Rethinking Hormone Therapy
The North American Menopause Society (NAMS) released its 2017 Hormone Therapy Position Statement (1), which said:
• Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (like hot flashes), problems with the genitourinary tract, and has been shown to prevent bone loss and fracture.
• The risks of HT differ depending on the specific hormone, dose, duration of use, route of administration, timing of initiation, and which type of progestogen (i.e., synthetic progestin or natural progesterone) is used.
• Treatment should be individualized to maximize benefits and minimize risks.
Findings from the Women's Health Initiative (WHI) indicated a greater risk of breast cancer and coronary heart disease among women who used a combination of conjugated estrogens and the synthetic progestin medroxyprogesterone acetate as menopausal hormone replacement therapy, than women who used estrogen alone. In the branch of the WHI study that investigated the use of estrogen alone, there was a decrease in the risk of breast cancer and heart disease, and a lower rate of death in comparison with women who received a placebo. (2)
These widely publicized findings frightened many women and some physicians, and the use of hormone replacement therapy rapidly declined. Doctors and researchers at the Yale University School of Medicine examined the effect of estrogen avoidance on mortality rates for women in the WHI trial who were aged 50 to 59 years and previously had a hysterectomy, as compared to the entire population of similar women in the United States. They calculated that a minimum of 18,601 and as many as 91,610 postmenopausal women died prematurely because of the avoidance of estrogen therapy. "Sadly, the media, women, and health care providers did not appreciate the difference between the two kinds of hormone therapy [referring to estrogen alone, or estrogen with a synthetic progestin]," commented lead researcher Philip Sarrel, MD. He concluded that informed discussion between the women and their health care providers about the different effects of various regimens of hormone therapy is a matter of considerable urgency, pointing out that the selection of a natural estrogen can make a difference. "Essentially, estradiol inhibits the development of atherosclerosis and helps maintain normal arterial blood flow." (2)
Evidence also shows that natural progesterone has beneficial effects that some synthetic progestins do not. Studies indicate that the use of natural progesterone with estrogens confers less or even no risk of breast cancer as opposed to the use of synthetic progestins. (3)
In September 2017, JoAnn Manson, MD, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, and lead author of the WHI shared the following perspectives: (4)
• For women (below age 60) and closer proximity to onset of menopause (within 10 years), the absolute risks of heart disease, stroke, deep venous thrombosis (DVT), and breast cancer, related to hormone therapy, are lower.
• Women who are at greater risk for and have a higher frequency of hot flashes and night sweats are more likely to derive quality-of-life benefits from hormone therapy.
• Transdermal hormone therapy is less likely to increase clotting protein or triglyceride levels and avoids some of the other concerns associated with the oral route of administration.
• In contrast to the vasomotor symptoms (hot flashes and night sweats), genitourinary symptoms actually progress over time. Genitourinary conditions can cause urinary tract infections, discomfort with sexual activity, and physical health. Low-dose vaginal estrogen is the most effective treatment and does not increase the blood level of estrogen above the usual postmenopausal range. There is no evidence of an increased risk for heart disease, stroke, DVT, dementia, or breast cancer with low-dose vaginal estrogen.
• Women with early menopause (including hysterectomy) have an increased risk for heart disease, cognitive decline, bone loss, and osteoporosis, and are particularly good candidates for hormone therapy.
• The WHI observational follow-up urges caution when considering initiating hormone therapy at an older age in women with diabetes, as these women are at the greatest risk for cognitive decline.
(1) Menopause. 2017; 24(7):728-753 (2) Am J Public Health. 2013 Sep;103(9):1583-8.
(3) Maturitas. 2008; 60:185-201.
(4) NAMS1 New Hormone Therapy Position Statement: Clinical Takeaways - Medscape - Aug 15, 2017.
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