Anovulation after precocious pubarche: Early markers and time course in adolescence

Adolescent girls with a history of precocious pubarche (PP) are known to be at increased risk for ovarian hyperandrogenism, an endocrinopathy related to reduced fetal growth, but the characteristics of their ovulatory functio n have not been fully documented. We assessed ovulatory function by weekly urinary LH and salivary progestero ne measurements over 3 consecutive months in 85 adolescent girls with known weight and gestational age at birth: 49 girls had no history of PP (age, 1 4.7 +/- 1.7 yr), and 36 had a history of PP (age, 14.4 +/- 2.0 yr); 55 girl s were in the early postmenarcheal phase (0-3 yr after menarche), and 30 we re in the late postmenarcheal phase (>3 yr after menarche). in girls with P P, the 17-hydroxyprogesterone (17-OHP) response to ACTH was determined at p repubertal diagnosis of PP, and serum androgen and gonadotropin concentrati ons were measured in adolescence together with insulin responses to an oral glucose load. Early postmenarche, the fraction of girls with ovulations was similar in th e non-PP and PP subgroups (61% us. 62%), as was the fraction of ovulatory c ycles (25% us. 22%). Late postmenarche, however, the fractions of ovulating girls and ovulatory cycles were strikingly higher (P less than or equal to 0.001) in the non-PP than in the PP subgroup (91% us. 20% and 47% us. 12%) . Within the PP subgroup, anovulatory girls were found to have a lower weight so score at birth (mean +/- SEM) than ovulatory girls (-1.22 +/- 0.3 vs. - 0.36 +/- 0.3; P = 0.03), a higher 17-OHP response to ACTH before puberty (3 33.1 +/- 31 vs. 203.8 +/- 26 ng/dL; P < 0.002), and, in adolescence, lower serum sex hormone-binding globulin levels and higher circulating LH, free a ndrogen indexes, and insulin responses. In conclusion, these findings indicate that girls with PP are at increased risk for anovulation from late (not early) adolescence onward, particularly those girls with a low weight at birth and/or a high 17-OHP response to AC TH at prepubertal diagnosis of PP.