Why is hormone therapy controversial?

Sharine Forbes
Geriatric Medicine

Hormone therapy is a very controversial issue because estrogen has been proven to decrease the risk of osteoporosis, vaginitis and symptoms associated with menopause. It reduces the risk of osteoporosis because the presence of estrogen can slow down bone mineral loss. Conversely, it has been linked to increase the risk of certain cancers, like breast and uterine cancer, and even increase the risk of cardiovascular disease. It increases the risk of uterine cancer by causing a buildup of uterine tissue. It increases the risk of breast cancer as it causes the breast tissue to grow. Furthermore, estrogen therapy has been linked to adversely affect soluble plasma glycoprotein, plasma viscosity, and insulin sensitivity, along with endothelial cell activation. There are three important receptors in estrogen that are all linked to different mechanism and processes of the body.  One of the receptors is found in the breast and the uterine tissue. Therefore, any estrogen that attaches itself to this receptor has been linked to aid in the development of breast and uterine tissue, which can lead to the development of cancer. The other estrogen receptor is linked to the skeletal system, as it allows for estrogen to aid in the strengthening of the bones. The final receptor deals with the cardiovascular system. In some instances, the estrogen has been proven to protect the heart and arties, but in other instances with women with previous diseases, it has been linked to actually cause cardiovascular disease. Therefore, data reveals that hormone therapy does have physiological effect on the cardiovascular system. A woman’s cardiovascular cells, along with reproductive tissue, consist of two well-known estrogen receptors, estrogen receptor (ER) and estrogen receptor-B (ER-B). Both of these receptors play an essential part in transcription as they support the expression of the gene that has been linked to protect against the onset of diseases of the heart. There is much controversy behind CVD and hormone therapy, as some studies have revealed that women who were closer to going through menopause were at a lower risk of developing CVD when compared to women who were still premenopausal. Therefore, hormone therapy acts a facilitator for CVD for women who are younger. 

Dr. Michael Roizen, MD
Internal Medicine
The reason why hormone therapy is controversial is this: The early studies of women who replaced estrogen were epidemiological—just collections of information on everyone who could be found. These studies compared postmenopausal women who did and did not take estrogen, but there was no attempt to select by a randomized process who took the estrogen and who did not; it was just a side-by-side comparison.

These epidemiological (and not random) studies showed that women taking estrogen had a dramatic decrease in heart attacks and ischemic strokes compared to those women who weren't taking hormone therapy (not just a little decrease; up to a 75 percent decrease). And the women who took estrogen also had higher HDL (good) cholesterol, increased bone strength, and substantially decreased menopausal symptoms. Hot flashes, mood swings, and insomnia practically disappeared.

These early studies made estrogen seem truly beneficial, but with time, women on estrogen replacement also suffered a buildup of uterine tissue that led to an increase in uterine cancer, as well as a proliferation of breast tissue, associated with an increase in breast cancer.

To reduce the risk of uterine cancer, a cyclical dose of a specific progestin (nonbioidentical, synthetic progesterone) was added to the estrogen. The progestin caused the excess estrogen-stimulated uterine tissue to slough off (continued menstruation was the side effect associated with this reduction in cancer risk). Only women who have undergone hysterectomies should consider taking unopposed estrogen.
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