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Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study

Bhupathiraju, Shilpa N., PhD1,2; Grodstein, Francine, ScD1,3; Stampfer, Meir J., MD, DrPH1,2,3,4; Willett, Walter C., MD, DrPH1,2,3; Crandall, Carolyn J., MD, MS5; Shifren, Jan L., MD6; Manson, JoAnn E., MD, DrPH1,3,4

doi: 10.1097/GME.0000000000001284
Original Study: PDF Only

Objective: To examine the associations between vaginal estrogen use and multiple health outcomes including cardiovascular disease (total myocardial infarction, stroke, and pulmonary embolism/deep vein thrombosis), cancer (total invasive, breast, endometrial, ovarian, and colorectal cancer), and hip fracture.

Methods: We included postmenopausal women from the Nurses’ Health Study (1982-2012) who were not current users of systemic hormone therapy at the start of the study or during follow-up. Vaginal estrogen use was self-reported on the biennial questionnaires. Information on incident health outcomes were self-reported and confirmed by medical records. We used Cox proportional hazards regression to model the multivariable adjusted hazard ratios and the 95% confidence intervals for vaginal estrogen use and multiple health outcomes.

Results: Over 18 years of follow-up, after adjusting for covariates, risks for cardiovascular disease, cancer, and hip fracture were not different between users and nonusers of vaginal estrogen. No statistically significant increase in risk of any health outcome was observed with vaginal estrogen use. In sensitivity analyses, when we examined associations by hysterectomy status, the stratified results were generally similar to those for the total cohort.

Conclusions: Vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer. Our findings lend support to the safety of vaginal estrogen use, a highly effective treatment for genitourinary syndrome of menopause.

1Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

2Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA

4Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

5Department of Medicine, University of California at Los Angeles, Los Angeles, CA

6Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Address correspondence to: Dr JoAnn E. Manson, MD, DrPH, Chief, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave, 3rd Floor, Boston, MA 02215. E-mail:

Received 23 August, 2018

Revised 5 November, 2018

Accepted 5 November, 2018

Funding/support: S.N.B. is supported by a Career Development Grant from the NIH (K01 DK107804). The Nurses’ Health Study is supported by grants from the National Institutes of Health UM1 CA186107, P01 CA87969, R01 HL034594, and R01 HL088521.

Financial disclosures/conflicts of interest: None reported.

© 2019 by The North American Menopause Society.