Oral Contraceptives in Women with Systemic Lupus Erythematosus

A systematic review and meta-analysis 3 evaluated the risks associated with estrogen use for women with SLE. 20 full-text articles were included and 32 meta-analyses were developed. One of 11 meta-analyses evaluating the risk for SLE associated with oral contraceptives (OC) exposure had a marginally significant result. However, women with high disease activity/thromboses or antiphospholipid-antibodies were excluded from most of the studies. There were no associations between hormonal replacement therapy (HRT) or OC exposure and specific outcomes of SLE. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration. A significant association between HRT exposure and an increased risk of developing SLE was found (RR 1.96, 95% CI 1.51 to 2.56; P-value<0.001).

In an RCT 1 183 women with inactive or stable active SLE were assigned to receive either oral combined contraceptives (COC; ethinyl estradiol 35 µg + norethindrone 0.5 to 1 mg) or placebo. Patients with moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis were excluded. The primary end point, a severe lupus flare, occurred in 7/91 subjects receiving COC as compared with 7/92 subjects receiving placebo. The 12-month rates of flare were similar. In the COC group there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial).

In a single-blind clinical trial 2 162 Mexican women with SLE were randomly assigned to COC (ethinyl estradiol 30 µg + 150 microg levonorgestrel), a progestin-only pill (levonorgestrel 30 µg), or a copper intrauterine device (IUD). During the 12-month trial, there were no significant differences among the groups in the primary outcome (the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] score), in global or maximum disease activity, incidence or probability of flares, or medication use. Thromboses occurred in four patients (two in each of the two groups receiving hormones), and severe infections were more frequent in the IUD group.

Comment: The grade of evidence was downgraded by indirectness (short duration of the studies) and low numbers of adverse events.

References

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• Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, Mestanza-Peralta M, Lara-Reyes P, Seuc AH, Cravioto MD. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005 Dec 15;353(24):2539-49. [PubMed]
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