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 a role in their risk of developing RA. Females are almost three times more likely than males to have RA, according to the journal BMC Medicine.

This inflammatory disease can lead to joint damage over time. This damage is caused by antibodies attacking healthy joints and tissues — the way the immune system would attack invaders in the body. A combination of factors appears to increase a person’s risk of developing RA. These include genetics, hormones, and excess body weight.

Sex Differences in RA and Autoimmune Diseases

Nearly 80 percent of autoimmune conditions, such as RA, occur in females, according to the journal Nature Reviews Immunology. These conditions also include other types of arthritis — such as osteoarthritis — and rheumatic diseases such as systemic lupus erythematosus and systemic sclerosis.

Researchers have found several reasons why females are more likely to develop RA than their male counterparts.

Stronger Immune Response

Research suggests that females have stronger immune system responses than males, according to Nature Reviews Immunology. This means that sometimes females can clear infections more quickly than males. However, a heightened immune response may also mean females’ immune systems are more likely to attack healthy tissues, putting them at a higher risk of developing autoimmune conditions like RA.

Hormonal Changes

The main sex hormone in biological females is estrogen, which helps 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 might play a role in how RA develops and progresses.

A 2019 review of studies in the Journal of Rheumatology found that rheumatoid arthritis symptoms improved in 60 percent of people while they were pregnant — and then worsened in 46 percent of people postpartum (after giving birth). Researchers suggested that changes in hormone levels during and after pregnancy were responsible for changes in the severity of RA symptoms.

Other research suggests that hormonal changes from pregnancy can affect a person’s risk of developing RA. For example, the Centers for Disease Control and Prevention (CDC) notes that women who’ve never given birth may have a greater risk of developing RA. The CDC also notes that women who breastfeed their children have a lower risk of developing RA.

Other changes that affect estrogen levels may have a large influence on RA. During menopause, your estrogen levels drop, potentially leading to increased levels of inflammation. One study from 2012 found that women who went through menopause early had a higher risk of developing RA. 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 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, 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.

Women tend to have wider hips than men, according to the Hospital for Special Surgery, and they have hip joints that are set at different angles than men’s. This difference in hip structure helps in giving birth. However, if a person’s hip bones are wider than their knees, it can cause stress on their joints.

Females’ joints are also more flexible than males’, according to Nepal Medical College Journal, due to the makeup of their muscles and connective tissue. This flexibility may make their joints more prone to damage, which inflammation can worsen.

General Risk Factors Associated With RA

Some factors can increase a person’s risk for developing RA, regardless of their sex.

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. Other factors include exposure to certain types of fibers or dust and to bacterial or viral infections.

Sex Differences in Symptoms of RA

Research studies have found that females are more likely to have worse RA symptoms than males do. In one study, rheumatologists found that women had worse RA disease activity than men, as measured by tools like an RA disease activity score, the presence of rheumatoid factor, rheumatoid nodules, deformities, and the use of DMARDs.

Another research study found sex differences in RA disease severity and rates of remission. Researchers found that women had worse disease severity and lower rates of RA remission as compared to men. However, not all research on this topic is in agreement, and getting an objective measure of RA disease activity can be difficult.

Talk to Your Doctor

Overall, regardless of your sex, you should talk to your health care provider or rheumatologist if you feel like your RA is affecting your quality of life. They can help determine more effective treatments and work with you to minimize the impacts of RA on your daily life. If you’re at a high risk of developing RA, it’s also a good idea to talk to your doctor. They can suggest ways to reduce your risk of RA that are suitable for you.

Talk With Others Who Understand

On myRAteam, the social network for people with rheumatoid arthritis and their loved ones, more than 197,000 members come together to ask questions, give advice, and share their stories with others who understand life with RA.

Are you a woman living with RA? Have you found that any of the risk factors discussed in this article contributed to your RA? Share your thoughts and experience in the comments below, or start a conversation by posting on myRAteam.