The Ontogeny of Distinct Reproductive Phenotypes in Girls at Risk for PCOS During the Postmenarchal Transition

Area of Science:

• Reproductive Endocrinology
• Pediatric Endocrinology
• Metabolic Disorders

Background:

• Polycystic ovary syndrome (PCOS) risk is elevated in daughters of affected women (PCOS-d) and girls with overweight/obesity (OW-g).
• Both groups exhibit childhood hyperandrogenemia (HA), but distinct early reproductive phenotypes suggest different underlying mechanisms.
• Understanding these early differences is crucial for identifying distinct PCOS developmental trajectories.

Purpose of the Study:

• To investigate and compare the early reproductive and metabolic phenotypes of adolescent girls at risk for PCOS.
• To differentiate the characteristics of PCOS daughters (PCOS-d) from those of overweight girls (OW-g) during the early postmenarchal transition.

Main Methods:

• A cross-sectional study involving 15 PCOS-d, 12 OW-g, and 17 lean control (LC) adolescent girls within 0.2-1.2 years of menarche.
• Assessment of metabolic and reproductive phenotypes, including hormone levels (SHBG, Free T, DHEAS, LH, FSH) and ovulatory function.
• Evaluation of LH and FSH responses to GnRH analog stimulation.

Main Results:

• Both PCOS-d and OW-g exhibited lower SHBG and increased HA prevalence compared to LC girls.
• PCOS-d showed higher DHEAS levels and elevated basal and stimulated LH/FSH responses to GnRH analog compared to OW-g.
• Ovulatory dysfunction (OD) was more prevalent in PCOS-d than in OW-g and LC girls.

Conclusions:

• Persistent HA is present in both PCOS-d and OW-g during early adolescence.
• Distinct neuroendocrine abnormalities and ovulatory dysfunction are characteristic of PCOS-d, not OW-g.
• Findings support separate developmental pathways to PCOS: neuroendocrine dysregulation in PCOS-d and peripheral androgen excess linked to adiposity in OW-g.