EXECUTIVE SUMMARY

Results of recent research indicate that vaginal estrogen is effective and safe for the treatment of genitourinary symptoms. Such low-dose vaginal estrogen options keep blood levels within the normal postmenopausal range.

  • In women with an intact uterus, the risks of stroke, invasive breast cancer, colorectal cancer, endometrial cancer, and pulmonary embolism were not significantly different between vaginal estrogen users and nonusers.
  • All low-dose vaginal estrogen preparations now approved by the Food and Drug Administration carry the same boxed warning about health risks as systemic formulations of estrogen alone and combination formulas. The regulatory agency is reviewing a proposal to modify package labeling so that it better reflects the safety profile of vaginal estrogen.

During menopause, estrogen deficiency can lead to thinning of the vaginal epithelium. As a result, women may experience vaginal dryness, itching, dyspareunia, and urinary symptoms. Results of recent research indicate that vaginal estrogen is effective and safe for the treatment of these genitourinary symptoms.1

No previous U.S. studies have focused on an overall index of benefits and harms of using vaginal estrogen in a large group of women followed for many years, says Carolyn Crandall, MD, MS, professor of medicine in the Division of General Internal Medicine and Health Services Research at the David Geffen School of Medicine at the University of California in Los Angeles. Although estrogen pills have been linked with increased risks of cancer and cardiovascular disease, scientists hypothesized it was possible that vaginal estrogen had a different risk profile, especially because vaginal estrogen use results in much lower estrogen levels than estrogen pill use does, says Crandall, lead author of the current paper.

To perform the prospective observational cohort study, researchers used data from participants of the Women’s Health Initiative Observational Study, who were recruited at 40 U.S. clinical centers. Participants ranged in age from 50 to 79 years at baseline and did not use systemic estrogen therapy during follow-up. The scientists collected data regarding incident coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, death, and self-reported use of vaginal estrogen in either cream or tablet form. The analysis notes that in women with an intact uterus, the risks of stroke, invasive breast cancer, colorectal cancer, endometrial cancer, and pulmonary embolism were not significantly different between vaginal estrogen users and nonusers. Data indicate that women using vaginal estrogen were found to be at less risk for coronary heart disease, fracture, and all-cause mortality than nonusers. When researchers looked at results based on hysterectomy status, the risk of invasive breast cancer, stroke, colorectal cancer, endometrial cancer, and venous thromboembolism was not significantly different in vaginal estrogen users than in nonusers.1

Vulvovaginal atrophy, also known as genitourinary syndrome of menopause, represents a common progressive condition in menopausal women that has an important negative effect on sexuality and overall quality of life, says Andrew Kaunitz, MD, University of Florida Research Foundation Professor and Associate Chairman of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine–Jacksonville. Unfortunately, concerns about the safety of vaginal estrogen have resulted in this syndrome being undertreated in U.S. women. Few large-scale studies have assessed the association between use of vaginal estrogen and the risk of developing cancer or cardiovascular disease, notes Kaunitz, a paper co-author.

“The findings of this large, long-term Women’s Health Initiative cohort study should provide reassurance regarding the safety of vaginal estrogen therapy,” he says.

Understand the Symptoms

What populations of menopausal women are served best by use of vaginal estrogen? According to JoAnn Pinkerton, MD, executive director of the North American Menopause Society, bothersome symptoms of the vagina and vulva increase during and after the menopause transition or may start several years after menopause. The major contributor is the loss or decrease of estrogen, notes Pinkerton.

“Up to 70% of women may suffer from progressive vaginal changes, most without treatment,” says Pinkerton. “These women may have symptoms such as vaginal dryness and painful intercourse, or urinary urgency or recurrent urinary tract infections.”

The results of the current study suggest that the use of low-dose vaginal estrogen does not carry the same health risks as the use of systemic hormone therapy, says Pinkerton. Thus, it is safer and should be considered as an effective and safe therapy for women with indications of progressive bothersome vaginal changes, painful sex, or recurrent urinary tract infections, she notes.

“These findings should reassure women and their healthcare providers that low-dose vaginal estrogen, which keeps blood levels within the normal postmenopausal range, is effective and safe for postmenopausal women who need relief from only vaginal symptoms,” says Pinkerton. “The boxed warnings about the risk of heart disease, stroke, blood clots, and cancer do not apply to these low-dose vaginal therapies. Instead, women who experience bleeding or those with breast cancer should include their healthcare providers and oncologists in deciding about this option.”

Women who are having vaginal dryness, itching, burning, or pain with sex should talk to their providers about options, such as nonhormonal lubricants and vaginal moisturizers, low-dose vaginal estrogen therapy, or the new intravaginal DHEA daily suppositories, says Pinkerton. Results of a recent analysis of vaginal estrogen therapy options indicate that such treatments appear to have similar efficacy and safety.2

At the current time, all low-dose vaginal estrogen preparations approved by the Food and Drug Administration carry the same boxed warning about health risks as systemic formulations of estrogen alone and combination formulas. The boxed warning, which reflects estrogen class labeling, states: “WARNING: endometrial cancer, cardiovascular disorders, breast cancer, and probable dementia.” The regulatory agency is reviewing a proposal to modify package labeling so that it better reflects the safety profile of vaginal estrogen. 

REFERENCES

  1. Crandall CJ, Hovey KM, Andrews CA, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative Observational Study. Menopause 2017; doi: 10.1097/GME.0000000000000956.
  2. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2016;8:CD001500.