Hormone Replacement Therapy Does Not Increase Severe Lupus Flares

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The summary below is from the full report titled "The Effect of Combined Estrogen and Progesterone Hormone Replacement Therapy on Disease Activity in Systemic Lupus Erythematosus: A Randomized Trial." It is in the 21 June 2005 issue of Annals of Internal Medicine (volume 142, pages 953-962). The authors are J.P. Buyon, M.A. Petri, M.Y. Kim, K.C. Kalunian, J. Grossman, B.H. Hahn, J.T. Merrill, L. Sammaritano, M. Lockshin, G.S. Alarcón, S. Manzi, H.M. Belmont, A.D. Askanase, L. Sigler, M.A. Dooley, J. Von Feldt, W.J. McCune, A. Friedman, J. Wachs, M. Cronin, M. Hearth-Holmes, M. Tan, and F. Licciardi.

What is the problem and what is known about it so far?

People with systemic lupus erythematosus (lupus) have antibodies that react against their tissues and organs. They may have a variety of findings and symptoms, including skin rashes that are worsened by sunlight, swollen and painful joints, ulcers in the nose or mouth, fatigue, fever, and inflammation of the lining around the lungs (pleuritis) or heart (pericarditis). Typically, symptoms flare up intermittently for a few weeks and then become less severe, sometimes for months or years.

We do not know what causes lupus, but it is much more common among women than men. It occurs most often after menarche and before menopause. Thus, some doctors think that estrogen hormones may play a role in activating the disease. Because of this belief, they may not recommend hormone replacement therapy (HRT) in menopausal women with lupus.

Why did the researchers do this particular study?

To see whether HRT increases disease activity and flares in menopausal women with lupus.

Who was studied?

351 menopausal women with inactive or stable lupus (average age, 50 years). None had a history of blood clots in their legs or lungs.

How was the study done?

Women were randomly assigned to HRT or a dummy pill (placebo). HRT consisted of conjugated estrogen (0.625 mg daily) and medroxyprogesterone (5 mg daily for days 1 through 12 of each month). Neither the women nor their doctors were told who received HRT or placebo. The researchers followed women monthly for 3 months and every 3 months thereafter for 1 year. At each visit, they asked women about symptoms and did tests to assess disease activity.

What did the researchers find?

Severe flares of disease were infrequent in both groups, and were not increased in women taking HRT. Women taking HRT had mild to moderate flares of disease slightly more often than did women taking placebo. Four women taking HRT and 1 taking placebo developed some type of blood clot during the trial.

What were the limitations of the study?

Women taking HRT for long periods have increased risk for adverse effects, such as blood clots, strokes, heart attacks, and breast cancer. This trial was too small to assess those risks, and it was stopped early by researchers when other studies showed those risks. In addition, women in this trial had inactive or stable lupus; those with very active lupus could not enter the trial until their disease was under better control.

What are the implications of the study?

HRT given for 1 year does not increase the risk for severe lupus flares but does slightly increase the risk for mild to moderate flares in menopausal women with lupus.