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Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome
Abstract
BACKGROUND: Insulin-sensitizing drugs (ISDs) have recently been advocated as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of ISDs versus OCPs in the long-term treatment of women with PCOS. OBJECTIVES: To assess the effectiveness and safety of ISDs versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2005), Cochrane Central Register of Controlled Trials (CENTRAL (Ovid), third quarter 2005), MEDLINE (1966 to September 2005), CINAHL (1982 to September 2005), and EMBASE (1988 to September 2005). References of the identified articles were handsearched, and pharmaceutical companies and experts in the field were also contacted for additional relevant studies. SELECTION CRITERIA: Randomised controlled trials which compared ISDs versus the OCP (alone or in combination). DATA COLLECTION AND ANALYSIS: Performed independently by two review authors. MAIN RESULTS: Six trials were included for analysis, four of which compared metformin versus OCP (104 participants) and two of which compared OCP combined with metformin versus OCP alone (70 participants). Limited data demonstrated no evidence of difference in effect between metformin and the OCP on hirsutism and acne. There was either insufficient or no data on the relative efficacy of metformin or the OCP (alone or in combination) for preventing the development of diabetes, cardiovascular disease, or endometrial cancer. Metformin was less effective than the OCP in improving menstrual pattern (Peto odds ratio (OR) 0.08, 95% CI 0.01 to 0.45). Metformin resulted in a higher incidence of gastrointestinal (Peto OR 7.75, 95% CI 1.32 to 45.71), and a lower incidence of non-gastrointestinal (Peto OR 0.11, 95% CI 0.03 to 0.39), severe adverse effects requiring stopping of medication. Metformin was less effective in reducing serum androgen levels (total testosterone: weighted mean difference (WMD) 0.54, 95% CI 0.22 to 0.86; free androgen index: WMD 3.69, 95% CI 2.56 to 4.83). Metformin was more effective than the OCP in reducing fasting insulin (WMD -3.46, 95% CI -5.39 to -1.52) and not increasing triglyceride (WMD -0.48, 95% -0.86 to -0.09) levels, but there was insufficient evidence regarding comparative effects on reducing fasting glucose or cholesterol levels. AUTHORS' CONCLUSIONS: Up to 12-months treatment with the OCP is associated with an improvement in menstrual pattern and serum androgen levels compared with metformin; but metformin treatment results in a reduction in fasting insulin and lower triglyceride levels than with the OCP. Side-effect profiles differ between the two drugs. There is either extremely limited or no data on important clinical outcomes such as the development of diabetes, cardiovascular disease, or endometrial cancer. There are no data comparing ISDs other than metformin (that is rosiglitazone, pioglitazone, and D-chiro-inositol) versus OCPs (alone or in combination).
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“This meta-analysis was also inconclusive on the efficacy of metformin or the OCP alone or in combination, in the diabetes prevention, because of insufficient data.”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [49]
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“Another Cochrane meta-analysis [49] compared metformin with oral contraceptive pill (OCP) and did not find significant differences for FBG.”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [49]
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Jadhav, A. S., & Dabade, R. (2025) · International Journal of Reproduction Contraception Obstetrics and Gynecology · doi:10.18203/2320-1770.ijrcog20250879
CLINICAL PROFILE AND OUTCOMES OF PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME
Poonia, M. (2025) · Journal of Population Therapeutics and Clinical Pharmacology · doi:10.53555/6vtsz040
Wang, X., Zhang, C., Gou, J., Zhang, L., Wang, Y., Du, Z., Gao, J. Q., & Xia, H. (2025) · Russian Journal of Developmental Biology · doi:10.1134/s1062360425700213
Metadata
- Authors
- Costello, M. F., Shrestha, B., Eden, J., Johnson, N., & Moran, L. J.
- Affiliations
- Royal Hospital for Women (AU)
- UNSW Sydney (AU)
- University of Auckland (NZ)
- Monash Medical Centre (AU)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2007-01-24
- Issue
- 1
- Pages
- CD005552-CD005552
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- OpenAlex
- W1954184248
- Cited by
- 197
- References
- 47
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 15 · 2016: 19 · 2015: 21 · 2014: 25 · 2013: 8 · 2012: 4
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Update notices
- new_version (2020-08-13)
- Open access
- closed
- Locations
- Cochrane Database of Systematic Reviews (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 › Dermatology › Acne and Rosacea Treatments and Effects
- Keywords
- polycystic ovary syndrome, metformin, combined oral contraceptives, hirsutism, acne, diabetes prevention, cardiovascular disease, endometrial cancer, menstrual pattern, gastrointestinal adverse effects, long-term treatment, drug safety and efficacy comparison, insulin resistance, hyperandrogenism, hypertriglyceridemia, dyslipidemia, hypercholesterolemia
- MeSH terms
- Acne Vulgaris, Cardiovascular Diseases, Contraceptives, Oral, Combined, Female, Hirsutism, Humans, Hypoglycemic Agents, Menstruation Disturbances, Metformin, Polycystic Ovary Syndrome, Randomized Controlled Trials as Topic, Endometrial Neoplasms
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