NCT00929006

Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism

Study to Assess Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: University of Virginia · Academic / Other
• Sex: Female
• Age: 10 Years – 17 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is two-fold. (1) We will determine if in mid- to late pubertal girls without hyperandrogenism (HA), progesterone (P4) acutely reduces waking luteinizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. (2) We will determine if in mid- to late pubertal girls with HA, P4 will acutely suppress waking LH frequency to a lesser degree than it does in girls without HA.

Detailed description

This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypotheses: (1) In normal mid- to late pubertal girls without hyperandrogenism (HA), progesterone acutely suppresses waking LH pulse frequency more than sleep-associated LH pulse frequency; and (2) compared to normal mid- to late pubertal girls without HA, acute progesterone suppression of waking LH pulse frequency is impaired in mid- to late pubertal girls with HA. Studies will be performed in mid- to late pubertal girls (at least Tanner breast stage 3 but no more than 2 years postmenarcheal). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Immediately before and during the first CRU admission, either oral micronized progesterone (0.8 mg/kg/dose) or placebo (randomized) will be given at 0700, 1500, 2300, and 0700 h. During the CRU admission, blood will be obtained every 10 minutes through an indwelling iv catheter from 1800 to 1200 h. This will allow full characterization of pulsatile LH secretion in addition to other hormone measurements. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo will exchanged for progesterone or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) Results in pubertal girls without HA were recently published (Kim et al, J Clin Endocrinol Metab 2018;103:1112-1121). Data from girls with HA will be compared to recently-published results in girls without HA. Mean LH pulse frequency while awake will be analyzed via a hierarchical linear mixed model (HLMM). HA status (HA vs. non-HA), sleep status (wake vs. sleep), and treatment (progesterone vs. placebo) will represent fixed-effects, along with all associated interactions. Random effects will be used to account for hierarchical variance-covariance structure of the crossover study design. With regard to hypothesis testing, the association between HA status and wake LH pulse frequency will be evaluated via linear contrasts of HLMM least squares pulse frequency means. The differential impact of exogenous progesterone on wake LH pulse frequency in pubertal girls with and without HA (primary analysis) will be evaluated via the same testing method. Using published and preliminary data, we determined that, if 16 pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.2 pulse/hour differential effect of P4 on wake LH pulse frequency between the HA and the non-HA groups with a two-sided false positive rejection rate of no more than 0.05.

Conditions

• Puberty
• Hyperandrogenism

Interventions

Type	Name	Description
DRUG	Micronized progesterone suspension	Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone.
DRUG	Placebo	Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Timeline

• Start date: 2008-06-01
• Primary completion: 2025-10-01
• Completion: 2025-12-01
• First posted: 2009-06-26
• Last updated: 2025-08-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study