NCT03401047

Study to Assess Potential Impairments in Estradiol Augmentation of Gonadotropin Secretion in Polycystic Ovary Syndrome

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Sponsor: University of Virginia · Academic / Other
• Sex: Female
• Age: 18 Years – 30 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to determine if estradiol augmentation of luteinizing hormone (LH) secretion secretion (primary endpoint) and follicle-stimulating hormone (FSH) secretion (secondary endpoint) is reduced in adult women with polycystic ovary syndrome.

Detailed description

This is a two-group controlled study to test the following hypothesis: compared to body mass index (BMI)-matched normal controls, women with polycystic ovary syndrome (PCOS) will demonstrate blunted LH responses to preovulatory estradiol concentrations. We will study both normally-cycling controls and women with PCOS. We aim to recruit BMI-matched pairs (PCOS vs. control within 2 kg/m2). To provoke a gonadotropin surge, subjects will receive graded transdermal estradiol dosing, and we will use a dose adjustment protocol to maintain serum estradiol levels of 250-400 pg/ml. To enhance reliability of estradiol delivery, transdermal estradiol patches will be placed/replaced daily by Clinical Research Unit (CRU) nurses, and abdominal sites will be rotated. All subjects will begin estradiol on menstrual cycle day 4. Starting 24 hours before E2 administration, all subjects will collect all urine output in 12-hour time blocks for later urinary LH and FSH analysis; this will continue until the end of the study. Additionally, subjects will have daily morning blood draws in the CRU for later hormone measurements. Transvaginal ovarian ultrasound will be performed on study day 6 -- near the time of expected surge initiation -- to document largest follicle sizes. We will measure serum estradiol daily and employ an estradiol dose-adjustment protocol to maintain target estradiol levels. We will also measure LH daily. The study will be stopped after either (a) serum LH increases to 5-fold higher than baseline and subsequently falls to within 200% of baseline, or (b) the subject has received estradiol for a full 7 days, whichever comes first. The primary endpoint will be estradiol-induced change in 24-hour urinary LH excretion, defined as 24-hour mean values immediately prior to estradiol administration vs. peak 24-hour mean values during estradiol administration. A comparison of 24-hour LH changes between healthy normal and PCOS groups will be conducted by way of a random-effects analysis of covariance (ANCOVA) model. The ANCOVA model will be specified so that each BMI-matched pair will represent an independent observational unit with respect to comparing 24-hour LH change between groups. With regard to hypothesis testing, we will test whether the component of variability in 24-hour LH change attributed to "Study Group" (healthy normal control vs. PCOS) is a significant component of the overall variability in 24-hour LH change. Variability in 24-hour LH change attributed to baseline disparities in LH will be accounted for by treating subject-specific baseline LH as a covariate in the ANCOVA model. If BMI matching is inadequate, we will also include BMI as a covariate in the model. If 11 women with PCOS and 11 controls complete study, we expect at least 80% power to detect a 33% difference in E2-induced augmentation of urinary LH excretion.

Conditions

• Polycystic Ovary Syndrome

Interventions

Type	Name	Description
DRUG	Estradiol	Subjects will receive graded doses of transdermal estradiol patches for up to 7 days. Blood estradiol tests will be performed daily, and the number of estradiol patches used will be adjusted to maintain serum estradiol levels of 250-400 pg/ml. Estradiol is a natural hormone.

Timeline

• Start date: 2017-11-30
• Primary completion: 2025-10-01
• Completion: 2025-12-01
• First posted: 2018-01-17
• Last updated: 2025-08-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study