ACCELERATED 24-HOUR LUTEINIZING-HORMONE PULSATILE ACTIVITY IN ADOLESCENT GIRLS WITH OVARIAN HYPERANDROGENISM - RELEVANCE TO THE DEVELOPMENTAL PHASE OF POLYCYSTIC OVARIAN SYNDROME

A study was initiated to delineate the neuroendocrine characteristics of hyperandrogenic adolescent girls with the aim of discerning feature s that may relate to the pubertal onset of the polycystic ovarian synd rome. Thirteen 11- to 18-yr-old girls with mild to moderate signs of h yperandrogenism (HA) and increased ovarian volume and 28 age matched n ormal girls were recruited for the study. LH pulsatility and FSH level s were analyzed based on serum concentrations measured with sensitive immunofluorometric assays in samples taken at 10-min intervals for 24 h under basal conditions, GnRH antagonist (Nal-Glu) suppression, and d examethasone suppression. Adrenal and ovarian contributions to serum c ortisol, dehydroepiandrosterone, androstenedione, testosterone (T), es trone (E(1)), estradiol (hourly), 17-hydroxypregnenolone, and 17-hydro xyprogesterone (17PO) concentrations were compared during basal and su ppression conditions and after gonadotropin and adrenal stimulations b y bolus GnRH (10 mu g) and CRF (1 mu g/kg). The progression from sleep -augmented pulsatile LH secretion to higher LH levels during wake than sleep observed during normal pubertal development occurred 2 yr earli er in the HA group. The number of LH pulses was significantly higher i n the HA group during both sleep and waking, whereas pulse amplitude w as higher only during the awake time. Thus, mean LH was 2.0-fold highe r during the awake time and only 1.6-fold higher during sleep in the H A group compared to the normal group. The elevation of FSH in HA was s mall relative to that of LH, resulting in an increased LH/FSH ratio (P < 0.008). The HA group had higher concentrations of 17PO (1.8-fold), androstenedione (1.9-fold), T (2.4-fold), and El (1.7-fold) than the n ormal group (all P < 0.001), with no alteration in circadian rhythm. T hese elevated steroid levels were significantly correlated with LH lev els in the basal state and decreased in proportion to the change in LH during Nal-Glu suppression. During adrenal suppression with dexametha sone, concentrations of cortisol, dehydroepiandrosterone, and 17-hydro xypregnenolone decreased in both groups (P < 0.001), but significant s uppression of 17PO, T, and E(2) occurred only in the normal girls, ind icating the ovarian origin of the increased levels of these steroids w ith enhanced expression of 17 alpha-hydroxylase activity in HA girls. We conclude that adolescent hyperandrogenism with increased ovarian vo lume is associated with augmented LH pulsatility, particularly during waking hours, an increased LH/FSH ratio, and a selective elevation of ovarian androgens compatible with enhanced 17 alpha-hydroxylase activi ty. These neuroendocrine features in HA girls, demonstrated for the fi rst time, are in accord with those found in adult women with polycysti c ovarian syndrome, supporting the long-suspected peripubertal onset o f this syndrome.