Life Extension Magazine®

Issue: Oct 2000

New Data on the Dangers of Hormone Replacement Therapy

Research reveals that the benefits may not outweigh the risks associated with hormone drugs.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, on January 2021.

Hormone Replacement Therapy  

Data on the risks of prescription hormones is stacking up at the same time that the benefits are becoming increasingly questionable. Drugs such as Premarin cause cancer with or without added progestins. Adding progestins simply moves the cancer to another organ.

A new study from the University of Toronto is the latest to show that prescription estrogen greatly increases the risk of endometrial cancer. The first studies on the high risk of endometrial cancer and synthetic estrogen were published in 1975. Subsequently it was proven that risk could be reduced if progestins were added. That strategy has been proven to increase the risk of breast cancer-in some cases, double it.

Despite 40 years of data, researchers are still preoccupied with the serious side effects of hormone drugs. The database on the long-term effects of these drugs is huge. Tens of thousands of women have taken part in hormone replacement studies published in the past two years alone. A recent Swedish study involved over three thousand woman with breast cancer. It found that non-obese women were more likely than obese women to develop breast cancer after long-term (10 years) use of estrogens, with or without progestins.

Another study, The Breast Cancer Detection Demonstration Project, analyzed over 2000 women out of a database of 46,000+ participants before concluding that the risk of breast cancer is increased every year a woman takes hormone drugs. Another study tracked over 10,000 women at risk for breast cancer plus over 8,000 women at risk for endometrial cancer for 5 years. It concluded that women who take estrogen drugs without progestins for at least 6 years have a four-times increased risk of invasive endometrial cancer, with no increase in breast cancer. But women who take estrogen drugs with progestin drugs have about a 50% increased risk of breast cancer over those who don't. The size and consistency of these studies is hard to argue with.

One of the things that has recently emerged from breast cancer/drug studies is that the combination of estrogen and progestins dramatically increases breast density. This may confound the results of mammograms. Yet women who do take drug hormones may have reduced mortality because they are more likely to get a mammogram and have early detection since they are seeing a physician on a regular basis. The answer, of course, is for women to see a doctor regularly whether or not they’re taking prescription drugs.

Large “breakthrough” studies have periodically made doctors and patients aware that hormone drugs increase the risk of cancer. Prescriptions plummet after these episodes of public awareness. In response, the drug industry develops new marketing strategies. The latest include claims that hormone drugs protect the heart and bone. Heart protection never had much support in the scientific literature, yet this fact has been obscured by multi-million dollar ad campaigns. In 1998, doubts were confirmed when results of a large study on “Prempro” (Premarin plus progestins) were released. The drug increased, not decreased, the risk of heart attack. This shouldn't have been surprising given that the propensity of estrogen drugs to cause deadly blood clots has been well-documented since the 1960s.

Women who take estrogen drugs
with progestin drugs have about
a 50% increased risk of breast
cancer over those who don’t.

Blood clots are a good reason not to take prescription hormones for osteoporosis. The risk far outweighs the benefit–especially considering that safe alternatives such as reduced animal-protein diets and phytoestrogens are widely available and inexpensive. Why take a chance on dying when there are viable alternatives?

Given the prognosis of women who take hormone drugs long-term, it’s probably fortunate that the adverse effects drive almost half the women away within a few months. And the good news is that even if a woman has taken hormone drugs for years, the risk of breast cancer will decline if she stops. Endometrial cancer may be different, however. A study from Oxford indicates that the elevated risk for endometrial cancer caused by the drugs goes away very slowly, if at all.

The Food and Drug Administration, which reviews drug applications, is supposed to apply a risk/benefit analysis when considering whether a drug should go on the market. If a drug is designed for a life-threatening condition, serious adverse reactions such as cancer and blood clots are considered acceptable. However, if a drug is designed to treat non-life-threatening conditions and less toxic alternatives are available, the risk/benefit analysis fails. In the case of hormone replacement therapy drugs, the risk/benefit analysis fails despite the fact that these drugs remain on the market.


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Gajdos C, et al. 2000. Breast cancer diagnosed during hormone replacement therapy. Obstet Gynecol 95:513-18.

Hill DA, et al. 2000. Adherence to postmenopausal hormone therapy during the year after the initial prescription: a population-based study. Am J Obstet Gynecol 182:270-6.

Hulley S, et al. 1998. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 280:605-13.

Lundström E, et al. 1999. Mammographic breast density during hormone replacement therapy: differences according to treatment. Am J Obstet Gynecol 181:348-52.

Magnusson C, et al. 1999. Breast cancer risk following long-term oestrogen and oestrogen-progestin replacement therapy. Int J Cancer 81:339-44.

Persson I, et al. 1999. Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Canc Causes Control 10:253-60.

Ross RK, et al. 2000. Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst 92:328-32.

Schairer C, et al. 2000. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 283:485-91.

Weiderpass E, et al. 1999. Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst 91:1131-7.