PCOS (Polycystic Ovary Syndrome) of Bilateral OvariesNCT06041204
Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical Hypothyroidism
A study testing Letrozole 2.5mg and Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet in people with PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries and Subclinical Hypothyroidism, run by Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy at 1 site in Egypt.
Trial summary
The goal of this randomized controlled trial is to compare letrozole alone versus letrozole plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical hypothyroidism. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Subclinical Hypothyroidism, Female Infertility
- What is being tested?
- Letrozole 2.5mg and Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteEgypt
- Study dates
- 6 May 2021to 28 Jun 2026
- 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 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age between 20-40 years
- BMI between 18-35 kg/m2
- Meet diagnostic criteria for PCOS based on the Rotterdam consensus criteria and ESHRE/ASRM modifications (2018):
- Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries on ultrasound
- Subclinical hypothyroidism defined as TSH level between 5-10 mIU/L with normal free T4
- Infertility duration ≥ 1 year
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- Intact ovaries and uterus, confirmed by physical exam and imaging
- Normal semen analysis in male partner
- No tubal or peritoneal factor contributing to infertility
- Effective contraception if not attempting conception
- Willing and able to provide informed consent
Who cannot join
- Known thyroid disease or on thyroid medications
- Abnormal thyroid function tests other than subclinical hypothyroidism
- Hyperprolactinemia
- Presence of other causes of infertility such as:
- Moderate to severe male factor infertility Bilateral tubal occlusion or peritoneal factors Stage III-IV endometriosis Ovarian failure or insufficiency (high FSH or low AMH)
- Previous diagnosis of any type of congenital adrenal hyperplasia
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- Uncontrolled diabetes (HbA1C >8%)
- History of deep vein thrombosis or thromboembolic events
- Any contraindication to letrozole or levothyroxine
- Previous use of letrozole or levothyroxine in past 6 months
- Current or suspected pregnancy
- Breastfeeding
- Inability to comply with treatment and follow-up procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site, 1 recruiting
- Recruiting
Al-Hussein University Hospital
Cairo, 11633
Muhamed A Alhagrasy, M.D., 00201017313413, MuhamedAhmed.216@azhar.edu.eg
About this study
Official title: Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.
The goal of this randomized controlled trial is to compare letrozole alone versus letrozole plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical hypothyroidism. The main questions it aims to answer are:
Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth rates compared to letrozole alone?
Read more
Participants will be randomized into two groups:
Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a maximum treatment period of 6 months or until pregnancy is achieved.
Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.
- Conditions
- PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Subclinical Hypothyroidism, Female Infertility
- Being tested
- Letrozole 2.5mg, Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
- Keywords
- Letrozole, Levothyroxine, PCOS, Subclinical hypothyroidism
- Medical subject headings
- Polycystic Ovary Syndrome, Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letrozole 2.5mgDrug
Participants will receive 2.5mg letrozole tablets orally daily for 5 days starting on day 3 of menstrual cycle. The 2.5mg dose will be maintained for at least the first 3 cycles. If no ovulation after 3 cycles, dose cautiously increased up to 7.5mg maximum. Once minimum ovulation dose determined, it will be continued for up to 6 cycles total or until pregnancy occurs. Compliance monitored by pill counts and diary. Ovulation assessed by follicular monitoring and progesterone levels. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Maximum treatment duration is 6 ovulatory cycles or 6 months. Tablets taken at same time each day.
Levothyroxine 25 Mcg (0.025 Mg) Oral TabletDrug
Also called levothyroxine 25
Participants will take letrozole at same doses as letrozole only group. Also receive levothyroxine starting at 25mcg orally once daily, titrated by 25mcg every 4 weeks to reach normal TSH, maximum 100mcg daily. Once appropriate dose determined to normalize TSH, it is maintained throughout treatment period. Compliance monitored by pill counts, TSH levels, and diary. Treatment continues for up to 6 ovulatory cycles or until pregnancy, whichever is first, maximum 6 months. Ovulation assessed by monitoring and progesterone. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Letrozole and levothyroxine taken daily at same time. All other procedures same as letrozole only group.
| Study group | Role | What they receive |
|---|---|---|
| Letrozole Group | Active comparator | Participants randomized to letrozole group will take 5mg tablets orally daily for 5 days starting on day 3 of cycle. Dose can be adjusted up to 7.5mg based on ovulation response, maintained for subsequent cycles. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Tablets taken at same time each day. Maximum treatment period is 6 months. Receives: Drug: Letrozole 2.5mg |
| Letrozole plus levothyroxine | Experimental | Participants randomized to this group will take letrozole tablets at same dose and schedule as letrozole only group. In addition, they will take levothyroxine tablets orally once daily. Levothyroxine dose will start at 25mcg and be titrated based on TSH level, with a target TSH in the normal range. Participants will take levothyroxine at approximately same time each day. Letrozole dosing and schedule as described for other group. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts, TSH levels and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Maximum treatment period is 6 months. Receives: Drug: Letrozole 2.5mg; Drug: Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancy rate
Biochemical evidence of pregnancy by positive urine or serum β-hCG test.
Measured: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Live birth rate
The number of deliveries that resulted in a live born baby, documented by hospital delivery records.
Measured: Through study completion average 1 year.
Secondary outcomes (4)
Ovulation rate
Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level > 3 ng/mL in mid-luteal phase.
Measured: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Miscarriage rate
Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.
Measured: Through study completion average 1 year.
Menstrual regularity
Normal ovulatory menstrual cycles defined as cycle length 21-35 days.
Measured: Through study completion average 1 year.
Side effects
Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.
Measured: Through study completion average 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start6 May 2021
- Primary completion30 May 2026 (estimated)
- Study completion28 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PCOS (Polycystic Ovary Syndrome) of Bilateral OvariesStudies of the same condition, open and under way.
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy, Al-Azhar University
- Investigators
- Muhamed Alhagrasy, M.D., Principal investigator, Al-Azhar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06041204
- Sponsor's protocol ID
- Gyne2021
- Status last verified
- Aug 2025
- First submitted
- 5 Sep 2023
- Last updated
- 3 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To protect participant confidentiality, individual-level data from this study will not be made publicly available. However, de-identified aggregated data and results can be shared with other researchers upon request after publication. Any data provided will be limited, non-identifiable, and subject to a data use agreement to ensure participant privacy. Only select excerpts needed to validate findings will be shared under approved research objectives. The investigators reserve the right to reject requests that may compromise anonymity. We aim to promote transparency through controlled data access rather than public availability of the full dataset due to re-identification risks for participants.
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.
- ClinicalTrials.gov ID
- NCT06041204
- Acronym / sponsor ID
- Gyne2021
- Conditions
- PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Subclinical Hypothyroidism, Female Infertility
- Keywords
- Letrozole, Levothyroxine, PCOS, Subclinical hypothyroidism
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Muhamed Ahmed Abdelmoaty Muhamed AlhagrasyUniversity, hospital or other
- Study start
- 6 May 2021 (actual)
- Primary completion
- 30 May 2026 (estimated)
- Study completion
- 28 Jun 2026 (estimated)
- First posted
- 18 Sep 2023 (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 goal of this randomized controlled trial is to compare letrozole alone versus letrozole plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical hypothyroidism. The main questions it aims to answer are:
Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth rates compared to letrozole alone?
Participants will be randomized into two groups:
Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a maximum treatment period of 6 months or until pregnancy is achieved.
Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole Group | Active comparator | Drug: Letrozole 2.5mgParticipants randomized to letrozole group will take 5mg tablets orally daily for 5 days starting on day 3 of cycle. Dose can be adjusted up to 7.5mg based on ovulation response, maintained for subsequent cycles. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Tablets taken at same time each day. Maximum treatment period is 6 months. |
| Letrozole plus levothyroxine | Experimental | Drug: Letrozole 2.5mg, Drug: Levothyroxine 25 Mcg (0.025 Mg) Oral TabletParticipants randomized to this group will take letrozole tablets at same dose and schedule as letrozole only group. In addition, they will take levothyroxine tablets orally once daily. Levothyroxine dose will start at 25mcg and be titrated based on TSH level, with a target TSH in the normal range. Participants will take levothyroxine at approximately same time each day. Letrozole dosing and schedule as described for other group. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts, TSH levels and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Maximum treatment period is 6 months. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Age between 20-40 years
- BMI between 18-35 kg/m2
- Meet diagnostic criteria for PCOS based on the Rotterdam consensus criteria and ESHRE/ASRM modifications (2018):
- Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries on ultrasound
- Subclinical hypothyroidism defined as TSH level between 5-10 mIU/L with normal free T4
Key exclusion criteria (13 listed)
- Known thyroid disease or on thyroid medications
- Abnormal thyroid function tests other than subclinical hypothyroidism
- Hyperprolactinemia
- Moderate to severe male factor infertility Bilateral tubal occlusion or peritoneal factors Stage III-IV endometriosis Ovarian failure or insufficiency (high FSH or low AMH)
- Previous diagnosis of any type of congenital adrenal hyperplasia
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 |
|---|---|---|
| Letrozole 2.5mgParticipants will receive 2.5mg letrozole tablets orally daily for 5 days starting on day 3 of menstrual cycle. The 2.5mg dose will be maintained for at least the first 3 cycles. If no ovulation after 3 cycles, dose cautiously increased up to 7.5mg maximum. Once minimum ovulation dose determined, it will be continued for up to 6 cycles total or until pregnancy occurs. Compliance monitored by pill counts and diary. Ovulation assessed by follicular monitoring and progesterone levels. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Maximum treatment duration is 6 ovulatory cycles or 6 months. Tablets taken at same time each day. | Drug | Letrozole Group, Letrozole plus levothyroxine |
| Levothyroxine 25 Mcg (0.025 Mg) Oral TabletAlso: levothyroxine 25Participants will take letrozole at same doses as letrozole only group. Also receive levothyroxine starting at 25mcg orally once daily, titrated by 25mcg every 4 weeks to reach normal TSH, maximum 100mcg daily. Once appropriate dose determined to normalize TSH, it is maintained throughout treatment period. Compliance monitored by pill counts, TSH levels, and diary. Treatment continues for up to 6 ovulatory cycles or until pregnancy, whichever is first, maximum 6 months. Ovulation assessed by monitoring and progesterone. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Letrozole and levothyroxine taken daily at same time. All other procedures same as letrozole only group. | Drug | Letrozole plus levothyroxine |
Primary outcome
Pregnancy rate
Time frame: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Biochemical evidence of pregnancy by positive urine or serum β-hCG test.
Live birth rate
Time frame: Through study completion average 1 year.
The number of deliveries that resulted in a live born baby, documented by hospital delivery records.
4 secondary outcomes
Ovulation rate
Time frame: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Miscarriage rate
Time frame: Through study completion average 1 year.
Menstrual regularity
Time frame: Through study completion average 1 year.
Side effects
Time frame: Through study completion average 1 year.
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 3 Sep 2025.
- Individual participant dataSharing planned: No. To protect participant confidentiality, individual-level data from this study will not be made publicly available. However, de-identified aggregated data and results can be shared with other researchers upon request after publication. Any data provided will be limited, non-identifiable, and subject to a data use agreement to ensure participant privacy. Only select excerpts needed to validate findings will be shared under approved research objectives. The investigators reserve the right to reject requests that may compromise anonymity. We aim to promote transparency through controlled data access rather than public availability of the full dataset due to re-identification risks for participants.
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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.
Muhamed Alhagrasy, M.D. principal investigator
Al-Azhar 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 Letrozole 2.5mg and Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet in people with PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries and Subclinical Hypothyroidism, run by Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy at 1 site in Egypt.
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 11 inclusion and 13 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 3 Sep 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 Egypt. 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.
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 Muhamed Alhagrasy, M.D. (01017313413, MuhamedAhmed.216@azhar.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pregnancy rate (time frame: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.). 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 3 Sep 2025.