I Think I Need Hormones, But Aren’t They Dangerous?

There is so much information available about hormone replacement these days that it is difficult even for doctors to keep it straight. About 19 years ago the largest study ever done on hormone replacement called the “Women’s Health Initiative” (WHI) changed the way we think about hormones. That study was widely and poorly reported, and many broad and out-of-context statements such as “estrogen causes cancer” or “hormones cause heart disease” were perpetuated in the media. As a result many doctors and patients alike decided to avoid hormone replacement therapy altogether, which caused many perimenopausal (close to menopause) and postmenopausal patients to suffer unnecessarily. As with most things, the truth is somewhere in the middle.

The WHI was a huge study involving over 16,000 women. Patients in the study took an oral product called Premarin (an estrogen that was popular at the time, which is shockingly made from pregnant mares’ urine, hence the name) or PremPro (a combination of Premarin and Provera, the latter being a progesterone-like drug added to prevent uterine cancer). The study was stopped earlier than planned when the investigators found that patients taking Prempro had a higher risk of breast cancer, blood clotting, heart disease, and stroke than the group taking placebo. The actual number of adverse events was very small, but it was surprising since earlier data from other large studies suggested that estrogen actually lowered the risk of heart disease. In fact, even in the WHI, patients taking estrogen-only did NOT have an increased risk of breast cancer and other diseases; it was the Provera compound that was the bad actor.

One of the most important facts that were not reported in the media was that the average age of patients in the study was 65, and study participants included patients who smoked, were obese, and had a history of heart disease, among other things. So when we are considering prescribing hormones to a young (45-55 year old), healthy patient suffering from menopause symptoms, one cannot assume that her risks will be the same as a 65 year old obese smoker. Similarly patients who need hormones due to surgical removal of the ovaries before age 50 were not involved in the study, and without hormone replacement the quality of life for these patients can be seriously affected.

Importantly the products that we use now are different than those used in the study. The trend is now to use estrogen transdermally (across the skin) rather than in pill form. Transdermal estrogen in the form of a patch, cream, sublingual or pellet form, has been shown in many studies to have NO increased risk of blood clot, heart disease and stroke, compared to that seen with oral estrogen. (Transdermal estrogen avoids the liver and is directly absorbed into the bloodstream, which may be why we see those risks decrease). It’s also now clear after many studies that bio-identical hormones (those that look biologically identical to human hormones) have lower risk than other animal derived or synthetic hormones.

Many studies have looked at the association of estrogen replacement to breast cancer and some studies suggest a small increased risk after prolonged use of estrogen. How long? There is no clear answer, but it does seem clear that short term use (a few years or less) has no adverse effect on the breast. After many studies looking at bio-identical estradiol and breast cancer, there appears to be NO increased risk of breast cancer, although hormones will cause an existing cancer to grow faster and possibly spread more quickly. One problem is that many women have breast cancer, 1:8 is the current lifetime risk in this country, and the vast majority of those patients did not take hormones. So any of us might get breast cancer, and some of us might take hormones, but of all patients who have breast cancer and took hormones very few of them have a cancer caused by the hormones. There are so many factors that affect the development of breast cancer, deciding cause and effect is very difficult. For patients taking estrogen of course we recommend an annual mammogram, as we do for all of our patients over 50. The great news is that testosterone decreases breast cancer risk, so for patients who take both estradiol and testosterone, overall breast cancer risk is lowered.

Clearly the issues surrounding hormone replacement are complex and individual. Certain patients should not take hormones for menopausal relief, including patients with a prior history of breast cancer or epilepsy. But for most other patients, correctly administered hormone replacement can improve quality of life dramatically, as well as helping with bone density and reducing colon cancer and Alzheimer’s risk. So we don’t have to throw the baby out with the bathwater, talk to your doctor about hormones and we will help to decide what is best for you.