Assessing Estradiol's Effect on Hormone Secretion in Women with Polycystic Ovary Syndrome

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

This study is testing how a hormone called estradiol affects other hormones in women with polycystic ovary syndrome (PCOS) to see if they respond differently than women without PCOS.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years to 30 Years
• Sex: Female
• Sponsor: University of Virginia (Academic / other)
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT03401047 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate how estradiol affects luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in women with polycystic ovary syndrome (PCOS) compared to BMI-matched controls. Participants will receive transdermal estradiol and undergo daily monitoring of hormone levels and ovarian ultrasound to assess follicle development. The study will involve collecting urine samples for hormone analysis and maintaining specific estradiol serum levels throughout the intervention. The goal is to determine if women with PCOS exhibit a reduced LH response to estradiol compared to healthy controls.

Who should consider this trial

Good fit: Ideal candidates are women aged 18-30 with a diagnosis of PCOS or healthy women with regular menstrual cycles for comparison.

Not a fit: Patients who are not within the specified age range or do not meet the criteria for PCOS or healthy controls may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and treatment options for women with polycystic ovary syndrome.

How similar studies have performed: While similar studies have explored hormone responses in PCOS, this specific approach of estradiol augmentation is relatively novel.

Eligibility criteria

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.

Where this trial is running

Charlottesville, Virginia

• University of Virginia Clinical Research Unit — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Christine Burt Solorzano, M.D. — University of Virginia
• Study coordinator: Melissa G Gilrain, B.S.

Conditions Polycystic Ovary Syndrome; Polycystic ovary syndrome