Combined metformin‐clomiphene in clomiphene‐resistant polycystic ovary syndrome: a systematic review and meta‐analysis of randomized controlled trials

Hashim, Hatem Abu; Foda, Osama; Ghayaty, Essam

doi:10.1111/aogs.12673

Cited by 30 publications

(32 citation statements)

References 45 publications

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“…However, the above evidences were at low or very low quality. Another meta-analysis with low to moderate quality evidence demonstrated no differences in reproductive outcomes among metformin+CC, BLOD and letrozole 7 ; gonadotropin therapy was more effective in improving ovulation rate and pregnancy rate than them 7 ; it was similar to our results. Nevertheless, a Cochrane systemic review and meta-analysis conducted by Farquhar et al .…”

Section: Discussionsupporting

confidence: 86%

Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

Fang

Zhang

et al. 2017

Sci Rep

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The comparative efficacies of ovulation-induction treatments in patients with clomiphene citrate-resistant (CCR) polycystic ovary syndrome (PCOS) are not well known. Therefore, we conducted a network meta-analysis to rank the reproductive efficacies of these treatments. We ultimately included 26 randomized clinical trials with 2722 participants and 9 types of therapies: clomiphene citrate (CC), metformin, letrozole, follicle stimulating hormone (FSH), human menopausal gonadotropin (hMG), unilateral laparoscopic ovarian drilling (ULOD), bilateral laparoscopic ovarian drilling (BLOD), the combination of metformin with letrozole (metformin+letrozole), and the combination of metformin with CC (metformin+CC). The network meta-analysis demonstrates that hMG therapy result in higher pregnancy rates than BLOD, ULOD and CC therapies. Pregnancy, live birth and ovulation rates are significantly higher in metformin+letrozole and FSH groups than CC group. The abortion rate in the metformin+letrozole group is significantly lower than that in the metformin+CC group. Ranking probabilities show that, apart from gonadotropin (FSH and hMG), metformin+letrozole is also potentially more effective in improving reproductive outcomes than other therapies. In conclusion, owing to the low quality of evidence and the wide confidence intervals, no recommendation could be made for the treatment of ovulation-induction in patients with CCR PCOS.

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Section: Discussionsupporting

confidence: 86%

Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

Fang

Zhang

et al. 2017

Sci Rep

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“…25 Metformin is also used to manage infertility and anovulation among women who desire to become pregnant either alone or in combination with clomiphene. 25,26 The value of metformin in the management of PCOS stems from its insulin-sensitizing activity, improving insulin resistance, which is common among PCOS patients; [27][28][29] lowering the insulin level is associated with a reduction in free testosterone and androstenedione. 30 In addition, metformin reduces hepatic production of glucose, 31 thereby decreasing the release of free fatty acids from the adipose tissue, and lowering the level of fasting free fatty acids.…”

Section: Introductionmentioning

confidence: 99%

<p>Metformin Improves the Depression Symptoms of Women with Polycystic Ovary Syndrome in a Lifestyle Modification Program</p>

Alhussain¹,

AlRuthia²,

Al‐Mandeel³

et al. 2020

PPA

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Background: Metformin is commonly prescribed to manage polycystic ovary syndrome (PCOS), which is one of the most common endocrine disorders among women of childbearing age and is associated with high prevalence rates of depression and anxiety.Objective: This study's objective was to determine the impact of prescribed metformin on depression and anxiety levels of patients with PCOS. Methods: This prospective, multi-center, cohort study examined the impact of prescribed metformin on the depression and anxiety of women with PCOS in four gynecology clinics in Saudi Arabia and Jordan. The women had recently been prescribed metformin along with lifestyle modifications, such as diet and exercise, and were compared to another group of women with PCOS who were prescribed lifestyle modifications only. Depression and anxiety were assessed at baseline and three months later using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) scale, respectively. Health-related quality of life was measured using the Short Form Health Survey (SF-36). Multiple logistic regression analyses were conducted to examine the impact of metformin on depression and anxiety. Results: Eighty-six women participated in the study: 53 were prescribed metformin with lifestyle modifications, and 33 were prescribed lifestyle modifications only. The women on metformin had 70% lower odds of having major depression (PHQ-9≥10) (OR=0.302, P=0.045); however, no significant effect of metformin on anxiety (GAD-7≥10) was found. Conclusion: Metformin may have a role in the management of depression symptoms among patients with PCOS; however, its potential antidepressant effect should be further examined in randomized double-blind placebo-controlled clinical trials.

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“…A search update to 20 May 2015 was carried out to identify newly relevant citations. Overall, this search produced 947 articles, 18 of which met the selection criteria (four RCT and 14 meta-analyses of RCT) (Abu Hashim et al, 2015;Cassina et al, 2014;Costello et al, 2006;Creanga et al, 2008;Hamed et al, 2010;Hosseini et al, 2013;Johnson, 2011;Karimzadeh and Javedani, 2010;Misso et al, 2013;Palomba et al, 2004Palomba et al, , 2009aPalomba et al, , 2009bPalomba et al, , 2013Palomba et al, , 2014Siebert et al, 2006Siebert et al, , 2012Tang et al, 2012;Tso et al, 2014). A flow diagram of the study is presented in Figure 2.…”

Section: Methodsmentioning

confidence: 99%

Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?

Hashim

2016

Reproductive BioMedicine Online

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The potential reproductive benefits of metformin, a drug endowed with the capacity to ameliorate insulin resistance in polycystic ovary syndrome (PCOS), has garnered much interest over the past 2 decades. In this review, randomized-controlled trials (RCT) and meta-analyses of RCT comparing metformin are critically appraised and summarized. PubMed and CENTRAL databases were consulted. Evidence is insufficient to favour the use of metformin or metformin plus clomiphene citrate instead of clomiphene citrate for ovulation induction in women with newly diagnosed PCOS. Evidence is also insufficient to recommend metformin as a primary treatment for non-obese women with PCOS. Metformin plus clomiphene citrate should be considered as an effective option in clomiphene citrate-resistant PCOS. In women with PCOS undergoing gonadotrophin ovulation induction, metformin significantly increased pregnancy and live birth rates (P< 0.0001 and P = 0.020, respectively) with reduced risk of cancelled cycles. A beneficial effect of metformin co-treatment in increasing clinical pregnancy rates and reducing the risk of OHSS in PCOS patients undergoing assisted reproduction techniques has been shown. No evidence was found of reduced risk of spontaneous abortion or increased risk of major anomalies in women with PCOS taking metformin during the first trimester.

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Combined metformin‐clomiphene in clomiphene‐resistant polycystic ovary syndrome: a systematic review and meta‐analysis of randomized controlled trials

Cited by 30 publications

References 45 publications

Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

<p>Metformin Improves the Depression Symptoms of Women with Polycystic Ovary Syndrome in a Lifestyle Modification Program</p>

Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?

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