Vaginal Estrogen Use Not Associated With Elevated Chronic Disease Risk
Limited data are available for chronic disease outcomes following long-term, low-dose vaginal estrogen therapy.
No excess risk for cardiovascular disease, cancer, or hip fracture was associated with vaginal estrogen use among postmenopausal women, according to study results published in Menopause.
The investigators of this prospective study sought to assess the relationship between long-term vaginal estrogen use and chronic health outcomes, including cardiovascular disease, cancer, and hip fracture, in postmenopausal women not using systemic hormone therapy.
The study sample included 53,797 postmenopausal women recruited from the Nurses' Health Study who were not undergoing systemic hormone therapy. Participants reported vaginal estrogen use and incident health outcomes via validated questionnaires administered every 2 years over an 18-year follow-up period; health status was confirmed by medical records or state cancer registries.
Specific outcomes of interest were major cardiovascular events, including myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis; all cancer types, including breast, ovarian, endometrial, and colorectal cancers; and hip fractures. To characterize the association between vaginal estrogen use and various health outcomes, the investigators used Cox proportional regression models to estimate hazard ratios (HRs).
In the overall sample, vaginal estrogen users (n = 896) had lower risk for total myocardial infarction (HR, 0.56; 95% CI, 0.36-0.87) and stroke (HR, 0.71; 95% CI, 0.47-1.09) compared with nonusers (n = 52,901). However, the investigators found no significant differences in risk for other cardiovascular outcomes, cancer outcomes, or hip fracture between the 2 groups. After adjusting for major confounders, there were no significant differences in the risk for all cardiovascular outcomes, cancer outcomes, and hip fracture between vaginal estrogen users and nonusers. Sensitivity analyses that accounted for associations with hysterectomy status also yielded similar results to the overall sample.
Limitations to the study included the lack of data on individual types of vaginal estrogen therapy formulations or doses, and that the study sample included health professionals who were mostly white with high educational attainment, potentially limiting the generalizability of the results. The observational nature of the study may not account for residual confounding and prevents the ability to infer causation.
Overall, vaginal estrogen use or nonuse did not carry different risks for cardiovascular outcomes, cancer outcomes, or hip fracture. The study investigators suggested these findings support the safety of long-term, low-dose vaginal estrogen use to manage postmenopausal symptoms in women.
Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses' Health Study [published online December 17, 2018]. Menopause. doi:10.1097/GME.0000000000001284