A longitudinal analysis on the effect of hormone use on allostatic load in perimenopausal women

• Hormonal therapy has been used for years to relieve menopausal symptoms, with studies showing both benefits and risks. • Aging causes decline in function and higher inflammation, known as allostatic load, due to chronic stress. • This study of 2199 women found no link between hormone therapy and increased allostatic load, supporting its use for menopausal symptoms. Allostatic load (AL), a measure of physiologic dysregulation across multiple systems, has been shown to increase as women age and go through menopause. While hormone use has been shown to help with the relief of menopausal symptoms, it is not clear whether the use of hormone replacement therapy and hormonal contraceptives in the perimenopausal period has an impact on alleviating allostatic load in aging women. We conducted a target trial emulation to estimate the on-treatment (i.e., per-protocol) effect of hormone replacement therapy or hormonal contraceptives use on AL score evolution over time. We included in our analysis 2,199 women from the SWAN cohort that were followed-up between 1996 and 2005. To estimate the effect of the continuous use of hormone replacement therapy or hormonal contraceptives on AL score evolution over the follow-up period we used marginal structural models estimated using inverse probability weighting. The mean AL score at baseline was 2.45 ± 1.85 (Mean ± SD). The AL score remained relatively stable in women that never used hormone replacement therapy or hormonal contraceptives, with an average increase of 0.014 ± 0.011 (Mean ± SE) per year, whereas in women that used hormone replacement therapy or hormonal contraceptives continuously, the AL score increased, on average 0.087 ± 0.014 (Mean ± SE) per year. We did not find conclusive evidence to support that continuous use of hormone replacement therapy or hormonal contraceptives modifies the AL score trajectory (mean difference between trends = 0.073; CI 95% : -0.027, 0.173; P = 0.1538). Continuous use of hormone replacement therapy or hormonal contraceptives during the menopause transition period was not associated with increased allostatic load. The findings suggest continuous use of hormone therapy as a treatment for perimenopausal symptoms in aging women doesn't confer a risk for increased allostatic load.