Polycystic Ovarian Syndrome in Adolescent FemalesNCT04355572
Evaluation of the Clinical and Psychological Impact of Vitamin D Replacement in Adolescent Females at Risk for Polycystic Ovarian Syndrome (PCOS)
A study testing Vitamin D 4000IU daily in people with Polycystic Ovarian Syndrome in Adolescent Females and Vitamin D Deficiency, run by Yale University at 1 site in United States.
Trial summary
This study is a double blind, placebo controlled, randomized trial of study subjects with PCOS and low vitamin D to 2 groups- placebo and vitamin D replacement. Participants and investigators will be blinded to treatment modality until the end of the trial period Read more about this study
- Who is it for?
- Ages 13 to 21 years, women only
- Conditions the study is for
- Polycystic Ovarian Syndrome in Adolescent Females, Vitamin D Deficiency
- What is being tested?
- Vitamin D 4000IU daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2026to 31 Aug 2028
- Phase
- Interventional
- 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 13 to 21 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Postmenarchal adolescent females aged 13-21 who meet modified Rotterdam criteria for PCOS, with a serum vitamin D level between 6-29 ng/mL.
Who cannot join
- Other causes for hyperandrogenism,
- Chronic renal diseases,
- Acquired or inherited calcium and vitamin D metabolic disorders.
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
Yale New Haven Children's Hospital
New Haven, Connecticut, 06510
Alla Vash-Margita, Principal Investigator, MD, 203-785-7409, alla.vash-margita@yale.edu
Kathleen Miclette, nurse coordinator, RN, 203-444-3720, kathleen.miclette@ynhh.org
About this study
This study is a double blind, placebo controlled, randomized trial of study subjects with PCOS and low vitamin D to 2 groups- placebo and vitamin D replacement. Participants and investigators will be blinded to treatment modality until the end of the trial period
Read the detailed description
Patients referred to the pediatric endocrinology clinic or adolescent gynecology clinic at Yale New Haven Children Hospital with a primary complaint of hirsutism, acne, or amenorrhea and/or oligomenorrhea persisting 2 years after their menarche will be evaluated for polycystic ovarian syndrome through history, physical exam, pelvic ultrasound, and laboratory evaluation, to include androgen testing, thyroid testing, female hormone testing, and diabetic risk testing (this is standard of care). A vitamin D level will also be drawn. While vitamin D level is not currently part of the diagnostic algorithm for PCOS, it is not unreasonable to check in patients in which there is concern for an endocrine disorder. If the patient meets Rotterdam criteria and their serum vitamin D level is between 6 and 29 ng/mL, the patient and their guardian(s) will be approached for inclusion in our study by the physician or dedicated research nursing staff.
If patient and guardian agree to participate and sign a consent / assent form, the patient will then be randomized to receive vitamin D supplement versus placebo and will be followed for 6 months on their randomized replacement with repeat laboratory testing of AMH, vitamin D, lipid profile, glucose and insulin testing, androgen testing, and female hormone testing at the randomization, 3 months and at the end of the course of the trial(6 months). Patients with vitamin D levels 5ng/mL or less will not be randomized, they will be given recommended treatment. Depressive symptoms will be assessed at time of randomization, 3 months post randomization, and 6 months post randomization using the Beck Depression Inventory-II, the gold standard self-report depression inventory. A depression screen is currently administered to all adolescents seen at Yale New Haven Children Hospital outpatient clinics with a protocol for patients who report clinically significant levels of depression. This protocol will remain in place and will not be altered during this research study.
After post-trial testing, patients will be unblinded and patients who still have vitamin D below threshold will be offered vitamin D treatment.
Aim 1: To investigate the effect of vitamin D replacement upon biochemical parameters of polycystic ovarian syndrome (PCOS) in adolescent female patients. Hypothesis: Replacement of vitamin D to normal levels in adolescents with PCOS and/or at risk for PCOS and low levels of vitamin D will lower serum androgen and anti-mullerian hormone (AMH) levels.
Aim 2: To investigate the effect of vitamin D replacement on clinical features of PCOS in adolescent female patients. Hypothesis: Replacement of vitamin D in adolescents with PCOS and/or at risk for PCOS and low levels of vitamin D will improve symptoms of menstrual irregularities, acne, and hirsutism.
Aim3: To investigate the effect of vitamin D replacement on depressive symptoms in adolescent female patients with PCOS. Hypothesis: Replacement of vitamin D in adolescents with PCOS or at risk for PCOS and low levels of serum vitamin D will improve symptoms of depression.
- Being tested
- Vitamin D 4000IU daily, Placebo
- Keywords
- Anti-Mullerian Hormone (AMH)
- Medical subject headings
- Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D 4000IU dailyDrug
Randomized to receive vitamin D 4000IU daily
PlaceboDrug
Randomized to placebo daily
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D Supplement | Experimental | Patients will take vitamin D tablet with 4,000IU daily for 6 months. Receives: Drug: Vitamin D 4000IU daily |
| Placebo | Placebo comparator | Patients will take placebo for 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in oligomenorrhea
The change in oligomenorrhea, i.e restoration of monthly menses or improvement in the menstrual pattern during 6 months while enrolled in the trial based on self report
Measured: 6 months
Changes Vitamin D (25-hydroxyvitamin D) level
25-hydroxyvitamin D level will be measured by liquid chromatography-mass spectrometry (LC-MS/MS) or immunoassay
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Secondary outcomes (7)
Change in DHEAS level
The serum DHEA-S concentration is the traditional marker for adrenal androgen excession because it is produced almost exclusively by the adrenal glands and concentrations remain stable across the day and cycle. Preferred testing is done by immunoassay.
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Changes in Androstenedione level
Androstenedione concentration assesses for hyperandrogenemia as well, it is produced by the ovary and the adrenal cortex and serves as precursor of testosterone. Data suggests that levels are elevated in approximately 20% of women with PCOS. Evaluation is done by Liquid Chromatography/Tandem Mass Spectrometry
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Change in Anti-Mullerian hormone (AMH) level
AMH is a dimeric glycoprotein of the transforming growth factor-β superfamily that is involved in growth and differentiation of ovarian follicles. AMH is expressed in granulosa cells in the ovary and serves as a marker of ovarian reserve as well as marker of several ovarian pathologies such as PCOS, granulosa cell tumors and premature ovarian insufficiency. Level will be measured using Immunoassay (IA)
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Change in testosterone level
Testosterone levels are elevated in vast majority of adolescents with PCOS. The free testosterone level is more sensitive for diagnosis of hyperandrogenic disorders compared with the total testosterone. Evaluation is done by Chromatography/Mass Spectrometry
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Change in Hirsutism
Hirsutism is defined as excessive male-pattern facial and body hair. This will be measured by using the modified Ferriman Gallwey score by a provider with scores of less than 6 indicating no evidence of hirsutism, 6-8 indicating mild hirsutism, scores 8-15 indicating moderate hirsutism and scores greater than 15 indicating severe hirsutism.
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Change Body Acne
European Dermatology Forum Guidelines group (2011) grading system will be used to describe acne in 4 areas of the body- face, upper chest, upper back, upper arms: minimal - comedonal acne, mild to moderate: moderate papulopustular acne, severe: severe papulopustular acne, moderate nodular acne; severe nodular acne,conglobate acne
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Change in Facial
European Dermatology Forum Guidelines group (2011) grading system will be used to describe acne in 4 areas of the body- face, upper chest, upper back, upper arms: minimal - comedonal acne, mild to moderate: moderate papulopustular acne, severe: severe papulopustular acne, moderate nodular acne; severe nodular acne,conglobate acne
Measured: at enrollment, at 3 months after randomization and 6 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2020
- Study startSep 2026 (estimated)
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovarian Syndrome in Adolescent FemalesStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alla Vash-Margita, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04355572
- Sponsor's protocol ID
- 2000028054
- Other IDs
- 000
- Status last verified
- Aug 2026
- First submitted
- 17 Apr 2020
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Clinical and Psychological Impact of Vitamin D Replacement in Adolescent Females at Risk for Polycystic Ovarian Syndrome (PCOS)
- ClinicalTrials.gov ID
- NCT04355572
- Acronym / sponsor ID
- 2000028054
- Keywords
- Anti-Mullerian Hormone (AMH)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 21 Apr 2020 (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.
This study is a double blind, placebo controlled, randomized trial of study subjects with PCOS and low vitamin D to 2 groups- placebo and vitamin D replacement. Participants and investigators will be blinded to treatment modality until the end of the trial period
Detailed description
Patients referred to the pediatric endocrinology clinic or adolescent gynecology clinic at Yale New Haven Children Hospital with a primary complaint of hirsutism, acne, or amenorrhea and/or oligomenorrhea persisting 2 years after their menarche will be evaluated for polycystic ovarian syndrome through history, physical exam, pelvic ultrasound, and laboratory evaluation, to include androgen testing, thyroid testing, female hormone testing, and diabetic risk testing (this is standard of care). A vitamin D level will also be drawn. While vitamin D level is not currently part of the diagnostic algorithm for PCOS, it is not unreasonable to check in patients in which there is concern for an endocrine disorder. If the patient meets Rotterdam criteria and their serum vitamin D level is between 6 and 29 ng/mL, the patient and their guardian(s) will be approached for inclusion in our study by the physician or dedicated research nursing staff.
If patient and guardian agree to participate and sign a consent / assent form, the patient will then be randomized to receive vitamin D supplement versus placebo and will be followed for 6 months on their randomized replacement with repeat laboratory testing of AMH, vitamin D, lipid profile, glucose and insulin testing, androgen testing, and female hormone testing at the randomization, 3 months and at the end of the course of the trial(6 months). Patients with vitamin D levels 5ng/mL or less will not be randomized, they will be given recommended treatment. Depressive symptoms will be assessed at time of randomization, 3 months post randomization, and 6 months post randomization using the Beck Depression Inventory-II, the gold standard self-report depression inventory. A depression screen is currently administered to all adolescents seen at Yale New Haven Children Hospital outpatient clinics with a protocol for patients who report clinically significant levels of depression. This protocol will remain in place and will not be altered during this research study.
After post-trial testing, patients will be unblinded and patients who still have vitamin D below threshold will be offered vitamin D treatment.
Aim 1: To investigate the effect of vitamin D replacement upon biochemical parameters of polycystic ovarian syndrome (PCOS) in adolescent female patients. Hypothesis: Replacement of vitamin D to normal levels in adolescents with PCOS and/or at risk for PCOS and low levels of vitamin D will lower serum androgen and anti-mullerian hormone (AMH) levels.
Aim 2: To investigate the effect of vitamin D replacement on clinical features of PCOS in adolescent female patients. Hypothesis: Replacement of vitamin D in adolescents with PCOS and/or at risk for PCOS and low levels of vitamin D will improve symptoms of menstrual irregularities, acne, and hirsutism.
Aim3: To investigate the effect of vitamin D replacement on depressive symptoms in adolescent female patients with PCOS. Hypothesis: Replacement of vitamin D in adolescents with PCOS or at risk for PCOS and low levels of serum vitamin D will improve symptoms of depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D Supplement | Experimental | Drug: Vitamin D 4000IU dailyPatients will take vitamin D tablet with 4,000IU daily for 6 months. |
| Placebo | Placebo comparator | Drug: PlaceboPatients will take placebo for 6 months |
Who may qualify
- Ages
- 13 to 21 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Postmenarchal adolescent females aged 13-21 who meet modified Rotterdam criteria for PCOS, with a serum vitamin D level between 6-29 ng/mL.
Key exclusion criteria (3 listed)
- Other causes for hyperandrogenism,
- Chronic renal diseases,
- Acquired or inherited calcium and vitamin D metabolic disorders.
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 |
|---|---|---|
| Vitamin D 4000IU dailyRandomized to receive vitamin D 4000IU daily | Drug | Vitamin D Supplement |
| PlaceboRandomized to placebo daily | Drug | Placebo |
Primary outcome
Change in oligomenorrhea
Time frame: 6 months
The change in oligomenorrhea, i.e restoration of monthly menses or improvement in the menstrual pattern during 6 months while enrolled in the trial based on self report
Changes Vitamin D (25-hydroxyvitamin D) level
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
25-hydroxyvitamin D level will be measured by liquid chromatography-mass spectrometry (LC-MS/MS) or immunoassay
7 secondary outcomes
Change in DHEAS level
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
Changes in Androstenedione level
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
Change in Anti-Mullerian hormone (AMH) level
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
Change in testosterone level
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
Change in Hirsutism
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
Change Body Acne
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
Change in Facial
Time frame: at enrollment, at 3 months after randomization and 6 months after randomization
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 20 Aug 2026.
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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.
Alla Vash-Margita, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin D 4000IU daily in people with Polycystic Ovarian Syndrome in Adolescent Females and Vitamin D Deficiency, run by Yale University 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 1 inclusion and 3 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 20 Aug 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Alla Vash-Margita, MD (203-785-4010, alla.vash-margita@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in oligomenorrhea (time frame: 6 months). The study lists 2 primary outcomes in all. 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 20 Aug 2026.