RECRUITING

Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.

Official Title

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

Quick Facts

Study Start:2022-10-26

Study Completion:2025-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04597099

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 30 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Melissa Gilrain, BS

CONTACT

4342436911

pcos@virginia.edu

Christopher M McCartney, MD

CONTACT

Principal Investigator

Christopher M McCartney, MD

PRINCIPAL_INVESTIGATOR

Univsersity of Virginia

Study Locations (Sites)

University of Virginia

Charlottesville, Virginia, 22901

United States

Collaborators and Investigators

Sponsor: University of Virginia

Christopher M McCartney, MD, PRINCIPAL_INVESTIGATOR, Univsersity of Virginia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-10-26

Study Completion Date2025-10-01

Study Record Updates

Study Start Date2022-10-26

Study Completion Date2025-10-01

Terms related to this study

Keywords Provided by Researchers

PCOS
Polycystic Ovary Syndrome

Additional Relevant MeSH Terms

PCOS
Polycystic Ovary Syndrome