Systemic Lupus Erythematosus and Contraception
Abstract & Commentary
By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: Estrogen-progestin oral contraceptives do not increase disease activity in women with mild to moderate, stable systemic lupus erythematosus.
Source: Sanchez-Guerrero J, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2539-2549.
In a clinical trial conducted in Mexico City, 162 women with systemic lupus erythematosus were randomized to treatment with 1 of 3 contraceptive methods: estrogen-progestin oral contraceptives, oral progestin-only, or a copper IUD. Disease activity remained equally mild and stable over 1 year in all 3 groups. There were no differences in the use of antiinflammatory drugs. There were 4 cases of lower-limb thromboses, 2 in the group receiving oral contraceptives and 2 with progestin-only pills. All 4 had low titers of antiphospholipid antibodies. The authors concluded that estrogen-containing contraceptives do not exacerbate systemic lupus erythematosus.
The NIH-supported OC-SELENA (Safety of Estrogens in Lupus Erythematosus National Assessment) trial was a double-blind, randomized trial of 183 women with stable systemic lupus erythematosus treated either with a 35 mg ethinyl estradiol oral contraceptive or placebo and followed for 1 year.1 Patients were excluded if they had elevated levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. Lupus flares, the primary end point, occurred equally in the 2 groups. Venous thrombosis did not occur more frequently in the oral contraceptive group. The authors concluded that low-dose, estrogen-progestin oral contraceptives can be used by patients with inactive or stable, moderate systemic lupus erythematosus who are at low risk for thrombosis.
These studies are important for at least 2 good reasons. First, there has been a general clinical impression that exogenously administered estrogens would increase lupus disease activity. Second, there are important effects of oral contraceptives that would be beneficial for patients with lupus. These beneficial effects include: 1) Contraception is a chief component of care for lupus patients because pregnancy outcome is adversely affected by unstable, active disease; 2) Patients with lupus experience major bone loss and an increase in fractures as an unwanted side effect of their medical treatment; and 3) Estrogen-progestin contraceptives may moderate the intensity of lupus.
The SELENA trial had another arm, one with estrogen-progestin therapy in postmenopausal women. The trial was ended prematurely in August 2002 by the NIH in response to the publications of the Women’s Health Initiative. The results in postmenopausal women were reported for 1 year of treatment in 351 women with lupus.2 Severe flares were not increased by the treatment, and there was a slight increase in mild to moderate flares. In actual numbers, 59% of treated patients had an increase compared with an increase noted in 50% of placebo patients, a small difference. There was no evidence of worsening of SLE in the treated group. The investigators emphasized that the most meaningful finding clinically was the lack of an increase in the rate of severe flares.
The results of these studies are reassuring. Postmenopausal hormone therapy and oral contraceptives can be considered in patients with stable or inactive disease, without renal involvement and high antiphospholipid antibodies. Patients with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis were excluded from the SELENA study. If hormone therapy is to be provided to these patients, some form of chronic anticoagulation should be considered (such as statins or low-dose aspirin).
- Petri M, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2550-2558.
- Buyon JP, et al. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. 2005;142:953-962.