RECRUITING

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

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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

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.

Official Title

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

Quick Facts

Study Start:2017-11-30

Study Completion:2025-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03401047

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
* 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	* 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.

Inclusion Criteria

Exclusion 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

* 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.

Contacts and Locations

Study Contact

Melissa G Gilrain, B.S.

CONTACT

434-243-6911

mg7zb@hscmail.mcc.virginia.edu

Christopher McCartney, M.D.

CONTACT

434-982-6324

cm2hq@hscmail.mcc.virginia.edu

Principal Investigator

Christopher McCartney, M.D.

PRINCIPAL_INVESTIGATOR

University of Virginia

Study Locations (Sites)

University of Virginia Clinical Research Unit

Charlottesville, Virginia, 22908

United States

Collaborators and Investigators

Sponsor: University of Virginia

Christopher McCartney, M.D., PRINCIPAL_INVESTIGATOR, University 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 Date2017-11-30

Study Completion Date2025-12-01

Study Record Updates

Study Start Date2017-11-30

Study Completion Date2025-12-01

Terms related to this study

Keywords Provided by Researchers

Polycystic ovary syndrome

Additional Relevant MeSH Terms

Polycystic Ovary Syndrome