Oral Contraceptives and Hormone Replacement Therapy May Increase Risk for Gout Among Postmenopausal Women

Reproductive factors, including endogenous estrogen, and the use of oral contraceptives and hormone replacement therapy (HRT) were found to increase the risk for gout among postmenopausal women, according to study results published in Arthritis Research & Therapy.

The incidence and risk factors for gout vary according to sex, with gout being 3 to 10 times more common among men. However, studies on the association between reproductive factors and gout are limited.

In a nationwide population-based cohort study of 1 million postmenopausal women, researchers of the current study sought to evaluate the association between reproductive factors and the incidence of gout.

Data from postmenopausal women who participated in the cardiovascular health and breast cancer screening program in 2009 were identified from the Korean National Health Insurance Service (NHIS) database.

The primary outcome of the study was incident gout, defined as 2 outpatient visits or 1 hospitalization with the diagnostic code for gout (International Classification of Diseases, Tenth Revision [ICD-10] code M10).

Participants were followed-up with from 1 year after the health screening date until the date of outcome occurrence, death, or the end of the study (December 31, 2018), whichever came first. The mean follow-up duration was 8.1 years.

A total of 1,076,378 postmenopausal women aged between 40 and 69 years were included in the analysis. The analysis was stratified according to body mass index (BMI) and the presence and absence of chronic kidney disease (CKD). 

A total of 64,052 incident gout cases (incidence rate, 7.31 per 1000 person-years) were reported. High risk for gout was observed in women with later menarche, earlier menopause, and a shorter reproductive span. No association between parity and gout incidence was observed.

An increased risk for gout was observed in women who used vs those who never used oral contraception. The adjusted hazard ratio (aHR) was 1.03 (95% CI, 1.00-1.06) in those who used oral contraceptives for less than 1 year and the aHR was 1.05 (95% CI, 1.02-1.08) in those who used oral contraceptives for 1 year or more. Similarly, the use of HRT was associated with an increased risk for gout, and the risk was highest among those who used HRT for more than 5 years (aHR, 1.19; 95% CI, 1.14-1.23).

In the stratified analysis, no significant association was observed between reproductive factors and gout among women with a BMI of or greater than 30. The use of oral contraceptives and HRT did not increase risk for gout in patients with CKD.

Researchers also reported a low risk for gout in women who breastfed for less than 6 months and no significant risk for gout in women who breastfed for more than 6 months (aHR, 0.93 and 0.98, respectively).

Limitations of the study included potential bias because of data collection after 40 years, limited information regarding type and dose of oral contraception and HRT used, lack of details on the association between uric acid levels and reproductive factors, and risk of collinearity and confounding due to inclusion of various reproductive factors.

Researchers concluded, “Exposure to exogenous estrogens, such as [oral contraceptives] and HRT, was associated with a high risk of incident gout. However, this association was weak in women [with a BMI of 30 or greater] and in women with CKD.”

Reference

Eun Y, Kim IY, Han K, et al. Association between female reproductive factors and gout: a nationwide population-based cohort study of 1 million postmenopausal women. Arthritis Res Ther. 2021;23(1):304.doi:10.1186/s13075-021-02701-w