Vaginal oestrogen does not carry increased risk of cancer, cardiovascular disease
Use of vaginal oestrogens among postmenopausal women does not contribute to an increase in the risks of cardiovascular disease and cancer, according to a study.
In a cohort of 45,663 women aged 50 to 79 years who were enrolled in the Women's Health Initiative Observational Study, the risks of stroke, invasive breast cancer, colorectal cancer, endometrial cancer and pulmonary embolism/deep vein thrombosis did not significantly differ between self-reported vaginal oestrogen users (n=41,563) and nonusers (n=4,100) during a median follow-up of 7.2 years. [Menopause 2017;doi:10.1097/GME.0000000000000956]
There also was no evidence of an elevated risk of coronary heart disease (CHD) or death among users. Rather, vaginal oestrogen reduced the risk of CHD by 48 percent (adjusted hazard ratio [aHR], 0.52; 95 percent CI, 0.31 to 0.85), hip fracture by 60 percent (aHR, 0.40; 0.19 to 0.85) and global index event (GIE; defined as time to first occurrence of CHD) by 24 percent (aHR, 0.76; 0.64 to 0.91).
When results were stratified by hysterectomy status, the risks of invasive breast cancer, stroke, colorectal cancer, endometrial cancer, venous thromboembolism and GIE were likewise similar among hysterectomized vaginal oestrogen users and nonusers.
In contrast, among women with intact uterus, the risk of several outcomes was significantly lower with vaginal oestrogen use vs nonuse (aHR for GIE, 0.68; aHR for death, 0.62; aHR for CHD, 0.39; aHR for hip fracture, 0.40).
Consistent with the results of a number of previous prospective observational studies evaluating CHD, stroke, and breast and endometrial cancer risk among vaginal oestrogen users, the present data help fill important knowledge gaps regarding the safety of vaginal oestradiol, the authors said. [Hum Reprod 2016;31:804-809; Obstet Gynecol 2006;108:1354-1360; Climacteric 2010;13:228-237; Obstet Gynecol 2010;116:876-883]
The increased risks of venous thromboembolism, stroke and invasive breast cancer reported to be associated with systemic oestrogen and oestrogen þ progestogen in previous randomized trials were adopted into oestrogen class labelling that is applied to all oestrogen preparations, the authors noted. “[This is] despite the lack of clinical trial evidence demonstrating that vaginal oestrogens confer these same risks.” [JAMA 2013;310:1353-1368; Cochrane Database Syst Rev 2015;CD002229; Ann Intern Med 2012;157:104-113]
Low-dose vaginal oestrogen preparations approved by the US Food and Drug Administration (FDA) have been found to carry a product labelling that states: ‘‘WARNING: endometrial cancer, cardiovascular disorders, breast cancer, and probable dementia.’’
The authors expressed worry that the warning, which is based on extrapolations of data from clinical trials of systemic hormone therapy and not on evidence from clinical trials of vaginal oestrogen, may discourage the use of a highly effective local treatment for a common condition that negatively affects quality of life.
“Currently, the US FDA is considering a proposal to modify package labelling so that it better reflects the safety profile of vaginal oestrogen,” they said.
The study has several limitations including residual confounding by alterations in serum lipoproteins and increased bone-density linked to low-dose vaginal oestradiol rings.
Still, the present findings, along with the available evidence, “should provide reassurance to women and their health providers regarding the safety of vaginal oestrogen and will help to inform menopausal hormone therapy clinical decision-making,” the authors said.