Metformin Effects on Clinical Features, Endocrine and Metabolic Profiles, and Insulin Sensitivity in Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled 6-Month Trial, followed by Open, Long-Term Clinical Evaluation1
Abstract
In the last few years some studies assessed the effects of attenuation of hyperinsulinemia and insulin resistance, obtained by insulin sensitizing agents, in women with polycystic ovary syndrome (PCOS), suggesting potential scope for these drugs in treating the whole spectrum of reproductive, endocrine, and metabolic abnormalities found in such subjects. However, the results of these studies, mostly uncontrolled and short-term, are still inconclusive, and there is no long-term follow-up. In the present study, 23 PCOS subjects [mean (+/- SE) body mass index 30.0+/-1.1 kg/m2] were randomly assigned to double-blind treatment with metformin (500 mg tid) or placebo for 6 months, while maintaining their usual eating habits. Before and after treatment, menstrual history, endocrine and metabolic profiles, serum 17-hydroxyprogesterone response to GnRH-agonist testing, and insulin sensitivity measured by the glucose clamp technique were assessed. Eighteen of these women, as well as 14 additional PCOS patients, were subsequently given metformin in an open trial for 11.0+/-1.3 months (range 4-26), to assess long-term effects of treatment and baseline predictors of metformin efficacy on reproductive abnormalities. After metformin treatment, mean frequency of menstruation improved (P = 0.002), due to striking amelioration of menstrual abnormalities in about 50% of subjects. Women given metformin showed reduced plasma insulin (at fasting: P = 0.057; during the clamp studies: P<0.01) and inc…
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SHBG concentrations increase with insulin sensitiser treatment.
“This is consistent with mechanistic studies demonstrating that SHBG production is suppressed by IR and hyperinsulinaemia (Le et al., 2012) and that SHBG concentrations increase with insulin sensitiser treatment (Moghetti et al., 2000).”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Moghetti et al., 2000
Low SHBG levels are increased by insulin-sensitising medication.
“Low SHBG levels are also increased by insulin-sensitising medication (Ehrmann et al., 1997;Moghetti et al., 2000;Moran et al., 2013);”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Moghetti et al., 2000
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- Authors
- Moghetti, P., Castello, R., Negri, C., Tosi, F., Perrone, F., Caputo, M., Zanolin, E., & Muggeo, M.
- Affiliations
- University of Verona (IT)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2000-01
- Volume
- 85
- Issue
- 1
- Pages
- 139-146
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2165523894
- Cited by
- 660
- References
- 5
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 12 · 2022: 11 · 2021: 20 · 2020: 9 · 2019: 15 · 2018: 14 · 2017: 15 · 2016: 19 · 2015: 16 · 2014: 16 · 2013: 35 · 2012: 26
- FWCI
- 58.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Keywords
- metformin, polycystic ovary syndrome, insulin resistance, insulin sensitivity, hyperinsulinemia, menstrual disorders, ovarian hyperandrogenism, free testosterone, 17-hydroxyprogesterone, GnRH agonist stimulation, glucose clamp, long-term treatment outcomes, predictors of treatment response, body mass index, insulin sensitizers, long-term follow-up
- MeSH terms
- Adolescent, Adult, Blood Glucose, Buserelin, Cholesterol, Double-Blind Method, Endocrine Glands, Female, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin Resistance, Gonadotropin-Releasing Hormone, Menstruation Disturbances, Metformin, Polycystic Ovary Syndrome, Triglycerides, Glucose Clamp Technique, 17-alpha-Hydroxyprogesterone
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