Context. Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females.

Objective. To evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and PCOS adolescents.

Design. Prospective, longitudinal, randomized and double-blind study.

Setting: Pediatric endocrinology clinical research center.

Participants: Seven nonobese PCOS adolescents and 7 matched controls (C) were studied in the early follicular phase of 3 consecutive menstrual cycles or in 3 consecutive mo.

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 (IFMA) and T (ECLIA) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy (ApEn) analyses.

Results. On T-LD, C and PCOS serum T levels increased 2–3 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 ApEn (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.