HRT associated with 46% increase in rheumatoid arthritis, suggest study results

Despite study results showing an increased risk of rheumatoid arthritis, the British Menopause Society cautions that the results are unlikely to change HRT prescribing practice.
Woman taking HRT

Results from a prospective cohort study suggest that the use of hormone replacement therapy (HRT) was associated with a 46% higher risk of rheumatoid arthritis (RA), but the British Menopause Society says it is unlikely to change practice.

The study, published by The BMJ on 9 January 2024, collected information on hormonal and reproductive factors of 223,526 women, aged 40 to 69 years, between 2006 and 2010 via the UK Biobank database. Of these, 64,342 women had taken HRT.

The authors reviewed the incidence of RA against several hormonal and reproductive factors, including age at menarche, pregnancy history, number of live children, menopause, age at menopause, reproductive years, history of hysterectomy, history of oophorectomy, contraceptive pill, duration of oral contraceptive pill use, HRT and duration of HRT use.

During a median follow-up of 12.4 years, 3,313 (1.5%) incidents of RA were reported. Further analysis showed that the use of HRT was associated with a 46% increase in risk of developing RA compared to non-HRT users (hazard ratio [HR] 1.46; P<0.001).

This was the highest association among all of the hormonal and reproductive factors, along with age at menopause <45 years (HR 1.46; P<0.001), history of hysterectomy (HR 1.40; P <0.001) and age during reproductive years <33 (HR 1.39; P<0.001).

Only a small increase was observed with the duration of HRT and RA, at a mean duration of 6 years (HR 1.02; P <0.001).

However, the study authors highlighted several limitations, such as having a study population unreflective of the UK, because most of the population was from a “relatively healthy and affluent
people of white ethnic background”, self-reporting of clinical information, residual effects of unadjusted confounders and potential for left truncation bias.

Paula Briggs, chair of the British Menopause Society and consultant in sexual and reproductive health at Liverpool Women’s NHS Foundation Trust, described the study as “interesting”, but said “it wouldn’t change my clinical practice or restrict any type of HRT prescribing”.

“The results found a 46% increased risk of RA among HRT users compared to non-users, but this isn’t what is reflected in clinical practice and not what I see,” she added.

“I think there are confounding factors here and more research is needed to change HRT prescribing practice based on this risk.”

The number of HRT products prescribed in England has increased exponentially in recent years, with data published by the NHS Business Services Authority showing a 47% rise in prescription items between 2022 and 2023.

An estimated 2.3 million patients in England were prescribed HRT in 2022/2023, compared with 1.8 million in 2021/2022, an increase of 29%.

The increase in demand for HRT products has led some experts to fear that hormone therapies are being overprescribed, owing to greater awareness of menopause symptoms.

Last updated
The Pharmaceutical Journal, PJ, January 2024, Vol 312, No 7981;312(7981)::DOI:10.1211/PJ.2024.1.209093

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