Home > Funded Projects > Longitudinal study of reproductive hormones in Prader-Willi syndrome from infancy through adulthood

Hypogonadism (decreased production of testicular or ovarian hormones resulting in incomplete sexual development) is considered to be a cardinal feature of Prader-Willi syndrome, however, the clinical expression is variable. Most, but not all PWS males have unilateral or bilateral undescended testes.  Arrested pubertal development leads to inadequate virilization in PWS men.  While some PWS women experience spontaneous onset of menstrual periods, nearly all develop secondary amenorrhea. Consequences of inadequate production of sex hormones include immature body appearance, decreased muscle strength, and osteoporosis. Nevertheless, some PWS children experience onset of puberty at an abnormally early age and rare cases of pregnancy in PWS women have been described.

Although the cause of hypogonadism in PWS was generally attributed to hypothalamic dysfunction, we have recently shown that a specific gonadal (testes and ovaries) defect plays a major role in contributing  to the inadequate sex hormone production in this syndrome.  There are no studies, however, which describe the natural development of sexual hormones in a large group of PWS individuals over several years.  In view of the unpredictable variability in clinical expression of hypogonadism, these data are needed in order to develop clear guidelines regarding sex hormone replacement in PWS.

We plan to study over 90 patients with PWS who are followed in our national, multidisciplinary PWS clinic.  We will obtain blood samples for pituitary and gonadal hormones including LH, FSH, testosterone, and estradiol.  In addition, we will measure levels of newer, specific indicators of gonadal function, inhibin B and anti-Mullerian hormone.  Hormone levels will be compared with levels obtained from the same patients one to two years earlier, which were taken as part of our initial cross-sectional study.

These results will increase our understanding of the natural history of sexual hormone and pubertal development in PWS and help to determine which patients and at what age hormonal replacement therapy should be given.   Evidence of primary gonadal vs hypothalamic causes of hypogonadism may be relevant the type of hormonal replacement should be offered based on the individual patient’s hormonal profile.  These findings may identify those PWS women who are potentially fertile in order to recommend contraceptive measures.

Funded Year:


Awarded to:

Harry Hirsch, MD




Shaare Zedek Medical Center, Israel

Research Outcomes:

Management of hypogonadism in adolescent girls and adult women with Prader-Willi syndrome