Effects of metformin on polycystic ovary syndrome: a randomized, double-blind, placebo-controlled study

Background and objectives: Metformin improves manifestations of polycystic ovary syndrome (PCOS) by reducing insulin resistance. The objective of this study was to determine how metformin, in combination with lifestyle changes, affects the clinical manifestations of PCOS. Materials and Methods: Patients with PCOS attending the outpatient of a tertiary care hospital were enrolled in the study. Revised Rotterdam Consensus 2003 criteria were used to diagnose cases of PCOS. Clinical information, anthropometric measurement, serum progesterone and polycystic ovarian morphology (PCOM) of each subject were recorded in a prescribed data sheet at baseline and after a period of nine months. Randomized placebo controlled double blind design was used to assign participants in respective groups. Participants were randomly assigned to receive 9-month course of either metformin (1500 mg/day) or placebo. Both groups were advised regarding schedule of lifestyle modification. Outcome variables were clinical manifestations related to metabolic, reproductive and androgenic status of PCOS. Results: Out of 80 enrolled PCOS cases, 49 completed the study (metformin=26, placebo=23). The mean age of the study participants of metformin and placebo groups was 23.52±5.18 and 22.09±3.58 years respectively (p=0.262). Menstrual cycle significantly improved in both the study groups (before vs. after - metformin: 19.2% vs. 76.9%, p=0.003; placebo: 19.2% vs. 47.8%, p=0.02) after 9 months, but compared to placebo group no such significant (p=0.12) improvement occurred in metformin group. Severity of hirsutism, presence of acne, serum progesterone level and ovulatory status improved significantly in both groups after completion of the study. Except acanthosis nigricans, other metabolic manifestations did not significantly improve in metformin compared to placebo group after the intervention. While comparing the percentage changes, body mass index (BMI) and waist circumference (WC) reduced significantly in metformin than placebo group (BMI in kg/m2- metformin vs. placebo: -3.63±8.22 vs. +1.42±6.67, p= 0.024; WC in cm - 2.81±7.74 vs. +1.68±7.89, p= 0.05). No significant adverse event was observed in metformin group. Conclusion: Metformin, in conjunction with lifestyle modifications, has favorable impacts on clinical manifestations of PCOS. Ibrahim Med. Coll. J. 2021; 15(2): 1-12

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Impact of Metformin on IVF Outcomes in Overweight and Obese Women With Polycystic Ovary Syndrome: A Randomized Double-Blind Controlled Trial

Reproductive Sciences ◽

10.1177/1933719118765985 ◽

2018 ◽

Vol 26 (10) ◽

pp. 1336-1342 ◽

Cited By ~ 4

Author(s):

Osama S. Abdalmageed ◽

Tarek A. Farghaly ◽

Ahmed A. Abdelaleem ◽

Ahmed E. Abdelmagied ◽

Mohammed K. Ali ◽

...

Keyword(s):

Placebo Group ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Study ◽

Obese Women ◽

Ovary Syndrome ◽

Double Blind ◽

Ivf Outcomes ◽

Metformin Group ◽

The Impact

Objectives: To evaluate the impact of metformin on in vitro fertilization (IVF) outcomes in overweight and obese women with polycystic ovary syndrome (PCOS). Methods: This was a randomized double-blind placebo-controlled study ( ClinicalTrials.gov : NCT 02910817) carried out in a University IVF Center. The study included 102 overweight and obese women (body mass index [BMI] >24 kg/m2) with PCOS who underwent their first fresh autologous IVF-embryo transfer cycle and agreed to participate in the study. The study participants were randomized into 2 groups: metformin group received metformin (1000 mg per day) at the start of controlled ovarian stimulation (COH) until the day of the pregnancy check, and placebo group received placebo tablets in the same duration. The primary outcome measure was the total number of retrieved oocytes. Results: Both groups were homogenous in baseline demographic characteristics. Metformin group versus the placebo group demonstrated decrease in the mean number of the retrieved oocytes (9.06 ± 4.23 vs 16.86 ± 8.3, P < .01) and similar live birth rate (LBR; 25.5% vs 17.6%, P = .34). The number of fertilized oocytes was lower in the metformin group (5.65 ± 2.66 vs 9 ± 4.55, P < .01). However, the fertilization rate was similar in both groups (62.3% vs 53.4%, P = .10). There was no difference in the implantation rate (15.7% vs 11.8%, P = .32), multiple pregnancy rate (13.4% vs 3.9%, P = .08), or miscarriage rate (23.5% vs 35.7%, P = .46). No cases of ovarian hyperstimulation syndrome (OHSS) were observed in both groups. Conclusion: Short-term administration of metformin to overweight or obese women with PCOS undergoing IVF decreased number of the retrieved oocytes but did not improve the LBR. Synopsis Metformin use could decrease the number of retrieved oocytes in overweight and obese women with polycystic ovary syndrome undergoing IVF.

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Faculty Opinions recommendation of The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1163693.625469 ◽

2009 ◽

Author(s):

Sarah Berga ◽

Pavna Brahma

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Study ◽

Ovary Syndrome ◽

Double Blind ◽

Double Blind Placebo

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Atorvastatin Increases 25-Hydroxy Vitamin D Concentrations in Patients with Polycystic Ovary Syndrome

Clinical Chemistry ◽

10.1373/clinchem.2010.144014 ◽

2010 ◽

Vol 56 (11) ◽

pp. 1696-1700 ◽

Cited By ~ 35

Author(s):

Thozhukat Sathyapalan ◽

John Shepherd ◽

Charlotte Arnett ◽

Anne-Marie Coady ◽

Eric S Kilpatrick ◽

...

Keyword(s):

Vitamin D ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Statin Treatment ◽

Vitamin D Supplementation ◽

Significant Rise ◽

Controlled Study ◽

Ovary Syndrome ◽

Double Blind ◽

Markers Of Inflammation

BACKGROUND It has been shown that many women with polycystic ovary syndrome (PCOS) are 25-hydroxyvitamin D (25OHD) insufficient. Both statin treatment and vitamin D supplementation have been shown to improve biochemical hyperandrogenemia, insulin resistance, and markers of inflammation in patients with PCOS, raising the possibility that some of the statin effects are mediated through vitamin D. METHODS We conducted this randomized, double-blind placebo controlled study to assess the effect of atorvastatin on serum 25OHD concentrations in patients with PCOS. Forty medication-naive patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. After completing the initial 3 months of atorvastatin or placebo, both groups of patients participated in a 3-month extension study with metformin 1500 mg daily. We measured changes in 25OHD concentrations by use of tandem mass spectrometry. RESULTS Mean (SD) baseline 25OHD concentrations were comparable between the 2 groups [45.9 (2.4) vs 44.8 (1.8) nmol/L; P = 0.7]. There was a significant increase in 25OHD concentrations with atorvastatin [45.9 (2.4) vs 60.8 (3.5) nmol/L] compared with placebo [44.8 (1.8) vs 41.8 (3.2) nmol/L; P = 0.02]. Three-month treatment with metformin maintained the improvement of 25OHD with atorvastatin compared to baseline [45.9 (2.4) vs 61.8 (3.5), P ≤ 0.01). There were no significant changes in 25OHD concentrations in the placebo group after 12 weeks of metformin. CONCLUSIONS Among patients with polycystic ovary syndrome, 12 weeks of atorvastatin led to a clinically significant rise in 25OHD concentrations. This may represent a beneficial pleiotropic effect of statins on 25OHD concentrations.

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The Effect of Atorvastatin in Patients with Polycystic Ovary Syndrome: A Randomized Double-Blind Placebo-Controlled Study

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(09)79060-5 ◽

2009 ◽

Vol 2009 ◽

pp. 127-128

Author(s):

J.S. Dungan

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Study ◽

Ovary Syndrome ◽

Double Blind ◽

Double Blind Placebo

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Effects of synbiotic supplementation and lifestyle modifications on women with polycystic ovary syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab369 ◽

2021 ◽

Author(s):

Izabela Chudzicka-Strugała ◽

Anna Kubiak ◽

Beata Banaszewska ◽

Barbara Zwozdziak ◽

Martyna Siakowska ◽

...

Keyword(s):

Placebo Group ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Trial ◽

Reproductive Age ◽

Control Group ◽

Lifestyle Modifications ◽

Ovary Syndrome ◽

Double Blind ◽

Synbiotic Supplementation

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Objective This study was designed to evaluate effects of lifestyle modifications and synbiotic supplementation on PCOS. Design A randomized (1:1) double-blind, placebo-controlled trial. Setting Academic hospital. Patients or Other Participants Overweight and obese women with PCOS were identified according to the Rotterdam criteria. Evaluations were performed at baseline and repeated after 3 months of treatment. Intervention Lifestyle modifications in combination with synbiotic supplementation or placebo. Main Outcome Measures Change in BMI and testosterone level. Results In the Placebo Group, a 5% decrease in BMI was accompanied by significant decreases of the waist, hip, and thigh circumferences. The Synbiotic Group experienced an 8% decrease in BMI, which was significantly greater than that in the Control Group (P=0.03) and was accompanied by decreases in the waist, hip, and thigh circumferences. Testosterone did not decrease significantly in the Placebo Group (decrease of 6%), while in the Synbiotic Group it decreased by 32% (P<0.0001). The decrease of testosterone was significantly greater in the Synbiotic Group than in the Placebo Group (P=0.016). Conclusions Synbiotic supplementation potentiated effects of lifestyle modifications on weight loss and led to significant reduction of serum testosterone.

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A Double Blind Controlled Study of the Hormonal and Clinical Effects of Bromocriptine in the Polycystic Ovary Syndrome

Obstetrical & Gynecological Survey ◽

10.1097/00006254-198702000-00019 ◽

1987 ◽

Vol 42 (2) ◽

pp. 115-117

Author(s):

JACQUES BUVAT ◽

MICHELE BUVAT-HERBAUT ◽

GERARD MARCOLIN ◽

ANDRE RACADOT ◽

JEAN CLAUDE FOURLINNIE ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Study ◽

Clinical Effects ◽

Ovary Syndrome ◽

Double Blind

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The Effect of Atorvastatin in Patients with Polycystic Ovary Syndrome: A Randomized Double-Blind Placebo-Controlled Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-1750 ◽

2009 ◽

Vol 94 (1) ◽

pp. 103-108 ◽

Cited By ~ 73

Author(s):

Thozhukat Sathyapalan ◽

Eric S. Kilpatrick ◽

Anne-Marie Coady ◽

Stephen L. Atkin

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Study ◽

Ovary Syndrome ◽

Double Blind ◽

Double Blind Placebo

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A randomized, double-blind, placebo-controlled study of liraglutide 3 mg [LIRA 3mg] on weight, body composition, hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome (PCOS)

10.21203/rs.3.rs-799341/v1 ◽

2021 ◽

Author(s):

Karen Elkind-Hirsch ◽

Neil Chappell ◽

Donna Shaler ◽

John Storment ◽

Drake Bellanger

Keyword(s):

Body Composition ◽

Body Weight ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Study ◽

Ovary Syndrome ◽

Double Blind ◽

Once Daily ◽

Double Blind Placebo ◽

Change In Mean

Abstract BackgroundThe efficacy of lifestyle modifications for established obesity is limited in women with polycystic ovary syndrome (PCOS) and more aggressive interventions are needed. We assessed the efficacy and safety of the GLP-1 analogue liraglutide 3mg (LIRA 3mg) versus placebo (PL) for reduction of body weight and hyperandrogenism in women with obesity and PCOSMethodsThis randomized, double-blind, placebo-controlled study enrolled women from a single-outpatient center diagnosed with PCOS (NIH criteria) with a body-mass index of at least 30 kg/m.2 Participants were randomly allocated (2:1) to treatment with a subcutaneous injection LIRA 3mg or visually matching placebo, once daily for 32 weeks, plus lifestyle intervention. Study visits at baseline, and 32 weeks included weight, blood pressure (BP), waist (WC) measures and body composition evaluated by dual-energy X-ray absorptiometry (DXA). Oral glucose tolerance tests (OGTT) were done to assess glycemia, mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), complete metabolic profile and lipid profiles were measured in the fasting sample. Co-primary endpoints were change in body weight (BW) and FAI. Safety was assessed in all patients who received at least one dose of study drug. This study was registered with ClinicalTrials.gov NCT03480022FindingsFrom October 2018 to June 2020, 88 patients were screened, of whom 82 were randomly assigned to LIRA 3mg (n = 55) or PL (n = 27). Change in mean BW from baseline to week 32 was − 5.7% (SE 0·.75) with LIRA 3mg vs. -1.4% (1.09) with PL (P < 0.002). At week 32, more patients on LIRA 3 mg than on placebo achieved weight reductions of at least 5% (25[57%] of 44 vs. 5 [22%] of 23; (p < 0·007). LIRA 3mg resulted in significant reduction of FAI, improvements in SI and IS as well as OGTT MBG, and improved body fat by DXA. Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 32 (58.2%) of 55 patients with LIRA 3mg, and 5 (18.5%) of 27 with PL.InterpretationIn obese women with PCOS, LIRA 3mg once daily achieved a superior and clinically meaningful decrease in BW and androgenicity and improved cardiometabolic parameters compared with placebo.

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Metformin Versus Placebo from First Trimester to Delivery in Polycystic Ovary Syndrome: A Randomized, Controlled Multicenter Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-0853 ◽

2010 ◽

Vol 95 (12) ◽

pp. E448-E455 ◽

Cited By ~ 170

Author(s):

Eszter Vanky ◽

Solhild Stridsklev ◽

Runa Heimstad ◽

Pål Romundstad ◽

Kristin Skogøy ◽

...

Keyword(s):

Diabetes Mellitus ◽

Placebo Group ◽

Gestational Diabetes ◽

Polycystic Ovary Syndrome ◽

Gestational Diabetes Mellitus ◽

Pregnancy Complications ◽

Polycystic Ovary ◽

First Trimester ◽

Ovary Syndrome ◽

Metformin Group

Context: Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking. Objectives: Our objective was to test the hypothesis that metformin, from first trimester to delivery, reduces pregnancy complications in women with PCOS. Design and Setting: We conducted a randomized, placebo-controlled, double-blind, multicenter study at 11 secondary care centers. Participants: The participants were 257 women with PCOS, in the first trimester of pregnancy, aged 18–42 yr. Intervention: We randomly assigned 274 singleton pregnancies (in 257 women) to receive metformin or placebo, from first trimester to delivery. Main Outcome Measures: The prevalence of preeclampsia, gestational diabetes mellitus, preterm delivery, and a composite of these three outcomes is reported. Results: Preeclampsia prevalence was 7.4% in the metformin group and 3.7% in the placebo group (3.7%; 95% CI, −1.7–9.2) (P = 0.18). Preterm delivery prevalence was 3.7% in the metformin group and 8.2% in the placebo group (−4.4%; 95%, CI, −10.1–1.2) (P = 0.12). Gestational diabetes mellitus prevalence was 17.6% in the metformin group and 16.9% in the placebo group (0.8%; 95% CI, −8.6–10.2) (P = 0.87). The composite primary endpoint prevalence was 25.9 and 24.4%, respectively (1.5%; 95% CI, −8.9–11.3) (P = 0.78). Women in the metformin group gained less weight during pregnancy compared with those in the placebo group. There was no difference in fetal birth weight between the groups. Conclusions: Metformin treatment from first trimester to delivery did not reduce pregnancy complications in PCOS.

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