Combination Letrozole and Clomiphene Citrate Versus Letrozole Alone

Combination Letrozole and Clomiphene Citrate Versus Letrozole Alone for Ovulation Induction in Women With Polycystic Ovary Syndrome: A Randomized Control Trial

Clomiphene citrate is a non-steroidal triphenylethylene derivative distantly related to diethylstilbestrol. It acts as a selective estrogen receptor modulator (SERM), similar to tamoxifen and raloxifene. All three drugs are competitive inhibitors of estrogen binding to estrogen receptors (ERs) and have mixed agonist and antagonist activity, depending upon the target tissue.

Letrozole is a potent, nonsteroidal, aromatase inhibitor, originally used for postmenopausal breast cancer therapy.

Study Overview

• Status: Recruiting
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Letrozole 2.5mg

Detailed Description

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women and the most common cause of anovulatory infertility. The treatment of infertility in patients with PCOS focuses on ovulation induction. Many treatment regimens have been used, with varying success, to achieve ovulation, pregnancy, and live birth.

Clomiphene citrate (CC) is a commonly prescribed pharmacologic agent used to induce ovulation in women with PCOS. It works as a selective estrogen receptor modulator by competitively attaching to nuclear estrogen receptors. As the negative feedback of estrogen is reduced, secretion of gonadotropin hormones increases, inducing ovarian follicular growth.

Clomiphene citrate (CC) also has an anti-estrogenic effect on endometrial development and cervical mucus production,which has been suggested to contribute to a relatively low pregnancy rate despite a high ovulation rate.

Letrozole is another commonly used oral ovulation induction agent, with a different mechanism of action. It works as a highly selective aromatase inhibitor, preventing androgen-to-estrogen conversion. One proposed mechanism is via suppressed estrogen production resulting in decreased negative feedback on the hypothalamus and increased secretion of Follicular Stimulating Hormone (FSH). An additional proposed mechanism of improved ovulatory rates with the use of letrozole is increased follicular sensitivity to FSH resulting from temporarily increased intraovarian androgens .

Letrozole may offer a benefit over CC for ovulation induction because it does not block estrogen receptors in both central and peripheral target tissues, and normal central feedback mechanisms remain intact. The Pregnancy and Polycystic Ovary Syndrome (PPCOS) trial, a randomized controlled trial comparing letrozole and CC, demonstrated that letrozole was associated with a higher live birth rate (27.5% vs. 19.1%; P=007; rate ratio 1.44, 95% confidence interval [CI] 1.10-1.87) and cumulative ovulation rate (61.7% vs. 48.3%; P<.001) among women with PCOS.

Other than letrozole or CC for ovulation induction, there are few treatment options available to PCOS patients except proceeding to gonadotropin injections or in vitro fertilization, both of which are associated with increased cost and risk.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed Adel Mousa, MSC; Phone Number: +201093429998; Email: sedyyasedy@gmail.com

Study Locations

• Egypt
  • Abbasia
    • Cairo, Abbasia, Egypt
      • Recruiting
      • Ain Shams University Hospitals
      • Contact: Mohamed Adel Mousa, Resident; Phone Number: +201093429998; Email: sedyyasedy@gmail.com
      • Principal Investigator: Rania Gamal Anwar Elskaan, Lecturer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of infertility, defined as the inability of couple to achieve a pregnancy after 12 months of regular timed unprotected intercourse in women <35 years of age or after 6 months in women >35 years of age.
• Diagnosis of PCOS based on the Rotterdam criteria, including two of the following three findings: oligomenorrhea or chronic anovulation, hyperandrogenism (clinical or laboratory), and polycystic ovary(ies) on ultrasound .
• Normal HSG
• Normal semen analysis.
• Has capacity to participate in the study.

Exclusion Criteria:

• Unexplained infertility.
• Other conditions that can cause chronic anovulation and androgen excess such as hyperthyroidism by thyroid profile.
• congenital adrenal hyperplasia
• Cushing
• Untreated hyperprolactinemia.
• Medical conditions not well controlled or contraindicated to get pregnant with it like (uncontrolled diabetes mellitus, hypertension) .
• endometrial hyperplasia/cancer
• Allergy or contraindications to letrozole or CC. (by history)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 (Letrozole group); About 32 patients will receive letrozole 2.5 mg tablets only , once daily from the third date of the menses for 5 days for 3 successive periods	Drug: Letrozole 2.5mg; to assess and compare the efficacy of Combination of letrozole and clomiphene citrate versus letrozole alone for ovulation induction in women with polycystic ovary syndrome (PCOS); Other Names: Clomiphene Citrate
Active Comparator: Group 2 (Letrozole and Clomiphene Citrate); About 32 patients will receive combined letrozole 2.5 mg tablets once daily and clomiphene citrate 50 mg tablets once daily from the third date of the menses for 5 days for 3 successive periods	Drug: Letrozole 2.5mg; to assess and compare the efficacy of Combination of letrozole and clomiphene citrate versus letrozole alone for ovulation induction in women with polycystic ovary syndrome (PCOS); Other Names: Clomiphene Citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy Check	The participants required to make pregnancy test after Receiving the drugs of the study	2 weeks after ovulation

Collaborators and Investigators

• Sponsor: Egymedicalpedia
• Collaborators: Ain Shams University
• Investigators: Study Chair: Dina Yahia, Professor, Department of Obstetrics & Gynecology,Ain Shams University; Study Director: Al Hassan Mohammad Khedr, Lecturer, Department of Obstetrics & Gynecology,Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 10, 2024

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Clomiphene
• Other Study ID Numbers: Mohamed Adel Mousa

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No