Acute effects of testosterone infusion on the serum luteinizing hormone profile in eumenorrheic and polycystic ovary syndrome adolescents.

CONTEXT: Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females. OBJECTIVE: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. DESIGN AND SETTING: We conducted a prospective, longitudinal, randomized, double-blind study at a pediatric endocrinology clinical research center. PARTICIPANTS: Seven nonobese PCOS adolescents and seven matched controls (C) were studied in the early follicular phase of three consecutive menstrual cycles or in three consecutive months. INTERVENTION: Pulsatile LH release was determined during saline [baseline (B)] and constant testosterone (T) infusions: low dose (T-LD) 0.75 and high dose (T-HD) 2.5 mg/12 h iv. Blood samples were drawn every 20 min overnight. MAIN OUTCOME MEASURES: LH (immunofluorometric assay) and T (electrochemiluminescence immunoassay) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy analyses. RESULTS: On T-LD, C and PCOS serum T levels increased 2- to 3-fold vs. B. On T-HD, T values doubled in both groups vs. T-LD. Controls on T-LD had greater 12-h pulsatile LH secretion rate (P < 0.05 vs. B) and on T-HD had lower mean, pulsatile, basal LH release and LH approximate entropy (vs. B, P < 0.05). PCOS did not respond to T-LD. High-dose T did not alter mean LH in PCOS but increased pulsatile and reduced basal LH secretion. CONCLUSIONS: PCOS adolescents have impaired suppression of pulsatile LH secretion rate consistent with reduced androgen negative feedback. Attenuation of T feedback in nonobese adolescents with PCOS extends the pathophysiology of this syndrome.

Acceleration of luteinizing hormone pulse frequency in adolescent girls with a history of central precocious puberty with versus without hyperandrogenism.

UNLABELLED: 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.