Maturation of the hypothalamo-pituitary-ovarian axis in adolescent girls

The first menstrual cycles after menarche are irregular and anovulatory. To determine whether these cycles reflect immature pituitary responsiveness to gonadotropin-releasing hormone (GnRH) in relationship to ovarian steroid secretion, we measured basal plasma estradiol (E2), progesterone (P), and gonadotropins as well as LH and FSH responses to GnRH in 90 healthy girls during the first 5 yr after menarche. During the first year postmenarche, sex steroids, basal gonadotropins, and responses to GnRH had not yet reached adult values. During the second year, the increase in E2 was accompanied by a higher secretion of gonadotropins, both basally and in response to GnRH, which was similar to that observed in control adult women during both phases of the menstrual cycle, although P remained low. From the third to the fifth postmenarchal years, there was a progressive increase in the luteal LH and FSH responses to GnRH, resulting in significantly higher responses than in adult controls. Despite the progressive increase in sex steroids there was still a low percentage of ovulatory cycles over the 5 postmenarchal yr (0-63%). When the data were classified according to luteal P levels, it was found that anovulatory cycles (P less than 0.9 ng/ml) with normal E2 levels (100 pg/ml) resulted in exaggerated responses to GnRH, while in ovulatory cycles with P levels greater than 10 ng/ml and normal E2 concentrations, a lower response was observed, suggesting that high concentrations of P exerted a negative feedback on LH and FSH secretion. In contrast, the association of lower E2 (less than 100 ng/ml) and P (less than 5 ng/ml) levels resulted in a synergistic positive action on gonadotropin secretion. These data extend to endogenous sex steroids the dose-dependent positive and negative actions on gonadotropin secretion previously demonstrated with exogenously administered steroids in women.