Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion

Launched by UNIVERSITY OF VIRGINIA · Oct 17, 2020

Keywords

ClinConnect Summary

This clinical trial is studying whether a medication called flutamide, which blocks the effects of testosterone, can help improve a specific function of the pituitary gland in women with Polycystic Ovary Syndrome (PCOS). The researchers believe that using flutamide along with progesterone may enhance the release of a hormone called FSH, which is important for ovulation. The study is for women aged 18 to 30 who have PCOS and related symptoms, and it is currently recruiting participants.

To be eligible for this trial, women must be in generally good health and not pregnant, and they need to avoid pregnancy during the study using reliable non-hormonal methods. Participants will be randomly assigned to receive either the medication or a placebo (a non-active treatment) during different periods of the study, and they can expect to undergo some health assessments and blood tests. It’s important to note that women with certain health conditions, like liver issues or specific hormone imbalances, may not qualify for this study. If you or someone you know has PCOS and is interested in participating, this trial could provide valuable insights into possible new treatments.

Gender

FEMALE

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