Anovulation after Precocious Pubarche: Early Markers and Time Course in Adolescence¹

Abstract

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 function have not been fully documented. We assessed ovulatory function by weekly urinary LH and salivary progesterone 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, 14.7+/-1.7 yr), and 36 had a history of PP (age, 14.4+/-2.0 yr); 55 girls were in the early postmenarcheal phase (0-3 yr after menarche), and 30 were in the late postmenarcheal phase (> 3 yr after menarche). In girls with PP, the 17-hydroxyprogesterone (17-OHP) response to ACTH was determined at prepubertal diagnosis of PP, and serum androgen and gonadotropin concentrations were measured in adolescence together with insulin responses to an oral glucose load. Early postmenarche, the fraction of girls with ovulations was similar in the non-PP and PP subgroups (61% vs. 62%), as was the fraction of ovulatory cycles (25% vs. 22%). Late postmenarche, however, the fractions of ovulating girls and ovulatory cycles were strikingly higher (P < or = 0.001) in the non-PP than in the PP subgroup (91% vs. 20% and 47% vs. 12%). Within the PP subgroup, anovulatory girls were found to have a lower weight SD 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 (333.1+/-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 androgen 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 ACTH at prepubertal diagnosis of PP.

Plasminogen Activator Inhibitor-1 in Girls with Precocious Pubarche: A Premenarcheal Marker for Polycystic Ovary Syndrome?

“…PP has been established as a major risk factor for PCOS from adolescence onwards, particularly if PP itself was preceded by a low birth weight. Accordingly, PP is currently explored as a model to study incipient PCOS (4,14). However, previous studies have failed to identify, in young PP girls, an endocrine or metabolic variable that might serve as a prepubertal or early pubertal marker for subsequent PCOS and, ultimately, for type 2 diabetes and cardiovascular disease (14).…”

“…Girls with PP [appearance of pubic hair before 8 y (1)] due to pronounced adrenarche are known to be at risk for hyperinsulinism, dyslipidemia, and, in postmenarche, ovarian hyperandrogenism (2)(3)(4)(5). These endocrine-metabolic abnormalities are reminiscent of those seen in PCOS, and may be associated with increased risk of adulthood type 2 diabetes and cardiovascular disease (6 -10).…”

Delayed first cycle in intrauterine growth-retarded and postnatally undernourished female rats: follicular growth and ovulation after stimulation with pregnant mare serum gonadotropin at first cycle

“…Our results are partly analogous to those from human studies showing that intrauterine growth retardation in girls leads to an earlier onset of puberty and a reduced ovarian size at the time of puberty (Ibáñez et al 2000a, b). Girls with precocious pubarche and a low birth weight have an increased risk for anovulation from late adolescence onward (Ibáñez et al 1999). The greater number of follicles in the ovaries of the PFR rats may reflect the recruitment of a larger cohort and the impairment of follicle maturation after stimulation with gonadotropins, as also observed in women with polycystic ovaries (van der Meer et al 1998).…”

The incidence of metabolic syndrome in adolescents with different phenotypes of PCOS

“…However, there is great heterogeneity in ovarian morphology among adolescents, and the ultrasonographic diagnosis of polycystic appearance of the ovaries before the age of 17 is inaccurate [6]. Moreover, other studies suggested that ovarian hyperandrogenism might not become prominent during early adolescence, and adolescents who had only anovulation and polycystic ovaries might also be diagnosed with PCOS in the follow-up period [7,8]. Therefore, it is not appropriate to exclude the diagnosis of PCOS in the absence of hyperandrogenism or polycystic ovarian morphology in adolescents.…”