Guidelines Set for Common, But Untreated, Sex Organ Issues of Women With PWS

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by Marta Figueiredo PhD |

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Researchers have developed guidelines for screening and treating hypogonadism, or underdeveloped sex organs, in women with Prader-Willi syndrome (PWS), noting this condition is frequent in these patients, but often left undiagnosed.

Given that the resulting low levels of sex hormones can cause osteoporosis (weak and brittle bones) and PWS patients are already at risk of this bone disorder, screening for and treating hypogonadism is crucial to help avoid it, the researchers noted.

The recommendations, along with results of a hypogonadism study in 64 women with PWS in the Netherlands, were outlined in a report, “Hypogonadism in Women with Prader-Willi Syndrome — Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion,” published in the Journal of Clinical Medicine.

PWS is characterized by weak muscle tone, excessive appetite, intellectual disability, and hypogonadism, which left untreated can cause osteoporosis. PWS patients are already at risk for osteoporosis due to growth hormone deficiency and reduced physical activity.

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Hunger-regulating Hormone Levels Found to Be Abnormal in PWS

As such, “timely detection and treatment of hypogonadism is crucial” to avoid osteoporosis in this patient population, the researchers wrote.

To better understand this bone condition in women with PWS, and prevent it from being untreated, a team of researchers in the Netherlands retrospectively analyzed the demographic and clinical data of 64 women with the disease.

They also conducted a systematic review of published data on the subject to June 2021 and provided clinical recommendations based on a discussion from an international panel of experts who had experience with treating hypogonadism in females with PWS.

All 64 women, with a median age of 28 (range, 18–58), had undergone a health screening at a Dutch PWS reference center that included a medical questionnaire and interview, physical examination, and measurements of relevant sex hormones.

Given that estradiol, a major female sex hormone, can be found at normal levels in obese women due to its production in fat cells, hypogonadism was defined as absent or irregular menstruation, regardless of estradiol levels in the blood.

Results showed that among the 50 women with available information about their menstrual cycles, 94% had hypogonadism, which was consistent with the frequency range reported in previous studies (54–100%; most commonly above 80%).

However, hypogonadism had not been diagnosed prior to the center’s screening in 34% of these women, and 28% did not receive treatment for it.

Laboratory measures of relevant sex hormones, as well as data from the literature review, suggest that hypogonadism in women may not only be caused by impaired function of the hypothalamus, “but possibly also by combined ovarian and hypothalamic hypogonadism, as is seen in males with PWS,” the researchers wrote.

The hypothalamus, a brain region highly affected in PWS, controls not only hunger, but also the production of sex hormones by the ovaries.

The team found no significant association between laboratory measurements and genetic subtype, growth hormone treatment, body mass index, or age in these women.

At the time of the study, 47 of the women were receiving some kind of hormonal therapy (with treatment starting at a median age of 20), the most common being oral contraceptives, followed by hormone-replacement therapy. Common side effects included spotting, or light bleeding outside a regular period, and an increase in challenging behavior.

The review of published data also highlighted that, besides bone health, hypogonadism hormone therapy is associated with benefits to muscle function, body composition, psychological outcomes, and cardiovascular health — all concerns in PWS patients.

These findings indicate that hypogonadism is frequent, but commonly undiagnosed and untreated, in women with PWS.

“This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or [medication] interactions,” the team wrote.

The researchers recommended, based on these results, the literature review, and expert opinions, that all women with PWS be screened yearly for hypogonadism by assessing their menstrual cycle.

“If the cycle is irregular or absent, treatment should be considered,” the team wrote, adding that bone density should also be analyzed, since signs of its reduction makes hypogonadism treatment “even more urgent.”

The treatment regimen should be adjusted to minimize interactions with common medications in PWS, such as growth hormone therapy and psychotropic therapies. If risks are unacceptable, treatment should not be initiated, but bone measures and risk assessment should be conducted every year.

Before initiating hypogonadism treatment, physicians should discuss hygiene measures and possible side effects, including bleedings and behavioral changes, with patients and their caregivers, the researchers advised.

Treatment should also be adjusted in case of sexual activity, as standard hypogonadism hormone therapy does not protect against pregnancy, and contraceptives should be used.

Discussing hypogonadism and sexual activity may provide “a good opportunity” to talk about the sensitive topic of “sex for food” — receiving food in exchange for sexual acts. Women with PWS can have both an insatiable appetite and intellectual disabilities, making them “especially vulnerable to become victims of sexual abuse,” the team wrote.

The researchers also recommended that patients’ treatment compliance, adverse events, and behavior be assessed regularly, and bone density be measured every two to three years. Hypogonadism hormone therapy should be continued “until the natural age of menopause (around 50 years), similar to the clinical practice for non-PWS women,” they added.

“To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS,” the researchers concluded.