After four decades of steady decline, the number of new cases of rheumatoid arthritis in women has started to inch up, a finding that leaves researchers puzzled.

A study carried out by a team at the Mayo Clinic in Rochester, Minn., determined that while the incidence of rheumatoid arthritis in men dropped slightly from 1995 to 2007, it increased by 2.5 percent a year in women. “This modest but statistically significant rise is unlikely to have occurred by chance alone,” says epidemiologist Sherine Gabriel, M.D., lead author of the study.

The Mayo team had previously analyzed trends from 1955 to 1994 among people living in Olmsted County, Minn., and found a steady drop in the number of cases of rheumatoid arthritis in both men and women. For this study they screened the records of 1,761 patients over age 18 who had received a diagnosis of arthritis. After reviewing the medical reports, a diagnosis of rheumatoid arthritis was made in 145 men and 321 women with an average age of 56 years.

Although it’s not clear why the rate of rheumatoid arthritis is rising among women, the researchers speculate that environmental factors are the likely cause. About 1.3 million Americans have rheumatoid arthritis—two and a half times as many women as men, according to the Arthritis Foundation.

Cigarette smoking is unquestionably associated with the development of rheumatoid arthritis and is perhaps the strongest environmental villain. While smoking rates are falling for both sexes, the rate of decline is significantly slower in women than men, which may help explain the upsurge of the disease in women. “Here’s yet another reason not to smoke,” says Gabriel. “As if we needed any more.”

The researchers also note that lower doses of synthetic estrogens found in modern oral contraceptives offer less protection against the development of rheumatoid arthritis than the higher doses found in older medications.

Further, the authors point to evidence that suggests vitamin D deficiency has a role to play in the development of rheumatoid arthritis. Coupled with reports that a growing number of adults, especially women, lack sufficient vitamin D, the Mayo researchers consider it a possible contributor to rising rates among women.

“Rheumatoid arthritis is a complicated disease caused by both genetic and environmental influences,” says University of California, San Diego rheumatologist Gary Firestein, M.D., who was not associated with the research. “These observations are extremely important because they provide clues that will allow us to understand the kinds of environmental changes that make people susceptible to developing the disease.”

The study appeared in the June issue of Arthritis & Rheumatism.

Nissa Simon is a freelance writer who lives in New Haven, Conn.