldview, mood, attitude, behavior, and overall life satisfaction. We can look forward to continued growth and expansion of this research including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.
 

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

After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.

Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).

Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.

Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
 

What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?

All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.

In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
 

Which psychedelic agents are under investigation in the United States, and for which indications?

Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.

Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.

A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.

Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.

LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.

Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.

Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.
 

What is the typical treatment regimen for psychedelic agents?

It is hard to speak of a “treatment regimen” in agents that are not used in clinical practice. Ongoing clinical trials with psilocybin generally involve one or two 6- to 8-hour sessions involving the oral administration of a moderately high dose under psychologically supported conditions.

Based on the current evidence base, which agents show the most promise?

Psilocybin is currently the most promising classic psychedelic undergoing clinical trials.

Do psychedelics have to be administered in a controlled setting in order to be effective?

Although many people have had meaningful experiences whether inside or outside of a controlled setting, there are serious potential risks associated with use of psilocybin and other classic psychedelics. The safety of psilocybin has been established in clinical studies in which participants have been carefully screened physically and psychologically, are psychologically prepared before their first session, and are psychologically supported during and after sessions. In vulnerable individuals, psilocybin has been associated with enduring psychiatric problems and sometimes persisting visual perceptual conditions. When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others – including life-threatening risk. Thus, for safety reasons, the optimal environment for using these agents is in a controlled setting.

Do results differ between patients who have used psychedelic agents previously and those who have not?

We have not found any difference between psychedelic-naive volunteers and those who have used psychedelics in the past.

Do you provide patient education prior to treatment initiation?

All of our study participants are thoroughly screened for medical concerns or mental health history such as psychosis, which would preclude their participation. They are educated about the effects of these agents and what they might expect and typically receive several hours of psychological preparation before the first session. They are also provided with psychological support after sessions. Additionally, we spend time developing trust and rapport prior to the first session.

How durable are the effects of psychedelic treatment?

Studies in patients and healthy participants suggest that the positive effects of psilocybin are long lasting, with most individuals reporting positive changes in moods, attitudes, and behavior that they attribute to psilocybin and which endure months or years after the session. The qualities of the acute session experience can vary widely ranging from experiences of transcendence or psychological insight to experiences of intense anxiety or fear.

An enduring shift in worldview and sense of self, as well as psychological insight, may increase psychological flexibility, thereby allowing individuals to subsequently avoid maladaptive patterns of behavior or thought and to make more healthy choices.

Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experience of their lives.
 

Do participants experience any adverse effects? If so, how are they managed?

Sometimes, despite all the preparation, screening, and support we provide, some participants can have frightening experiences, such as fear and anxiety during the session. When that occurs, it is often shorted lived. The psychological preparation we provide before the session and the psychological support we provide during the session are important for managing such effects.

We provide support and encourage participants to stay with that experience, which may open to experiences of deep meaning or insight. A number of people report that these psychologically challenging states are a valuable part of the overall experience.

We conducted a survey of roughly 2,000 people who took high doses of psilocybin mushrooms and then had a challenging experience. About 10% reported they put themselves or others at risk of physical harm. Of more concern, of those whose experience occurred more than 1 year before, 8% sought treatment for enduring psychological symptoms. These findings underscore potential risks of psilocybin use but do not provide an estimate of the actual incidence of such effects.

Importantly, in our research at Johns Hopkins, we have not observed such effects in over 700 sessions that we have conducted with almost 400 participants, likely because we thoroughly screen and prepare participants and support them after they have completed the study. The potential for serious lasting harm represents a concern and points to the importance of adequate screening and aftercare.
 

What are the implications for future therapeutics?

We are living in exciting times, in terms of psychedelic research. The potential for a single treatment with a classic psychedelic to produce rapid and sustained therapeutic effects, possibly across a range of psychiatric conditions, is unprecedented in psychiatry. The effect appears to be an “inverse PTSD effect.”

In PTSD, a single exposure to a traumatic event can rewire the nervous system to the point that it produces enduring harm and toxicity. In the case of psychedelics, a single exposure appears to have enduring positive effects in worldview, mood, attitude, behavior, and overall life satisfaction. We can look forward to continued growth and expansion of this research including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.
 

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

After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.

Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).

Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.

Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
 

What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?

All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.

In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
 

Which psychedelic agents are under investigation in the United States, and for which indications?

Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.

Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.

A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.

Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.

LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.

Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.

Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.
 

What is the typical treatment regimen for psychedelic agents?

It is hard to speak of a “treatment regimen” in agents that are not used in clinical practice. Ongoing clinical trials with psilocybin generally involve one or two 6- to 8-hour sessions involving the oral administration of a moderately high dose under psychologically supported conditions.

Based on the current evidence base, which agents show the most promise?

Psilocybin is currently the most promising classic psychedelic undergoing clinical trials.

Do psychedelics have to be administered in a controlled setting in order to be effective?

Although many people have had meaningful experiences whether inside or outside of a controlled setting, there are serious potential risks associated with use of psilocybin and other classic psychedelics. The safety of psilocybin has been established in clinical studies in which participants have been carefully screened physically and psychologically, are psychologically prepared before their first session, and are psychologically supported during and after sessions. In vulnerable individuals, psilocybin has been associated with enduring psychiatric problems and sometimes persisting visual perceptual conditions. When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others – including life-threatening risk. Thus, for safety reasons, the optimal environment for using these agents is in a controlled setting.

Do results differ between patients who have used psychedelic agents previously and those who have not?

We have not found any difference between psychedelic-naive volunteers and those who have used psychedelics in the past.

Do you provide patient education prior to treatment initiation?

All of our study participants are thoroughly screened for medical concerns or mental health history such as psychosis, which would preclude their participation. They are educated about the effects of these agents and what they might expect and typically receive several hours of psychological preparation before the first session. They are also provided with psychological support after sessions. Additionally, we spend time developing trust and rapport prior to the first session.

How durable are the effects of psychedelic treatment?

Studies in patients and healthy participants suggest that the positive effects of psilocybin are long lasting, with most individuals reporting positive changes in moods, attitudes, and behavior that they attribute to psilocybin and which endure months or years after the session. The qualities of the acute session experience can vary widely ranging from experiences of transcendence or psychological insight to experiences of intense anxiety or fear.

An enduring shift in worldview and sense of self, as well as psychological insight, may increase psychological flexibility, thereby allowing individuals to subsequently avoid maladaptive patterns of behavior or thought and to make more healthy choices.

Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experience of their lives.
 

Do participants experience any adverse effects? If so, how are they managed?

Sometimes, despite all the preparation, screening, and support we provide, some participants can have frightening experiences, such as fear and anxiety during the session. When that occurs, it is often shorted lived. The psychological preparation we provide before the session and the psychological support we provide during the session are important for managing such effects.

We provide support and encourage participants to stay with that experience, which may open to experiences of deep meaning or insight. A number of people report that these psychologically challenging states are a valuable part of the overall experience.

We conducted a survey of roughly 2,000 people who took high doses of psilocybin mushrooms and then had a challenging experience. About 10% reported they put themselves or others at risk of physical harm. Of more concern, of those whose experience occurred more than 1 year before, 8% sought treatment for enduring psychological symptoms. These findings underscore potential risks of psilocybin use but do not provide an estimate of the actual incidence of such effects.

Importantly, in our research at Johns Hopkins, we have not observed such effects in over 700 sessions that we have conducted with almost 400 participants, likely because we thoroughly screen and prepare participants and support them after they have completed the study. The potential for serious lasting harm represents a concern and points to the importance of adequate screening and aftercare.
 

What are the implications for future therapeutics?

We are living in exciting times, in terms of psychedelic research. The potential for a single treatment with a classic psychedelic to produce rapid and sustained therapeutic effects, possibly across a range of psychiatric conditions, is unprecedented in psychiatry. The effect appears to be an “inverse PTSD effect.”

In PTSD, a single exposure to a traumatic event can rewire the nervous system to the point that it produces enduring harm and toxicity. In the case of psychedelics, a single exposure appears to have enduring positive effects in worldview, mood, attitude, behavior, and overall life satisfaction. We can look forward to continued growth and expansion of this research including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.
 

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

The state of Tennessee, where I worked and attended medical school, did not have legislation in place prohibiting termination of employment based on sexual orientation alone. As a lesbian, I never felt safe at work knowing that I could be fired at any time simply because of who I loved and how I identified. When I started medical school in rural Appalachia, I decided I would be “out” but remained cautious. That meant inspecting everyone I encountered for signs of acceptance and safety before sharing details about my life. As a third-year medical student, I started wearing a rainbow triangle on my white coat. One of the first patients I cared for cried and thanked me for wearing the pin. She then proceeded to tell me about her partner, her own struggles with depression, and the secrets she had to keep from her community. It was overwhelming and, yet, so familiar. I was struck by how wearing this pin, a small gesture, made this patient feel safe enough to come out to me and seek help for her depression. Although I found a supportive community in Tennessee, it was only after I moved to Massachusetts for residency—where antidiscrimination laws protected lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, plus all other gender and sexual minority (LGBTQIA+) identified people—did I feel safe to freely share about my partner and our life together.

A landmark decision in the Supreme Court

This past June, in a 6 to 3 decision, the US Supreme Court ruled in the case of Bostock v Clayton County that Title VII’s ban on discrimination also protects LGBTQIA+ employees. Title VII is a federal law that protects employees from discrimination based on race, color, national origin, sex, and religion.¹ In this decision, the court determined that “sex” cannot be differentiated from sexual orientation. Justice Neil Gorsuch, who wrote the majority opinion, stated, “It is impossible… to discriminate against a person for being homosexual or transgender without discriminating against that individual based on sex.”² Title VII not only protects employees in hiring and firing practices but also protects against harassment and retaliation. Prior to this ruling, there were no federal antidiscrimination laws for LGBTQIA+ individuals, and only 22 states and the District of Columbia had laws in place that specified antidiscrimination protection for this community.³ Because of this landmark decision, Title VII now protects all employees in all states from discrimination, including due to an individual’s sexual orientation.

This is a huge victory in the battle for equality; however, the fight is not over. Justice Gorsuch stated, “We do not purport to address bathrooms, locker rooms or anything else of the kind…whether other policies and practices might or might not qualify as unlawful discrimination or find justifications under other provisions of Title VII are questions for future cases, not these.”² This victory sets a new precedent and will continue to be further defined with more court cases as states and employers push back against these protections.

Continue to: A worrying shift in the Court...

A worrying shift in the Court

We have already started to see the repercussions of this ruling from Supreme Court justices themselves. Justice Clarence Thomas, who dissented in the Obergefell v Hodges decision in 2015, which established the constitutional right for marriage equality, recently wrote a petition to have the Supreme Court reconsider that ruling. He wrote “Obergefell enables courts and governments to brand religious adherents who believe that marriage is between one man and one woman as bigots, making their religious liberty concerns that much easier to dismiss.”³ After the passing of Justice Ruth Bader Ginsburg, the Supreme Court became decidedly more conservative with the appointment of Judge Amy Coney Barrett, whose mentor was the late Justice Antonin Scalia, who also dissented in the 2015 case.

As we celebrate this huge win for equality in this June decision, we also must recognize that LGBTQIA+ rights are still at risk.

LGBTQIA+ patients at higher risk for litany of conditions

Even with the Bostock v Clayton County ruling, we must not forget that discrimination will continue to exist. As health care providers, we have a responsibility to advocate on behalf of our LGBTQIA+ colleagues and patients. According to the Healthy People 2020 survey, there are higher rates of obesity, tobacco dependence, and sexually transmitted infection, as well as lower adherence to cancer screening recommendations in the LGBTQIA+ community.⁴ These disparities are a result of systemic, legal, and social factors, including limited access to affirming and inclusive health care.⁵ The LGBTQIA+ community deserves better.

Take action

In the coming months and years, as the US Supreme Court hears more cases that will threaten the rights of the LGBTQIA+ community, I challenge all clinicians to take action. Even the smallest of gestures, such as wearing a rainbow pin, can be transformative for our patients and within our communities.

• Advocate for your state to enact nondiscrimination laws protecting the LGBTQIA+ community. Find out if your state has a law.
• Support your LGBTQIA+ colleagues by establishing an employee support group.
• Educate yourself and your colleagues on LGBTQIA+ inclusive medical practices.

The state of Tennessee, where I worked and attended medical school, did not have legislation in place prohibiting termination of employment based on sexual orientation alone. As a lesbian, I never felt safe at work knowing that I could be fired at any time simply because of who I loved and how I identified. When I started medical school in rural Appalachia, I decided I would be “out” but remained cautious. That meant inspecting everyone I encountered for signs of acceptance and safety before sharing details about my life. As a third-year medical student, I started wearing a rainbow triangle on my white coat. One of the first patients I cared for cried and thanked me for wearing the pin. She then proceeded to tell me about her partner, her own struggles with depression, and the secrets she had to keep from her community. It was overwhelming and, yet, so familiar. I was struck by how wearing this pin, a small gesture, made this patient feel safe enough to come out to me and seek help for her depression. Although I found a supportive community in Tennessee, it was only after I moved to Massachusetts for residency—where antidiscrimination laws protected lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, plus all other gender and sexual minority (LGBTQIA+) identified people—did I feel safe to freely share about my partner and our life together.

A landmark decision in the Supreme Court

This past June, in a 6 to 3 decision, the US Supreme Court ruled in the case of Bostock v Clayton County that Title VII’s ban on discrimination also protects LGBTQIA+ employees. Title VII is a federal law that protects employees from discrimination based on race, color, national origin, sex, and religion.¹ In this decision, the court determined that “sex” cannot be differentiated from sexual orientation. Justice Neil Gorsuch, who wrote the majority opinion, stated, “It is impossible… to discriminate against a person for being homosexual or transgender without discriminating against that individual based on sex.”² Title VII not only protects employees in hiring and firing practices but also protects against harassment and retaliation. Prior to this ruling, there were no federal antidiscrimination laws for LGBTQIA+ individuals, and only 22 states and the District of Columbia had laws in place that specified antidiscrimination protection for this community.³ Because of this landmark decision, Title VII now protects all employees in all states from discrimination, including due to an individual’s sexual orientation.

This is a huge victory in the battle for equality; however, the fight is not over. Justice Gorsuch stated, “We do not purport to address bathrooms, locker rooms or anything else of the kind…whether other policies and practices might or might not qualify as unlawful discrimination or find justifications under other provisions of Title VII are questions for future cases, not these.”² This victory sets a new precedent and will continue to be further defined with more court cases as states and employers push back against these protections.

Continue to: A worrying shift in the Court...

A worrying shift in the Court

We have already started to see the repercussions of this ruling from Supreme Court justices themselves. Justice Clarence Thomas, who dissented in the Obergefell v Hodges decision in 2015, which established the constitutional right for marriage equality, recently wrote a petition to have the Supreme Court reconsider that ruling. He wrote “Obergefell enables courts and governments to brand religious adherents who believe that marriage is between one man and one woman as bigots, making their religious liberty concerns that much easier to dismiss.”³ After the passing of Justice Ruth Bader Ginsburg, the Supreme Court became decidedly more conservative with the appointment of Judge Amy Coney Barrett, whose mentor was the late Justice Antonin Scalia, who also dissented in the 2015 case.

As we celebrate this huge win for equality in this June decision, we also must recognize that LGBTQIA+ rights are still at risk.

LGBTQIA+ patients at higher risk for litany of conditions

Even with the Bostock v Clayton County ruling, we must not forget that discrimination will continue to exist. As health care providers, we have a responsibility to advocate on behalf of our LGBTQIA+ colleagues and patients. According to the Healthy People 2020 survey, there are higher rates of obesity, tobacco dependence, and sexually transmitted infection, as well as lower adherence to cancer screening recommendations in the LGBTQIA+ community.⁴ These disparities are a result of systemic, legal, and social factors, including limited access to affirming and inclusive health care.⁵ The LGBTQIA+ community deserves better.

Take action

In the coming months and years, as the US Supreme Court hears more cases that will threaten the rights of the LGBTQIA+ community, I challenge all clinicians to take action. Even the smallest of gestures, such as wearing a rainbow pin, can be transformative for our patients and within our communities.

• Advocate for your state to enact nondiscrimination laws protecting the LGBTQIA+ community. Find out if your state has a law.
• Support your LGBTQIA+ colleagues by establishing an employee support group.
• Educate yourself and your colleagues on LGBTQIA+ inclusive medical practices.

The state of Tennessee, where I worked and attended medical school, did not have legislation in place prohibiting termination of employment based on sexual orientation alone. As a lesbian, I never felt safe at work knowing that I could be fired at any time simply because of who I loved and how I identified. When I started medical school in rural Appalachia, I decided I would be “out” but remained cautious. That meant inspecting everyone I encountered for signs of acceptance and safety before sharing details about my life. As a third-year medical student, I started wearing a rainbow triangle on my white coat. One of the first patients I cared for cried and thanked me for wearing the pin. She then proceeded to tell me about her partner, her own struggles with depression, and the secrets she had to keep from her community. It was overwhelming and, yet, so familiar. I was struck by how wearing this pin, a small gesture, made this patient feel safe enough to come out to me and seek help for her depression. Although I found a supportive community in Tennessee, it was only after I moved to Massachusetts for residency—where antidiscrimination laws protected lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, plus all other gender and sexual minority (LGBTQIA+) identified people—did I feel safe to freely share about my partner and our life together.

A landmark decision in the Supreme Court

This past June, in a 6 to 3 decision, the US Supreme Court ruled in the case of Bostock v Clayton County that Title VII’s ban on discrimination also protects LGBTQIA+ employees. Title VII is a federal law that protects employees from discrimination based on race, color, national origin, sex, and religion.¹ In this decision, the court determined that “sex” cannot be differentiated from sexual orientation. Justice Neil Gorsuch, who wrote the majority opinion, stated, “It is impossible… to discriminate against a person for being homosexual or transgender without discriminating against that individual based on sex.”² Title VII not only protects employees in hiring and firing practices but also protects against harassment and retaliation. Prior to this ruling, there were no federal antidiscrimination laws for LGBTQIA+ individuals, and only 22 states and the District of Columbia had laws in place that specified antidiscrimination protection for this community.³ Because of this landmark decision, Title VII now protects all employees in all states from discrimination, including due to an individual’s sexual orientation.

This is a huge victory in the battle for equality; however, the fight is not over. Justice Gorsuch stated, “We do not purport to address bathrooms, locker rooms or anything else of the kind…whether other policies and practices might or might not qualify as unlawful discrimination or find justifications under other provisions of Title VII are questions for future cases, not these.”² This victory sets a new precedent and will continue to be further defined with more court cases as states and employers push back against these protections.

Continue to: A worrying shift in the Court...

A worrying shift in the Court

We have already started to see the repercussions of this ruling from Supreme Court justices themselves. Justice Clarence Thomas, who dissented in the Obergefell v Hodges decision in 2015, which established the constitutional right for marriage equality, recently wrote a petition to have the Supreme Court reconsider that ruling. He wrote “Obergefell enables courts and governments to brand religious adherents who believe that marriage is between one man and one woman as bigots, making their religious liberty concerns that much easier to dismiss.”³ After the passing of Justice Ruth Bader Ginsburg, the Supreme Court became decidedly more conservative with the appointment of Judge Amy Coney Barrett, whose mentor was the late Justice Antonin Scalia, who also dissented in the 2015 case.

As we celebrate this huge win for equality in this June decision, we also must recognize that LGBTQIA+ rights are still at risk.

LGBTQIA+ patients at higher risk for litany of conditions

Even with the Bostock v Clayton County ruling, we must not forget that discrimination will continue to exist. As health care providers, we have a responsibility to advocate on behalf of our LGBTQIA+ colleagues and patients. According to the Healthy People 2020 survey, there are higher rates of obesity, tobacco dependence, and sexually transmitted infection, as well as lower adherence to cancer screening recommendations in the LGBTQIA+ community.⁴ These disparities are a result of systemic, legal, and social factors, including limited access to affirming and inclusive health care.⁵ The LGBTQIA+ community deserves better.

Take action

In the coming months and years, as the US Supreme Court hears more cases that will threaten the rights of the LGBTQIA+ community, I challenge all clinicians to take action. Even the smallest of gestures, such as wearing a rainbow pin, can be transformative for our patients and within our communities.

• Advocate for your state to enact nondiscrimination laws protecting the LGBTQIA+ community. Find out if your state has a law.
• Support your LGBTQIA+ colleagues by establishing an employee support group.
• Educate yourself and your colleagues on LGBTQIA+ inclusive medical practices.

Carvalho Gazarra LB, Bonacordi CL, Yela DA, et al. Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives. Menopause. 2020;27:1110-1116.

EXPERT COMMENTARY

Premature ovarian insufficiency (POI) refers to a condition in women in whom ovarian function ceases prior to age 40 years. Although hormone therapy (HT) is a mainstay of treatment for women with POI, it is uncertain which approach to HT is most effective in terms of bone mineral density (BMD). Investigators recently published their results of an observational study that aimed to evaluate the use of combined oral contraceptives (COCs) for preserving BMD in women with POI.

Details of the study

At an academic center in Brazil, Carvalho Gazarra and colleagues identified women with POI who had undergone 2 or more BMD assessments performed 2 or more years apart.¹ HT regimens (all of which were taken continuously) employed the following: a COC with ethinyl estradiol (EE) 30 µg and levonorgestrel; low-dose estrogen plus progestin therapy (EPT, conjugated equine estrogen [CEE] 0.625 mg with medroxyprogesterone acetate or estradiol 1.0 mg with norethindrone acetate); or high-dose estrogen plus progestin (CEE 1.25 mg or estradiol 2.0 mg combined with the same progestins).

Results. Among 119 evaluable women with POI (mean age, 30.3 years), the use of COC was associated with the most positive BMD trends. For women using COC or high-dose EPT, BMD at the lumbar spine increased. By contrast, BMD of the lumbar spine declined in women who used no treatment or low-dose EPT.¹

Other studies’ take on dose, route of administration, and cost considerations

Sequelae of POI include infertility, bothersome hot flashes, vaginal dryness, sexual dysfunction, mood disorders, and an elevated risk of cardiovascular disease, dementia, Parkinson’s disease, and osteoporosis. Importantly, clinicians and patients need to understand that the results from the Women’s Health Initiative studies do not apply to women with POI.² Physiologic doses of HT (that is, doses higher than those used to treat menopausal symptoms in women with normal/spontaneous menopause) are appropriate for women with POI, at least until they reach the normal age of menopause (51 to 52 years).

A clinical trial conducted in Scotland in women with POI found that high-dose transdermal estrogen (application of one to two 0.1-mg estradiol patches) daily had an impact on BMD that was more positive than that of an oral contraceptive formulated with EE 30 µg.³ Likewise, a trial in the United States found that, among oligo-amenorrheic athletes, a hormone replacement regimen using a 0.1-mg estradiol patch had a more positive impact on BMD than an oral contraceptive formulated with EE 30 µg.⁴

Although Carvalho Gazarra and colleagues acknowledged awareness of reports suggesting the skeletal health benefits of high-dose estradiol patches, in the Brazilian public health system oral hormone therapy is less expensive and oral contraceptives are available at no charge.¹ ●

Carvalho Gazarra LB, Bonacordi CL, Yela DA, et al. Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives. Menopause. 2020;27:1110-1116.

EXPERT COMMENTARY

Premature ovarian insufficiency (POI) refers to a condition in women in whom ovarian function ceases prior to age 40 years. Although hormone therapy (HT) is a mainstay of treatment for women with POI, it is uncertain which approach to HT is most effective in terms of bone mineral density (BMD). Investigators recently published their results of an observational study that aimed to evaluate the use of combined oral contraceptives (COCs) for preserving BMD in women with POI.

Details of the study

At an academic center in Brazil, Carvalho Gazarra and colleagues identified women with POI who had undergone 2 or more BMD assessments performed 2 or more years apart.¹ HT regimens (all of which were taken continuously) employed the following: a COC with ethinyl estradiol (EE) 30 µg and levonorgestrel; low-dose estrogen plus progestin therapy (EPT, conjugated equine estrogen [CEE] 0.625 mg with medroxyprogesterone acetate or estradiol 1.0 mg with norethindrone acetate); or high-dose estrogen plus progestin (CEE 1.25 mg or estradiol 2.0 mg combined with the same progestins).

Results. Among 119 evaluable women with POI (mean age, 30.3 years), the use of COC was associated with the most positive BMD trends. For women using COC or high-dose EPT, BMD at the lumbar spine increased. By contrast, BMD of the lumbar spine declined in women who used no treatment or low-dose EPT.¹

Other studies’ take on dose, route of administration, and cost considerations

Sequelae of POI include infertility, bothersome hot flashes, vaginal dryness, sexual dysfunction, mood disorders, and an elevated risk of cardiovascular disease, dementia, Parkinson’s disease, and osteoporosis. Importantly, clinicians and patients need to understand that the results from the Women’s Health Initiative studies do not apply to women with POI.² Physiologic doses of HT (that is, doses higher than those used to treat menopausal symptoms in women with normal/spontaneous menopause) are appropriate for women with POI, at least until they reach the normal age of menopause (51 to 52 years).

A clinical trial conducted in Scotland in women with POI found that high-dose transdermal estrogen (application of one to two 0.1-mg estradiol patches) daily had an impact on BMD that was more positive than that of an oral contraceptive formulated with EE 30 µg.³ Likewise, a trial in the United States found that, among oligo-amenorrheic athletes, a hormone replacement regimen using a 0.1-mg estradiol patch had a more positive impact on BMD than an oral contraceptive formulated with EE 30 µg.⁴

Although Carvalho Gazarra and colleagues acknowledged awareness of reports suggesting the skeletal health benefits of high-dose estradiol patches, in the Brazilian public health system oral hormone therapy is less expensive and oral contraceptives are available at no charge.¹ ●

Carvalho Gazarra LB, Bonacordi CL, Yela DA, et al. Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives. Menopause. 2020;27:1110-1116.

EXPERT COMMENTARY

Premature ovarian insufficiency (POI) refers to a condition in women in whom ovarian function ceases prior to age 40 years. Although hormone therapy (HT) is a mainstay of treatment for women with POI, it is uncertain which approach to HT is most effective in terms of bone mineral density (BMD). Investigators recently published their results of an observational study that aimed to evaluate the use of combined oral contraceptives (COCs) for preserving BMD in women with POI.

Details of the study

At an academic center in Brazil, Carvalho Gazarra and colleagues identified women with POI who had undergone 2 or more BMD assessments performed 2 or more years apart.¹ HT regimens (all of which were taken continuously) employed the following: a COC with ethinyl estradiol (EE) 30 µg and levonorgestrel; low-dose estrogen plus progestin therapy (EPT, conjugated equine estrogen [CEE] 0.625 mg with medroxyprogesterone acetate or estradiol 1.0 mg with norethindrone acetate); or high-dose estrogen plus progestin (CEE 1.25 mg or estradiol 2.0 mg combined with the same progestins).

Results. Among 119 evaluable women with POI (mean age, 30.3 years), the use of COC was associated with the most positive BMD trends. For women using COC or high-dose EPT, BMD at the lumbar spine increased. By contrast, BMD of the lumbar spine declined in women who used no treatment or low-dose EPT.¹

Other studies’ take on dose, route of administration, and cost considerations

Sequelae of POI include infertility, bothersome hot flashes, vaginal dryness, sexual dysfunction, mood disorders, and an elevated risk of cardiovascular disease, dementia, Parkinson’s disease, and osteoporosis. Importantly, clinicians and patients need to understand that the results from the Women’s Health Initiative studies do not apply to women with POI.² Physiologic doses of HT (that is, doses higher than those used to treat menopausal symptoms in women with normal/spontaneous menopause) are appropriate for women with POI, at least until they reach the normal age of menopause (51 to 52 years).

A clinical trial conducted in Scotland in women with POI found that high-dose transdermal estrogen (application of one to two 0.1-mg estradiol patches) daily had an impact on BMD that was more positive than that of an oral contraceptive formulated with EE 30 µg.³ Likewise, a trial in the United States found that, among oligo-amenorrheic athletes, a hormone replacement regimen using a 0.1-mg estradiol patch had a more positive impact on BMD than an oral contraceptive formulated with EE 30 µg.⁴

Although Carvalho Gazarra and colleagues acknowledged awareness of reports suggesting the skeletal health benefits of high-dose estradiol patches, in the Brazilian public health system oral hormone therapy is less expensive and oral contraceptives are available at no charge.¹ ●

Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.¹ In the same year, the investigators reported 11,788 cases of cervical cancer.¹ A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.¹

Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.² HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.³

Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.

Which HPV types are associated with oropharyngeal cancer?

HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.^4-7

The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).⁷ This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.

Men are more likely than women to harbor oral HPV

Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.⁸ The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.

In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).⁹ Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).⁹ The results of this observational study support the important role of vaccination in reducing oral HPV infection.

Continue to: Vaccinate boys and girls to prevent cancer...

Vaccinate boys and girls to prevent cancer

Most population studies report that males are less likely to receive an HPV vaccine than females. For example, based on the National Health Interview Survey of people aged 18 to 26, the percentage of women who self-reported receiving at least one dose of HPV vaccine was 37% in 2013 and 54% in 2018.¹⁰ By contrast, among men, the rates of self-reported vaccination were much lower—8% in 2013 and 27% in 2018.¹⁰

The percentage of women who received the recommended number of doses of HPV vaccine (see “9vHPV vaccine: Indications and immunization schedule”) was 26% in 2013 and 35% in 2018.¹⁰ For men, these percentages were 2% in 2013 and 9% in 2018.¹⁰ These data indicate that, compared with women, men are less likely to receive an HPV vaccination and far less likely to have received the recommended number of doses.

It is heartening that there has been a slow and steady increase in the prevalence of HPV vaccination. In fact, increasing the HPV vaccination rate among both boys and girls has the potential to markedly reduce the incidence of oropharyngeal cancer.

The reasons for the female-male gap in vaccination rates are not fully characterized. For one, parental awareness of the importance of HPV vaccination to prevent cancer among men is limited, and represents an important opportunity for additional public health education. In a qualitative interview study of mothers with children aged 11 to 19, the investigators reported that most mothers were aware that HPV vaccination could prevent cervical cancer in women, but most mothers did not know that HPV causes cancer of the mouth and that vaccination could prevent oropharyngeal cancer in boys and girls.¹¹ Because of this lack of knowledge, the mothers did not think their sons needed to have an HPV vaccine. The research report is aptly titled, “I don’t think he needs the HPV vaccine cause boys can’t have cervical cancer.”¹¹

Clinicians are highly influential in guiding parents to accept HPV vaccination of their children. Offering consistent messaging to parents that HPV vaccination prevents cancer in both women and men, and reducing the out-of-pocket cost of vaccination surely will result in an increase in the vaccination rate of boys and girls. ●

Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.¹ In the same year, the investigators reported 11,788 cases of cervical cancer.¹ A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.¹

Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.² HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.³

Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.

Which HPV types are associated with oropharyngeal cancer?

HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.^4-7

The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).⁷ This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.

Men are more likely than women to harbor oral HPV

Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.⁸ The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.

In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).⁹ Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).⁹ The results of this observational study support the important role of vaccination in reducing oral HPV infection.

Continue to: Vaccinate boys and girls to prevent cancer...

Vaccinate boys and girls to prevent cancer

Most population studies report that males are less likely to receive an HPV vaccine than females. For example, based on the National Health Interview Survey of people aged 18 to 26, the percentage of women who self-reported receiving at least one dose of HPV vaccine was 37% in 2013 and 54% in 2018.¹⁰ By contrast, among men, the rates of self-reported vaccination were much lower—8% in 2013 and 27% in 2018.¹⁰

The percentage of women who received the recommended number of doses of HPV vaccine (see “9vHPV vaccine: Indications and immunization schedule”) was 26% in 2013 and 35% in 2018.¹⁰ For men, these percentages were 2% in 2013 and 9% in 2018.¹⁰ These data indicate that, compared with women, men are less likely to receive an HPV vaccination and far less likely to have received the recommended number of doses.

It is heartening that there has been a slow and steady increase in the prevalence of HPV vaccination. In fact, increasing the HPV vaccination rate among both boys and girls has the potential to markedly reduce the incidence of oropharyngeal cancer.

The reasons for the female-male gap in vaccination rates are not fully characterized. For one, parental awareness of the importance of HPV vaccination to prevent cancer among men is limited, and represents an important opportunity for additional public health education. In a qualitative interview study of mothers with children aged 11 to 19, the investigators reported that most mothers were aware that HPV vaccination could prevent cervical cancer in women, but most mothers did not know that HPV causes cancer of the mouth and that vaccination could prevent oropharyngeal cancer in boys and girls.¹¹ Because of this lack of knowledge, the mothers did not think their sons needed to have an HPV vaccine. The research report is aptly titled, “I don’t think he needs the HPV vaccine cause boys can’t have cervical cancer.”¹¹

Clinicians are highly influential in guiding parents to accept HPV vaccination of their children. Offering consistent messaging to parents that HPV vaccination prevents cancer in both women and men, and reducing the out-of-pocket cost of vaccination surely will result in an increase in the vaccination rate of boys and girls. ●

Surprisingly, in the United States, the most common cancer associated with human papillomavirus (HPV) is oropharyngeal squamous cell cancer (SCC), with one study reporting 15,479 cases among men and 3,428 cases among women in 2015.¹ In the same year, the investigators reported 11,788 cases of cervical cancer.¹ A public health concern is that cases of oropharyngeal SCC are increasing, while cases of cervical cancer are decreasing. From 1999 to 2015, the rate of oropharyngeal SCC increased annually among both men and women, at rates of 2.7% and 0.8% per year, respectively. By contrast, the rate of cervical cancer decreased by 1.6% per year.¹

Although the incidence of HPV-negative oropharyngeal SCC (cases associated with cigarette smoking) has declined by 50% from 1988 to 2004, the incidence of HPV-positive oropharyngeal SCC has increased by 225%, with much of the increase occurring among young, white men.² HPV infection is a major cause of oropharyngeal SCC at the base of the tongue and tonsils, but not in the soft palate or oropharyngeal walls.³

Most physicians and parents recognize that the 9-valent (9v)HPV vaccine prevents the majority of cervical cancers and precancers in women. Far fewer people realize that there is an important opportunity to prevent a large number of oropharyngeal cancers by improving 9vHPV vaccination in men and women.

Which HPV types are associated with oropharyngeal cancer?

HPV16 is the most common HPV type associated with oropharyngeal SCC. Among these cancer types, greater than 80% harbor HPV16, with greater than 90% harboring HPV16 or 18 and less than 10% of tumors associated with HPV types 31, 33, 45, 52, or 58.^4-7

The high prevalence of HPV16 in patients with oropharyngeal cancer raises the question of the HPV status of the intimate partner of the index patient. In one study of 164 people with HPV detected in their oropharyngeal, the partner of the index patient had a low prevalence of high-risk HPV types (1.2%) in oral rinse and gargle samples, similar to the rate in the general population (1.3%).⁷ This finding is reassuring and suggests that intimate partners of patients with HPV-positive oropharyngeal cancer effectively clear high-risk HPV virus from the oropharynx. The HPV status of the genital tissue of the intimate partner of an index patient with oropharyngeal SCC has not been adequately studied.

Men are more likely than women to harbor oral HPV

Among a sample of 5,501 men and women aged 14 to 69 years from the National Health and Nutrition Examination Survey, oral rinses were obtained and analyzed for the presence of HPV.⁸ The prevalence of any oral HPV and any oral high-risk HPV was 6.9% and 3.7%, respectively. Oral HPV-16 was detected in 1.6% of men and 0.3% of women. The prevalence of HPV was higher among current smokers, heavy alcohol drinkers, and people with a history of a greater number of sexual partners. In men and women reporting more than 20 lifetime sexual partners, the prevalence of oral HPV was 20%.

In a study of 2,627 men and women aged 18 to 33 years, the prevalence of oral HPV 16/18/6/11 was lower among those vaccinated versus those unvaccinated (0.11% and 1.6%, respectively; P = .008).⁹ Among men, oral HPV 16/18/6/11 was lower among those vaccinated versus unvaccinated (0.0% and 2.13%, respectively; P = .007).⁹ The results of this observational study support the important role of vaccination in reducing oral HPV infection.

Continue to: Vaccinate boys and girls to prevent cancer...

Vaccinate boys and girls to prevent cancer

Most population studies report that males are less likely to receive an HPV vaccine than females. For example, based on the National Health Interview Survey of people aged 18 to 26, the percentage of women who self-reported receiving at least one dose of HPV vaccine was 37% in 2013 and 54% in 2018.¹⁰ By contrast, among men, the rates of self-reported vaccination were much lower—8% in 2013 and 27% in 2018.¹⁰

The percentage of women who received the recommended number of doses of HPV vaccine (see “9vHPV vaccine: Indications and immunization schedule”) was 26% in 2013 and 35% in 2018.¹⁰ For men, these percentages were 2% in 2013 and 9% in 2018.¹⁰ These data indicate that, compared with women, men are less likely to receive an HPV vaccination and far less likely to have received the recommended number of doses.

It is heartening that there has been a slow and steady increase in the prevalence of HPV vaccination. In fact, increasing the HPV vaccination rate among both boys and girls has the potential to markedly reduce the incidence of oropharyngeal cancer.

The reasons for the female-male gap in vaccination rates are not fully characterized. For one, parental awareness of the importance of HPV vaccination to prevent cancer among men is limited, and represents an important opportunity for additional public health education. In a qualitative interview study of mothers with children aged 11 to 19, the investigators reported that most mothers were aware that HPV vaccination could prevent cervical cancer in women, but most mothers did not know that HPV causes cancer of the mouth and that vaccination could prevent oropharyngeal cancer in boys and girls.¹¹ Because of this lack of knowledge, the mothers did not think their sons needed to have an HPV vaccine. The research report is aptly titled, “I don’t think he needs the HPV vaccine cause boys can’t have cervical cancer.”¹¹

Clinicians are highly influential in guiding parents to accept HPV vaccination of their children. Offering consistent messaging to parents that HPV vaccination prevents cancer in both women and men, and reducing the out-of-pocket cost of vaccination surely will result in an increase in the vaccination rate of boys and girls. ●

Chances are your female patients of childbearing age with multiple sclerosis—particularly if they become pregnant—will ask about breastfeeding. What are they likely to ask, and how should you answer? Here’s a quick rundown.

What kind of impact will breastfeeding have on my child?

We know that MS is not a genetic disease per se-it is neither autosomal recessive nor dominant. But there is an increased risk among family members, particularly first-degree relatives. If a patient asks, you can tell them it appears that infants who are breastfed are less likely to develop pediatric-onset MS.

In 2017, Brenton and colleagues asked individuals who experienced pediatric-onset MS (n=36)  and those in a control group (n=72) to complete a questionnaire that covered breastfeeding history and other birth and demographic features. While most demographic and birth features were similar, 36% of those in the pediatric-onset MS group reported being breastfed, compared with 71% of controls. Individuals who were not breastfed were nearly 4.5 times more likely to be diagnosed with pediatric-onset MS.

How will breastfeeding impact my risk of MS relapse after giving birth?

The issue of breastfeeding and MS relapses is somewhat controversial. In 1988, Nelson and colleagues  found that among 191 women with MS who became pregnant, 10% relapsed during pregnancy, but relapse rate rose to 34% during the 9 months after birth. Moreover, nearly 4 in 10 of those who breastfed experienced exacerbations, versus 3 in 10 among those who did not.

However, more recent studies demonstrate no association with breastfeeding and relapse. Just this year, Gould and colleagues published a study showing that among 466 pregnancies, annualized relapse rates declined during pregnancy, and there was no increase seen in the postpartum period. Moreover, women who exclusively breastfed saw their risk of an early postpartum relapse lowered by 63%.

In late 2019, Krysko and colleagues  published a meta-analysis of 24 studies involving nearly 3,000 women with MS which showed that breastfeeds were 43% less likely to experience postpartum relapse compared with their non-breastfeeding counterparts. The link was stronger in studies where women breastfed exclusively.

The bottom line: There is a plurality of physicians who believe that breastfeeding has a protective effect – and most will tell you that you should recommend exclusive breastfeeding.

What medicines can I take that will not adversely affect me and my baby?

Once a woman knows that breastfeeding could help her offspring avoid developing MS, and minimize her chance of a postpartum relapse, she will likely ask what to do about medications. You answer will depends on what she’s taking.

• Drugs she can take with relative peace of mind. Most experts believe it is safe to take corticosteroids and breastfeed. In fact, women who relapse while breastfeeding will in all likelihood be given intravenous corticosteroids, such as methylprednisolone. These medications are present in the blood at very low levels, peak an hour after infusion, and quickly dissipate. So, it’s important to tell your patients to delay breastfeeding by 2 to 4 hours after they receive the steroid.

• Drugs that are potentially concerning and require close monitoring. For the so-called platform therapies—such as interferon beta/glatiramer acetate, natalizumab, and their generic equivalents—there are no large studies that clearly demonstrate safety. Still, they are generally thought to be safe. Be sure to heed FDA labeling: weigh breastfeeding benefit against the potential risk

• Drug to avoid entirely. Under no circumstances should breastfeeding women receive teriflunomide, cladribine, alemtuzumab, or mitoxantrone. The jury is still out on rituximab—which is not yet approved for MS in the United States—and ocrelizumab. For now, err on the safe side and switch to another therapy.

Chances are your female patients of childbearing age with multiple sclerosis—particularly if they become pregnant—will ask about breastfeeding. What are they likely to ask, and how should you answer? Here’s a quick rundown.

What kind of impact will breastfeeding have on my child?

We know that MS is not a genetic disease per se-it is neither autosomal recessive nor dominant. But there is an increased risk among family members, particularly first-degree relatives. If a patient asks, you can tell them it appears that infants who are breastfed are less likely to develop pediatric-onset MS.

In 2017, Brenton and colleagues asked individuals who experienced pediatric-onset MS (n=36)  and those in a control group (n=72) to complete a questionnaire that covered breastfeeding history and other birth and demographic features. While most demographic and birth features were similar, 36% of those in the pediatric-onset MS group reported being breastfed, compared with 71% of controls. Individuals who were not breastfed were nearly 4.5 times more likely to be diagnosed with pediatric-onset MS.

How will breastfeeding impact my risk of MS relapse after giving birth?

The issue of breastfeeding and MS relapses is somewhat controversial. In 1988, Nelson and colleagues  found that among 191 women with MS who became pregnant, 10% relapsed during pregnancy, but relapse rate rose to 34% during the 9 months after birth. Moreover, nearly 4 in 10 of those who breastfed experienced exacerbations, versus 3 in 10 among those who did not.

However, more recent studies demonstrate no association with breastfeeding and relapse. Just this year, Gould and colleagues published a study showing that among 466 pregnancies, annualized relapse rates declined during pregnancy, and there was no increase seen in the postpartum period. Moreover, women who exclusively breastfed saw their risk of an early postpartum relapse lowered by 63%.

In late 2019, Krysko and colleagues  published a meta-analysis of 24 studies involving nearly 3,000 women with MS which showed that breastfeeds were 43% less likely to experience postpartum relapse compared with their non-breastfeeding counterparts. The link was stronger in studies where women breastfed exclusively.

The bottom line: There is a plurality of physicians who believe that breastfeeding has a protective effect – and most will tell you that you should recommend exclusive breastfeeding.

What medicines can I take that will not adversely affect me and my baby?

Once a woman knows that breastfeeding could help her offspring avoid developing MS, and minimize her chance of a postpartum relapse, she will likely ask what to do about medications. You answer will depends on what she’s taking.

• Drugs she can take with relative peace of mind. Most experts believe it is safe to take corticosteroids and breastfeed. In fact, women who relapse while breastfeeding will in all likelihood be given intravenous corticosteroids, such as methylprednisolone. These medications are present in the blood at very low levels, peak an hour after infusion, and quickly dissipate. So, it’s important to tell your patients to delay breastfeeding by 2 to 4 hours after they receive the steroid.

• Drugs that are potentially concerning and require close monitoring. For the so-called platform therapies—such as interferon beta/glatiramer acetate, natalizumab, and their generic equivalents—there are no large studies that clearly demonstrate safety. Still, they are generally thought to be safe. Be sure to heed FDA labeling: weigh breastfeeding benefit against the potential risk

• Drug to avoid entirely. Under no circumstances should breastfeeding women receive teriflunomide, cladribine, alemtuzumab, or mitoxantrone. The jury is still out on rituximab—which is not yet approved for MS in the United States—and ocrelizumab. For now, err on the safe side and switch to another therapy.

Chances are your female patients of childbearing age with multiple sclerosis—particularly if they become pregnant—will ask about breastfeeding. What are they likely to ask, and how should you answer? Here’s a quick rundown.

What kind of impact will breastfeeding have on my child?

We know that MS is not a genetic disease per se-it is neither autosomal recessive nor dominant. But there is an increased risk among family members, particularly first-degree relatives. If a patient asks, you can tell them it appears that infants who are breastfed are less likely to develop pediatric-onset MS.

In 2017, Brenton and colleagues asked individuals who experienced pediatric-onset MS (n=36)  and those in a control group (n=72) to complete a questionnaire that covered breastfeeding history and other birth and demographic features. While most demographic and birth features were similar, 36% of those in the pediatric-onset MS group reported being breastfed, compared with 71% of controls. Individuals who were not breastfed were nearly 4.5 times more likely to be diagnosed with pediatric-onset MS.

How will breastfeeding impact my risk of MS relapse after giving birth?

The issue of breastfeeding and MS relapses is somewhat controversial. In 1988, Nelson and colleagues  found that among 191 women with MS who became pregnant, 10% relapsed during pregnancy, but relapse rate rose to 34% during the 9 months after birth. Moreover, nearly 4 in 10 of those who breastfed experienced exacerbations, versus 3 in 10 among those who did not.

However, more recent studies demonstrate no association with breastfeeding and relapse. Just this year, Gould and colleagues published a study showing that among 466 pregnancies, annualized relapse rates declined during pregnancy, and there was no increase seen in the postpartum period. Moreover, women who exclusively breastfed saw their risk of an early postpartum relapse lowered by 63%.

In late 2019, Krysko and colleagues  published a meta-analysis of 24 studies involving nearly 3,000 women with MS which showed that breastfeeds were 43% less likely to experience postpartum relapse compared with their non-breastfeeding counterparts. The link was stronger in studies where women breastfed exclusively.

The bottom line: There is a plurality of physicians who believe that breastfeeding has a protective effect – and most will tell you that you should recommend exclusive breastfeeding.

What medicines can I take that will not adversely affect me and my baby?

Once a woman knows that breastfeeding could help her offspring avoid developing MS, and minimize her chance of a postpartum relapse, she will likely ask what to do about medications. You answer will depends on what she’s taking.

• Drugs she can take with relative peace of mind. Most experts believe it is safe to take corticosteroids and breastfeed. In fact, women who relapse while breastfeeding will in all likelihood be given intravenous corticosteroids, such as methylprednisolone. These medications are present in the blood at very low levels, peak an hour after infusion, and quickly dissipate. So, it’s important to tell your patients to delay breastfeeding by 2 to 4 hours after they receive the steroid.

• Drugs that are potentially concerning and require close monitoring. For the so-called platform therapies—such as interferon beta/glatiramer acetate, natalizumab, and their generic equivalents—there are no large studies that clearly demonstrate safety. Still, they are generally thought to be safe. Be sure to heed FDA labeling: weigh breastfeeding benefit against the potential risk

• Drug to avoid entirely. Under no circumstances should breastfeeding women receive teriflunomide, cladribine, alemtuzumab, or mitoxantrone. The jury is still out on rituximab—which is not yet approved for MS in the United States—and ocrelizumab. For now, err on the safe side and switch to another therapy.