Gonadal Function in Infants, Adolescents and Young Adults with Prader-Willi Syndrome.

Harry J. Hirsch and Varda Gross-Tsur

The Multidisciplinary Clinic for Patients with Prader-Willi Syndrome, Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel

Hypogonadism is considered to be a consistent finding in all individuals with Prader-Willi syndrome.  Nearly all PWS male infants have micropenis and/or cryptorchidism (undescended testes).   Pubertal development is both sexes is usually delayed and incomplete. Although girls often have significant breast development, spontaneous menstrual periods are uncommon.  Pregnancy has been reported in a few PWS women, but there are no reports of fertility in men.  Hypogonadism results not only in immature appearance and behavior, but increases the risk of osteoporosis. 

Recent studies have challenged the concept that hypogonadism results only from a central hypothalamic-pituitary gland defect. Longitudinal studies in a small number of male infants with PWS suggested that they may have a primary testicular defect with normal pituitary gland responses.   

In the Israel patient population, they have observed that reproductive hormone levels are variable, and that some individuals have sex hormone levels within the normal range for age.  In addition, some of their adolescent and young adult PWS patients are interested in dating and other age-appropriate sexual activities.  These observations suggest that the degree and expression of hypogonadism in the PWS population is more variable and less consistent than has been previously reported. 

They plan to measure pituitary gonadotropins and gonadal hormones across the age spectrum.  They will interview older adolescents and adult patients regarding sexual interests and behavior.   These findings should help determine the relative contributions of gonadal vs central (hypothalamic-pituitary) dysfunction in explaining hypogonadism in PWS.  Assessment of sexual interests and behavior will provide information regarding normative behavior which will be important for families and supportive living caretakers. 

 edited: 02/21/2008