A 2010 study showed that for the first time in 40 years, the number of new cases of rheumatoid arthritis (RA) in American women appeared to be on the rise.

Researchers say they don’t know exactly what’s behind the recent uptick – the number of new cases appears to have increased by about 2.5 percent between 1995 and 2007 – but they think environmental factors may be to blame.

“It was a statistically significant observation, which means it is unlikely to have occurred by chance alone,” explains lead author Sherine Gabriel, MD, a professor of medicine and epidemiology at the Mayo Clinic in Rochester, Minn.

For the study, published in Arthritis & Rheumatism, Dr. Gabriel and her team sorted through medical records of 1,761 patients older than age 18 who had been diagnosed with arthritis. They found 466 of those patients were diagnosed with RA, and 69 percent of them were women. And while rates were increasing each year among women, they fell 0.5 percent a year among men.

This is an observational study, so while researchers were able to track the population over a long period of time, the data didn’t allow them to determine a cause for the difference in rates among women and men; and they don’t know exactly why more women are getting the inflammatory condition.

But they can make a few educated guesses about the increase.

“There are only two broad reasons for such a change – genetic or environmental,” Dr. Gabriel explains. “Genetic changes do not happen that quickly, as it takes many generations to change the gene pool. So it is much more plausible to assume an environmental factor.”

Scientists say there is evidence in published literature suggesting three environmental factors may increase the risk of RA.  The most obvious is cigarette smoking. Researchers say while fewer people in the U.S. are smoking than years past, women are stopping at a slower rate than men – which might account for the higher RA rates among women.

Ted Mikuls, MD, an associate professor in the division of rheumatology at the University of Nebraska Medical Center in Omaha, wrote an editorial accompanying the study stressing the importance of figuring out why RA is on the rise in women. He says there is strong data showing that smoking is one good possibility.

“It’s well known, and it probably increases risk by between 60 and 80 percent. It’s a significant risk factor. There have been changes in smoking rates, particularly in women and that’s the group in which we really see this increase. Women are smoking more than they used to,” Dr. Mikuls says. But, he adds, “is that the explanation for this? It’s really speculation.”

Another possible environmental factor, researchers say, is vitamin D deficiency. Several studies have shown it could also be a cause of RA, and more people have developed this condition in recent years, especially women.

Newer oral contraceptives are another possibility. They contain less estrogen than older pills. Researchers think estrogen has a protective effect against the development of RA, so reducing it may lead to a greater risk of developing the condition and may account for differences in rates between men and women.

“There’s some data that oral contraceptives influence the risk of getting RA,” Dr. Mikuls says, but he adds, “that’s not been as consistent a relationship as we’ve seen with smoking. “

Researchers admit there may also be other factors at play like infections, immunizations, obesity or socioeconomic status or other causes they haven’t identified yet.

While the medical community tries to pin down exact reasons for this increase, Dr. Mikuls says he’d like to see what the data looks like over even more time.

“It would be nice to see where this is going to go,” Dr. Mikuls says. “But it’s interesting and it’s a cautionary tale that it may be on the rise.”

And Dr. Gabriel says despite the unknowns, there is something to be learned from this study for people at risk for RA because their relatives have it.

“It is likely that environmental factors affect your RA risk,” she says. “Smoking certainly does – another reason not to smoke. Vitamin D deficiency may, so be checked for this. Hormonal factors may also play a role. Talk to your doctor about what you can do to decrease your risk.”