It’s always reassuring to know that taking any medication will not increase your risk of death. Women can now thus be reassured about hormone therapy. A recent study from the Cochrane Foundation has now confirmed that taking hormones does not increase your risk of dying from a number of medical problems.

The findings were based on a large analysis (meta-analysis) of 43 randomized clinical trials that had been published over time, including the WHI (Women’s Health Initiative). Some of the studies were 6 months in duration and some longer, but the mean average was around 5 years. The study was presented March 6 at the Endocrine Society’s annual meeting, ENDO 2015, by Khalid Benkhadra, MD, a postdoctoral research fellow in Evidence-Based Practice Research Program-Knowledge and Evaluation Research Unit, Mayo Clinic, in Rochester, MN.[1]

The study population was more than 52,000 women with a mean age of 62 years old over a mean follow-up time of 5 years. The conclusion of the study was that there was no associated mortality related to hormone therapy, including no increase in risk of heart disease. In other words, death rate from MI was the same whether the women took hormones or did not take hormones.

The problem of the study was that it covered only around 5 years. Multiple other studies from prior years have shown a significant decrease in heart disease when women use hormone therapy[2],[3]. In addition, over time there is decreased risk of developing colon cancer, osteoporosis,[4] dementia and Alzheimer’s disease[5],[6]. At the same time, as this study confirms, there is no increased risk of developing breast cancer or ovarian cancer when taking estrogen alone. We believe this is especially true when bioidentical hormones are used.

Another recent study[7] confirmed 27 prior studies[8] that demonstrated how estrogen replacement reduces all-cause mortality and increases general well-being in estrogen-deficient women. Optimizing testosterone levels also improves quality of life, including increase in libido and thought process. Optimal testosterone levels were linked with better performance on mental status examination[9] and have been associated positively with multiple aspects of cognitive function.[10], [11]

The current Cochrane study simply summarized what we already had heard from the 2002 WHI which also covered only 5 years (and is included in the Cochrane study). Interestingly, extension of the estrogen only arm of the WHI study over the subsequent 12 years demonstrated a positive effect regarding breast cancer occurrence and survival rate with estrogen therapy versus placebo.(http://www.truemd.com/hormone-replacement-therapy/hormone-therapy-and-breast-cancer-12-years-after-whi/)

One of the problems of the Cochrane study was that it was not very accurate. Dr. Benkhadra even admitted that the result of the study is “low to moderate” and that the length of the study of 5 years was probably not long enough to yield long term conclusions.

The present meta-analysis did confirm what other studies have shown; that women who started hormone therapy right after they began menopause seemed to have the best benefits, with a decreased risk of developing heart disease, and this is important since heart disease is the number one killer of women. The study also showed there was no increased risk in death from stroke, but there was an increase in stroke risk when oral estrogen was used.

Most experts agree that the increase in risk of stroke from oral estrogen (over age 60) has to do with the first pass effect of oral estrogens through the liver. This changes the clotting factors with resultant increased risk of thromboembolic problems, such as stroke. However, other studies have proven that transdermal estrogen does not increase the risk of stroke since they do not have a first pass effect. Thus, the best way to prevent this is by using the transdermal route, such as what is used when bioidentical hormones are used, pellets or creams.

Women can thus benefit from hormone therapy with reassurance but there is a window of opportunity for this. This window is when a woman first enters menopause, if she starts on hormone therapy, she has the best benefit. Women over 60 who then start hormone therapy do not get as much benefit from the disease reducing benefits of hormone therapy. However, all women could benefit from the other benefits of hormone therapy, such as a reduction in hot flashes, mood changes, emotional rollercoasters, vaginal dryness and atrophy. They also may enjoy a better sex life with improved libido and ability for orgasm.

 

References:

[1] Benkhadra, K, et al. “Menopausal Hormone Therapy and Mortality: A Systematic Review and Meta-Analysis.” Cochrane Study. https://endo.confex.com/endo/2015endo/webprogram/Paper20414.html

[2] Davison S, Davis SR. :New markers for cardiovascular disease risk in women: impact of endogenous estrogen status and exogenous postmenopausal hormone therapy”. J Clin Endocrinol Metab. 2003;88(6):2470–2478

[3] Arnal JF, Laurell H, et al. “Estrogen receptor actions on vascular biology and inflammation: implications in vascular pathophysiology”. Climacteric. 2009;12 Suppl 1: 12-17.

[4] Gambacciani M , Vacca F. “Postmenopausal osteoporosis and hormone replacement therapy”. Minerva Med. 2004 Dec;95(6):507-20.

[5] Vest RS, Pike CJ. “Gender, sex steroid hormones, and Alzheimer’s disease”. Horm Behav. 2013 Feb;63(2):301-7.

[6] Gouras GK, Xu H, Gross RS, et al. “Testosterone reduces neuronal secretion of Alzheimer’s beta-amyloid peptides”. Proc Natl Acad Sci USA. 2000 Feb;97(3):1202-05.

[7] Sarrel PM, et al. :”The mortality toll of estrogen avoidance: An analysis of excess deaths among hysterectomized women aged 50 to 59 years”. Am J Public Health. 2013 Jul 18.

[8] Salpeter SR, et. Al. “Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal women”. Am J Med. 2009 Nov;122(11):1016-22

[9] Hogervorst E , Matthews FE, Brayne C. :Are optimal levels of testosterone associated with better cognitive function in healthy older women and men?” Biochim Biophys Acta. 2010 Oct;1800(10):1145-52

[10] Moffat SD , et al. “Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men”. J Clin Endocrinol Metab. 2002 Nov;87(11):5001-7.

[11] Barrett-Connor E 1, Goodman-Gruen D, Patay B. “Endogenous sex hormones and cognitive function in older men”. J Clin Endocrinol Metab. 1999 Oct;84(10):3681-5