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Reproduction, Menopause and Lupus

Like many autoimmune diseases, the cause of systemic lupus erythematosus (SLE, lupus) is unknown, but it is thought that environmental factors trigger the disease in genetically predisposed people. Eighty to 90 percent of people with lupus are women, and reproductive and menopausal factors may play an important role in its development in women.

What Problem Was Studied?

Arthritis Foundation-funded researcher Karen H. Costenbader, MD, MPH, and colleagues at Brigham and Women's Hospital in Boston sought to examine possible associations between reproductive factors, menopause and the development of lupus in women. Several different associations had been identified in small studies, but those associations were not consistent. Dr. Costenbader and team wanted to look at a large group of women over time to determine similarities among the women who developed lupus during the course of the study.

The team evaluated two large cohorts of women. The Nurses' Health Study (NHS) includes 121,700 female nurses (age 30 to 55 years in 1976 when the study began) and the second NHS (NHSII) includes 116,608 female nurses (age 25 to 42 years in 1989 when the study began). Of the total available questionnaires, 3,958 women reported a doctor's diagnosis of lupus and 14,282 women reported having another connective tissue disease. After screening out women who did not have a confirmed diagnosis of lupus, 262 cases of lupus were newly diagnosed between 1976 and 2003.

The research team then examined information from those 262. This information, collected before the onset of their lupus, included age at first menses, age at first pregnancy, number of pregnancies, length of breastfeeding, use of oral contraceptives, age at menopause, use of hormone replacements, etc. The data were analyzed and statistical associations were determined.

What Were the Study Results?

The incidence of lupus among this large cohort was ~6 per 100,000 person-years of follow-up. This rate is consistent with recent estimates of lupus in U.S. women. Early age of menarche (age at first period of 10 years or younger) was associated with a doubled risk of lupus compared with women who got their first period at age 12 or older. Women who underwent natural menopause before age 47 were at greater than twice the risk of developing lupus than women who experienced menopause at age 53 or older. Estrogen use (either oral contraceptives or postmenopausal hormone replacement) also significantly elevated a woman’s risk of developing lupus. The authors note, however, "we did not find any association between number of ovulatory years and the risk of SLE, suggesting that it may not be duration of estrogen exposure, but rather the timing of estrogen exposure, that is related to SLE risk."

What Does This Mean for Women?

These results provide scientists valuable information regarding the possible mechanisms underlying the cause of lupus. They do not, however, suggest that women alter their use of oral contraceptives or hormone replacement therapy. The results also do not answer the question of why women get lupus so much more frequently than men.

Costenbader KH, Feshanich D, Stampfer MJ, et al. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum 2007;56:1251-62.

Epidemiology Basics

Incidence: The number of new cases of disease occurring in a population during a defined time interval.

Person-years: The number of people studied multiplied by the number of years of data available.

News of Note from EULAR

A study released at the 2007 European League Against Rheumatism Annual Congress in June showed that 36 percent of people with lupus who did not respond to standard therapy found benefit from B-cell depletion therapy using rituximab, and remained well for up to six months without additional standard immunosuppressive therapy. Although these results were preliminary and not based on a double-blind trial, the researchers are encouraged, "They show that B-cell depletion therapy is a promising therapeutic option for lupus patients who have a historically difficult to treat disease, and potentially could minimize the need for continuous immunosuppressive therapy."


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