ORAL CONTRACEPTIVES AND SLE

Combined Oral Contraceptive Use Linked to Risk for Systemic Lupus Erythematosus

April 13, 2009 — Use of combined oral contraceptives (COCs) is linked to increased risk for systemic lupus erythematosus (SLE), according to the results of a population-based, nested case–control study reported in the April 15 issue of Arthritis Care & Research.

"Endogenous hormonal factors are believed to play an important part in the etiology of SLE," write Marie-Odile Bernier, MD, MSc, from McGill University in Montreal, Quebec, Canada, and colleagues. "Estrogen contained in contraceptives has been also questioned.... However, the role of exogenous estrogen as a trigger of SLE remains controversial because studies of the link between exogenous hormonal exposure and SLE risk have produced conflicting results."

The study population consisted of women aged 18 to 45 years identified from the United Kingdom's General Practice Research Database (GPRD). From 1994 to 2004, there were 786 patients with SLE found in the database and matched with up to 10 control individuals (n = 7817) among women without SLE at the time of the diagnosis of the patient with SLE.

The adjusted rate ratio (RR) of incident SLE associated with any use of COC was 1.19 (95% confidence interval [CI], 0.98 – 1.45). For current use of COC, adjusted RR was 1.54 (95% CI, 1.15 – 2.07). Current users who had only recently started COC use had a higher RR than did longer-term current users (RR, 2.52; 95% CI, 1.14 – 5.57 vs RR, 1.45; 95% CI, 1.06 – 1.99). Current exposure to first- or second-generation contraceptives was associated with especially increased risk (RR, 1.65; 95% CI, 1.20 – 2.26). Risk increased further with increasing dose of ethinyl estradiol (RR, 1.42, 1.63, and 2.92 for ≤30 µg, 31 – 49 µg, and 50 µg, respectively).

"The use of COCs is associated with an increased risk of SLE," the study authors write. "This risk is particularly elevated in women who recently started contraceptive use, suggesting an acute effect in a small subgroup of susceptible women."

Limitations of this study include lack of data on racial and socioeconomic status; incomplete information on gynecologic history, which could be a potential confounding factor; and lack of systematic collection of information concerning smoking or drinking habits.

"Although COC use may be associated with a significant increased risk of incident SLE, some have argued that the low relative risk of ~2 is probably insufficient to explain the 9:1 sex ratio in this disease," the study authors write. "Thus, although our findings add considerably to the existing literature, further studies on the acute effects of COCs will be needed to better identify the characteristics of women susceptible to developing SLE when exposed to COCs."