Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2
Visser, J.; Snel, M.; Van Vliet, H.A.A.M.
Cochrane Database of Systematic Reviews 4: Cd003990
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. 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. 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 May 2005. In addition, experts in the field and pharmaceutical companies marketing contraceptives were contacted to identify published, unpublished or ongoing studies. 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 microg estrogen versus contraceptives containing > or = 50 microg 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. 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. Three 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 two trials were of limited methodological quality. Both compared progestogen-only pills with different estrogen/progestogen combinations. The trials reported blood glucose levels to remain stable during treatment with most regimens. Only high-dose combined oral contraceptives were found to slightly impair glucose homeostasis. Combined oral contraceptives also appeared to have a minor adverse effect on lipid metabolism whereas progestogen-only contraceptives slightly improved lipid-metabolism. 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. Minor adverse effects were reported in one study. The trial found progestogen-only pills to cause more bleeding irregularities when compared with combined oral contraceptives. Unintended pregnancies were not observed during any of the studies. The three 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. Two of the three 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.