Women’s reproductive factors and the risk of rheumatoid arthritis

Study suggests prolonged preventive effect of breastfeeding and links irregular menstrual cycles to increased risk of disease

Rheumatoid arthritis (RA), an inflammatory disease of the immune system, is between two and four times more likely to strike women than men. Among women, RA is more likely to develop when reproductive hormonal levels are changing, such as in the first few months following a pregnancy and around the time of menopause. Although previous researchers have studied this topic, the relationship between hormones and the risk of developing RA remains unclear.

Seeking more conclusive evidence, a team of researchers led by Elizabeth Karlson, M.D. at Brigham and Women’s Hospital in Boston drew on a large sample – 121,700 women – to explore the contribution of hormonal factors occurring prior to the onset of RA and the impact of postmenopausal hormone replacement therapy on the risk of disease. Their findings, published in the November 2004 issue of Arthritis & Rheumatism, strongly support the lasting benefits of breastfeeding in protecting against the disease. What’s more, the researchers identified a new risk factor for RA: irregular menstrual cycles.

The study’s subjects were all women enrolled in the Nurses’ Health Study, a sweeping investigation of disease, health, and lifestyle, ongoing since 1976. Through extensive questionnaires, the research team documented each woman’s reproductive history with attention to potential RA risk factors, including age at menarche, age at first birth, history of breastfeeding, use of oral contraceptives, and regularity of menstrual cycles and in older women studied the use of estrogen after menopause. Among these women, the researchers confirmed 674 RA patients, diagnosed anywhere between 1976 and 2002. Most of the women were middle-aged at disease onset; the mean age was 56 years.

Upon analyzing the data, adjusting for variables such age and cigarette smoking, the researchers noted several interesting trends. One of the strongest was a decreasing risk of RA with increasing duration for breastfeeding. Looking at total lifetime breastfeeding, regardless of number of children, women who had breast-fed for between 13 and 23 months had a 20 percent reduction in the risk of RA compared with women who did not breastfeed. Women who had breast-fed for at least 24 months – two full years out of their childbearing years – increased their risk reduction to 50 percent. “Our data suggest breast-feeding confers long lasting protection against developing RA,” Dr. Karlson states, “because the mean time since the last pregnancy among women with RA was 25 years.” In addition, women who experienced irregular menstrual cycles between the ages of 20 and 35 were shown to have an increased risk of subsequent RA. Women who had begun menstruating at an early age, 10 or younger, were more likely to develop seropositive RA. The study’s results did not show any association between a history of oral contraceptive use and disease risk, or any significant differences in disease risk related to a woman’s number of pregnancies.

Focusing on the sample of RA patients, compared to women who did not develop RA, the researchers confirmed that the risk of RA increases with age and demonstrated a peak risk at the typical time of menopause, age 50 to 54. Because the onset of RA often coincides with menopause, some studies have linked the disease to falling estrogen levels, indicating the potential benefits of estrogen therapy. In this study, however, estrogen therapy among postmenopausal women did not protect against RA. “These findings suggest avenues for further research into the hormonal mechanisms involved in RA, because the complex relationships between RA and reproductive hormones clearly warrant further study,” Dr. Karlson concludes.