Intervention Review

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

  1. Michael F Costello1,*,
  2. Bhushan Shrestha2,
  3. John Eden3,
  4. Neil Johnson4,
  5. Lisa J Moran5

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 14 NOV 2006

DOI: 10.1002/14651858.CD005552.pub2

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Additional Information

How to Cite

Costello MF, Shrestha B, Eden J, Johnson N, Moran LJ. 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. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005552. DOI: 10.1002/14651858.CD005552.pub2.

Author Information

  1. 1

    School of Women's & Children's Health, Royal Hospital for Women and IVF Australia, Division of Obstetrics & Gynaecology, Sydney, Australia

  2. 2

    University of New South Wales, School of public health and community medicine, Concord, NSW, Australia

  3. 3

    Royal Hospital for Women, Sydney Menopause Centre & Natural Therapies Unit, Randwick, NSW, Australia

  4. 4

    University of Auckland, Department of Obstetrics & Gynaecology, Auckland, New Zealand

  5. 5

    Monash University, The Jean Hailes Clinical Research Unit, School of Public Health and Preventive Medicine, Clayton, Victoria, Australia

*Michael F Costello, Division of Obstetrics & Gynaecology, School of Women's & Children's Health, Royal Hospital for Women and IVF Australia, Barker Street, Randwick, Sydney, NSW 2031, Australia. mfcostello@unsw.edu.au.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 21 JAN 2009

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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 methods

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).

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Insulin-sensitising drugs versus the combined oral contraceptive pill for symptoms and risks of polycystic ovary syndrome.

Women with polycystic ovary syndrome suffer from excessive hairiness (hirsutism), irregular periods, and acne. They are also at greater risk of developing diabetes, cardiovascular disease, and endometrial cancer.
In women with polycystic ovary syndrome (PCOS), the oral contraceptive pill (OCP) is more effective than insulin-sensitising drugs in improving menstrual pattern and reducing serum androgen (male hormone) levels whilst metformin, an insulin-sensitising drug (ISD), is more effective than the OCP in reducing fasting insulin levels and not increasing triglyceride levels.
There is insufficient evidence in favour of either metformin or the OCP in treating hirsutism or acne (pimples); nor in preventing the development of diabetes, heart disease, or endometrial cancer. The limited data available does not support the preferential use of either insulin-sensitising drugs or OCP (alone or in combination) for the long-term medical management of PCOS.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

胰島素增敏藥物與組合口服避孕劑在多囊性卵巢症候群中對於多毛症、痤瘡、以及糖尿病、心血管疾病、及子宮內膜癌風險之比較

針對具有多囊性卵巢症候群 (polycystic ovary syndrome；PCOS) 之婦女，胰島素增敏藥物 (insulinsensitizing drugs；ISDs) 近來已被倡導為一種可能較口服避孕藥 (oral contraceptive pill；OCP) 更為安全及有效之長期治療。直接比較ISDs相對於OCPs就PCOS婦女之長期治療而言的功效及安全性是極為重要的。

目標

評估ISDs相對於OCP (單獨或組合) 在改善PCOS之臨床、荷爾蒙、及代謝特徵方面的有效性及安全性。

搜尋策略

我們搜尋 Cochrane Menstrual Disorders以及Subfertility Group Trials Register (2005年9月) 、 Cochrane Central Register of Controlled Trials (CENTRAL (Ovid) 、 2005年第3季) 、 MEDLINE (1966年2005年9月) 、 CINAHL (1982年2005年9月) 、以及EMBASE (1988年2005年9月) 。 人工搜尋所找到研究的參考文獻，並與藥廠及本領域專家聯繫以補充相關研究。

選擇標準

比較ISDs相對於OCP (單獨或組合) 之隨機對照試驗。

資料收集與分析

由2位回顧作者獨立進行。

主要結論

共收錄6項試驗進行分析，其中4項比較metformin對OCP (104名參與者) 且其中2項比較OCP與metformin之組合對單獨使用之OCP (70名參與者) 。有限之數據並未顯示metformin與OCP對於多毛症及痤瘡之效應間具有差異證據。有關metformin或OCP (單獨或組合) 對於預防糖尿病、心血管疾病、或子宮內膜癌發生之相對功效，其中亦僅有不足之數據或無數據。就改善月經模式而言，metformin不如OCP有效 (Peto勝算比 (odds ratio；OR) 0.08, 95% CI 0.01 to 0.45) 。就必須中止給藥之嚴重不良作用而言，metformin造成較多之胃腸性嚴重不良作用 (Peto OR 7.75, 95% CI 1.32 to 45.71) 及較少之非胃腸性嚴重不良作用 (Peto OR 0.11, 95% CI 0.03 to 0.39) 。就降低血清雄性激素之含量而言，metformin較不具功效 (總睪固酮：加權平均差 (weighted mean difference；WMD) 0.54, 95% CI 0.22 to 0.86; 游離雄性激素指數：WMD 3.69, 95% CI 2.56 to 4.83) 。Metformin可較OCP更為有效的降低空腹胰島素含量 (WMD −3.46, 95% CI −5.39 to −1.52) ，且其不會造成三酸甘油酯含量之增加 (WMD −0.48, 95% −0.86 to −0.09) ，但針對降低空腹血糖及膽固醇含量之比較效應而言，其中並無足夠之證據。

作者結論

相較於 metformin，長達12個月之OCP治療可改善月經模式及血清雄性激素含量；但metformin治療會造成較OCP更大量之空腹胰島素含量降低及較低之三酸甘油酯含量。兩種藥物的副作用性質不同。對於重要之臨床結果，諸如，糖尿病、心血管疾病、及子宮內膜癌之發生，其中僅有極為有限之數據或是無數據。並無比較非metformin之ISDs (亦即rosiglitazone、pioglitazone、及Dchiroinositol) 對OCPs (單獨或組合) 之數據。

翻譯人

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

胰島素增敏藥物與口服避孕劑對於多囊性卵巢症候群之症狀及風險的比較。患有多囊性卵巢症候群之婦女具有毛髮過多 (男樣多毛症) 、經期不規則、以及痤瘡之情形。其亦有發生糖尿病、心血管疾病、及子宮內膜癌之較高風險。就患有多囊性卵巢症候群 (polycystic ovary syndrome；PCOS) 之婦女而言，口服避孕藥 (oral contraceptive pill；OCP) 在改善月經模式及降低血清雄性激素 (男性荷爾蒙) 含量方面較胰島素增敏藥物更為有效，而metformin (一種胰島素增敏藥物 (insulinsensitising drug；ISD) 則可較OCP更為有效的降低空腹胰島素含量並不會增加三酸甘油酯含量。並無足夠之證據可說明，metformin或OCP，何者對於男樣多毛症或痤瘡 (青春痘) 有較佳之治療；亦不知何者對於預防糖尿病、心血管疾病、或子宮內膜癌之發生有較佳效果。目前取得之有限證據並無法支持應選擇胰島素增敏藥物或是OCP (單獨或組合) 以進行PCOS之長期藥物治療。

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