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Let’s make a quick search in PubMed, using the key words ‘menopause’ and ‘hormone therapy’ (HT), and looking at included publications dated 2015. My search was done on May 10 and I found 143 hits in English, but among those only 16 were relevant articles. There were three trials [1-3], and one report on the methodology of an ongoing trial [4], one Cochrane systematic review [5], no meta-analyses, no guidelines or consensus papers, eight reviews (six on estrogen/progestin; two on DHEA), one editorial, one letter, one paper detailing a mobile app for menopausal symptom management and hormonal/non-hormonal therapy decision-making. Although a 4-month survey may not be enough to draw conclusions, this gloomy yield reflects the real-life situation when the scientific interest in HT is very minimal and the money invested in related research has been constantly decreasing. Large databases, such as from the WHI observational study, the Korean KNHANES study, the US SWAN study and others are still producing statistics on various aspects of the menopause, yet it seems that the leftover topics that are currently published are sometimes focused on narrow clinical scenarios, rather than on the main issues. Here are some recent examples: BMI and sexual functioning, BMI and proton pump inhibitors, reproductive history and risk of lung cancer, antioxidant micronutrients and the risk of renal cell carcinoma, age at first delivery and osteoporosis risk, are some of the recent issues that were investigated; a Cochrane review summarized the data on HT and progression of SLE. 


Thus, it seems that the enthusiasm to know and to better understand the mechanisms and outcomes of HT that led to a flood of information 15–20 years ago has disappeared. On the other hand, the post-WHI tornado with endless debates on the benefit–risk balance of HT has also come to an end, and the recent reviews by the principal WHI investigators on the association of hormone use and breast cancer or coronary artery disease risk actually narrowed the gaps between the various opinions and strengthened the points of overall agreement. Chlebowski and Anderson wrote that ‘The absolute breast cancer risk for relatively short-term (2–4 years) use of combined hormone therapy is small … there was an overall reduction of breast cancer incidence seen with estrogen alone use … women with prior hysterectomy can be assured that short-duration estrogen-alone use for climacteric symptom management is relatively safe’ [6]. Bhupathiraju and Manson addressed the coronary and breast issues as follows: ‘For CHD, the risks were elevated for women with metabolic syndrome or high low-density lipoprotein cholesterol concentrations but not in women without these risk factors … CEE+MPA increased breast cancer risk, whereas CEE alone had a protective effect. The absolute risks of HT were low in younger women (ages 50–59 years) and those who were within 10 years of menopause onset’ [7].


The above-mentioned Cochrane systematic review on prevention of cardiovascular disease concluded that ‘Those who started hormone therapy less than 10 years after the menopause had lower mortality (moderate-quality evidence) and coronary heart disease (composite of death from cardiovascular causes and non-fatal myocardial infarction) (moderate-quality evidence), though they were still at increased risk of venous thromboembolism (high-quality evidence) compared to placebo or no treatment. There was no strong evidence of effect on risk of stroke in this group. In those who started treatment more than 10 years after the menopause, there was high-quality evidence that it had little effect on death or coronary heart disease between groups, but there was an increased risk of stroke (high-quality evidence) and venous thromboembolism (high-quality evidence)’ [5]. 


So, if a PubMed search reflects the future of HT, my impression is that we may expect a quiet period in what used to be a war zone. Instead, we should look for innovations and excitements in the other fields of adult women’s health, such as new therapies for female cancers, the effects of the individual gene expression on health and disease, understanding the aging processes, etc.


  • Amos Pines
    Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Tuomikoski P, Ylikorkala O, Mikkola TS. Postmenopausal hot flushes and bone mineral density: a longitudinal study. Acta Obstet Gynecol Scand 2015;94:198-203
  2. Ensrud KE, Guthrie KA, Hohensee C, et al. Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes. Sleep 2015;38:97-108
  3. Mikkola TS, Tuomikoski P, Lyytinen H, et al. Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality. Menopause 2015 Mar 23. Epub ahead of print
  4. Mirkin S, Amadio JM, Bernick BA, Pickar JH, Archer DF. 17β-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review. Maturitas 2015;81:28-35
  5. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Boardman HM, Hartley L, Eisinga A, et al. Cochrane Database Syst Rev 2015 Mar 10;3:CD002229. doi: 10.1002/14651858.CD002229.pub4
  6. Chlebowski RT, Anderson GL. Menopausal hormone therapy and breast cancer mortality: clinical implications. Ther Adv Drug Saf 2015;6:45-56
  7. Bhupathiraju SN, Manson JE. Menopausal hormone therapy and chronic disease risk in the Womens Health Initiative: is timing everything? Endocr Pract 2014;20:1201-13
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