Early menopause and more children linked to rheumatoid arthritis risk in women

Early menopause and having four or more children are among a number of factors that place women at a higher risk of developing rheumatoid arthritis, a study has suggested.

Researchers have now called for hormonal and reproductive factors to be considered in women diagnosed with the long-term condition – which causes pain, swelling and stiffness in the joints.

According to the NHS, about 400,000 people have rheumatoid arthritis in the UK, with about three times as many women impacted than men.

The study by Chinese academics analysed data from 223,526 people included in the UK Biobank, whose health was tracked for an average of 12 years.

During the period, 3,313 women developed rheumatoid arthritis.

Researchers found going through the menopause before the age of 45 was associated with a 46% heightened risk of developing the condition compared with women who went through menopause before the ages of 50-51.

Those with four or more children carried an 18% higher risk compared to women with two children, while those with fewer than 33 reproductive years – the time between starting periods and menopause – had a 39% higher risk.

The team also found starting periods after the age of 14 was linked to a 17% higher risk than starting them at 13.

Being on hormone replacement therapy (HRT), which helps ease menopause symptoms, was associated with a 46% higher risk, researchers said.

While researchers acknowledged limitations to the study, published in RMD Open, they added that the findings “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”.

Dr Benjamin Ellis, a consultant rheumatologist and senior clinical policy adviser at charity Versus Arthritis, said women are more likley to be impacted “for reasons we don’t fully understand”.

“One of the chromosomes that determines sex, the X chromosome, contains genes that control the immune system,” he added.

“Most women have two X chromosomes in each cell, and most men only have one. This may explain some of the differences in immune system diseases between men and women. Female hormones, particularly oestrogen, seem also to be important too in regulating the immune system – and this research highlights the impact of exposure to female hormones.”

GP and menopause specialist Dr Louise Newson said the study “should not be a cause of concern for women who take body-identical hormones”.

“We have known for decades that our natural sex hormones oestradiol – the main type of oestrogen – and progesterone, which decline during menopause, are anti-inflammatory,” she added.

“Women who go through an earlier menopause – that is, before the age of 45 – are without these natural hormones for longer and are therefore at greater risk of inflammation and autoimmune diseases, including rheumatoid arthritis.”

Dr Newson also said it is “important” to highlight the study is observational “and as such cannot definitively establish cause and effect”.

She added: “This study is not set up to study HRT and because it uses older data, it is likely to include women prescribed older, synthetic types of HRT, rather than the natural, body-identical hormones that we prescribe nowadays that have the same molecular structure as the hormones women naturally produce.

“Older tablet oestrogen can be converted to oestrone which is an inflammatory type of oestrogen, while older synthetic progestogens do not have the same anti-inflammatory effects of body-identical progesterone.”

Dr Ellis added: “Any change in a risk of rheumatoid arthritis is unlikely to be a main factor in whether or not to take HRT, which is always an individual decision based on many different factors.”