Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2

 

Abstract

Background

Adequate contraceptive advice is important in women with diabetes mellitus type 1 and 2 to reduce the risk of maternal and infant morbidity and mortality in unplanned pregnancies. A wide variety of contraceptives are available for these women. However hormonal contraceptives might influence carbohydrate and lipid metabolism and increase micro- and macrovascular complications. So caution in selecting a contraceptive method is required.

Objectives

To investigate whether progestogen-only, combined estrogen/progestogen or non-hormonal contraceptives differ in terms of effectiveness in preventing pregnancy, in their side effects on carbohydrate and lipid metabolism and in long-term complications such as micro- and macrovascular disease, when used in women with diabetes mellitus.

Search methods

The search was performed in MEDLINE, EMBASE, CENTRAL/CCTR, POPLINE, CINAHL, WorldCat, ECO, ArticleFirst, the Science Citation Index, the British Library Inside, and reference lists of relevant articles. Last search was performed in December 2008. In addition, experts in the field and pharmaceutical companies marketing contraceptives were contacted to identify published, unpublished or ongoing studies.

Selection criteria

Randomised and quasi-randomised controlled trials that studied women with diabetes mellitus comparing:
1. hormonal versus non-hormonal contraceptives
2. progestogen-only versus estrogen/progestogen contraceptives
3. contraceptives containing <50 µg estrogen versus contraceptives containing >= 50 µg estrogen
4. contraceptives containing 'first'-, 'second'- and 'third'-generation progestogens, drospirenone and cyproterone acetate.
Principal outcomes were contraceptive effectiveness, diabetes control, lipid metabolism and micro- and macrovascular complications.

Data collection and analysis

Two investigators evaluated the titles and abstracts from the literature search. Quality assessment was performed independently with discrepancies resolved by discussion or consulting a third reviewer. Because the trials differed in studied contraceptives, participant characteristics and methodological quality, we could not combine the data in a meta-analysis. The trials were therefore examined on an individual basis and narrative summaries were provided.

Main results

Four randomised controlled trials were included. Only one was of good methodological quality. It compared the influence of levonorgestrel-releasing IUD versus copper-IUD on carbohydrate metabolism in women with type 1 diabetes mellitus. No difference was found in daily insulin requirement, glycosylated hemoglobin (HbA1c) or fasting blood sugar after twelve months. The other three trials were of limited methodological quality. Two compared progestogen-only pills with different estrogen/progestogen combinations and one also included the levonorgestrel-releasing IUD and copper IUD. The trials reported blood glucose levels to remain stable during treatment with most regimens. Only high-dose combined oral contraceptives and 30 µg ethinylestradiol + 75 µg gestodene were found to slightly impair glucose homeostasis. The three studies found conflicting results regarding lipid metabolism. Some combined oral contraceptives appeared to have a minor adverse effect while others appeared to slightly improve lipid metabolism. The copper-IUD and progestogen-only contraceptives also slightly improved lipid-metabolism and no influence was seen while using levonorgestel-releasing IUD. Only one study reported on micro- and macrovascular complications. No signs or symptoms of thromboembolic incidents or visual disturbances were observed. However study duration was short. Only minor adverse effects were reported in two studies. Unintended pregnancies were not observed during any of the studies.

Authors' conclusions

The four included randomised controlled trials in this systematic review provided insufficient evidence to assess whether progestogen-only and combined contraceptives differ from non-hormonal contraceptives in diabetes control, lipid metabolism and complications. Three of the four studies were of limited methodological quality, sponsored by pharmaceutical companies and described surrogate outcomes. Ideally, an adequately reported, high-quality randomised controlled trial analysing both intermediate outcomes (i.e. glucose and lipid metabolism) and true clinical endpoints (micro- and macrovascular disease) in users of combined, progestogen-only and non-hormonal contraceptives should be conducted. However, due to the low incidence of micro- and macrovascular disease and accordingly the large sample size and follow-up period needed to observe differences in risk, a randomised controlled trial might not be the ideal design.

 

Plain language summary

Not enough evidence is available to prove that hormonal contraceptives do not influence glucose and fat metabolism in women with diabetes mellitus.

It is important for women with diabetes mellitus type 1 and 2 to receive good advice which contraceptive method is best to use. Unplanned pregnancies can lead to serious health issues for both mother and child in women with diabetes. Yet, hormonal contraceptives have been reported to influence glucose and fat metabolism. In this review, both progestogen-only methods (pills and intrauterine device (IUD)) and low-dose combined oral contraceptives appeared to have only minor influences on glucose and fat metabolism. However, only four studies most of limited quality, examining a small number of women were included in this review. Only one of the studies reported on true clinical endpoints i.e. micro- and macrovascular disease. It found no signs or symptoms of thromboembolic incidents or visual disturbances. However this trial was performed over a short period of time. Therefore no definite conclusions can be made based on this review. Future trials analysing glucose and fat metabolism as well as long-term complications for all available contraceptive methods are needed.

 

摘要

背景

荷爾蒙避孕藥與非荷爾蒙避孕在第一型及第二型糖尿病婦女的比較

充分的避孕諮詢對於減少第一型及第二型糖尿病婦女非計畫懷孕下的孕婦和嬰兒的發病率和死亡率是相當重要的。對這些婦女有各種的避孕方式可以使用。然而荷爾蒙避孕藥可能影響碳水化合物和脂肪的代謝，增加微細血管和大血管的併發症。因此，謹慎選擇的避孕方法是必需的。

目標

調查糖尿病婦女使用僅有黃體素或合併雌激素/黃體素或非荷爾蒙避孕，在避孕效果及副作用如對碳水化合物和脂肪代謝，長期併發症如微細血管和大血管的病變是否有所差別。

搜尋策略

搜索MEDLINE、EMBASE、CENTRAL/CCTR、POPLINE 、CINAHL 、WorldCat、ECO、ArticleFirst、the Science Citation Index、the British Library Inside、及相關研究的參考文獻。最後一次搜索是在2005年5月。此外，也聯絡該領域的專家和上市避孕藥的製藥公司，以確定已出版，未出版或正在進行的研究。

選擇標準

隨機和半隨機對照試驗，研究糖尿病婦女比較：1. 荷爾蒙避孕藥與非荷爾蒙避孕， 2. 黃體素與合併雌激素/黃體素 避孕藥， 3. 避孕藥含有低於50微克雌激素與避孕藥含有高於或等於50微克雌激素， 4. 避孕藥含有“第一代”, “第二代”, “第三代”黃體素， drospirenone和 cyproteron acetate。主要結果為避孕效果，糖尿病控制，脂肪代謝及微細血管和大血管併發症。

資料收集與分析

兩名研究員從文獻檢索中評估標題和摘要。品質評估獨立進行，差異經由與第三方評論者討論或諮詢來解決。由於這些試驗研究有不同的避孕藥，受試者不同的特點和不同的方法學品質，我們無法將數據相結合進行統合分析(Metaanalysis)。因此，這些試驗在個別的基礎上被檢驗和提供有限的摘要。

主要結論

三個隨機對照試驗被列入。其中只有一個試驗有良好的方法學品質。這個試驗比較levonorgestrel釋放子宮內避孕器與含銅子宮內避孕器對第1型糖尿病婦女糖代謝的影響。12個月後在日常生活中胰島素的要求，糖化血色素(HbA1c)或空腹血糖並沒有差異。其他兩個試驗只有有限的方法學品質。這兩個試驗皆比較黃體素避孕藥與不同含量的雌激素/黃體素避孕藥組合。試驗報告在大多數的配方治療過程中血糖保持穩定。只有高劑量的口服避孕藥的組合，發現輕微影響血糖穩定。合併雌激素/黃體素口服避孕藥對於脂質代謝似乎也有輕微的不利影響而只含黃體素的避孕藥對脂質代謝則略有改善。只有一個研究報告有微血管和大血管的併發症。沒有觀察到血栓事件或是視力障礙的徵兆或症狀。然而研究時間很短。有一項研究報告一些輕微的不良反應。這項試驗發現只含黃體素的避孕藥比合併雌激素/黃體素的避孕藥有較多不規則的出血。在所有研究中沒有觀察到任何的意外懷孕。

作者結論

在這次的系統回顧研究中收錄的三個隨機對照試驗並沒有提供足夠的證據評估只含黃體素避孕藥和合併雌激素/黃體素避孕藥對於糖尿病控制、脂質代謝和併發症與非荷爾蒙避孕有何不同。其中兩個由藥商公司贊助的研究僅有有限的方法學品質和描述代理產品的結果。理想的情況下，高品質的隨機對照試驗，對於使用合併雌激素/黃體素避孕藥及只含黃體素避孕藥和非荷爾蒙避孕的使用者，分析中間成果(即糖，脂代謝)和真正臨床終點(微血管和大血管疾病)應被適當地報告。然而，由於微血管和大血管疾病的低發病率，並需要大樣本和後續追蹤期間來觀察不同的風險，一個隨機對照試驗可能不是理想的設計。

翻譯人

本摘要由臺灣大學附設醫院林冠宏翻譯。

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

總結

沒有足夠的證據可以證明，荷爾蒙避孕藥在患有糖尿病的婦女不會影響葡萄糖和脂肪代謝。對於患有第一型和第二型糖尿病的婦女而言，重要的是得到良好的建議選擇對其最有利的避孕方式。非計劃懷孕可能會對患有糖尿病的母親和小孩導致嚴重的健康問題。然而，荷爾蒙避孕藥已被報告會影響葡萄糖和脂肪代謝。在此回顧性研究中，僅有三項檢查少量的婦女和品質有限的研究被收錄進來，不論只含黃體素(避孕藥和子宮內避孕器)和合併低劑量雌激素/黃體素的避孕藥對於糖類和脂量的代謝只有輕微的影響。只有其中一個研究報告真正的臨床終點即微血管和大血管疾病。它沒有發現血栓事件或視力障礙的任何徵兆或症狀。但是這次試驗只進行了很短的時間。因此，在此回顧性研究的基礎上沒有明確的結論。未來的試驗分析所有的避孕方法對於葡萄糖和脂肪代謝及長期併發症是必要的。