Is vaginal estrogen used for GSM associated with a higher risk of CVD or cancer?

Health outcomes for specific invasive cancers (risk for endometrial cancer included only women with an intact uterus) were:

• invasive breast cancer: HR, 1.07 (95% CI, 0.78–1.47)
• ovarian cancer: HR, 1.17 (95% CI, 0.52–2.65)
• endometrial cancer: HR, 1.62 (95% CI, 0.88–2.97)
• colorectal cancer: HR, 0.77 (95% CI, 0.45–1.34).

Study strengths and weaknesses

A causal relationship cannot be proven as the study was observational. However, a strength included the 18 years of follow-up. Women used vaginal estrogen for an average of 3 years, which provided longer-term safety data than available 12-month clinical trial data. Data were collected through self-report on questionnaires every 2 years, which is a drawback; however, participants were registered nurses, who have been shown to provide reliable health-related information. Comparisons between therapies were not possible as data were not collected about type or dosage of vaginal estrogen. Available therapies during the NHS included vaginal estrogen tablets, creams, and an estradiol ring, with higher doses available during earlier parts of the study than the lower doses commonly prescribed in current day.

Overall

The findings from this long-term follow-up of the NHS provide support for the safety of vaginal estrogen for treatment of GSM. No statistically significant increased health risks were found for users of vaginal estrogen, similar to earlier reported findings from the large Women’s Health Initiative.² Low-dose vaginal estrogen is recommended for treatment of GSM by The North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society.

Absorption of low-dose vaginal estrogen preparations appears minimal, and they are effective and generally safe for the treatment of GSM for women at any age. Progesterone is not recommended with low-dose vaginal estrogen therapies, based primarily on randomized clinical trial safety data of 12 months.³ Postmenopausal bleeding, however, needs to be thoroughly evaluated. For women with breast cancer, include the oncologist in decision making about the use of low-dose vaginal estrogen.