Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus

Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised with progestin-only contraceptives as well as contraceptives containing estrogen. Such potential effects could influence recommendations for, and use of, these widely used and effective contraceptives.

To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight.

We searched the computerized databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. We wrote to investigators for information about other published or unpublished trials.

All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin levels, which were generally reported as fasting value or response to an oral glucose tolerance test.

We assessed for inclusion all titles and abstracts identified during the literature searches with no language limitations. The data were abstracted and entered into RevMan. Studies were examined for methodological quality. For continuous variables, the mean difference was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated.

We found 43 trials that met the inclusion criteria. No study stratified by body weight (normal-weight versus overweight women). Results for desogestrel were often favorable regarding carbohydrate metabolism but inconsistent overall. Glucose and insulin means were more favorable for norethisterone in studies of progestin-only contraceptives. For other progestins, little or no difference was noted across trials.

Current evidence suggests that hormonal contraceptives have limited effect on carbohydrate metabolism in women without diabetes. Strong statements cannot be made, though, due to having few studies that compared any particular types of contraceptives. Many trials had small numbers of participants and some had large losses. Many studies had poor reporting of methods. No information was available regarding the effects among women who were overweight.