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Hormonal Replacement Therapy

With all of us baby-boomers passing into our 50's and 60's menopausal issues have assumed great importance in our lives (men and women!). No doubt you have already investigated many of these issues on your own. You have been bombarded with menopause information through the popular media and other women your age. Are you totally confused yet? Since I am a cancer specialist I do not feel qualified to address all menopausal issues but I will tackle the most common questions that seem to come up. I'll start by declaring myself as a proponent of Hormone Replacement Therapy (HRT).

 

Taking estrogen after menopause is not natural

Oh, really? For a slightly different way to look at an answer to this issue let's look at the rest of the mammalian kingdom. Many mammalian species experience gradually declining fertility followed by midlife cessation of menses. This “menopausal” state is seen primarily in captive laboratory and zoo animals protected from natural sources of mortality and provide a good diet and medical care. With few exceptions (short-finned pilot whales, some species of monkeys) complete cessation of menses is not seen in the wild.

Unlike human females, most mammalian females will continue to produce estrogen even if they no longer ovulate. Elephants, for example, have an increasing incidence of enlarging uterine leiomyomas (fibroids), an estrogen dependent benign tumor, as they age. Castration of elderly domestic cats results in up to a 90% decrease in uterine weight (uterine weight is dependent on circulating estrogen levels).

Exceptions to this general rule include Rhesus and some macaque species. These primates will exhibit “hot flashes” and develop osteoporosis with cessation of ovarian estrogen production (just like humans). So, what is “unnatural”?

In the mammalian kingdom it would seem that animals with a finite number of oocytes would eventually fail to ovulate if they live long enough in captivity (an exception to this rule is the female mouse lemur which does not demonstrate reproductive senescence). Cessation of ovulation is usually not seen in the wild since life expectancy is reduced. This is quite similar to human females if we compare living conditions and life expectancy prior to and subsequent to 1900.

Until the beginning of the 20th century human females also ovulated until death! Of course the average life expectancy at that time was only about 50 years. In 1900, for example, only 6% of women in the United States were post-menopausal. Now almost 35% are post-menopausal.

With advances in medicine, sanitation and diet, you (just like captive laboratory and zoo animals) can expect to live a third of your life after cessation of menses. As noted above, some captive primates will not only cease ovulation (if they live long enough) but will also stop producing estrogen. The majority of mammals, however, continue to produce estrogen until death even if they no longer ovulate.

So, I would contend that human menopause (cessation of ovulation and estrogen production) is an unintended consequence of living beyond age 50. The “natural state” of mammalian evolution leads to functioning ovaries until death. It would seem that maintaining circulating estrogen levels during the entire adult life is the overwhelming intention of mammalian evolution.

(Thanks to Alan Conley, DVM, University of California, Davis and Donna Holmes, DVM, University of Idaho)

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I'm 70 years old and never taken hormone replacement. Is there any reason to start now?

Early results of a prospective, randomized, blinded study of postmenopausal women known as the Women’s Health Initiative (WHI) have cast doubts on the benefits of initiating HRT too many years after menopause. Of the 16,600 women recruited to the study, 67% were over the age of 60, and only 1,700 women were between the ages of 50 and 54. In the end, the average age of a woman in the WHI was 63. To date, early results from the WHI have shown that initiating HRT with a combination of estrogen and progestin (PremPro) in older women does not prevent heart disease or confer other significant advantages.

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What about the increased risk of cancer in HRT users?

It gets a little confusing when the available information is scrutinized. Here are some accepted facts about HRT and cancer risk;
  1. The risk of breast cancer in HRT users is related to dose and duration of use. To date 5 meta-analyses of 25 English-language studies in the literature show this risk to be small. The predicted lifetime increase in breast cancer risk in HRT users is 1%. The baseline breast cancer risk is 12% in Orange County, CA. A 1% increase in risk amounts to an overall increase in lifetime risk to a little over 13%. Although this is a statistical increase I would argue that this is not an important “clinical” increase in risk. In other words, HRT users do not need additional breast cancer surveillance. A yearly mammogram and breast check is sufficient.
  2. Women who develop breast cancer while taking HRT have a better survival (i.e. 90% cure rate) than non-HRT users.
  3. The risk of uterine cancer is increased if a HRT regimen of both estrogen and progestin is not used (of course, this applies only to women who have a uterus!).
  4. The risk of uterine cancer is decreased below baseline levels if HRT consists of a combination of estrogen and progestin (i.e. HRT, if used properly in women with a uterus decreases risk of uterine cancer).
  5. HRT may decrease risk of colon cancer. Let’s look at the issue of HRT and cancer risk from a slightly different perspective. Prostate cancer is a disease of men over 50 years of age. Approximately 190,000 men will be diagnosed with this cancer each year. 30,000 men will die this year of prostate cancer. The comparable figures for breast cancer are 180,000 new cases each year and 43,000 deaths. Prostate cancer is a testosterone-dependent cancer. Castration (either surgical or medically induced) is an accepted form of treatment of advanced disease. Interestingly, prophylactic castration at age 50 would likely dramatically reduce or even completely eliminate prostate cancer as a killer of older men! If this is the case then why do we not recommend that all men be castrated at age 50?
I find it interesting that we recoil at the thought of men being prophylactically castrated at age 50 (even though this might prevent 190,000 cases of prostate cancer and 30,000 deaths each year) but we readily accept “castration” (i.e. menopause) in women at the same age (even though only 2000 – 15,000 new cases of breast cancer and 200 – 1500 deaths would theoretically be prevented each year if no woman received HRT after menopause!).

When I ask a man if he would want testosterone replacement if he was castrated in an industrial accident at age 50 I always get the same answer – “Yes!!!” When I then ask that man why he would want replacement of sexual steroids I always get the same answer – “I want to be able to have a happy sexual life!!!” Why do we, as a society, think so differently about sexual steroid replacement in our female population???

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Which HRT regimen should I take?

I'll give you a simple, "tongue in cheek" answer - "It doesn't matter what type of estrogen regimen you use". At a cellular level "estrogen is estrogen". Estrogens do vary in their potency and their relative effect on alpha and beta estrogen receptors. From a practical standpoint, however, finding the particular estrogen that a particular patient will be most happy with at a particular point in her life is not a predictable exercise. You may need to try several different HRT regimens before finding the one that you are most satisfied with at a given time of your life. What's more, you'll be a totally different person 5 - 10 years from now and will probably need to alter your regimen again.

Here are a few additional points to ponder:
  1. If you still have a uterus you must take a progestin with your estrogen (more about this later).
  2. Like any medication you should take the minimum amount of estrogen needed to accomplish your goals. In other words "more is not better".
  3. Switching from one regimen to another is OK. However, you should remain on a regimen for at least 3 months before changing to another regimen (it takes that long for your body to adjust to a change in estrogen environment).
  4. Take HRT prescribed by your physician. It never ceases to amaze me that otherwise intelligent people will put herbal or condensed soy products into their bodies and believe that they are doing something beneficial! Rigorous studies of herbal products show minimal to no improvement in the prevention of “hot flashes” and no effect on prevention of osteoporosis. We should all be acutely aware of the substances we put in our bodies. My wife, for example, is very careful when buying food for our children (as I'm sure you are/were for yours). The orange juice has got to be calcium fortified and the milk has to be low-fat, for instance.  Remember that all herbs and other "natural" products contain numerous chemicals. When you take an FDA approved medication you know what is going into your body with certainty. When you take an herbal product, which is not under the purview of any government agency, you have absolutely no idea what chemical soup you are ingesting!
  5. An androgen may need to be added to your HRT regimen. This is most commonly needed if your libido is decreased. It is not yet clear that androgen therapy is necessary for all women.
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Why do I need progestin?

You only need a progestin in your HRT regimen if you have a uterus. Progestins prevent overstimulation of the endometrium (the inner lining of the uterus) and eventual development of a uterine cancer. In women not taking estrogen replacement, orally administered progestin has a moderate effect on the prevention of “hot flashes”. Studies do not show the same impact when progestin is administered as a topical cream.

The “Big Picture”

We can expect to live longer and healthier than any human beings in history. For the first time humans are living longer than 50 years. For the first time in history, we are seeing diseases of old age that were never seen previously.

Alzheimer's disease, prostate cancer, osteoporotic hip fractures are just a few of the medical problems that were never really seen until the last 100 years. It is a fact that as we get older our bodies will start to break down. We will need treatment for various bothersome aches and pains as well as some serious illnesses. This does not mean that
we should not look for ways to optimize our health and extend our lives.

Believe it or not, there really are very few proactive actions you can take to maximize your longevity, health and physical happiness. You can:
  1. Avoid obesity. This implies watching your diet and maintaining a regular, moderate exercise program.
  2. Don't smoke. While you're at it, don't abuse alcohol and other drugs.
  3. HANG ON TO YOUR SEXUAL STEROIDS!

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