Home > Funded Projects > Longitudinal investigation of pubertal development and reproductive hormones in Prader-Willi syndrome from infancy through adulthood (year 2)

Background: Hypogonadism (impaired sex hormone production) is a major feature of PWS, although the clinical expression is variable. Nevertheless, early onset of puberty has been seen in both sexes, and pregnancies have been documented in some PWS women. The causes of hypogonadism in PWS are heterogeneous, encompassing a spectrum which includes primary testicular and ovarian defects, combined gonadal and pituitary hormone deficiencies, and hypothalamic dysfunction resulting in gonadotropin deficiency. We previously reported reproductive hormone profiles in a cross-sectional, nationwide PWS population and showed that primary gonadal defects are the major contributor to hypogonadism in these patients. Pituitary gonadotropin deficiency is found in only a minority of PWS individuals.
Objectives: We wish to extend our current study of individual changes in hormone levels in our large, nationwide PWS population by addressing the following questions: (1) Does the type of hypogonadism (primary gonadal failure vs hypogonadotropic hypogonadism) persist or fluctuate from infancy through childhood, adolescence, and adulthood? (2) What is the age range for puberty onset in PWS children? (3) What is the time course of pubertal progression until pubertal arrest is noted? (4) Can we identify a subgroup of PWS women who may potentially be fertile? (5) Can we suggest appropriate recommendations for the timing and types of hormonal replacement based on each individual’s hormonal profile?
Aims: We plan to obtain a third clinical and laboratory evaluation of our initial cohort of 82 PWS individuals (37 males, 45 females; ages 6 weeks to 32 years). Data will include physical examination including Tanner staging, menstrual history, and blood sampling for reproductive and pubertal hormones including the specific gonadal hormones: anti-Mullerian hormone and inhibin B. Results of the initial evaluation will be used as each individual’s control data. Hormone levels will also be compared with normal age-appropriate reference standards
Significance: Detailed knowledge of the natural development of puberty and reproductive hormones among PWS individuals is needed in order to tailor appropriate recommendations for hormone replacement or contraception in PWS individuals. Furthermore, this information is important for planning age-appropriate sex education and counseling in this population.

Funded Year:


Awarded to:

Varda Gross-Tsur, MD




Shaare Zedek Medical Center, Israel

Research Outcomes:

Characterization of minipuberty in infants with Prader-Willi syndrome

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

Longitudinal Study of Reproductive Hormones in Prader-Willi Syndrome (PWS) from Early Infancy through the Fourth Decade

Sexual dichotomy of gonadal function in Prader-Willi syndrome from early infancy through the fourth decade