Childhood obesity has become a major health concern in recent decades, especially with regard to metabolic abnormalities that impart a high risk for future cardiovascular disease. Recent data suggest that excess adiposity during childhood may influence pubertal development as well. In particular, excess adiposity during childhood may advance puberty in girls and delay puberty in boys. Obesity in peripubertal girls may also be associated with hyperandrogenemia and a high risk of adolescent polycystic ovary syndrome. How obesity may perturb various hormonal aspects of pubertal development remains unclear, but potential mechanisms are discussed herein. Insulin resistance and compensatory hyperinsulinemia may represent a common thread contributing to many of the pubertal changes reported to occur with childhood obesity. Our understanding of obesity's impact on pubertal development is in its infancy, and more research into pathophysiological mechanisms and longer-term sequelae is important.

Polycystic ovarian syndrome (PCOS) is a common disorder characterized by ovulatory dysfunction and hyperandrogenemia (HA). Neuroendocrine abnormalities including increased gonadotropin-releasing hormone (GnRH) pulse frequency, increased luteinizing hormone (LH) pulsatility, and relatively decreased follicle stimulating hormone contribute to its pathogenesis. HA reduces inhibition of GnRH pulse frequency by progesterone, causing rapid LH pulse secretion and increasing ovarian androgen production. The origins of persistently rapid GnRH secretion are unknown but appear to evolve during puberty. Obese girls are at risk for HA and develop increased LH pulse frequency with elevated mean LH by late puberty. However, even early pubertal girls with HA have increased LH pulsatility and enhanced daytime LH pulse secretion, indicating the abnormalities may begin early in puberty. Decreasing sensitivity to progesterone may regulate normal maturation of LH secretion, potentially related to normally increasing levels of testosterone during puberty. This change in sensitivity may become exaggerated in girls with HA. Many girls with HA—especially those with hyperinsulinemia—do not exhibit normal LH pulse sensitivity to progesterone inhibition. Thus, HA may adversely affect LH pulse regulation during pubertal maturation leading to persistent HA and the development of PCOS.

Obesity exacerbates the reproductive and metabolic manifestations of polycystic ovary syndrome (PCOS). The symptoms of PCOS often begin in adolescence, and the rising prevalence of peripubertal obesity has prompted concern that the prevalence and severity of adolescent PCOS is increasing in parallel. Recent data have disclosed a high prevalence of hyperandrogenemia among peripubertal adolescents with obesity, suggesting that such girls are indeed at risk for developing PCOS. Obesity may impact the risk of PCOS via insulin resistance and compensatory hyperinsulinemia, which augments ovarian/adrenal androgen production and suppresses sex hormone–binding globulin (SHBG), thereby increasing androgen bioavailability. Altered luteinizing hormone (LH) secretion plays an important role in the pathophysiology of PCOS, and although obesity is generally associated with relative reductions of LH, higher LH appears to be the best predictor of increased free testosterone among peripubertal girls with obesity. Other potential mechanisms of obesity-associated hyperandrogenemia include enhanced androgen production in an expanded fat mass and potential effects of abnormal adipokine/cytokine levels. Adolescents with PCOS are at risk for comorbidities such as metabolic syndrome and impaired glucose tolerance, and concomitant obesity compounds these risks. For all of these reasons, weight loss represents an important therapeutic target in obese adolescents with PCOS.

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