Hormone contraceptives and how the body uses carbohydrates in women without diabetes

Hormone contraceptives may change how the body handles carbohydrates (starches and sugars). Changes may include lower ability to use sugar from food and more problems with the body's insulin. Insulin is a hormone that helps the body use sugar. Problems with blood sugar can increase risk for diabetes and heart disease. These issues have been raised mainly with birth control methods that contain the hormone estrogen.

In April 2014, we looked for randomized trials of how the body handles carbohydrates when using birth control methods with hormones. Outcomes were blood glucose or insulin levels. Birth control methods could contain estrogen and progestin or just progestin. The type could be pills, shots (injections), implants (matchstick-size rods put under the skin), the vaginal ring, or an intrauterine device (IUD). The studies had to compare two types of birth control or one type versus a placebo or 'dummy' method.

We included 31 trials. None had a placebo. Of 34 pairs of birth control methods compared, eight showed some difference by study groups. Twelve trials studied pills with desogestrel. The few differences were not consistent. Three trials looked at the etonogestrel ring. One showed the ring group had lower insulin than the pill group.

Eight trials looked at the progestin norethisterone. A group using norethisterone pills had less glucose change than those taking other pills. In another study, a group using the injectable ‘depo’ (depot medroxyprogesterone acetate) had higher glucose and insulin than the group using another injectable.

Of five new trials, two used different estrogen types. In one study, a group taking a pill with ethinyl valerate had lower glucose than a group taking a standard pill. Two other trials compared taking pills for several cycles without stopping (extended use) versus usual use. In one using a dienogest pill, the extended-use group had more glucose change. A small trial used two levonorgestrel pills, and looked at obese and normal weight women. The outcomes did not differ much between those groups.

In women without diabetes, hormone contraceptives have little effect on the body's carbohydrate use. Few studies compared the same types of birth control. Therefore, we cannot make strong statements. Many trials had small numbers of women, and many women dropped out. Older trials often did not report all the study methods. Many trials did not include overweight women.

Authors' conclusions: 

Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods.

We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).

Read the full abstract...
Background: 

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 primarily with contraceptives containing estrogen.

Objectives: 

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

Search strategy: 

In April 2014, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. The initial search also included EMBASE.

Selection criteria: 

All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be 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 measures.

Data collection and analysis: 

We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated.

Main results: 

We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome.

Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36).

Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38).

Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73).

Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly.

Share/Save