Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials

Objective This research was conducted to assess the therapeutic advantage of combined letrozole and clomiphene citrate versus monotherapy for polycystic ovarian syndrome (PCOS) patients.Study Design Five databases were searched using the search string: (letrozole and clomiphene) AND (clomiphene OR c...

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Main Authors: Anusha Ashkar, Bismeen Jadoon, Mirza Mehmood Ali Baig, Shayan A. Irfan, Mona El-Gayar, Fatima Zulfiqar Siddiqui
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Gynecological Endocrinology
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Online Access:https://www.tandfonline.com/doi/10.1080/09513590.2024.2405114
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author Anusha Ashkar
Bismeen Jadoon
Mirza Mehmood Ali Baig
Shayan A. Irfan
Mona El-Gayar
Fatima Zulfiqar Siddiqui
author_facet Anusha Ashkar
Bismeen Jadoon
Mirza Mehmood Ali Baig
Shayan A. Irfan
Mona El-Gayar
Fatima Zulfiqar Siddiqui
author_sort Anusha Ashkar
collection DOAJ
description Objective This research was conducted to assess the therapeutic advantage of combined letrozole and clomiphene citrate versus monotherapy for polycystic ovarian syndrome (PCOS) patients.Study Design Five databases were searched using the search string: (letrozole and clomiphene) AND (clomiphene OR clomiphene citrate OR CC) AND (letrozole OR LE) AND (ovulation induc* OR fertility induc* OR fertility preserv*) AND (polycystic ovarian syndrome OR PCOS). All statistical analyses were conducted in Review Manager 5.4.1. Random effect-effect model was used to pool risk ratio (RR), mean difference (MD), and odds ratio (OR) and their corresponding 95% confidence interval (CI). Moreover, qualitative analysis was conducted to qualitatively analyze ovulation, secondary outcomes, and cycle characteristics.Results One clinical trial and three randomized clinical trials (RCTs) were used in the study. Two studies were used in a quantitative analysis showing that combination was superior for ovulation induction (RR = 1.86 [1.37, 2.53]; p < 0.0001; I2 = 0%), but the number of follicles ≥15 mm was significantly associated with the combination (MD = 0.40[0.14, 0.66]; p = 0.002; I2 = 0%). On subgroup analysis, only hot flushes were significantly associated with the combination (RR = 2.67[1.12, 6.36]; p = 0.03; I2 = 0%). The meta-analysis of two studies reported a significantly higher ovulation rate and number of dominant follicles in the combination therapy group compared with the LE alone arm but no significant difference in pregnancy rate, endometrial thickness, and adverse events.Conclusion Our study demonstrates a significant effect of the combination on ovulation induction. The combination yielded a better chance of conception and viable pregnancy. Further studies are needed to determine the live birth rate. HighlightsCombined Letrozole and Clomiphene is superior to either of these drugs alone for ovulation induction in PCOS.Our results conclude that the combination results in better ovulation, cycle characteristics, and secondary changes.Only the incidence of hot flushes as an adverse effect is increasingly reported in combination.
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spelling doaj-art-6c870274aec044b598ba21f037dbae162025-08-20T02:00:02ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662024-12-0140110.1080/09513590.2024.2405114Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trialsAnusha Ashkar0Bismeen Jadoon1Mirza Mehmood Ali Baig2Shayan A. Irfan3Mona El-Gayar4Fatima Zulfiqar Siddiqui5Dow University of Health Sciences, Karachi, PakistanRoyal Berkshire Hospital, NHS Foundation Trust, Reading, UKDow University of Health Sciences, Karachi, PakistanDow University of Health Sciences, Karachi, PakistanUniversity of Central Florida, Orlando, USADow University of Health Sciences, Karachi, PakistanObjective This research was conducted to assess the therapeutic advantage of combined letrozole and clomiphene citrate versus monotherapy for polycystic ovarian syndrome (PCOS) patients.Study Design Five databases were searched using the search string: (letrozole and clomiphene) AND (clomiphene OR clomiphene citrate OR CC) AND (letrozole OR LE) AND (ovulation induc* OR fertility induc* OR fertility preserv*) AND (polycystic ovarian syndrome OR PCOS). All statistical analyses were conducted in Review Manager 5.4.1. Random effect-effect model was used to pool risk ratio (RR), mean difference (MD), and odds ratio (OR) and their corresponding 95% confidence interval (CI). Moreover, qualitative analysis was conducted to qualitatively analyze ovulation, secondary outcomes, and cycle characteristics.Results One clinical trial and three randomized clinical trials (RCTs) were used in the study. Two studies were used in a quantitative analysis showing that combination was superior for ovulation induction (RR = 1.86 [1.37, 2.53]; p < 0.0001; I2 = 0%), but the number of follicles ≥15 mm was significantly associated with the combination (MD = 0.40[0.14, 0.66]; p = 0.002; I2 = 0%). On subgroup analysis, only hot flushes were significantly associated with the combination (RR = 2.67[1.12, 6.36]; p = 0.03; I2 = 0%). The meta-analysis of two studies reported a significantly higher ovulation rate and number of dominant follicles in the combination therapy group compared with the LE alone arm but no significant difference in pregnancy rate, endometrial thickness, and adverse events.Conclusion Our study demonstrates a significant effect of the combination on ovulation induction. The combination yielded a better chance of conception and viable pregnancy. Further studies are needed to determine the live birth rate. HighlightsCombined Letrozole and Clomiphene is superior to either of these drugs alone for ovulation induction in PCOS.Our results conclude that the combination results in better ovulation, cycle characteristics, and secondary changes.Only the incidence of hot flushes as an adverse effect is increasingly reported in combination.https://www.tandfonline.com/doi/10.1080/09513590.2024.2405114Letrozoleclomiphenepcosovulationeffectiveness
spellingShingle Anusha Ashkar
Bismeen Jadoon
Mirza Mehmood Ali Baig
Shayan A. Irfan
Mona El-Gayar
Fatima Zulfiqar Siddiqui
Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials
Gynecological Endocrinology
Letrozole
clomiphene
pcos
ovulation
effectiveness
title Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials
title_full Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials
title_fullStr Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials
title_full_unstemmed Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials
title_short Is combined letrozole and clomiphene superior to either as monotherapy: a systemic review and meta-analysis based on clinical trials
title_sort is combined letrozole and clomiphene superior to either as monotherapy a systemic review and meta analysis based on clinical trials
topic Letrozole
clomiphene
pcos
ovulation
effectiveness
url https://www.tandfonline.com/doi/10.1080/09513590.2024.2405114
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