Women on anticoagulant therapy can take estrogen-containing contraception or hormone therapy without an increased risk of blood clots or uterine bleeding, findings from a recent study suggest.1
Clinicians are reluctant to prescribe estrogen-containing contraceptives or postmenopausal hormone therapy to women who use anticoagulants for venous thromboembolism (VTE) due to the documented increased risk of VTE with these hormonal agents.2-4 Product labeling for combined oral contraceptives, as a class, generally indicates that use is contraindicated in patients with an active or prior VTE event, although no reference is made to the concomitant use with anticoagulation.1
To answer the question of whether women can safely take hormone-containing medication with anticoagulants, Ida Martinelli, MD, PhD, head of the Thrombosis Center at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, and fellow researchers compared the incidences of recurrent blood clots and abnormal uterine bleeding in 1,888 women who received blood thinners with and without concurrent hormone therapy. To perform the analysis, the scientists looked at patient data from the EINSTEIN deep vein thrombosis (DVT) and pulmonary embolism (PE) study.5-6 The original research was designed to evaluate the safety and efficacy of two anticoagulants: the new direct oral anticoagulant, rivaroxaban, and the current standard of care, a low-molecular-weight heparin (enoxaparin) followed by a vitamin K antagonist (VKA). Women of childbearing age were advised to use adequate methods of contraception to avoid birth defects.
Of the total number of women in the analysis, 1,413 used no hormonal contraception, and 475 used some type of hormone therapy. Hormone therapy included estrogen-only pills, combined estrogen-progestin contraceptives (pills, patches, vaginal rings, and injectables), and progestin-only contraceptives (pills, implants, injectables, and intrauterine devices). Study participants were questioned about symptoms or signs of recurrent blood clots and bleeding, including uterine bleeding, during each follow-up visit.
Data indicate seven recurrent blood clot events occurred while patients were using hormone therapy, while 38 events occurred during a time when patients weren’t using hormone therapy. Researchers conclude that women on blood thinners and hormone therapy experienced recurrent blood clots at a rate of 3.7% per year. In contrast, those not on hormone therapy had a recurrence rate of 4.7% per year. Also, the incidence of abnormal uterine bleeding in those on hormonal therapy was 22.5%, compared to 21.4% in women not using hormone therapy. The similar incidence of blood clots and abnormal uterine bleeding in women who did and did not receive hormone therapy suggests that the combined use of these therapies is safe.1
More frequent bleeding
Study findings indicate that abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA. The bleeding rate was estimated at 29.8% per year for patients on rivaroxaban and 15.5% per year in the enoxaparin/VKA group. Researchers note the need for further studies on the oral anticoagulant, which often is preferred for its convenience over subcutaneous doses of enoxaparin/VKA.1
“For the first time, we demonstrate that women suffering from blood clots can safely take hormone-containing contraceptives or hormone replacement therapy with anticoagulants, providing women the freedom to choose the method of birth control and other hormone-containing medications they prefer,” says Martinelli. “While further investigation is needed to evaluate the inconvenience of abnormal uterine bleeding with rivaroxaban and the other direct oral anticoagulants, these results dispel former misconceptions and should allow clinicians to confidently treat their patients who take blood thinners and hormones concurrently.”
What is your call?
The U.S. Medical Eligibility Criteria for Contraceptive Use (US MEC) discourages use of combination contraceptives in women with a history of VTE on anticoagulation.7 However, it also notes that when a hormonal contraceptive is used not solely to prevent pregnancy, but also to prevent/treat gynecologic problems (which include not only heavy menstrual bleeding but also post-ovulatory hemorrhage), the risk/benefit ratio should be considered on a case-by-case basis.
Andrew Kaunitz, MD, University of Florida Research Foundation professor and associate chairman of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine – Jacksonville, says, “Unintended pregnancy among women with a history of VTE represents a high-risk condition; furthermore, vitamin K antagonists are teratogens. These observations underscore the importance of the authors’ findings that among women with a history of VTE who are currently anticoagulated, hormonal contraception does not increase recurrent VTE risk.”
Because the procoagulant effects of estrogen may not resolve for a number of weeks after stopping the medication, clinicians maintaining anticoagulated patients on combination contraceptives should stop such methods some six weeks prior to discontinuing anticoagulation, says Kaunitz.
- Martinelli I, Lensing AW, Middeldorp S, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood 2016; 127(11):1417-1425.
- Jick H, Jick SS, Gurewich V, et al. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346(8990):1589-1593.
- World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Venous thromboembolic disease and combined oral contraceptives: Results of international multicentre case-control study. Lancet 1995; 346(8990):1575-1582.
- Spitzer WO, Lewis MA, Heinemann LA, et al; Transnational Research Group on Oral Contraceptives and the Health of Young Women. Third generation oral contraceptives and risk of venous thromboembolic disorders: An international case- control study. BMJ 1996; 312(7023):83-88.
- Buller HR, Prins MH, Lensin AW, et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366(14):1287-1297.
- Bauersachs R, Berkowitz SD, Brenner B, et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363(26):2499-2510.
- Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use. Morb Mortal Wkly Rep MMWR 2010; 59(RR04):1-86.