Study Identifies Hormonal and Reproductive Triggers for Rheumatoid Arthritis

A comprehensive long-term study published in the open-access journal RMD Open reveals that women who experience early menopause (before the age of 45), use hormone replacement therapy (HRT), or have four or more children may face an elevated risk of rheumatoid arthritis. The study identifies these hormonal and reproductive factors as potential contributors to the increased susceptibility in women.

Researchers observe a higher susceptibility of women to this autoimmune disease compared to men. Women are 4–5 times more likely than men to develop rheumatoid arthritis before the age of 50 and twice as likely to do so between the ages of 60 and 70. Additionally, the disease appears to inflict a higher physical toll on women than on men.

Although hormonal and reproductive factors are believed to play a role in increasing women’s vulnerability to the disease, the specific influential factors remain unclear.

To address this knowledge gap, researchers examined data from 223,526 participants in the UK Biobank, monitoring their health over an average period of 12 years.

Throughout this period, 1.5% of the women, totaling 3,313 individuals, were diagnosed with rheumatoid arthritis. The study revealed an association between various hormonal and reproductive factors and an increased risk of the disease. These associations persisted even after adjusting for potentially influential factors such as lifestyle, social and economic status, ethnicity, and body weight (BMI).

Commencing menstruation after the age of 14 showed a 17% increased risk compared to starting at the age of 13. Similarly, undergoing menopause before the age of 45 was linked to a 46% higher risk compared to experiencing it at the age of 50-51.

Having fewer than 33 reproductive years, defined as the duration between the onset of periods and menopause, was linked to a 39% increased risk. Additionally, in comparison to having two children, having four or more was associated with an 18% higher risk.

Undergoing a hysterectomy or the removal of one or both ovaries (oophorectomy) was correlated with a 40% and 21% heightened risk, respectively, although the number of women who underwent these procedures was limited.

Although no distinct association was evident between Pill usage and the risk of rheumatoid arthritis, the use of hormone replacement therapy (HRT) and, to a lesser extent, its duration were linked to 46% and 2% higher risks, respectively.

It’s important to note that this is an observational study conducted over a substantial period, and as such, it cannot establish causation. The researchers acknowledge several limitations to their findings.

One notable limitation is that the UK Biobank comprises predominantly healthy and affluent individuals of white ethnic background, making it unrepresentative of the broader UK population.

Despite this limitation, the research outcomes lead the investigators to recommend a thorough examination of hormonal and reproductive factors in women diagnosed with rheumatoid arthritis.

And they conclude: “The findings of this study are significant and form a basis on which novel and target-specific intervention measures to curb the risk of [rheumatoid arthritis] in women may be developed.”

Source: BMJ

Journal reference: Jiang, L-Q., et al. (2024) Hormonal and reproductive factors in relation to the risk of rheumatoid arthritis in women: a prospective cohort study with 223 526 participants. RMD Open. doi.org/10.1136/rmdopen-2023-003338