Research signals safety of Pill use in lupus

Women with inactive or stable systemic lupus erythematosus — a disease in which the body’s immune system mistakenly attacks and damages healthy tissues of the skin, joints and internal organs — need effective contraception When women with inactive or stable systemic lupus erythematosus need effective contraception, clinicians rarely prescribe oral contraceptives (OCs) due to fears that the Pill might increase disease activity.

Results of two separate studies indicate that women with inactive or stable forms of the disease are able to use oral contraceptives without increased risk of flares that characterize the disease.1,2 The research provides prospective data that support the use of combined pills by those with inactive or moderately active, stable disease, according to an editorial accompanying the two publications.3

The Lupus Foundation of America estimates about 1.5 million Americans have some form of lupus. Although lupus can strike men and women of all ages, 90% of those diagnosed with the disease are women; 80% of those with systemic lupus develop it between the ages of 15 and 45.4

Women with lupus have the same needs as any other young women when it comes to contraception, says Jorge Sanchez-Guerrero, MD, head of the department of immunology and rheumatology at the National Institute of Medical Sciences and Nutrition in Mexico City and lead author of one of the studies.

With advances in treatment, women with inactive or stable lupus erythematosus are able to do anything they want, such as have a career and/or become a mother, because the prognosis of the disease is excellent, he says. However, when the disease is active, rheumatologists advise that patients wait until the disease is quiescent and disease activity is stable in order to become pregnant, because disease manifestations may be dangerous to the woman and the fetus, says Sanchez-Guerrero.

Is estrogen a concern?

Since effective contraception is so important for women with lupus, why have clinicians been hesitant to prescribe combined oral contraceptives?

In a study of mice with the disease, estrogen worsened the disease,5 says Michelle Petri, MD, MPH, professor in the division of rheumatology in the department of medicine at Johns Hopkins University in Baltimore and lead author of one of the current research papers. In humans with lupus and lupus kidney disease, a past study showed that oral contraceptives made the kidney disease flare up,6 she notes.

To perform the multicenter study, which was funded by the National Institutes of Health (NIH), scientists randomized 183 ethnically diverse young women with inactive or stable lupus to receive a combination OC or placebo. During a year of treatment, the two groups had nearly identical rates of severe disease flare and mild or moderate flare. Two thrombotic events occurred in the OC group, and three occurred in the placebo group.2

In the study led by Sanchez-Guerrero, which was funded by the World Health Organization, researchers looked at outcomes among 162 young women with lupus who were randomly assigned to use a combination pill, a progestin-only pill, or a copper intrauterine device. During a year of treatment, rates of overall flare and severe flare were similar in all three groups. Scientists recorded two thrombotic events in each pill group; low titers of antiphospholipid antibodies were found in all four patients. One woman in the combined pill group died from amoxicillin-related neutropenia during the study.1

What’s the next step?

The NIH-funded study is one of two separate randomized, placebo-controlled studies designed to examine the safety of estrogens in women with lupus erythematosus. Results from the other study, which looked at use of in hormone replacement therapy in postmenopausal women, indicated no increased risk of severe flares in the study group.7

For most women with moderate lupus that is inactive or stable, combined OCs appear to have no detrimental effect on disease activity, conclude researchers in the two current studies. However, both sets of researchers note that oral contraceptives are not advised for women who have a history or at high risk for venous thrombosis, because estrogen has have been associated with dangerous blood clots.

More research will need to focus on use of combined OCs in women with severe active systemic lupus erythematosus, because neither study included these women in the study groups. Whether combined OCs can be used safely in this subgroup has yet to be determined, notes the editorial accompanying the two publications.3

References

  1. Sanchez-Guerrero J, Uribe AG, Jimenez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005; 353:2,539-2,549.
  2. Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353:2,550-2,558.
  3. Bermas BL. Oral contraceptives in systemic lupus erythematosus — a tough pill to swallow? N Engl J Med 2005; 353:2,602-2,604.
  4. Lupus Foundation of America. Statistics About Lupus. Fact sheet. Accessed at: www.lupus.org/education/stats.html.
  5. Roubinian J, Talal N, Siiteri PK, et al. Sex hormone modulation of autoimmunity in NZB/NZW mice. Arthritis Rheum 1979; 22:1,162-1,169.
  6. Jungers P, Dougados M, Pelissier C, et al. Influence of oral contraceptive therapy on activity of systemic lupus erythematosus. Arthritis Rheum 1982; 25:618-623.
  7. Buyon JP, Petri MA, Kim MY, 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.

Resources

New research indicates that women with inactive or stable forms of systemic lupus erythematosus are able to use oral contraceptives without increased risk of flares that characterize the disease.

  • When women with inactive or stable systemic lupus erythematosus need effective contraception, clinicians rarely prescribe oral contraceptives (OCs) due to fears that the Pill might increase disease activity.
  • More research is needed on use of combined oral contraceptives in women with severe active systemic lupus erythematosus, because the new studies did not look at this subgroup.