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ESTROGEN AND PROGESTERONE: RESTORING A WOMAN'S LOSSES

One day in February, 1963, a new patient arrived in the office of Dr. Robert A. Wilson, a New York gynecologist. He saw nothing unusual in that, but when she said she was fifty-two, Dr. Wilson's interest level rose. He had assumed she was much younger. "Her breasts were supple and firm," he later wrote, "her carriage erect. She had good general muscle tone, no dryness of the mucous membranes and no visible genital atrophy. Above all, her skin was smooth and pliant as a girl's."

Fifty-two-year-old women of whom such things can be said are much more usual now than they were in 1963. The reason, of course, is estrogen replacement therapy. Approximately 10 million postmenopausal American women took the hormone over the next four decades.

Dr. Wilson went on in 1966 to write a bestseller, Feminine Forever, which stimulated the first major wave of estrogen replacement. He promised women "extended youth," and though estrogen remains controversial to this day—chiefly due to fears of cancer—Dr. Wilson's promise was, in most respects, far from hollow.

IS A MAJOR CHANGE OF LIFE NECESSARY?

Between the ages of forty-five and fifty-five, age descends upon women with a suddenness for which the male life cycle offers no such abrupt parallel. Yet most of these physical manifestations of aging can be slowed, or partially reversed. It is not necessary for a woman's skin to rapidly lose its elasticity and begin to wrinkle. Not necessary for her vagina to shrink and become painfully dry. Not necessary for her bones to lose calcium and begin an accelerated and potentially deadly crash process of thinning—too often a prelude to shattering. Not necessary, therefore, for her shoulders to slump, her spine to curve, her stature to shorten, her carriage to lose its air of erect and youthful vitality. And not necessary for her sex drive to lessen, her moods to swing wildly, her memory to have lapses. One and all—not necessary.

Yet the fact remains that those are the normal and expected consequences of menopause, even for the woman who does not suffer devastating hot flashes, night sweats, or major depression—that is, even for the woman who has a "good" change of life.

Those don't sound like positive additions to any woman's life. And I haven't even mentioned what is perhaps the most crucial dimension added to a woman's life by menopause—an increased risk of heart disease. Within fifteen years after a woman's ovaries shut down, she is as much at risk for a heart attack as a man.

It would certainly seem that a strong case for estrogen—or more properly for natural hormone replacement therapy, the combined replacement of both estrogen and progesterone in their natural, bioidentical forms)—can be made, and ought to be made, by most doctors to most women.

Yet, I enter with trepidation into this discussion of the female hormones. American women have come to associate the word "hormone" with the word "cancer." I don't think this association is fair, but it is deeply ingrained, more so after a recent flurry of deceptively frightening media releases, stemming from a clinical study named the "Women's Health Initiative.".

Estrogen might possibly be associated with a slightly increased risk of breast cancer, but only because those women live longer than women who do not take estrogen. As for increased uterine cancer, that risk no longer seems to exist, so long as estrogen is given with a balancing amount of progesterone.

In 1994 the National Institutes of Health launched the $628 million Women's Health Initiative research study. One part of that research project will involve 27,500 women, half of them randomly assigned to receive postmenopausal hormones, the other half a placebo. Scientists then tracked the women in the various groups, comparing heart disease, osteoporosis, and cancer rates. Women who received a synthetic progestin (medroxy-progesterone acetate, Provera®) were removed from the study prematurely because of apparent risks, including a less than one-tenth of one percent (< 0.01%) increased risk of breast cancer. None of the women in that study received natural progesterone. Therefore, the results of the Women's Health Initiative do not seem to apply to the regimen I recommend here.

In 2002 the news media was flooded with frightening reports from the "Women's Health Initiative," an ongoing clinical study, alleging that hormone replacement for menopause caused breast cancer. I'll analyze that study in more detail further on, but suffice it to say that this study was greatly flawed in design and that several other studies showed no such risk. Even if we assume that the most frightening interpretation was correct, the increased risk was less than 1/10th of one percent, and then only when estrogen was combined with a synthetic progestin—not the natural, bioidentical progesterone. Following that flurry of media reports, millions of women abruptly stopped their hormones and experienced a very unpleasant and rapid menopause. Recently, the scientific evidence has been reviewed in detail, showing that risk was minimal or absent. Some tiny risk seems quite justified in return for a longer life expectancy, and a greatly enhanced quality of life.

Consider that the mere fact of taking replacement hormones has been shown to lower the death rate and extend a woman's life very significantly. One of the many studies showing this benefit was published in January 1996.by Dr. Bruce Ettinger, a former classmate of mine at Harvard Medical School. He followed nearly 500 women who received their medical care from the Kaiser Permanente health system, a large HMO in California. Dr. Ettinger studied 232 women who were on estrogen replacement for an average of seventeen years, and compared them to 222 women who had used estrogen for less than one year during that same period. His observations showed that the death rate from all causes was reduced by 44 percent in the women on estrogen.

It seems obvious that if overall death rate declined by such a large amount, those women who lived longer on hormone replacement might eventually experience a slightly increase incidence of cancer, percentagewise. Cancer was not otherwise possible if they had already died of other causes. Think about it!

Forty-four percent reduction in death rate from all causes is a large number. How is such a difference possible? I think that it's possible and, indeed, unsurprising. Hormone loss in the second half of life may be "natural," but, in my opinion, it isn't healthy. That seems self-evident. Predictable hormone decline with age is a deficiency state, an undeclared disease, and the fact that older people have always suffered it does not alter the objectivity of that judgment. Old age remains the ultimate disease, and, in my opinion, a doctor who fails to treat it is untrue to his calling. You say that it's natural for hormones to decline? Well, I say that older people have also always suffered from hardening and narrowing of the arteries. Nevertheless, no respectable physician would suggest that such cardiovascular ills should—as a perfectly natural part of aging—be left unassisted to run their deadly course.

Virtually all the evidence we currently possess demonstrates that the loss of male and female sex hormones in the second half of life is every bit as damaging to health, vigor, mental function, energy, and ultimately to longevity as the loss of growth hormone, DHEA, and melatonin—major endocrine hormones that decline with age. These losses are natural all right—in the worst possible sense. Nature is preparing us for our departure. If we wish to depart life later, rather than sooner, we must be willing to make adjustments to her plan.

It is not surprising, therefore, that the sudden loss of the female hormones during menopause is tremendously damaging to youthfulness. And youthfulness is not just a fancy word for sex appeal. I don't think wanting to stay young is a negative characteristic or a frivolous desire unworthy of serious adults. Not many of us want at fifty to do exactly the same things we were doing at seventeen. But we do want to pack the maximum amount of life into living. We very much want a high quality of life, right up until the moment it ends.

Take a quick look at the following list of changes that occur at menopause and the advantages of hormone replacement therapy. The loss of the sex hormones constitutes a savage attack upon the functioning of the entire female body.

I think the argument for estrogen's overwhelming value to the lives of most postmenopausal women is a sound one, but even the words "increased incidence of cancer" are very emotional. The word "cancer" has hooks and barbs attached to it. It makes everyone uneasy. In the next few sections, I'm going to explain the important advantages that hormone replacement therapy offers to women—with emphasis on a combination of both natural, bioidentical forms of both estrogen and progesterone.

Postmenopausal Problems Relieved by Hormone Replacement

● Rapid increase in bone loss, osteoporosis, fractures

● Pain and stiffness in joints

● Mood swings

● Hot flashes

● Night sweats

● Tiredness

● Sleep disorders

● Memory lapses

● Depression

● Inability to concentrate

● Genital atrophy

● Vaginal dryness

● Decreased sexual desire

● Breast atrophy

● Dry hair

● Increased Facial hair

● Thinning and wrinkling of skin

● Leakage of urine on straining and coughing

● Constipation

● Bloating

● Heart disease

Potential Problems Associated with Female Hormone Replacement

● Uterine cancer, but only if estrogen is replaced without a proper balance of progesterone.

● A tiny increase in statistical risk of breast cancer, but the results of various studies are so conflicting that this is far from clear. At most, a tiny fraction of one percent.

● Return of menstrual bleeding, if a uterus is still present, sometimes unpredictably

● Breast and genital tenderness and fluid retention in some women (usually only during the early months of therapy)

I'll return later to a discussion of cancer and its alleged relationship to the female hormones.

OSTEOPOROSIS AND WOMEN

Osteoporosis—bone loss—is one of the most serious health hazards a woman faces in the second half of her life. As life expectancy increases, this rather mysterious illness will have to absorb a greater and greater share of medical attention. It isn't a problem that anyone gave much thought to before the second half of this century. In a period when typical life expectancy was less than fifty years, why be concerned about thinning bones—they're only likely to pose a real peril to people over sixty. Well, most women live to be over seventy now, and more than half of them live past eighty. As further steps toward longevity are taken, more women will make it past ninety. Unless we do something about bone loss, an alarmingly high percentage of them will be in wheelchairs.

The path to osteoporosis begins in females at around age twenty when bone growth is completed. From then on, an average of one percent of bone mass (structural calcium in bones) is lost yearly. At that rate, a woman of fifty will already have lost about 30 percent of her bone and a man (because male bone loss is more gradual and starts somewhat later) about 20 percent. The situation is more serious for a woman not only because she has lost a higher percent but because she has less bone to start with.

And then menopause arrives and precipitates a veritable holocaust of bone. Generally, from ages fifty to fifty-five, women lose 3-8 percent of their bone each year. An average woman may be down to as little as 35 to 45 percent of her original young adult bone mass by age fifty-five. Around that age, the rate of loss usually slows back to 1 percent a year. If we lived in the world of pure mathematics and theory, a woman would have no bone at all by age ninety. In the real world, the situation is grievous enough.

In the early 1990s, 24 million men and women were defined as having osteoporosis—most of them women—and this epidemic of bone disease was causing 1.2 million bone fractures a year. About 130,000 of these were women suffered broken necks, frequently fatal. Hip fractures caused the deaths of tens of thousands more; 20 percent of elderly adults who fracture their hips are dead within six months. By the age of seventy, almost 50 percent of women had had at least one osteoporotic fracture at an estimated cost of $7 to $10 billion annually.

Just how large a difference does estrogen and progesterone make?

Hormone Replacement = Bone Preservation

It is now well established that estrogen replacement therapy, taken as a preventive before advanced bone loss occurs, can reduce the incidence of bone fractures by approximately 50 percent. But, in this aspect of dealing with the menopause, a few medical scientists have become aware in recent years that natural progesterone is almost certainly an important part of this therapy.

To understand what happens not only in correcting bone loss but in all aspects of menopause, let's briefly consider the history and functions of estrogen and progesterone in the female body.

The Hormones of Femininity

Along with its sister hormone, progesterone, estrogen is the quintessential feminine hormone—the essential feminine accompaniment to conception and birth. Estrogen and progesterone are steroid hormones (like the major male hormone, testosterone, and also the adrenal hormones, cortisone and DHEA). The body makes these horones from cholesterol and DHEA. In childhood, estrogen is produced by the adrenal glands. Then, at puberty, ovarian production takes over, the amount rises many-fold, and a whole host of changes takes place in a girl's body: the breasts and genitalia develop, new sweat glands emerge, a layer of fat is deposited at appropriate places under the skin, and pubic and axillary hair develop.

All of this activity occurs around the time of menarche, usually between eleven and fourteen years old, when a girl first begins to menstruate. This is the beginning of her fertile life as a woman, and for the next thirty to forty years she will have a monthly ovulatory cycle designed to prepare an egg for fertilization. If that doesn't occur, she'll start over again the next month. At the beginning of each monthly cycle, estrogen causes the endometrial lining of the uterus to thicken as a preparation for fertilization. Midway through the cycle an egg is released by the ovary (ovulation), and, at that point, there is increased production of progesterone, the other major female hormone. Progesterone, which is also being produced in the ovaries, causes the endometrial lining to soften so that, if an egg is fertilized, it can be implanted there to form a placenta. Should pregnancy fail to occur, estrogen and progesterone levels fall during the final days of the monthly cycle, and the inner lining of the uterus is shed and expelled from the body along with some blood in a process called menstruation.

Overall production of estrogen and progesterone begin to decline during a woman's thirties, but the decline is usually not sufficient to produce symptoms or irregularities in a woman's menstrual cycle before her mid-forties. Menopause itself is defined as the last menstrual period, and since ovarian production has been declining and menstrual cycles are generally variable and unpredictable during the final few premenopausal years, a woman isn't really sure that she has reached menopause until many months after that final menstrual period.

Menopause is an inability of the ovaries to produce any more eggs combined with a radical reduction in ovarian production of the female sex hormones. Estrogen production after menopause suddenly falls by more than 65 percent. Progesterone falls correspondingly. The dramatic physical changes that we outlined earlier begin to occur.

What Happens to Your Bones?

Human bone is a continual hotbed of activity. Old or damaged bone is constantly being resorbed (dissolved) by a special class of cells called osteoclasts. Meanwhile, new bone is getting manufactured by the osteoclasts, good cousins, the osteoblasts. This Mutt 'n' Jeff team never stops working, for, contrary to the image you probably have of it, bone is very metabolically active, a living tissue.

So what does it mean when we say that women average a 1 percent yearly loss in bone mass over most of their adult lifetime? Clearly, the demolition team is accomplishing more work than the construction crew. Though whole chapters are written in medical textbooks analyzing why, that is the bottom line. At the end of a typical year, the osteoblasts haven't been able to make quite as much new bone as the osteoclasts have cleared away. Since without a skeleton you're going to have a difficult time standing up to the stresses of age, I think osteoporosis is a very real longevity issue for any human being and for women in particular.

Research has shown that the two hormones—estrogen and progesterone—that women largely lose at menopause, have contrasting effects on bone. Estrogen does not appear to aid in the formation of new bone, but it does greatly slow the dramatic increase in bone resorption that occurs after menopause—assuming, of course, that its use is begun before significant bone loss occurs. Progesterone, on the other hand, being anabolic in nature can actually enhance bone strength by increasing the activity of the osteoblasts. (And, as I'll explain shortly, there's also evidence that a small degree of supplemental testosterone, for women who test deficient, is also powerfully supportive of osteoblast activity in women. Women also need testosterone, but only about 10 percent as much as men.)

Research on natural progesterone, has reported actual reversal of bone loss in women who combine nutritional supplementation using calcium, magnesium, and vitamins C and D together with natural progesterone. Women in have been reported to experience as much as a 15 percent increase in bone density over a one-year period. Women over seventy, who had already suffered significant osteoporosis with collapse of vertebrae and loss of height, improved the most.

This rate of increase in the density of weakened bone is highly unusual, and clearly more studies will be needed to confirm it. But other studies already confirm the essential and amazing fact: It is possible to reverse bone loss. A ten-year double blind study published in Obstetrics and Gynecology found increases in bone mass when estrogen and progesterone therapy was initiated within three years of menopause.

The degree of protection from fractures is directly related to the duration of hormone use. In one study, after three to five years of replacement therapy, the likelihood of suffering a fracture had declined by 11 percent. After ten years, the reduction was 50 percent. Decreased risk of hip fractures, wrist fractures, and spinal fractures were all observed!

The evidence clearly indicates that most women don't need to go through the second half of life with curved spines and fragile, weakened skeletons. Once again, the hormones we had when young are capable of securing us a quality of physical life much closer to youth than to the conventional image of old age.

Estrogen Protects Your Mind

Research conducted by scientists at McGill University indicates that estrogen also helps protect women from Alzheimer's disease. The researchers studied 253 older women over several years and found that 18 percent of those who had not had estrogen therapy were subsequently diagnosed with Alzheimer's compared with 7 percent of the women who received the therapy after menopause. In another study researchers examined the death certificates and the medical charts of 2,418 women who had lived in Leisure World retirement communities in southern California and had died between 1981 and 1992. Those who had been on estrogen turned out to be 40 percent less likely to have suffered Alzheimer's.

Even in healthy postmenopausal women, estrogen seems to support memory. When doctors at Stanford University gave recall tests to seventy-two older women who were estrogen users (average duration of use: thirteen years) and a control group of seventy-two women of similar age and education who did not take the hormone, they found that the ability to remember names was 39 percent better among the estrogen users. As we mentioned previously, this corresponds very well with the known biochemistry of the brain. Men need estrogen for proper brain function just as much as women and therefore convert a small amount of testosterone to estrogen within their brains.

Eventually, as we learn more about the brain, all of this should make perfect sense. Research by Dr. Bruce McEwen at Rockefeller University in New York, indicates that the steroid hormones provide potent chemical signals to the neurons in our brains even when delivered by substances not originally generated in the brain. Thus estrogen, progesterone, and testosterone—all of which are potent steroids—appear to directly affect the central nervous system, and the female hormones have been shown to influence such crucial neurotransmitters as dopamine, acetylcholine, and serotonin.

Those neurotransmitters are also significant for controlling mood and that could explain the increased frequency of depression in postmenopausal women.

Whatever the final conclusions may be, research on estrogen and the brain indicates that it has a powerful role to play in maintaining healthy brain function.

MATTERS OF THE HEART

It's surprising but true that when interviews and surveys are conducted among American women, almost all of them are aware of the fact that bone loss accelerates after menopause but relatively few realize that heart disease also increases rapidly. So single-minded has been the emphasis on heart disease as a male health risk that few people realize that heart attacks are the greatest single cause of female death as well. Of course, few women have heart attacks in their forties or fifties. That tends to blunt the fearfulness of this killer. A whole crop of men are dead long before sixty because of heart attacks. The increased risk of heart disease does not really begin until several years after menopause.

Nevertheless, if longevity appeals to you—and you shouldn't be reading this if it doesn't—and if you're a woman, you had better start thinking about the health of your heart. The extraordinary fact is that women would almost certainly be more prone to heart disease than men if it weren't for the protection given them by their hormones. After all, women have smaller blood vessels, which are consequently easier to block. That's one reason that women catch up to men in cardiac risk after menopause. Most men have been blocking their arteries since they were in their twenties. A famous series of autopsies conducted on young American soldiers who had died in battle during the Korean war found that there was already considerable evidence of atherosclerosis in the arteries of these young men with an average age of twenty.

Yet, after women go through menopause, they catch up within a few years and by their late sixties, they are having heart attacks as often as men.

Epidemiologists—medical scientists who study disease as it appears in large populations—have been conducting studies for decades to determine if replacement of female hormones will help protect women from heart attacks. The evidence is strongly positive. Evaluations by some of the leading epidemiologists in the country at institutions like Harvard and the University of California have reported that when all the evidence is gathered, there is a reduction in the risk of death from heart disease among women receiving hormone replacement therapy of as much as 50 percent over nonusers. In other words, if you don't take estrogen, you may be twice as likely to die of a heart attack in the decades after menopause than if you do.

A meta-analysis comparing thirteen leading studies done in the '70s and '80s to determine estrogen's effect on heart disease concluded that in any group of postmenopausal women on estrogen, 5 percent more would die annually if they were not on the hormone.

The reason for this protective effect is quite complicated and, indeed, not completely understood, but higher levels of "good" HDL cholesterol and lower levels of "bad" LDL cholesterol are definitely part of the picture. Studies have also found that glucose and insulin levels are lower in treated groups, and doctors have become more and more aware in recent years that high insulin levels are a significant risk factor for heart disease.

WHAT SORT OF ESTROGEN? WHAT SORT OF PROGESTERONE?

Having done what I can to make the case for replacement of the female hormones, I want to talk about what I regard as the very best program you can use. I am indebted to Dr. Jonathan Wright of Kent, Washington, who did much of the original clinical research on this method of estrogen/progesterone replacement therapy. The therapy combines three kinds of estrogen with natural progesterone.

First, let's look at estrogen. In your body, estrogen is actually composed of three hormones called estrone, estradiol, and estriol. Estrone and estradiol are more commonly used in estrogen therapy because they are more potent estrogens. Unfortunately they are also more prone to promote cell growth and therefore may contribute to the possibility of cancer. Estriol is a much weaker estrogen but equally effective when given in sufficient quantities. Moreover, studies have shown that estriol actually has an anti-cancer effect. In 1978 Dr. Alvin Follingstad published an article in the Journal of the American Medical Association, in which he proposed that estriol should became the main form of estrogen used in hormone replacement. Further reinforcement of his views came from a study in which 37 percent of women with a fast-spreading form of breast cancer experienced arrest or regression of their lesions after taking estriol.

The most commonly used form of estrogen is known as conjugated estrogens, one of the most prescribed examples being Premarin® (made, incidentally, from pregnant mares' urine, sometimes referred to irreverently as "horse-piss" estrogen). Unfortunately estrogen in this form is mostly converted to estradiol in the body. Dr. Wright's breakthrough was to prescribe a form of estrogen that he called tri-estrogen. Tri-estrogen is a combination capsule containing 80 percent estriol, 10 percent estrone, and 10 percent estradiol. The estrone and estradiol components are needed because in order to obtain the optimal beneficial effects of estrogen using only estriol, it would be necessary to give 10 to 15 mg a day, and, at that dosage, some women experience nausea.

It is most convenient to use tri-estrogen combined with natural, bioidentical progesterone, specially compounded by a pharmacist to be all in the same capsule, for a total doses of either 1.25 mg or 2.5 mg of estrogen and 100 mg of progesterone. This is taken twice a day. The lower dose is equivalent to .625 mg of Premarin and the higher dose to 1.25 mg. The dose is individualized for each woman. By combining the estrogen with natural progesterone in the same capsule, menstrual bleeding is usually suppressed, which eliminates the need for monthly menses and also eliminates the need to cycle the dosage. Because the progesterone is taken throughout the month, the action of estrogen on the lining of the endometrium is blocked, i.e., there is no build-up of the lining and therefore nothing to be sloughed off and expelled from the uterus in the way a woman has experienced each month during menstruation. During the first few months after this replacement plan is put into place, there may be some unpredictable bleeding. Then as the lining of the uterus shrinks down due to the action of progesterone, and the bleeding will stop. In virtually all cases, bleeding has stopped within six months. Some women may need a higher dose of progesterone to fully suppress unwanted bleeding.

Another option is to take the tri-estrogen for two weeks, add progesterone for 10 days, then stop both hormones for a week to mimic a monthly menstrual flow while on hormone replacement. However, most women would rather not be bothered with monthly periods after menopause.

In women who have a uterus and have not had a hysterectomy, long-term estrogen without progesterone (certainly in the conjugated estrogen form usually prescribed) has been shown quite clearly to cause precancerous changes in the uterus that may eventually lead to uterine cancer. This is because the buildup in the lining of the uterus that, in a normal menstrual cycle occurs only during the first half of the month, becomes a continuously stimulated with unopposed estrogen, causing excessive cellular proliferation. Add progesterone to the estrogen, however, and this effect is prevented. It is also possible to cycle doses of estrogen and progesterone during different parts of the month in a more complicated regimen that more closely mimics a normal menstrual cycle, but, as described above, most women prefer to take progesterone throughout the month, sparing the themselves the need for lifelong monthly bleeding.

I believe it is much better to use natural progesterone, identical to that produced by the ovaries prior to menopause, and not a synthetic progestin. Most women receiving combined therapy are actually being prescribed synthetic progestins such as Provera (medroxy-progesterone acetate). Synthetic progestins have distinct differences from the natural forms of the hormone, which are usually derived from raw materials in soybeans or Mexican yams.

Research shows that synthetic progestins do not rebuild bone as effectively as natural progesterone. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial sponsored by the National Heart, Lung, and Blood Institute some years ago also showed that heart-protective HDL cholesterol levels were significantly higher in women using natural progesterone.

Some of the Most Commonly Asked Questions About Natural Oral Progesterone

Question: What's the difference between natural and synthetic progesterone?

Answer: Natural progesterone, first crystallized in 1934, was derived today from plant sources. Bioidentical progesterone is an exact chemical duplicate of the progesterone that is normally produced by the ovary. Synthetic progesterones, called progestins, only mimic some of the actions of progesterone. The body does not respond in the same way, and studies have shown that progestins actually reduce the level of progesterone in the blood stream. In the recent Women's Health Initiative study, it was only the women receiving synthetic progestins who allegedly had a 0.08 percent increased risk of breast cancer.

Question: Are there side effects with natural progesterone?

Answer: Natural progesterone is short on side effects because, unlike synthetic forms, it can make a perfect connection with progesterone receptor sites in cells of the body. Perhaps the only disadvantage to natural progesterone is that it is short-acting, and to maintain adequate blood levels it has to be taken at least twice daily. A small number of women initially experience transient lightheadedness or drowsiness. Natural progesterone can be absorbed by mouth by making the particle size is very fine—so-called "micronized." It is no longer necessary to use a skin cream, as in the past.

Question: Is the oral form of natural progesterone approved by the FDA?

Answer: Natural progesterone has FDA approval. When combined with estrogen in the same capsule, the oral form of natural progesterone can be compounded from a physician's prescription by a licensed pharmacist using approved ingredients.

The reason synthetic progestins (such as Provera®, generic name medroxy-progesterone acetate) were originally developed was because, at that time, natural progesterone was not efficiently absorbed when taken orally. This is no longer a problem, since micronized progesterone became available. Many hormones, including estrogen, progesterone, and DHEA are most effectively absorbed by mouth when taken in a micronized form.

In my opinion, the combination of tri-estrogen with natural progesterone is best. But simple estradiol and progesterone may also be OK. Progesterone is given in 100 mg doses two times a day. The only way to obtain natural progesterone combined with estrogen in the same capsule is for your doctor to have it custom made by a compounding pharmacy.

To properly understand the so-called "sex hormones," it is important to realize that they do not relate exclusively to one sex. For example, brain function is dependent on estrogen in both sexes. Men convert some testosterone into estrogen in their brains.

Women also produce testosterone, in addition to estrogen. It is the ratio between male and female hormones that differs with gender—not the presence or absence of sex-specific hormones. In a young adult woman, the level of testosterone is approximately one-tenth that of a male. This relatively small amount of testosterone is very important for the female quality of life. Yet, after menopause, testosterone levels may also fall in women. Or female testosterone may continue or increase with less estrogen to offset any potential for facial hair or masculinization. Thus women, too, can experience a measure of what in men has been called andropause. Studies have shown that a woman's total estrogen production decreases by 70 to 80 percent following menopause and her testosterone production, on average, can also fall by 50 percent or more.

Women are fearful that if they use testosterone it will cause them to grow beards and develop deep male voices, perhaps even male-pattern baldness. Well, it's true that if a woman were given a male dose of testosterone (especially if there were no estrogen to oppose it), she would probably experience some of those changes. (Similarly, men given high doses of estrogen will develop feminizing changes such as enlarged breasts) If the ratios between male and female hormones are correct for gender. If levels of both estrogen and testosterone do not exceed the normal hormonal output of a healthy woman of child-bearing age, then such problems are simply not observed.

In a study reported by Dr. Angela Bowen at a meeting of the North American Menopause Society in the 1990s, it was shown that a low dose of androgen (testosterone) given with estrogen replacement therapy was more effective than estrogen alone. In a randomized study, a number of older women were divided into two groups. One group received only estrogen, and the other group received estrogen combined with testosterone. Both treatments were well tolerated and both treatments improved the symptoms of menopause. But it was only the group whose treatment included testosterone that experienced significant relief from fatigue, insomnia, irritability, and nervousness. When treatment was stopped, benefits in the testosterone group continued for three weeks or longer. The estrogen group relapsed immediately.

There is an additional, gender-related factor. Testosterone promotes sexual desire in women just as it does in men, and the testosterone drop after menopause may cause loss of sex drive that is common after menopause. A study done as far back as 1983 showed a clear correlation between the levels of testosterone in women after menopause and their desire for sexual activity. Recent studies have shown that women who combine estrogen with testosterone in their hormone replacement therapy showed a statistical increase in sexual frequency and satisfaction compared with women who are treated with estrogen only or with nothing at all.

WHAT ABOUT CANCER RISK?

Finally, we come to the difficult question: will hormone replacement therapy cause cancer? After forty years of extensive research, the answer remains in doubt: Yes and No! Here's another question: Are there any cancers HRT will protect you from? And the answer is: Probably, yes.

I wouldn't deny any woman the right to be terrified of cancer. It's a terrible disease, and anyone who has seen a loved one suffer with it has earned the right to be cancer phobic. But the truth is now that we combine natural progesterone with estrogen to quell the threat of uterine cancer, I do not believe that the overall risk of cancer is significantly increased, and it is probably decreased.(Women who live longer because of hormone replacement may eventually have a slightly increased incidence of cancer, but we all eventually die of something, preferably later than sooner. Studies to date leave the cancer question in doubt, but if the risk is that difficult to detect, then it must be tiny, if not non-existent.

Let me give you an analogy, which I certainly don't offer in an attempt to be humorous. Without estrogen, breasts shrink—Presto!, less breast, less cancer. That is one choice, although many other potential benefits of estrogen are also lost.

Let's imagine that human beings had a specific incidence of cancer in their fingers. Suppose that if you lived to be a hundred with full finger function intact, you'd have a 10 percent chance of suffering finger cancer. Any way to lower that risk? Well, you could amputate a finger—or even all ten. No more finger cancer. There is, of course, a comparable analogy in the real world. One out of every three American women has had her uterus removed before the age of sixty.

In the situation that I'm imagining, there would be another approach. Let's assume that hormone replacement was necessary to maintain that full range of finger function we spoke of. Without hormones, the fingers would atrophy and have less bulk and cell mass. And let's also assume that without hormones the risk of finger cancer declines from 10 percent to 9 percent.

This is, I believe, a fairly exact description of what occurs with estrogen and breast cancer. It is not that estrogen causes cancer. Rather, it is that allowing breasts to shrink and atrophy from estrogen deficiency means there is less cell mass in which cancer can occur. By replacing deficient hormones, breasts reamin larger, have more and larger cells, and these cells divide more frequently to replace cells that have worn out and died. It's regrettable that this should increase cancer risk, but it may in a very small way.

You don't need, of course, to maintain normal, youthful breasts to enjoy the second half of your life, but, as we've seen, you certainly can use all the other advantages, including the probability of a longer life span, which hormone replacement therapy offers you.

My recommendations for treatment of a woman after menopause is first to ensure no history of breast cancer and, on physical examination, no evidence of breast lumps that could be malignant and have not been first evaluated, and no exceptionally strong family history suggesting a genetic trait. If indicated, mammograms should be done—sometimes even a biopsy. To ensure uterine safety, pap smears are done, and, if abnormal uterine bleeding has been present in the past, an endometrial or intrauterine sampling to rule out any hidden malignancies. An annual breast and gynecologic examination should detect any early warning signs in time to prevent serious problems. Some women on estrogen opt to have a mammogram yearly. It is no longer considered important to do PAP smears on women after hysterectomy.

Let me interpose a warning here, that there are a few women who inherit a genetic trait for high familial risk of breast cancer—and sometimes for ovarian cancer also. What I have written here does not apply to that small group. They will know whether or not this applies if a large percentage of female ancestors and female relatives had breast cancer.

A further encouraging note on the issue of estrogen therapy. The Journal of the National Cancer Institute reported in April 1995 on results from a seven-year study of estrogen use and colon cancer. They found that women who took estrogen—even though it was for less than a year—reduced their risk of dying of colon cancer by 19 percent. Women who had taken estrogen for eleven or more years were 46 percent less likely to die of the disease. Scientists have speculated that estrogen lowers the concentration of bile acids, thereby creating an environment less conducive to growth of cancer cells in the colon. Another theory has it that estrogen directly suppresses tumor growth in the lining of the colon. Either way, the effect on women's life expectancy is significant, since after the breast and lungs, colon cancer is the third highest killer cancer in women.

So, there is convincing evidence that estrogen actually prevents cancer.

To state this yet another way: Studies showing that estrogen replacement reduces the overall death rate by up to 40%. Included in those statistics is death from cancer. If, for example, post-menopausal hormone replacement reduces the death rate from cardiovascular disease, women who would otherwise succumb to heart attacks live longer and a few might eventually get breast cancer—when they would have died from another cause at a younger age. How can that be undesirable?

One final point about cancer. Preventing it can enhanced with the aid of a full program of healthy living. When percentages are given for the number of people who are going to get breast cancer or prostate cancer or any other common malignancy, those figures are based on a population that contains very sizable numbers of people who do not eat properly, who do not take supplemental vitamins and minerals, who do not exercise, and who smoke or drink too much. Their risks are much different from yours, if you're a person who's seriously trying for a long and healthy life.

In 2006 a study at Harvard Medical School concluded that women who begin hormone replacement soon after menopause experience a 30% reduction in coronary heart disease. This study contradicts previous scary interpretation of the Women's Health Initiative.

Stampfer MJ. Hormone Therapy and Coronary Heart Disease: The Role of Time since Menopause and Age at Hormone Initiation. Journal of Women's Health. Number 1, 2006 15(1):35-44.the Women's Health Initiative.

CONCLUSION

In spite of the abundant advantages of hormone replacement therapy, the estrogen choice remains a tough one for many women. They wonder how great the breast cancer risk is, they wonder whether the expectation of increased longevity is really as soundly based as it appears to be. A totally definitive answer cannot be given at this time, but the evidence I've given above is not only quite convincing but supported by a lot of research. The links below on my website will give you more about actual clinical studies.

HRT References

Women's Health Initiative Debate

Actual data from the Women's Health Initiative Study that caused many women so much grief.

Out of every 10,000 women in the study taking estrogen combined with a synthetic progestin, and followed for only 5 years, and many started on hormones for the first time at age 60 or older, many years after onset menopause:

38 developed breast cancer each year compared to 30 breast cancers for every 10,000 women taking placebo pills each year: from 0.30% to.38%, an increase of 0.08%

37 had a heart attack compared to 30 out of every 10,000 women taking placebo: from 0.30% to 0.37%, an increase of 0.08%.

29 had a stroke each year, compared to 21 out of every 10,000 women taking placebo: from 0.21% to.29%, an increase of 0.08%.

34 had blood clots in the lungs or legs, compared to 16 women out of every 10,000 women taking placebo: from 0.16% to.34%, an increase of 0.18%.

Copyright © 2012 Elmer M. Cranton, M.D., all rights reserved

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