Hormone therapy side effects challenge girls with PWS
Many stop treatment because of bleeding issues
Hypogonadism, a condition in which the body produces few or no sex hormones, is common in girls and young women with Prader-Willi syndrome (PWS). But while hormone replacement therapy (HRT) is often prescribed, many patients stop using it because of bothersome side effects, a U.S. study found.
“These findings highlight the need to tailor HRT regimens,” the researchers wrote. “Research is also needed to better understand the experience of patients and caregivers to inform the development of tailored HRT regimens to improve both adherence and quality of life.”
The study, “Sex Hormone Replacement Therapy and Bleeding Patterns among Adolescents and Young Adult Females with Prader-Willi Syndrome,” was published in the Journal of Pediatric and Adolescent Gynecology.
PWS is a genetic disease that can cause hormonal imbalances, developmental delays, early-onset obesity, and behavioral problems. “Puberty is delayed or absent in most patients with PWS,” the researchers wrote.
As many as half of girls with PWS don’t get their periods without HRT, and these are often irregular. “For females with PWS, practice recommendations include screening for hypogonadism with pubertal staging and tracking of menstrual cycle irregularities with subsequent individualization of hormone replacement therapy (HRT),” the researchers wrote.
When to begin therapy?
Because there are limited guidelines for treating female hypogonadism in PWS, especially for adolescents, doctors are often unsure when and how to begin therapy.
Females with PWS “may have unique considerations related to HRT, including difficulties with use of transdermal patches due to skin picking, and menstrual management concerns related to developmental delay,” the researchers wrote.
To better understand pubertal timing, vaginal bleeding patterns, and HRT practices in females with PWS, a team led by researchers at the University of Colorado retrospectively reviewed the medical records of 51 girls and young women with PWS who were seen at a single U.S. hospital between 2013 and 2023.
A total of 21 patients met criteria for hypogonadism, “accounting for 84% of the 25 patients aged 13 years and older,” the researchers wrote.
The median age of the 21 participants was 16 (range, 13-23), and most were white (71.4%). All but one had private or public insurance, and 71.4% had not been referred to a gynecology appointment.
A total of eight patients (38.1%) had complete hypogonadotropic hypogonadism (where puberty did not begin on its own), while the remaining 13 (61.9%) had partial hypogonadism — where some puberty changes occurred but estrogen, the main female sex hormone, remained too low.
In the complete hypogonadotropic hypogonadism group, three girls (37.5%) had not begun developing their breasts by age 13. In the partial hypogonadism group, four girls (30.8%) had no periods by age 15, and three (23.1%) lacked menstruation four years after breast development.
Puberty in girls normally begins between the ages of 8 and 13. In females with PWS, there was a delay in puberty, being diagnosed at a median age of 13.5 (range, 10-15) in the complete hypogonadism group and 14.5 (range, 13-18) in the partial hypogonadism group.
No participant reported spontaneous, regular periods. Six (28.6%) reported irregular or spontaneous vaginal bleeding, which is a sign that the body may be producing some estrogen on its own. However, the average levels of estradiol — the main form of estrogen — were lower than normal in both groups.
Most participants (85.7%) were prescribed HRT, in the form of estradiol patches, oral estradiol, or combined contraceptive pills, at a median age of 14. However, eight of them (44.4%) later stopped it. The most common reason for discontinuation was bleeding or spotting between menstrual periods (50%).
“Many patients reported they were ‘not interested in having periods’ and caregivers endorsed wanting to limit periods,” the researchers wrote. “One caregiver described periods as a ‘distraction’ and worried about hygiene at school.”
Additional caregiver-reported reasons for discontinuing HRT included difficulties in complying with complex medication schedules or worries about side effects such as blood clots or impact on fertility.
Still, about two-thirds of females who discontinued HRT (66.7%) eventually restarted after an average of 18 months (range, two months to four years).
These “findings emphasize the importance of routine screening for hypogonadism in females with PWS” and “the need for a multidisciplinary approach to managing hypogonadism and tailoring HRT regimens to improve long-term adherence, health outcomes, and quality of life,” the researchers concluded.
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