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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]
In the citing paper
“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]
Citations
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
(2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.10.004 · Cited by 9,050
Eckel, R. H., Alberti, K., Grundy, S. M., & Zimmet, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61794-3 · Cited by 6,317
The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2004) · Human Reproduction · doi:10.1093/humrep/deh098 · Cited by 6,138
Eckel, R. H., Grundy, S. M., & Zimmet, P. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66378-7 · Cited by 5,755
Franks, S. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509283331307 · Cited by 2,463
Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome
Dunaif, A., Segal, K. R., Futterweit, W., & Dobrjansky, A. (1989) · Diabetes · doi:10.2337/diab.38.9.1165 · Cited by 1,967
Users' Guides to the Medical Literature
Guyatt, G. H. (1993) · JAMA · doi:10.1001/jama.270.21.2598 · Cited by 1,185
Androgen Excess in Women: Experience with Over 1000 Consecutive Patients
Azziz, R., Sanchez, L. A., Knochenhauer, E. S., Moran, C., Lazenby, J., Stephens, K. C., Taylor, K., & Boots, L. R. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031122 · Cited by 1,132
Prevalence and Characteristics of the Metabolic Syndrome in Women with Polycystic Ovary Syndrome
Apridonidze, T., Essah, P. A., Iuorno, M. J., & Nestler, J. E. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1045 · Cited by 931
Publication bias and clinical trials
Dickersin, K., Chan, S., Chalmersx, T. C., Sacks, H. S., & Smith, H. (1987) · Controlled Clinical Trials · doi:10.1016/0197-2456(87)90155-3 · Cited by 715
Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus
Ovalle, F., & Azziz, R. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03111-4 · Cited by 428
Polycystic ovary syndrome and endometrial carcinoma
Hardiman, P. J., Pillay, O., & Atiomo, W. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13409-5 · Cited by 414
Tang, T. H., Norman, R. J., Balen, A. H., & Lord, J. M. (2003) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053 · Cited by 369
Hundal, R. S., & Inzucchi, S. E. (2003) · Drugs · doi:10.2165/00003495-200363180-00001 · Cited by 315
Morin-Papunen, L. C., Vauhkonen, I., Koivunen, R. M., Ruokonen, A., Martikainen, H. K., & Tapanainen, J. S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6792 · Cited by 261
Should Unpublished Data Be Included in Meta-analyses?: Current Convictions and Controversies
Cook, D. J. (1993) · JAMA · doi:10.1001/jama.1993.03500210049030 · Cited by 259
Long-term health consequences of PCOS
Wild, R. A. (2002) · Human Reproduction Update · doi:10.1093/humupd/8.3.231 · Cited by 232
Nestler, J. E., Stovall, D. W., Akhter, N., Iuorno, M. J., & Jakubowicz, D. J. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(01)02963-6 · Cited by 227
Costello, M. F., & Eden, J. A. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(02)04554-5 · Cited by 224
Self-citationHormones, genetic factors, and gender differences in cardiovascular disease
Rossouw, J. E. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00478-3 · Cited by 214
Polycystic ovary syndrome--from gynaecological curiosity to multisystem endocrinopathy
Homburg, R. (1996) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a019031 · Cited by 213
Metformin or Antiandrogen in the Treatment of Hirsutism in Polycystic Ovary Syndrome
Harborne, L., Fleming, R., Lyall, H., Sattar, N. A., & Norman, J. E. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030424 · Cited by 204
Morin-Papunen, L. C., Vauhkonen, I., Koivunen, R. M., Ruokonen, A., Martikainen, H. K., & Tapanainen, J. S. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020997 · Cited by 182
Diamanti‐Kandarakis, E., Baillargeon, J., Iuorno, M. J., Jakubowicz, D. J., & Nestler, J. E. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021528 · Cited by 172
Combined oral contraceptives in the treatment of polycystic ovary syndrome
Vrbíková, J., & Cibula, D. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi005 · Cited by 166
Morin-Papunen, L. C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.9.3161 · Cited by 157
Hasegawa, I., Murakawa, H., Suzuki, M., Yamamoto, Y., Kurabayashi, T., & Tanaka, K. (1999) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00454-3 · Cited by 156
Elter, K., İmir, G., & Durmuşoğlu, F. (2002) · Human Reproduction · doi:10.1093/humrep/17.7.1729 · Cited by 152
Conway, G. S., Jacobs, H. S., Holly, J. M. P., & Wass, J. A. H. (1990) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1990.tb03897.x · Cited by 145
Insulin Sensitizers for Polycystic Ovary Syndrome
Baillargeon, J., Iuorno, M. J., & Nestler, J. E. (2003) · Clinical Obstetrics & Gynecology · doi:10.1097/00003081-200306000-00011 · Cited by 132
Endometrial carcinoma; ovarian dysfunction — a risk factor in young women
Dahlgren, E., Friberg, L.-G., Johansson, S., Lindström, B., Odén, A., Samsioe, G., & Janson, P. O. (1991) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/0028-2243(91)90092-y · Cited by 111
Polycystic ovary syndrome: A risk for coronary artery disease?
Wild, R. A. (2002) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2002.119180 · Cited by 109
Insulin and the Polycystic Ovary Syndrome
Utiger, R. D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199608293350909 · Cited by 97
Cibula, D., Fanta, M., Vrbíková, J., Stanická, S., Dvorakova, K., Hill, M., Škrha, J., Zivny, J., & Skrenková, J. (2004) · Human Reproduction · doi:10.1093/humrep/deh588 · Cited by 83
Escobedo, L., Lee, N. C., Peterson, H., & Wingo, P. (1991) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(91)90508-3 · Cited by 81
Rautio, K., Tapanainen, J. S., Ruokonen, A., & Morin-Papunen, L. C. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01840 · Cited by 71
Insulin Resistance: A Chicken That Has Come to Roost
Reaven, G. M. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07784.x · Cited by 68
Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome
Checa, M. Á., Requena, A., Salvador, C., Tur, R., Callejo, J., Espinós, J. J., Fábregues, F., Herrero, J. C., & (Reproductive Endocrinology Interest Group of the Spanish Society of Fertility) (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi015 · Cited by 60
Systematic Literature Review and Meta-Analysis
Hughes, E. G. (1996) · Seminars in Reproductive Medicine · doi:10.1055/s-2007-1016324 · Cited by 46
Molecular Mechanisms of Insulin Resistance in the Polycystic Ovary Syndrome
Dunaif, A. E. (1994) · Seminars in Reproductive Medicine · doi:10.1055/s-2007-1016376 · Cited by 26
Pharmacologic Treatment of Polycystic Ovary Syndrome
Ehrmann, D. A., & Rychlik, D. F. (2003) · Seminars in Reproductive Medicine · doi:10.1055/s-2003-43305 · Cited by 21
20 µg versus >20 µg estrogen combined oral contraceptives for contraception
Gallo, M. F., Nanda, K., Grimes, D. A., Lopez, L. M., & Schulz, K. F. (2005) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003989.pub2 · Cited by 21
Combined use of metformin and ethinyl estradiol–cyproterone acetate in polycystic ovary syndrome
Mitkov, M., Pehlivanov, B. K., & Terzieva, D. D. (2004) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2004.06.035 · Cited by 18
Polycystic ovary syndrome--a management update.
Costello, M. (2005) · PubMed · Cited by 10
Self-citation
Cited by
Sorted by citations
Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., & Welt, C. K. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2350 · Cited by 1,919
Balen, A. H., Morley, L. C., Misso, M., Franks, S., Legro, R. S., Wijeyaratne, C. N., Stener-Victorin, E., Fauser, B. C. J. M., Norman, R. J., & Teede, H. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmw025 · Cited by 705
Tang, T., Lord, J. M., Norman, R. J., Yasmin, E., & Balen, A. H. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub5 · Cited by 698
The polycystic ovary syndrome: a position statement from the European Society of Endocrinology
Conway, G., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H. F., Franks, S., Gambineri, A., Kelestimur, F., Macut, D., Micic, D., Pasquali, R., et al. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0253 · Cited by 676
Martin, K. A., Chang, R. J., Ehrmann, D. A., Ibáñez, L., Løbo, R. A., Rosenfield, R. L., Shapiro, J., Montori, V. M., & Swiglo, B. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2437 · Cited by 511
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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