Female Reproductive Factors, Exogenous Hormone use, and Incident Chronic Kidney Disease and end-stage Renal Disease

Abstract

Context: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases.

Objective: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women.

Methods: A total of 260 108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders.

Results: During a median of ∼12.5 years of follow-up, 8766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before age 50 years, menopausal before age 45 years, and menopausal hormone therapy initiated before age 50 years was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (hazard ratio [HR] = 0.89; 95% CI, 0.87-0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI, 0.79-0.95). Each 5-year delay in starting menopausal hormone therapy was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI, 0.84-0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI, 0.73-0.99).

Conclusions: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

Keywords: UK biobank; chronic kidney disease; end-stage renal disease; menopausal hormone therapy; reproductive factors.