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

NCT03401047 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 19692
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Polycystic Ovary Syndrome

Keywords

Polycystic ovary syndrome

Outcome Measures

Primary Outcomes (1)

• Estradiol-induced change in 24-hour urinary LH excretion

  The estradiol-induced change in 24-hour urinary LH excretion is defined as the 24-hour urinary LH excretion immediately prior to estradiol administration vs. the peak 24-hour urinary LH excretion during estradiol administration.

  Change occurring over up to 7 days of estradiol administration

Secondary Outcomes (1)

• Estradiol-induced change in 24-hour urinary FSH excretion

  Change occurring over up to 7 days of estradiol administration

Study Arms (1)

Transdermal Estradiol

EXPERIMENTAL

Subjects will undergo estradiol administration for up to 9 days. Transdermal estradiol patches will be applied each day by study staff during study days two through nine (patches deliver 0.1 mg/day for a total dose of up to 0.6 mg/day).

Drug: Estradiol

Interventions

Estradiol DRUG

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.

Also known as: Vivelle

Transdermal Estradiol

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• PCOS group: post-pubertal (\> 4 years post-menarche) adult woman aged 18-30 years with PCOS, defined as clinical and/or laboratory evidence of hyperandrogenism (hirsutism and/or elevated serum \[calculated\] free testosterone concentration) plus ovulatory dysfunction (irregular menses, fewer than 9 per year), but without evidence for other potential causes of hyperandrogenism and/or ovulatory dysfunction
• Control group: post-pubertal (\> 4 years post-menarche) adult woman aged 18-30 years with regular menstrual periods (every 26-35 days) and no evidence of hyperandrogenism (i.e., no hirsutism, normal serum \[calculated\] free testosterone concentration)
• General good health (excepting overweight, obesity, PCOS, and adequately-treated hypothyroidism)
• Capable of and willing to provide informed consent
• Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period

You may not qualify if:

• Inability/incapacity to provide informed consent
• Males will be excluded (hyperandrogenism is unique to females)
• Age \< 18 years (we do not propose to study children because we have no preliminary data that would support this particular study in children)
• Age \> 30 years (since ovarian reserve may decrease beyond age 30)
• Obesity resulting from a well-defined endocrinopathy or genetic syndrome
• Positive pregnancy test or current lactation
• Evidence for non-physiologic or non-PCOS causes of hyperandrogenism and/or anovulation
• Evidence of virilization (e.g., rapidly progressive hirsutism, deepening of the voice, clitoromegaly)
• Total testosterone \> 150 ng/dl, which suggests the possibility of virilizing ovarian or adrenal tumor
• DHEA-S greater than upper reference range limit for controls; and DHEA-S elevation \> 1.5 times the upper reference range limit for PCOS. Mild elevations may be seen in PCOS, and will be accepted in this group.
• Early morning 17-hydroxyprogesterone \> 200 ng/dl measured in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase, the 17-hydroxyprogesterone will be repeated during the follicular phase). NOTE: If a 17-hydroxyprogesterone \> 200 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone \< 1000 ng/dl will be required for study participation.
• Abnormal thyroid stimulating hormone (TSH): Note that subjects with stable and adequately treated primary hypothyroidism, reflected by normal TSH values, will not be excluded.
• History and/or physical exam findings suggestive of Cushing's syndrome, adrenal insufficiency, or acromegaly
• History and/or physical exam findings suggestive of hypogonadotropic hypogonadism (e.g., symptoms of estrogen deficiency) including functional hypothalamic amenorrhea (which may be suggested by a constellation of symptoms including restrictive eating patterns, excessive exercise, psychological stress, etc.)
• Persistent hematocrit \< 36% and hemoglobin \< 12 g/dl

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Clinical Research Unit

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Christine Burt Solorzano, M.D.

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa G Gilrain, B.S.

CONTACT

434-243-6911; pcos@virginia.edu

Christine Burt Solorzano, M.D.

CONTACT

434-243-6911; pcos@virginia.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr., MD, Associate Professor of Pediatric Endocrinology

Model Details: This is a prospective interventional cohort study. Women with PCOS and controls will receive identical treatment (transdermal estradiol) and will be monitored using the same surveillance protocol. The study does not involve randomization, and it is not blinded.

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 17, 2018
• Study Start: November 30, 2017
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)