Acceleration of Luteinizing Hormone Pulse Frequency in Adolescent Girls with a History of Central Precocious Puberty with versus without Hyperandrogenism

Abstract

Some adolescents with a history of idiopathic central precocious puberty (ICPP) develop hyperandrogenism. Hypothesis: Luteinizing hormone (LH) hypersecretion could be a common mechanism underlying ICPP and polycystic ovary syndrome. Aim: To explore the GnRH-LH axis in those patients. Design: To compare overnight LH secretion in 7 healthy adolescents (CG) with that in patients with prior ICPP [5 with (CPPA) and 7 without (CPPB) hyperandrogenism]. To analyze daytime LH secretion in those patients. Methods: LH secretion was quantified by immunofluorometry and deconvolution analysis. Results: Nighttime mean LH (international units/liter) was higher in CPPA (6.9 ± 1.5) than in CPPB (3.2 ± 0.4, p < 0.05) and CG (2.9 ± 0.4, p < 0.01). Deconvolution analysis revealed a greater nighttime LH frequency (pulses/hour) both in CPPA (0.91 ± 0.06, p < 0.01) and CPPB (0.74 ± 0.02, p < 0.05) than in CG (0.45 ± 0.07). CPPA patients maintained a higher frequency than CPPB. Pulsatile LH production was greater in CPPA than in CG (50 ± 12 vs. 18 ± 3 IU/l/day, p < 0.01). Daytime mass of LH released per burst and pulsatile production rate were significantly greater in CPPA than in CPPB patients. Conclusions: Hyperandrogenic adolescents with prior ICPP show increased pulsatile LH secretion. Augmentation of LH pulsatility may predispose to or cause hyperandrogenism in some adolescents with a history of precocious puberty.

Prevalence of polycystic ovary syndrome in young women who had idiopathic central precocious puberty

“…Regarding clinical hyperandrogenism, the prevalence of hirsutism (23%) was similar to that reported by other authors in patients who had ICPP (14) and higher than the 12% reported for normal women (32).…”

“…Idiopathic central precocious puberty (ICPP) resembles PCOS in that it is characterized by increased LH levels and pulse frequency (12)(13)(14). Case observations have prompted speculation that an underlying neuroendocrine dysfunction manifests first as ICPP and later as PCOS (15).…”

GNRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome

“…In contrast, a large body of evidence has shown that GNRHa therapy does not provide similar beneficial effects in girls with early puberty (1,4). Furthermore, a high risk of developing polycystic ovary syndrome (PCOS) has been postulated in girls with CPP (5)(6)(7)(8)(9). PCOS is a heterogeneous endocrinopathy characterized by abnormal gonadotropin release and dysregulation of steroidogenesis (10), and based on the presence or absence of four key features: menstrual dysfunction, clinical and/or biochemical signs of androgen excess, and polycystic ovaries (11).…”

Endocrine Antecedents of Polycystic Ovary Syndrome in Fetal and Infant Prenatally Androgenized Female Rhesus Monkeys1

“…Conversely, circulating FSH levels have been reported to be low to normal in both PA female monkeys [12,20] and in women with PCOS [14,21], thereby elevating the serum LH:FSH ratio. It has been proposed that LH hypersecretion in PCOS may originate during adolescence, initially caused by hyperandrogenism and then, potentially, contributing to peripubertal hyperandrogenism (as in some adolescents with PCOS [22,23]). Such neuroendocrine dysfunction, however, may originate in utero from androgen/estrogen-induced changes in the fetal hypothalamo-pituitary axis [4,[24][25][26][27] before any subsequent peripubertal dysfunction.…”