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

NCT06041204 | Recruiting

• 1 other identifier: Gyne2021
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries; Subclinical Hypothyroidism; Female Infertility

Keywords

Letrozole; Levothyroxine; PCOS; Subclinical hypothyroidism

Outcome Measures

Primary Outcomes (2)

• Pregnancy rate

  Biochemical evidence of pregnancy by positive urine or serum β-hCG test.

  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.

  Through study completion average 1 year.

Secondary Outcomes (4)

• Ovulation rate

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

• Miscarriage rate

  Through study completion average 1 year.

• Menstrual regularity

  Through study completion average 1 year.

• Side effects

  Through study completion average 1 year.

Study Arms (2)

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.

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.

Drug: Letrozole 2.5mg; Drug: Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet

Interventions

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.

Letrozole Group; Letrozole plus levothyroxine

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.

Also known as: levothyroxine 25

Letrozole plus levothyroxine

Eligibility Criteria

• Age: 20 Years - 40 Years
• Gender Eligibility Details: This study will only enroll female participants. Patients must be of reproductive age with intact uteri and ovaries to meet the inclusion criteria. The study aims to induce ovulation for conception in infertile women with PCOS and subclinical hypothyroidism. As such, only individuals biologically born as females and currently identifying as women will be eligible. All enrolled participants must have functioning ovaries and intact reproductive organs capable of sustaining a pregnancy. Patients who have undergone surgical sterilization procedures like tubal ligation or hysterectomy will be excluded. Confirmation of female gender will be through medical history, physical examination, and review of medical records if needed. Pregnancy tests will be done at screening and before each treatment cycle. The reproductive status, ovaries and uterus will be assessed by medical history, physical examination and imaging like ultrasound when indicated.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy: lead

Study Sites (1)

Al-Hussein University Hospital

Cairo, 11633, Egypt

RECRUITING

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility, Female

Interventions

Letrozole; Thyroxine; Tablets

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Infertility

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Muhamed Alhagrasy, M.D.

  Al-Azhar University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Muhamed Alhagrasy, M.D.

CONTACT

01017313413; MuhamedAhmed.216@azhar.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: lecturer and consultant at Obstetrics and Gynecology Department.

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: September 18, 2023
• Study Start: May 6, 2021
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): June 28, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)