Metformin effects on ovarian ultrasound appearance and steroidogenic function in normal-weight normoinsulinemic women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial

Romualdi, Daniela; Giuliani, Maddalena; Cristello, Francesca; Fulghesu, Anna Maria; Selvaggi, Luigi; Lanzone, Antonio; Guido, Maurizio

doi:10.1016/j.fertnstert.2009.01.114

Cited by 46 publications

(30 citation statements)

References 41 publications

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“…Without changes in body composition or sex steroids, the change in insulin sensitivity may explain this finding. An improvement in insulin sensitivity with 6 months of metformin treatment in women with PCOS reduced ovarian volume by ~30% and stromal/total area ratio by ~25% as determined by ultrasound (23). …”

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confidence: 99%

Aerobic exercise in women with polycystic ovary syndrome improves ovarian morphology independent of changes in body composition

Redman

Elkind‐Hirsch

Ravussin

2011

Fertility and Sterility

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In a prospective study, 8 women with polycystic ovary syndrome completed 16 weeks of individualized aerobic exercise training. Independent of changes in body weight and adiposity there was a significant increase in aerobic fitness and insulin sensitivity and a significant decrease in the total number of follicles measured by magnetic resonance imaging.Recently and based initially on studies in obesity and type 2 diabetes, lifestyle modification has been adopted as the first line of treatment to manage both the reproductive and metabolic dysfunctions in overweight and obese women with PCOS (1-3). As a result a surge in clinical studies involving dietary restriction alone (4-7) or in combination with physical activity programs have been conducted (8,9). Collectively these studies indicate that a reduction in body weight of at least 5% leads to significant improvements in menstrual cyclicity, ovulation and biochemical hyperandrogenism in terms of the reproductive complaints (4,6-9) and improved glucose tolerance and reduced risk for cardiovascular disease (4,8). One intriguing finding was that in comparison to dietary restriction (800 kcal/ d), aerobic exercise led to a 40% higher rate of ovulation (25% versus 65%, respectively) and greater improvements in SHBG and testosterone despite less weight loss (10). Aerobic exercise resulted in a greater reduction in fasting insulin and insulin resistance (HOMA-IR) suggesting a possible mechanistic link. Exercise-induced changes in visceral fat and ectopic lipid in non-fatty tissues are probably important components however to our knowledge only one recent study using single slice computed tomography measured changes in visceral fat with exercise training in PCOS (11). Studies using magnetic resonance imaging or spectroscopy are seldom no studies have yet quantified the effects of exercise on the polycystic ovarian morphology.As detailed previously (13), eight young (18-30 years), overweight/obese (BMI ≥25 kg/m 2 ) women with PCOS completed a 16-week study of aerobic exercise. Seven normally cycling controls (BMI ≥25 kg/m 2 ) were also enrolled to complete baseline testing only. The Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All exercise training was performed under supervision at the PBRC Fitness Center five times per week. Exercise was prescribed on an individual basis with the objective to achieve specified exercise energy expenditure (ExEE) per day as previously described (13). Diet was not controlled throughout the exercise intervention however a standardized eucaloric diet (35% fat, 15% protein, 50% carbohydrate) ...

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confidence: 99%

Aerobic exercise in women with polycystic ovary syndrome improves ovarian morphology independent of changes in body composition

Redman

Elkind‐Hirsch

Ravussin

2011

Fertility and Sterility

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“…Result of analysis of 2372 studies and 12 RCTs presented that metformin treatment and lifestyle intervention versus lifestyle intervention alone or with placebo did not differ in lipids levels in PCOS women [26]. Some studies showed a beneficial influence of metformin therapy on lipid profiles [27][28][29][30], some did not [31][32][33]. The effect of metformin on lipid parameters differed between studies.…”

Section: Discussionmentioning

confidence: 99%

“…The dosage and duration of therapy varied between studies, e.g. women received 500 mg of metformin over 90 days [30], 500 mg of metformin three times a day for 3 months [27], 500 mg of metformin for 6 months [38], 500 mg of metformin twice a day and the lipids were assessed after 3 and 6 months of the therapy [32]. Studies with long follow-ups are needed to assess the long-term effects of metformin on lipid profile.…”

Section: Discussionmentioning

confidence: 99%

Metformin and changes in serum lipid profile in lean patients with polycystic ovary syndrome (PCOS)

Кялка¹,

Milewicz²,

Wajda³

et al. 2017

EJEA

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Metformin and changes in serum lipid profile in lean patients with polycystic ovary syndrome Wpływ metforminy na profil lipidowy pacjentek z zespołem policystycznych jajników i prawidłową należną masą ciała M. Kiałka et al. Introduction: The aim of our study was to assess the values of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides before and after treatment with metformin in lean patients with polycystic ovary syndrome (PCOS). Material and methods: 32 patients received metformin 1500 mg per day in three divided doses. Lipids measurements were performed twice: before and after 6 months of treatment with metformin. Results: In lean patients with PCOS after treatment with metformin we observed: statistically significant lower LDL-C levels (4.16±0.79 mmol/l vs 3.4±0.86 mmol/l, p<0.05) and triglycerides levels (1.8±0.53 mmol/l vs 1.12±0.64 mmol/l, p<0.05). We observed an increase in HDL values and a decrease in total cholesterol values, but these changes were not statistically significant (1.5±0.71 mmol/l vs 1.71±0.69 mmol/l, p=0.09; 5.87±0.92 mmol/l vs 5.69±0.97 mmol/l, p=0.11). Conclusion: Our study showed that treatment of 1500 mg metformin for about six months among PCOS women results in an improvement in serum lipid profiles. We observed a significant decrease in LDL-C and triglycerides values after metformin therapy. Wnioski: Wykazano, że leczenie metforminą w dawce 1500 mg przez okres sześciu miesięcy skutkuje poprawą profilu lipidowego u pacjentek z PCOS i prawidłową należną masą ciała. Zaobserwowano istotny spadek wartości cholesterolu LDL i triglicerydów po leczeniu metforminą.

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“…Metformin, another commonly used treatment of PCOS, has been shown to reduce oxidative stress, possibly in part by reduction of NADPH oxidase activity [34,35]. In at least two studies on women with PCOS, including a randomized placebo-controlled trial, metformin also reduced ovarian volume and/or stromal to total ovarian area [36,37]. One of the possible mechanisms of these effects of rosiglitazone and metformin may be related to reduction of oxidative stress and consequent antioxidant-like action on ovarian theca-interstitial cells.…”

Section: Discussionmentioning

confidence: 99%

Antioxidants Induce Apoptosis of Rat Ovarian Theca-Interstitial Cells1

Rzepczynska

Foyouzi

Piotrowski

et al. 2011

Biology of Reproduction

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Regulation of growth of ovarian theca-interstitial tissues is essential for normal ovarian development and function. Reactive oxygen species are involved in modulation of signal transduction pathways, including regulation of tissue growth and apoptosis. Previously, we have demonstrated that antioxidants inhibit proliferation of theca-interstitial cells. This report evaluates the effects of antioxidants on apoptosis of rat theca-interstitial cells. The cells were cultured in chemically defined media without or with vitamin E succinate and ebselen. Apoptosis was evaluated by cytochemical assessment of nuclear morphology, activity of executioner caspases 3 and 7, and determination of staining with annexin V in combination with propidium iodide. Both tested antioxidants induced significant morphological changes consistent with apoptosis, including chromatin condensation, nuclear shrinkage, and pyknosis. Antioxidants also induced other hallmarks of apoptosis including increased activity of caspases 3/7 as well as increased staining with annexin V. The present findings demonstrate that antioxidants with distinctly different mechanisms of action induce a series of events consistent with the process of apoptosis in ovarian mesenchyme. These observations may be of translational-clinical relevance, providing mechanistic support for the use of antioxidants in the treatment of PCOS, a condition associated with excessive growth and activity of theca-interstitial cells.

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Metformin effects on ovarian ultrasound appearance and steroidogenic function in normal-weight normoinsulinemic women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial

Cited by 46 publications

References 41 publications

Aerobic exercise in women with polycystic ovary syndrome improves ovarian morphology independent of changes in body composition

Aerobic exercise in women with polycystic ovary syndrome improves ovarian morphology independent of changes in body composition

Metformin and changes in serum lipid profile in lean patients with polycystic ovary syndrome (PCOS)

Antioxidants Induce Apoptosis of Rat Ovarian Theca-Interstitial Cells1

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