Polycystic Ovary SyndromeEarly Phase 1CRM009NCT03401047
Study to Assess Potential Impairments in Estradiol Augmentation of Gonadotropin Secretion in Polycystic Ovary Syndrome
A Early Phase 1 study testing Estradiol in people with Polycystic Ovary Syndrome, run by University of Virginia at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 30 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- Estradiol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2017to 1 Dec 2025
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 26Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Virginia Clinical Research Unit
Charlottesville, Virginia, 22908
Melissa G Gilrain, B.S., 434-243-6911, pcos@virginia.edu
Christine Burt Solorzano, M.D., 434-243-6911, cmb6w@virginia.edu
About this study
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.
Read the detailed description
This is a two-group controlled study to test the following hypothesis: compared to body mass index (BMI)-matched normal controls, women with polycystic ovary syndrome (PCOS) will demonstrate blunted LH responses to preovulatory estradiol concentrations. We will study both normally-cycling controls and women with PCOS. We aim to recruit BMI-matched pairs (PCOS vs. control within 2 kg/m2). To provoke a gonadotropin surge, subjects will receive graded transdermal estradiol dosing, and we will use a dose adjustment protocol to maintain serum estradiol levels of 250-400 pg/ml. To enhance reliability of estradiol delivery, transdermal estradiol patches will be placed/replaced daily by Clinical Research Unit (CRU) nurses, and abdominal sites will be rotated. All subjects will begin estradiol on menstrual cycle day 4. Starting 24 hours before E2 administration, all subjects will collect all urine output in 12-hour time blocks for later urinary LH and FSH analysis; this will continue until the end of the study. Additionally, subjects will have daily morning blood draws in the CRU for later hormone measurements. Transvaginal ovarian ultrasound will be performed on study day 6 -- near the time of expected surge initiation -- to document largest follicle sizes. We will measure serum estradiol daily and employ an estradiol dose-adjustment protocol to maintain target estradiol levels. We will also measure LH daily. The study will be stopped after either (a) serum LH increases to 5-fold higher than baseline and subsequently falls to within 200% of baseline, or (b) the subject has received estradiol for a full 7 days, whichever comes first. The primary endpoint will be estradiol-induced change in 24-hour urinary LH excretion, defined as 24-hour mean values immediately prior to estradiol administration vs. peak 24-hour mean values during estradiol administration. A comparison of 24-hour LH changes between healthy normal and PCOS groups will be conducted by way of a random-effects analysis of covariance (ANCOVA) model. The ANCOVA model will be specified so that each BMI-matched pair will represent an independent observational unit with respect to comparing 24-hour LH change between groups. With regard to hypothesis testing, we will test whether the component of variability in 24-hour LH change attributed to "Study Group" (healthy normal control vs. PCOS) is a significant component of the overall variability in 24-hour LH change. Variability in 24-hour LH change attributed to baseline disparities in LH will be accounted for by treating subject-specific baseline LH as a covariate in the ANCOVA model. If BMI matching is inadequate, we will also include BMI as a covariate in the model. If 11 women with PCOS and 11 controls complete study, we expect at least 80% power to detect a 33% difference in E2-induced augmentation of urinary LH excretion.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- Estradiol
- Keywords
- Polycystic ovary syndrome
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Also called Vivelle
Subjects will receive graded doses of transdermal estradiol patches for up to 7 days. Blood estradiol tests will be performed daily, and the number of estradiol patches used will be adjusted to maintain serum estradiol levels of 250-400 pg/ml. Estradiol is a natural hormone.
| Study group | Role | What they receive |
|---|---|---|
| Transdermal Estradiol | Experimental | Subjects will undergo estradiol administration for up to 9 days. Transdermal estradiol patches will be applied each day by study staff during study days two through nine (patches deliver 0.1 mg/day for a total dose of up to 0.6 mg/day). Receives: Drug: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estradiol-induced change in 24-hour urinary LH excretion
The estradiol-induced change in 24-hour urinary LH excretion is defined as the 24-hour urinary LH excretion immediately prior to estradiol administration vs. the peak 24-hour urinary LH excretion during estradiol administration.
Measured: Change occurring over up to 7 days of estradiol administration
Secondary outcomes (1)
Estradiol-induced change in 24-hour urinary FSH excretion
The estradiol-induced change in 24-hour urinary FSH excretion is defined as the 24-hour urinary FSH excretion immediately prior to estradiol administration vs. the peak 24-hour urinary FSH excretion during estradiol administration.
Measured: Change occurring over up to 7 days of estradiol administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start30 Nov 2017
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective interventional cohort study. Women with PCOS and controls will receive identical treatment (transdermal estradiol) and will be monitored using the same surveillance protocol. The study does not involve randomization, and it is not blinded.
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christine Burt Solorzano, University of Virginia
- Investigators
- Christine Burt Solorzano, M.D., Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401047
- Sponsor's protocol ID
- 19692
- Acronym
- CRM009
- Status last verified
- Jul 2025
- First submitted
- 9 Jan 2018
- Last updated
- 5 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Assess Potential Impairments in Estradiol Augmentation of Gonadotropin Secretion in Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT03401047
- Acronym / sponsor ID
- CRM009 / 19692
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Polycystic ovary syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a two-group controlled study to test the following hypothesis: compared to body mass index (BMI)-matched normal controls, women with polycystic ovary syndrome (PCOS) will demonstrate blunted LH responses to preovulatory estradiol concentrations. We will study both normally-cycling controls and women with PCOS. We aim to recruit BMI-matched pairs (PCOS vs. control within 2 kg/m2). To provoke a gonadotropin surge, subjects will receive graded transdermal estradiol dosing, and we will use a dose adjustment protocol to maintain serum estradiol levels of 250-400 pg/ml. To enhance reliability of estradiol delivery, transdermal estradiol patches will be placed/replaced daily by Clinical Research Unit (CRU) nurses, and abdominal sites will be rotated. All subjects will begin estradiol on menstrual cycle day 4. Starting 24 hours before E2 administration, all subjects will collect all urine output in 12-hour time blocks for later urinary LH and FSH analysis; this will continue until the end of the study. Additionally, subjects will have daily morning blood draws in the CRU for later hormone measurements. Transvaginal ovarian ultrasound will be performed on study day 6 -- near the time of expected surge initiation -- to document largest follicle sizes. We will measure serum estradiol daily and employ an estradiol dose-adjustment protocol to maintain target estradiol levels. We will also measure LH daily. The study will be stopped after either (a) serum LH increases to 5-fold higher than baseline and subsequently falls to within 200% of baseline, or (b) the subject has received estradiol for a full 7 days, whichever comes first. The primary endpoint will be estradiol-induced change in 24-hour urinary LH excretion, defined as 24-hour mean values immediately prior to estradiol administration vs. peak 24-hour mean values during estradiol administration. A comparison of 24-hour LH changes between healthy normal and PCOS groups will be conducted by way of a random-effects analysis of covariance (ANCOVA) model. The ANCOVA model will be specified so that each BMI-matched pair will represent an independent observational unit with respect to comparing 24-hour LH change between groups. With regard to hypothesis testing, we will test whether the component of variability in 24-hour LH change attributed to "Study Group" (healthy normal control vs. PCOS) is a significant component of the overall variability in 24-hour LH change. Variability in 24-hour LH change attributed to baseline disparities in LH will be accounted for by treating subject-specific baseline LH as a covariate in the ANCOVA model. If BMI matching is inadequate, we will also include BMI as a covariate in the model. If 11 women with PCOS and 11 controls complete study, we expect at least 80% power to detect a 33% difference in E2-induced augmentation of urinary LH excretion.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective interventional cohort study. Women with PCOS and controls will receive identical treatment (transdermal estradiol) and will be monitored using the same surveillance protocol. The study does not involve randomization, and it is not blinded.
| Arm | Type | Receives |
|---|---|---|
| Transdermal Estradiol | Experimental | Drug: EstradiolSubjects will undergo estradiol administration for up to 9 days. Transdermal estradiol patches will be applied each day by study staff during study days two through nine (patches deliver 0.1 mg/day for a total dose of up to 0.6 mg/day). |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EstradiolAlso: VivelleSubjects will receive graded doses of transdermal estradiol patches for up to 7 days. Blood estradiol tests will be performed daily, and the number of estradiol patches used will be adjusted to maintain serum estradiol levels of 250-400 pg/ml. Estradiol is a natural hormone. | Drug | Transdermal Estradiol |
Primary outcome
Estradiol-induced change in 24-hour urinary LH excretion
Time frame: Change occurring over up to 7 days of estradiol administration
The estradiol-induced change in 24-hour urinary LH excretion is defined as the 24-hour urinary LH excretion immediately prior to estradiol administration vs. the peak 24-hour urinary LH excretion during estradiol administration.
1 secondary outcome
Estradiol-induced change in 24-hour urinary FSH excretion
Time frame: Change occurring over up to 7 days of estradiol administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christine Burt Solorzano, M.D. principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Estradiol in people with Polycystic Ovary Syndrome, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melissa G Gilrain, B.S. (434-243-6911, pcos@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estradiol-induced change in 24-hour urinary LH excretion (time frame: Change occurring over up to 7 days of estradiol administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.