Rheumatoid arthritis (RA) is an autoimmune disease that causes the body’s immune system to attack the lining of the joints (the synovium). A person’s biological sex plays into their risk levels. Being biologically female means you are almost 3 times more likely than a biological male to have RA.

This inflammatory disease can lead to joint damage over time, caused by antibodies that attack healthy joints and tissues like the immune system would attack invaders in the body. This overactive immune system is likely caused by genetics, hormones, and excess body weight. Together, these factors may contribute to a person’s increased risk of developing RA.

Sex Differences in RA and Autoimmune Diseases

Nearly 80 percent of autoimmune conditions such as RA occur in people who are biologically female. These conditions include other types of arthritis — such as osteoarthritis — and conditions such as systemic lupus erythematosus and systemic sclerosis. Research has found there may be several reasons why females are more likely to develop RA or other related conditions than their male counterparts.

Stronger Immune Response

Research suggests that biological females have immune responses that are stronger and help them clear infections more quickly than males. However, this immune response may also mean that their immune systems are more likely to attack their healthy tissues, putting them at a higher risk of developing conditions like RA.

Hormonal Changes

The main sex hormone in biological females is estrogen, which has been found to help control inflammation in the body. Beginning in the 1940s, doctors noticed that RA symptoms improved in people who were pregnant. This finding led to the idea that hormones could play a role in the development and progression of RA. A 2019 study from the Journal of Rheumatology found that RA symptoms improved in 60 percent of pregnant people.

Other findings further suggest that hormonal changes caused by pregnancy can affect a person’s risk of developing RA. For example, biological females who have never given birth may have a greater risk of developing RA, while those who breastfeed their children are at a lower risk of developing RA.

Besides pregnancy, other changes that affect estrogen levels may have a large influence on RA. For example, many people are diagnosed with RA after they go through menopause, when estrogen levels drop and potentially lead to increased levels of inflammation. Other conditions associated with estrogen levels that can make RA worse include endometriosis and polycystic ovarian syndrome (PCOS).

Obesity and Body Fat

According to the Centers for Disease Control and Prevention (CDC), severe obesity is more common in women than in men (11.5 percent compared to 6.9 percent, respectively). Obesity is also linked to an increased risk of developing RA.

Fat accumulation can lead to more inflammation in a person’s body. Fat stores release hormones known as adipokines that can affect the immune system and make inflammation and joint pain much worse.

Besides increasing the risk of RA, excess weight and fat can also affect how well medications work in treating RA. Certain biologics and disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, may not work as well for treating RA in people who are obese. Maintaining a healthy weight can reduce inflammation while allowing treatment to work. A healthy weight can also help prevent other complications from developing, such as heart disease and diabetes.

Joint Flexibility and Positioning

Another factor that can contribute to a person’s increased risk of developing RA is their anatomy.

People who are biologically female tend to have wider hips than their male counterparts. This allowance to facilitate childbirth means that the sexes have hip joints that are set at different angles. If a person’s hip bones are wider than their knees, it can cause stress on their joints. The joints of females are also more flexible overall due to the makeup of their muscles and connective tissue. This flexibility may make their joints more prone to damage, which can then be exacerbated by inflammation.

General Risk Factors Associated With RA

There are some risk factors that the two sexes share.

Genes play a large role in the risk of developing RA. Specifically, variations in the human leukocyte antigen (HLA) genes can influence the immune system. The proteins made from HLA genes help the immune system tell the difference between normal, healthy proteins from the body and proteins from pathogens (germs and invaders). Family history of RA can also increase the risk of developing the condition.

In combination with genetics, some environmental factors can contribute to the risk. These factors include smoking and early exposure to secondhand smoke as a child. One study found that children who grew up in households with smoking people were twice as likely to develop RA when they became adults. Other factors can include exposure to certain types of fibers or dust and bacterial or viral infections.

Talk With Others Who Understand

On myRAteam, the social network for people with rheumatoid arthritis and their loved ones, more than 174,000 members come together to ask questions, give advice, and share their stories with others who understand life with RA.

Have something to add to the conversation? Share your thoughts and experience in the comments below, or start a conversation by posting on myRAteam.