Using flutamide to improve hormone release in women with PCOS

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

This study is testing if the medication flutamide can help improve hormone release in young women with PCOS by enhancing the effects of progesterone.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 30 Years
• Sex: Female
• Sponsor: University of Virginia (Academic / other)
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT04597099 on ClinicalTrials.gov

What this trial studies

This study investigates whether flutamide, an androgen-receptor blocker, can enhance the positive feedback of progesterone on gonadotropin release in women with Polycystic Ovary Syndrome (PCOS). It is a randomized, placebo-controlled, double-blinded, crossover study involving 10 women aged 18-30 with PCOS. Participants will undergo two assessments of progesterone's effect on hormone release after pretreatment with either flutamide or placebo, following a regimen of estradiol. Blood samples will be collected to measure hormone levels and assess the impact of the treatment.

Who should consider this trial

Good fit: Ideal candidates are post-pubertal women aged 18-30 diagnosed with PCOS and exhibiting signs of hyperandrogenism and ovulatory dysfunction.

Not a fit: Patients over 30 years old or those with obesity due to defined endocrinopathies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved hormonal regulation and treatment options for women with PCOS.

How similar studies have performed: While this approach is novel in its specific application, previous studies have explored hormonal treatments in PCOS with varying degrees of success.

Eligibility criteria

Inclusion Criteria:

* Post-pubertal (\> 4 years post-menarche) adult woman aged 18-30 years
* 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
* General good health (excepting overweight, obesity, hyperandrogenism, 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 (PCOS is unique to females)
* Age \< 18 years or \> 30 years (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 elevation \> 1.5 times the upper reference range limit. Mild elevations may be seen in PCOS, and will be accepted in these groups
* 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 performed by the subject's personal physician 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 \> 20% higher than the upper limit of normal. Mild prolactin elevations may be seen in women with 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 \< 37% 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%
* Given that this study involves flutamide use, any liver panel abnormality will be grounds for exclusion
* 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 allergy to micronized progesterone, flutamide, or transdermal estradiol
* BMI \< 18 or \> 40 kg/m2
* Due to the amount of blood being drawn, volunteers with body weight \< 110 pounds must be excluded

Where this trial is running

Charlottesville, Virginia

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

Study contacts

• Principal investigator: Christopher M McCartney, MD — Univsersity of Virginia
• Study coordinator: Melissa Gilrain, BS

Conditions PCOS; Polycystic Ovary Syndrome