Abstract
PURPOSE: To determine whether premenarchal girls exhibit positive estradiol feedback similar to regularly cycling adult women when given exogenous estradiol. METHODS: This was a prospective clinical cohort study at 2 institutions. Nine girls and 6 women received a 7-day course of transdermal estradiol designed to produce physiologic, mid-cycle circulating estradiol levels. Participants collected daily morning urine for luteinizing hormone (LH), estradiol metabolites (E1c), and progesterone metabolites (Pdg), corrected for creatinine. Main outcomes were percentage increase in LH from nadir to peak and the absolute value of peak LH between the 2 groups, using t testing and linear mixed-effects modeling. RESULTS: All participants exhibited a positive feedback response to estradiol. Adult women had a 532.8% (95% confidence interval [CI]: 253.7-1119) increase in LH after estradiol exposure; premenarchal girls had a 497.9% increase (95% CI: 274.5-903.2; P = .86). The absolute value of the LH surge in women was 9.50 mLU/mgCr (95% CI: 2.59- 43 34.90) and in premenarchal girls was 2.57 mLU/mgCr (95% CI: 0.53-12.49; P = .15). CONCLUSIONS: Premenarchal girls can mount an LH surge proportionally similar to regularly cycling adults. This occurs earlier in puberty than previously believed, in contrast to current dogma that maturation of the hypothalamic-pituitary-ovarian axis occurs after menarche and is the rate-limiting step for the establishment of regular, ovulatory cycles. Failure to achieve regular cycles may instead be due to nutritional or ovarian factors. Young girls who fail to ovulate shortly after menarche may warrant further evaluation for endocrinopathies.