Use of menopausal hormone therapy beyond age 65 and its effects on women's health outcomes by types, routes, and doses

Summary

Recently Baik et al. [1] performed a study that aimed to assess the use of menopausal hormone therapy (MHT) beyond the age of 65 and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. For this, they used prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and using Cox regression analyses adjusted for time-varying characteristics of the women, they examined the effects of different preparations of MHT on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. The authors found that compared with never use or discontinuation of MHT after age 65 years, the use of estrogen monotherapy beyond this age was associated with significant risk reductions in mortality, breast cancer, lung cancer, colorectal cancer, congestive heart failure (CHF), venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer, ovarian cancer, ischemic heart disease, CHF, and venous thromboembolism, whereas E+ progesterone exhibited risk reduction only in CHF. The investigators conclude that among senior Medicare women, the implications of MHT use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Commentary

In the early 90′ of the last century there were many articles that discussed the issue of hormone therapy for menopausal women. Physicians based their policy on guidelines and recommendations issued by relevant societies. As an example, in a 1996 review, an author wrote “the current American College of Physicians recommendations for hormone replacement are as follows: All women should be considered” [2]. At that time, it was believed that a woman should take MHT for life as part of preventive medicine. This concept turned up-side-down after the first publication of preliminary data from the Women’s Health Initiative (WHI) that seemed to demonstrate substantial risks associated with hormone use. However, when looking at the final results of the WHI study several years later it became clear that physicians must consider women’s age and type of hormone as major risk parameters. Timing of initiation of therapy, namely starting treatment before age 60, especially if using estrogen only, demonstrated a favorable safety balance in regard to benefits versus risks. As a result, recommendations on MHT use became much more positive, still, whether or not to continue therapy on the long-term, beyond age 60, remained controversial. But now, Baik et al. [1] go further, providing data on the effects of MHT in older women. They base their conclusions on analysis of ten million senior Medicare women from 2007-2020. In contrast to the previous assumptions that dictated clinical strategies, overall, the findings now point significant reduction in mortality risk, including due to certain cancers and cardiovascular conditions. It is clear, as also mentioned in the here commented article of Baik et al., that the study has methodology limitations and its results should therefore be considered with caution. Nevertheless, are we witnessing a “back to square one” process? In a commentary on the study, which appeared recently in Medscape [3], a professor from Chicago took it further by suggesting: “the best time to stop MHT is when you die”. Time will tell us if the winds will blow again in favor of long-term MHT even in older women.

Amos Pines, MD
Sackler Faculty of Medicine, Tel-Aviv University, Israel

References

1. 1. 1. Baik SH, Baye F, McDonald CJ. Use of menopausal hormone therapy beyond age 65 years and its effects on women’s health outcomes by types, routes, and doses. Menopause. 2024;31(5):363-371.
         https://pubmed.ncbi.nlm.nih.gov/38595196/
      2. Welty FK. Who Should Receive Hormone Replacement Therapy? J Thromb Thrombolysis. 1996;3(1):13-21.
         https://pubmed.ncbi.nlm.nih.gov/10608035/
      3. Frellick M. Hormone Therapy After 65 Good Option for Most Women.
         https://www.medscape.com/s/viewarticle/hormone-therapy-after-65-good-option-most-women-2024a10007b2?ecd=WNL_mdpls_240419_mscpedit_fmed_etid6454350&uac=34958FR&spon=34&impID=6454350

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