NCT04597099

Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion

Ability of Androgen-receptor Blockade to Normalize Progesterone-induced Augmentation of Gonadotropin Secretion in PCOS (CRM010)

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: University of Virginia · Academic / Other
• Sex: Female
• Age: 18 Years – 30 Years
• Healthy volunteers: Accepted

Summary

This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.

Detailed description

Women with PCOS appear to exhibit impaired progesterone (P4) augmentation of gonadotropin release (positive feedback), and this is at least partly independent of BMI differences. To test more directly the role of hyperandrogenemia/hyperandrogenism (HA), we will assess if the androgen-receptor blocker flutamide enhances P4 augmentation of gonadotropin release in estradiol (E2)-treated women with PCOS. We will study 10 women with PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study, with subjects undergoing two assessments of P4 positive feedback - once after 4 weeks' pretreatment with flutamide and once after 4-weeks' pretreatment with placebo (in random order). We will assess P4 positive feedback via frequent sampling for 16 hours. Subjects will be pretreated for 3 days (prior to CRU admission) with transdermal E2 (0.2 mg/day), starting no earlier than cycle day 7. Subjects will be admitted to the CRU the evening of day 3 of E2 treatment. Starting at 0200 h, blood will be collected for 16 hours. After 6 h of sampling (0800 h), subjects will receive a single oral dose of P4. A second CRU admission - performed at least 2 months later to permit adequate washout of flutamide (as needed) - will be identical to the first except that placebo pretreatment will be exchanged for flutamide pretreatment or vice versa. We will assess the P4-mediated augmentation of FSH release, with secondary endpoints including the P4-mediated augmentation of LH release. We hypothesize that in E2-pretreated women with PCOS, acute P4 augmentation of FSH release (positive feedback) will be enhanced by androgen-receptor blockade (flutamide).

Conditions

• PCOS
• Polycystic Ovary Syndrome

Interventions

Type	Name	Description
DRUG	Micronized progesterone	oral micronized progesterone suspension, 100 mg oral dose at 0800 during each study admission
DRUG	Placebo	Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.
DRUG	Flutamide	Flutamide, 250 mg taken orally twice daily for four weeks before study admission.
DRUG	Estradiol patch	Two 0.1 mg/day transdermal estradiol patches will be applied 3 days prior to each inpatient admission; on the morning of study admission, these two patches will be removed and immediately replaced with two new 0.1 mg/day patches.

Timeline

• Start date: 2022-10-26
• Primary completion: 2025-10-01
• Completion: 2025-10-01
• First posted: 2020-10-22
• Last updated: 2023-11-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study