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

Visser J, Snel M, Van Vliet HAAM

Published Online:

April 15, 2009

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.

Abstract (click to read)

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 strategy:

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.

This record should be cited as:

Visser J, Snel M, Van Vliet HAAM. Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003990. DOI: 10.1002/14651858.CD003990.pub3

Assessed as up to date:

December 18, 2008

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Primary Review Group:

Fertility Regulation Group

Health topics:

Gynaecology > Contraception > People with special characteristics or history

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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