Thromboembolism Risk Low With Hormonal Contraceptives in Diabetes

The risk for thromboembolism was low in reproductive-aged women with type 1 or type 2 diabetes using a hormonal contraceptive, according to data published in Diabetes Care.

“One concern with prescribing hormonal contraception to women with diabetes is the risk of thromboembolic complications, in particular cardiovascular disease and stroke,” the researchers wrote.

To evaluate the safety of hormonal contraceptive use in women with diabetes, Sarah H. O’Brien, MD, of the Nationwide Children’s Hospital and The Ohio State University in Columbus, and colleagues analyzed data from 2002 to 2011 in Clinformatics Data Mart of women aged 14 to 44 years in the United States with a diagnosis of diabetes or a prescription for a diabetes medication or device. Contraceptive claims were then compared with time to thromboembolism, including venous thrombosis, stroke, or myocardial infarction, among women with diabetes.

Researchers identified 146,080 women with type 1 or type 2 diabetes, 17.5% of whom had advanced diabetes. Only 28% had claims for hormonal contraception. Most women were receiving estrogen-containing contraceptives.

A total of 3012 thrombotic events occurred over 478,650 woman-years of observation, translating to a rate of 6.3 thrombotic events per 1000 woman-years of use (95% confidence interval [CI], 6.1-6.5 per 1000 woman-years). The crude incidence rate among women with diabetes using any hormonal contraception was 9.5 per 1000 woman-years for those aged younger than 35 (95% CI, 8.5-10.5) and 11.4 per 1000 woman-years for those aged 35 and older (95% CI, 10-13).

Arterial thrombosis, which accounted for 67% of thrombotic events among women with diabetes, was more common than venous thrombosis. Among women experiencing arterial thrombosis, strokes and transient ischemic attacks, which accounted for 41% of thrombotic events, were more common than myocardial infarction, which accounted for 26% of events.

Results showed that risk for thromboembolism appeared to vary with type of hormonal contraception used. Compared with no hormonal contraception, the hazard ratios [HRs] for estrogen-containing products were 3.83 (95% CI, 2.94-3.88) for women aged younger than 35 and 1.79 (95% CI, 1.54-2.09) for those aged 35 and older. For women younger than 35, progestin-only products were associated with a modest increase in risk for thromboembolism, as compared with no hormonal contraception (HR: 2.02; 95% CI, 1.51-2.70), but no association was noted in older women.

When both hormonal contraceptive products were compared directly, the researchers found that risk for thromboembolism was lower with progestin-only vs estrogen-containing contraception. The difference was significant in women younger than 35 (HR: 0.6; 95% CI, 0.44-0.81) but not in older women (HR: 0.74; 95% CI, 0.54-1.03).

Women using the contraceptive patch had the highest rate of thromboembolism (16 per 1000 woman-years) while those using intrauterine (6 per 1000 woman-years) and subdermal contraceptives (0 per 163 woman-years) had the lowest rates.

Additionally, risk for thromboembolism appeared to be increased with use of progestin-only injectable contraception vs intrauterine contraception (12.5 per 1000 woman-years; adjusted HR: 4.69; 95% CI, 2.51-8.77).

“Our results demonstrate the safety of hormonal contraception use in women with type 1 and type 2 diabetes with an overall low absolute risk of ~1 thromboembolic event per 100 woman-years of use,” the researchers concluded. “The contraceptives with the lowest absolute risk were the intrauterine and implantable subdermal contraceptives, and these highly effective reversible contraceptives are excellent options for women with diabetes.

Study Limitations

• Analysis of administrative data is dependent on proper documentation and medical coding.
• Administrative data do not contain information on family history of thrombosis and the potential undercoding of risk factors like smoking and obesity.
• Use of administrative data precluded researchers from knowing the exact timing of thromboembolism in relation to start of contraceptive use.
• The patient population studied was almost exclusively commercially insured.
• The potential for miscoding due to the availability of contraceptives at Title X clinics, which would then not be billed to insurance.
• The researchers did not control for acute thrombotic risk factors like major surgery.
• The number of implant users was small.

Disclosures: The researchers report no conflicts of interest.

Reference

1. O’Brien SH, Koch T, Vesely SK, Schwarz EB. Hormonal contraception and risk of thromboembolism in women with diabetes. Diabetes Care. 2016 Nov 29. doi:10.2337/dc16-1534 [Epub ahead of print].