Polycystic Ovary Syndrome (PCOS) and Prader-Willi Syndrome (PWS)

Jose Atilio Canas. Genetics-Pediatric Endocrinology, Winthrop University Hospital, 120 Mineola Blvd, Mineola NY 11501 USA.

Prader-Willi syndrome (PWS) is a genetic condition characterized by obesity, short stature, mental impairment, and hypogonadism. With a prevalence of 1 in 10,000, PWS is caused by the absence of segment 11-13 on the paternally derived chromosome 15q.

PCOS is a disorder of chronic androgen excess that may have its origin in childhood or even in utero. It is a common clinical condition during reproductive life and it is suspected in any adolescent female with hirsutism, acne, hyperhidrosis, menstrual irregularity, or obesity. Any one of these may be the sole feature. The anovulation characteristic of this condition usually seems to be attributable to intraovarian androgens excess, which in turn arises from functional ovarian hyperandrogenism (FOH). The primary cause of PCOS is unknown but appears to arise as a complex genetic disorder in which an intrinsic genetic trait interacts with other congenital or extrinsic environmental factors to cause dysregulation of steroidogenesis. The laboratory criteria for the diagnosis of “Classic PCOS” have been the association of hyperandrogenemia with either a “polycystic ovary” by ultrasound or an increased serum LH to FSH ratio. Insulin-resistant hyperinsulinism is often an important factor in the development of PCOS.

Objective: To compare the biochemical criteria of those individuals with PWS and clinical manifestations of PCOS with control PWS and non-PWS females with PCOS.

Method: Out a total of 57 PWS females between 15-35 years, 15 (26.3%) had in addition clinical manifestations of PCOS. Serum total testosterone (T), free testosterone (FT), LH, FSH, sex hormone binding globulins (SHBG) and insulin levels were measured in this subgroup, 23 control PWS and 38 non-PWS females with PCOS.

Group	BMI (kg/m²)	T (ng/ml)	FT (pg/ml)	LH/FSH	Insulin (uU/ml)	SHBG (nmol/L)
PWS-PCOS	43.4±10.9	57.3±31.6	17.3±13.7	1.4±1.3	47.7±37.6	11.4±4.5
PWS	40.9±13.6	27.2±14	5±1.7	0.6±0.3	16±11.6	38.8±20.5
PCOS	34.8±11.2	62.8±23.7	16.2±10.5	1.9±1.2	48.7±43.4	33.3±27.2

The biochemical markers in the PWS-PCOS were significantly different to the control PWS but similar to the non-PWS females with PCOS.

Discussion: The clinical and biochemical manifestations of functional ovarian hyperandrogenism (FOH) also known as PCOS was relatively common (26.3%) in our PWS population. Hypogonadotropic hypogonadism, characteristic of PWS individuals, brings further evidence compatible with the possibility that insulin excess may stimulate gonadotroph LH release directly by enhancing sensitivity to GnRH. Direct effect of LH on the ovaries and insulin on the ovaries and adrenal glands may explain the hyperandrogenism, characteristic of PCOS. Adolescents with PCOS are at risk for diabetes mellitus and cardiovascular disease, therefore PWS individuals with signs of hyperandrogenism and extreme difficulties in weight control should be evaluated for PCOS and treated accordingly.