Rheumatoid Arthritis Affects Women Differently Than Men

Differences, Causes, Research, and What Differences Mean

In This Article

More women have rheumatoid arthritis (RA) than do men. Prevalence studies from all over the world show women are about three times more likely to have RA. The disease also affects the sexes differently.

The answers to why gender differences exist in RA are still unclear, but researchers are continually working to bring these reasons to light. In fact, research to date has revealed factors and characteristics that may explain these differences, including differences in hormone production, genes, physiological features, gender-based roles, and behavioral expectations.

Woman holding her wrist symptomatic
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Causes

It is believed women get RA in greater numbers than do men for two main reasons—sex hormones and their stronger response to infections, vaccinations, and environmental triggers. Environmental triggers may include stress, the roles women play, and how they respond to external toxins.

Sex Hormones

Researchers believe that because women produce estrogen, they are at a higher risk for RA. In fact, research shows high estrogen levels can force a woman’s body to go awry and attack itself in a misdirected immune system response called autoimmunity.

Sex hormones play a role in B cell development. These B cells are known for causing dysfunction in the immune system’s responses.

Researchers have long known that estrogen heightens B cell isolation and increases the production of antibody proteins—called immunoglobulins (Ig)—that generally would help the immune system fight off bacteria, viruses, and harmful invaders. Too much immunoglobulin is a sign of autoimmune diseases like RA.

Genes

Genetic differences in men and women may explain why women are more likely to develop RA. Most studies allude to the idea that men and women have completely different cells throughout their bodies despite having similar tissues.

This is better explained by a 2012 report out of the University of Manchester UK that suggested X chromosomes play a big role in the development of RA and because women have two of these, making their risk for RA and other autoimmune diseases greater.

This was the first time a genetic association was established between RA and X chromosomes, leading the research team to conclude this was key towards understanding why RA is affecting women at higher rates than men.

In addition to sex hormones and genetics, some environmental factors, and how women respond to stressful situations and events may contribute to the development of RA.

Environment

Researchers are now paying more attention to the role environmental factors play in the development of RA. It is possible exposure to external toxins, including those specific to women, such as products women use and are exposed to in greater frequency (hair dyes and makeup) may increase risk.

One 2013 review of studies on sex-specific environmental influences finds cosmetic exposure in women is quite common. This includes the use of permanent hair dyes, other hair products, and make-up, and exposure in women who work as hairdressers and nail technicians.

Stress

Stress affects the way the body manages its immune response. In fact, autoimmunity can result because stress alters the ability of cortisol to regulate inflammation. Studies repeatedly have shown women and men report different reactions to stressors, with women more likely to report physical symptoms associated with stress.

With RA, researchers speculate that because women process stressors differently than do men, reduced cortisol encourages inflammation rather than inhibiting it.

In fact, a study reported in 2013 by the journal Arthritis Research & Therapy found stressful events can lead to the development of RA and once a person has RA, stress was associated with a less positive outlook and a higher sensitivity to stressful events.

Disease Experience—Women vs. Men

RA tends to be a more painful experience for women, even though men and women experience the same visible symptoms. Gender tends to affect several aspects of the disease, including presentation and severity, quality of life, and risk for shortened lifespan.

Disease Severity and Presentation

Women with RA tend to experience a more aggressive disease, higher levels of disease activity, and higher incidences of disability.

One study reported in 2019 in The Scientific World Journal aimed to compare the clinical characteristics of men and women with RA to determine if differences existed between the genders and offer explanations as to these differences.

The cross-sectional study included 50 men and 50 women from a rheumatology center in Ecuador. The researchers collected data on “clinical manifestations, comorbidities, treatment, and disease activity,” and tried to access any differences that existed between the two genders.

The researchers also examined lifestyle factors that could potentially explain these differences. What they found was that even though women were more engaged in housework­—66% of the women—and that men were consuming more tobacco (33%) and alcohol (38%), women were still experiencing more severe fatigue (60%), loss of appetite (54%) and weight loss (44%) than were the men in the study. No differences related to comorbidities (co-existing conditions) and treatment were found.

The women in the study had higher values for painful and swollen joints and overall physician assessment. The researchers concluded the results were similar to other studies showing women experiencing more aggressive disease, higher disease activity, and more incidences of disability.

Reasons they pointed to in explaining these differences and why women were experiencing a higher disease burden were that women had lower muscular strength and lowered pain sensitivity. Sex hormones, including lowered androgen levels (hormones responsible for male traits and reproductive activity), were also contributors.

Researchers further speculated that women with RA may not be receiving treatment as early as men are, and therefore, are living with longer disease durations. 

Remission

Studies on RA remission find men have higher rates of remission than women. Remission in RA means the disease is no longer active or that someone with RA experiences little or no symptoms related to the condition.

One 2010 systemic review examined the effect of gender on remission and found at least five studies showing men were successfully treating RA with non-biologic disease-modifying anti-rheumatic drugs (DMARDs), biologics, or both. The men were also experiencing persistent remission, whereas the women were less likely to achieve remission even while using the same therapies.

Quality of Life

Women with RA tend to have a decreased quality of life, especially in comparison to men with RA. One cross-sectional study reported in 2015 in the Journal of Arthritis, assessed 70 men and 70 women who met a specific RA diagnostic classification criteria.

The researchers examined the study participants based on medical history, disease severity, and comprehensive psychological and disease-related behaviors and coping strategies. Quality of life was assessed with questionnaires.

Study results showed the women were experiencing higher functional impairment, higher incidents for depression and osteoporosis, and increased levels of anxiety. The women were also experiencing much greater impairments with physical function, general health, and mental health in comparison to the men.

The researchers concluded women with RA tend to have a lower quality of life than men with RA, and that depression and osteoporosis may be important contributors in this effect.

A Shortened Lifespan

Women with RA are at a much higher risk for all-cause mortality, usually respiratory causes in comparison to women without the disease, this according to a study reported in 2016 in Arthritis Care & Research.

Using data from a Nurses' Health Study gathered from 1976 to 2012, researchers looked at 121,700 women and identified 28,808 deaths in the 36-year period.

Of 307 deaths of women with RA, the researchers were able to determine that women with RA had a 40% increased mortality from all causes. And women who had seropositive RA (where bloodwork shows specific proteins that promote RA development), their risk was 51% higher compared to women without RA.

The researchers concluded the study highlighted the importance of addressing complications of RA—especially cardiovascular and respiratory diseases—which are associated with early mortality.

Treatment and Outcomes

Men with RA may respond better to treatment early on and throughout the course of the disease. Researchers looked at two studies, one consisting of 83 patients in a 16-week study (RAIN study) and another 297 patients in an early aggressive treatment study (TEAR study). Most of the study participants in both studies were women.

In the RAIN study, the study participants that were showing the most improvement in disease activity were men. They were meeting the criteria for improvement using methotrexate monotherapy.

Study participants in the TEAR study who received the same monotherapy were meeting improved disease activity levels as early as 12 weeks, and the ones who were showing the most improvement were men.

Other studies have focused on the treatment of biologic therapies in women versus men. For example, women are more likely to experience severe side effects to and adverse reactions of biologic treatment—up to 50% to 75% more likely—leading to treatment failure.

Researchers think gender norms and roles may play some part, in the sense that women are more willing to speak up when a medication isn’t working or if side effects are severe. Additionally, there is little evidence to suggest men may respond better with biologic treatment.

What This Means for the Genders

Doctors don’t treat RA based on gender. This is because RA tends to be an objective disease—that means while symptoms are similar, one person can experience more pain, stiffness, and functional decline than someone else with the condition

But doctors do know women have a higher disease burden with RA and experience poorer quality of life and associated complications. That means doctors should and will implement screening for comorbid conditions associated with RA, including cardiovascular disease, osteoporosis, and depression.

Doctors will also aim to provide a collective and focused approach to treatment that considers a person’s lifestyle, which may include aspects of gender.

And for everyone with RA—male or female, early treatment is essential for slowing down and stopping the disease’s progression and in preventing joint damage and complications.

And treatment isn’t just about taking medicine. It is also helpful to get plenty of sleep or rest, keep moving, stay at a healthy weight, and eat a healthy and balanced diet. Most importantly, make sure you are getting the help and support you need from friends and family, especially on the days that RA is especially challenging. 

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