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NCT Number: NCT06041204

Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical 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?

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.

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Key information

Conditions

PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries Adnexal Diseases Cysts Endocrine System Diseases Female Infertility Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Gonadal Disorders Infertility Infertility, Female Neoplasms Ovarian Cysts Ovarian Diseases Polycystic Ovary Syndrome Subclinical Hypothyroidism Urogenital Diseases

Age range

20 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Al-Hussein University Hospital

Cairo, 11633, Egypt

Location status: Recruiting

Location contact

Muhamed A Alhagrasy, M.D.

CONTACT

[email protected]

00201017313413

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

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

Exclusion criteria

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

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

Treatment and study plan

Letrozole 2.5mg

Drug

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 Tablet

Drug

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.

Other names: levothyroxine 25

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. Ovulation rate

    Time frame: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.

    Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level > 3 ng/mL in mid-luteal phase.

  2. Miscarriage rate

    Time frame: Through study completion average 1 year.

    Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.

  3. Menstrual regularity

    Time frame: Through study completion average 1 year.

    Normal ovulatory menstrual cycles defined as cycle length 21-35 days.

  4. Side effects

    Time frame: Through study completion average 1 year.

    Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.

Study contacts

Contact information is provided by the study sponsor or research team.

Muhamed Alhagrasy, M.D.

CONTACT

[email protected]

01017313413

Sponsors and collaborators

Lead sponsor

Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy

Other

Registry information

Official study title

Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Sep 18, 2023
Registry last updated
Sep 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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