Study shines light on how Prader-Willi kids experience puberty
Puberty begins spontaneously for most, but often stalls
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More than half of children with Prader-Willi syndrome (PWS) show signs of spontaneous puberty, but more than three-quarters will have hypogonadism (reduced function of the reproductive organs), according to a study in Australia.
That means patients generally will not attain full sexual maturity without therapies to normalize hormone levels. Data also showed that use of these hormonal therapies did not increase the risk of psychiatric or behavioral problems — a concern that may make doctors reluctant to prescribe such therapies.
“Most adolescents with PWS demonstrate evolving hypogonadism by the time of transition to young adult care, usually after spontaneous pubertal onset at a normal age,” the researchers wrote. “However,” they added, “there remains a reluctance to diagnose and treat hypogonadism in PWS despite its presence in the great majority by young adult life.
The researchers called for further efforts to standardize care for PWS patients during puberty.
The study, “Spectrum of Hypogonadism and Its Management in Adolescents With Prader-Willi Syndrome: A Retrospective Cohort Study Over 35 Years,” was published in Clinical Endocrinology.
Exploring development in PWS
PWS symptoms include behavioral and developmental abnormalities. It’s been well established that young people with PWS often experience hypogonadism, “presenting as incomplete or delayed pubertal development, genital [underdevelopment], and infertility,” the researchers wrote.
Hypogonadism can have major health consequences, such as an increased risk of low bone density and, consequently, broken bones, during adulthood.
“Despite this high prevalence, hypogonadism is reported to be underdiagnosed and undertreated in adults with PWS,” the researchers wrote. There’s not much data on exactly how people with this condition typically experience adolescent development, they added. There’s also a dearth of data on the best approaches to care for PWS patients with hypogonadism.
The researchers reported on puberty outcomes for 65 PWS patients (37 girls, 28 boys) who were cared for at their center over more than three decades.
Results showed that about two-thirds of the children started puberty spontaneously, as assessed with associated physical and/or hormonal changes, with a median age at onset of 10.3 for girls and 12.3 for boys.
By the last visit, hypogonadism was common, diagnosed in more than three-quarters in both girls (77%) and boys (88%) at a median age of 14.1 in girls and 15.3 in boys. This was often associated with abnormal pubertal development, such as unusually underdeveloped testes or breasts, or a lack of regular menstrual periods.
“The majority of adolescents with PWS demonstrated hypogonadism by transition to adult care,” the researchers wrote. “This is despite two-thirds … entering puberty spontaneously (at any age), supporting the notion that hypogonadism in PWS is predominantly a disorder of incomplete puberty or pubertal arrest” rather than a total absence of pubertal development, they said.
In the general population, children with hypogonadism are commonly treated with hormone replacement therapy (HRT), which aims to normalize levels of sex-specific hormones in the body.
A major concern with using HRT in young people with PWS is that these hormonal treatments may increase the risk of psychiatric or behavioral issues, which are already a hallmark of the disease.
The researchers said most of the young people with PWS at their center received HRT treatment, and rates of behavioral problems were unchanged after initiating these hormonal therapies.
“Behavioural/psychiatric issues reported were not found to be associated with pubertal HRT in either sex,” the team wrote. However, they added, it’s possible that selection bias may have influenced the results.
In this case, selection bias would mean that doctors may have been less likely to prescribe HRT to patients who were having overt behavioral problems out of fear that these treatments might lead to worsening behavior.
“Further studies are required to determine the best biomarker for early and timely diagnosis and treatment of hypogonadism in PWS,” the team concluded. “While lack of significant adverse behavioural/psychiatric changes with pubertal HRT in our [study] is reassuring, there remains the need for a standardised protocol for the use of pubertal HRT in adolescents with PWS.”
