Recruiting
Early Phase 1

Estradiol

Sponsor:

University of Virginia

Code:

NCT03401047

Conditions

Polycystic Ovary Syndrome

Eligibility Criteria

Sex: Female

Age: 18 - 30

Healthy Volunteers: Accepted

Interventions

Estradiol

Study Details

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

Study ID

NCT03401047

Start date

Nov 30, 2017

Status verified date

Jul, 2025

Completion date

Dec 1, 2025

Anticipated

Primary completion date

Oct 1, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 30

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Hyperprolactinemia: Any degree of hyperprolactinemia (confirmed on repeat) will be grounds for exclusion for subjects without PCOS. Hyperprolactinemia > 20% higher than the upper limit of normal will be grounds for exclusion for subjects without PCOS. Mild prolactin elevations may be seen in PCOS, and elevations within 20% higher than the upper limit of normal will be accepted in this group.
  • 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
  • Severe thrombocytopenia (platelets < 50,000 cells/microliter) or leukopenia (total white blood count < 4,000 cells/microliter)
  • Previous diagnosis of diabetes, fasting glucose > or = 126 mg/dl, or a hemoglobin A1c > or = 6.5%
  • Persistent liver panel abnormalities, with two exceptions. Mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Also, mild transaminase elevations may be seen in obesity/PCOS; therefore, elevations < 1.5 times the upper limit of normal will be accepted in these groups.
  • Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure, asthma requiring intermittent systemic corticosteroids, etc.)
  • Decreased renal function evidenced by GFR < 60 ml/min/1.73m2
  • A personal history of breast, ovarian, or endometrial cancer
  • History of any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous cell skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years
  • History of allergy to transdermal estradiol patches
  • BMI < 18 or > 40 kg/m2; BMI < 18 kg/m2 is considered to be underweight, while > 40 kg/m2 is considered to be class 3 obesity -- both may have marked confounding effects for the outcomes of interest
  • Menstrual cycles lasting fewer than 26 days: Cycle frequency < 26 days suggest the possibility of relatively short follicular phases (e.g., < 12 days). If a subject with a follicular phase shorter than 12 days participates in Aim 1c, they could experience an endogenous gonadotropin surge under surveillance. Since we wish to capture only experimentally-induced surges, we will exclude such subjects.

Study Design

Enrollment

37 participants

Anticipated

Intervention Model

Single group

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Transdermal Estradiol

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).

Interventions

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.

Primary outcome measure

  • Estradiol-induced change in 24-hour urinary LH excretion [ Time Frame: Change occurring over up to 7 days of estradiol administration ]

Central Contacts and Locations

Central contacts

Melissa G Gilrain, B.S.

434-243-6911pcos@virginia.edu

Christine Burt Solorzano, M.D.

434-243-6911pcos@virginia.edu

Locations

University of Virginia Clinical Research Unit

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Melissa G Gilrain, B.S.

434-243-6911pcos@virginia.edu

Christine Burt Solorzano, M.D.

434-243-6911cmb6w@virginia.edu

Principal Investigator:

Christine Burt Solorzano, M.D.

More Information

Sponsor

University of Virginia

Last update posted

Aug 5, 2025

Last verified

Jul, 2025

Keywords

  • Polycystic ovary syndrome

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2025-08-05.