Estrogen Therapy

Estrogen: The New Reality Show

“What’s amazing is, I didn’t even think of lack of focus as a symptom. I thought my life force was being slowly drained. So just knowing there is a veil is a comfort. And after one day on bioidentical estrogen, I felt the veil lift. After three days, the sky was bluer, my brain was no longer fuzzy, my memory was sharper. I was literally singing and had a skip in my step.”
~ Oprah Winfrey on the subject of hormones

In my practice of Reproductive Endocrinology, I’ve had to evaluate and treat patients with excess of hormone and hormone deficiencies. The most common type of deficiency is found in menopausal women. If we consider that menopause occurs after the age of 40 and the average life expectancy for a woman in America is about 83, we can say that approximatively half of the American women are affected with hormone deficiency. Since women are representing about half of the US population, at least one fourth of the US citizens will eventually be hormonally deficient. In the current census, the population of the United States of America is about 330 million. Therefore, if we divide that number by four, it results in a lot of citizens with a naturally occurring hormone deficiency. It is estimated that only 30% are adequately treated, but only one third of them are compliant or follow their treatment conscientiously. This chapter is not going to be a boring scientific paper like the few I have written during my medical career regarding this particular subject. It’s only a story about my experience with this issue and a call for common sense.

Cultural Shock

When studying and reviewing the primate species, researchers found that humans are the only primates that don’t die within a few years of “fertility cessation.” For the vast majority of species, the animals don’t live long after they stop reproducing, and menopause appears to be a circumstance related to captivity that occurs only in some individuals, not the entire species. Menopause is a purely human phenomenon.

My first steps in Endocrinology (1967-1969) took place in a very conservative environment and the philosophy of my French professors was: “Let nature take its course.” When the ovaries stop working at the end of the reproductive life—between the ages of 38 and 45—causing a few miseries, there is no reason to intervene. Do not interfere with Mother Nature unless it’s absolutely necessary. Estrogens can correct hot flashes and cold sweats, but they should only be used for a short period of time. “Women need to adapt to their miseries by increasing their activities and all the associated complaints should be treated symptomatically.”

When I arrived in Augusta, I was exposed to Dr. Greenblatt’s philosophy: “All women will potentially be menopaused and if they complain of symptoms or miseries that can be attributed to a lack or decrease in estrogens, don’t hesitate. Treat them with the available hormone as long as you deem it necessary or as long as the patient wishes it.” Many patients were seeing Dr. Greenblatt for treatment consisting of hormone pellets. There were a huge number of ladies returning. A lot of them were from Augusta or the Central Savannah River Area, but also many were travelling four to ten hours to be seen and receive the salutary treatment. They were coming from states like Florida, Louisiana, Mississippi, North Carolina or Tennessee. It was amazing and the results were astounding. The women could be in their fifties, sixties or even seventies. They looked good, were alert, lively and grateful. They all had a story describing how the hormone treatment had saved them or transformed their lives. We would have to be blind or stubborn to refuse to acknowledge the obvious satisfactory results. It did not take me long to be convinced. Actually, it was not a new subject matter. In 1966, New York gynecologist Robert A. Wilson published a best-selling book, “Feminine Forever,” in which he maintained that menopause was an estrogen-deficiency disease that should be treated with estrogen replacement therapy to prevent the otherwise inevitable “living decay.” His book explored the issues raised by the convergence of Wilson’s campaign and the emergence of the women’s movement.

The Menopausal Miseries

Menopause means cessation of menses, but it’s not uncommon to see a persistence of menses when the ovaries have already stopped functioning. This short period in time is called peri-menopause. Let’s review the miseries that can affect menopausal or peri-menopausal women.

First, the subjective ones. The best known and most obvious to patients are hot flashes and cold sweats. Then come some isolated or combined symptoms such as migraine headaches, irritability, heart palpitations, mood swings, anxiety, depression and lack of memory. Other often mentioned subjective signs are insomnia, lack of energy and lack of sex drive (libido). Then there are the objective miseries that take a little longer to appear: vaginal dryness accompanied by painful intercourse (dyspareunia), urinary frequency and painful urination (dysuria) that mimic a urinary tract infection. Finally, the most insidious and dangerous one, osteoarthritis with a loss of bone structure or osteoporosis. If doubts persist it’s easy to confirm or evaluate the problems importance with laboratory tests.

When the miseries occur suddenly around or after the age of forty, you would think that the first thing to do for a physician would be to administer hormone and see if the symptoms disappear. None of that. Unfortunately, nowadays like in the past, traditional medicine does not see it that way. Most of the time, if a middle-age woman suffers from anxiety or depression, she will be referred to a psychiatrist and will be treated with tranquillizers and/or antidepressants. If she or her husband are unhappy about her lack of sex drive, they will see a psychologist or a marriage counselor. For heart palpitations or sinus tachycardia they will be sent to a cardiologist. For urinary symptoms like painful or frequent urination, even in the absence of a urinary tract infection they will go to the urologist or the emergency room. And when old women break their spine, their hip or forearm following a light fall, they have to be treated by an orthopedic surgeon when it would have been so easy to prevent osteoporosis with an adequate estrogen replacement prescribed much earlier by her primary care physician (PCP).

So many medical treatments or surgical procedures with all associated expenses, aggravations, loss of time and quality of life could have been prevented with a simple hormonal treatment. It should have been started when the patients were consulting for symptoms that could be attributed to menopause and when hormonal deficiency was detected. It’s true that a few women cannot take hormone because of contraindications, but most of them (98%) can. I cannot count the number of times when menopausal women reached our office after having visited two or three specialists with disappointing results because they were treated for their symptoms and not the real cause of their problems. After a complete evaluation we only have to give the patients an appropriate hormonal treatment to get rid of their miseries. The results are invariably good and they believe we are “miracle workers.” It’s that simple but stupid and sad that women have been denied proper treatment. Menopause, a Neglected Subject

Since menopause is an ailment that affects nearly one fourth of the population, we would think that a problem of such magnitude would be taken seriously by the national health care agencies, the insurance industry and academia. This is not the case. The problem is actually neglected. Third party payers cover poorly the reimbursement of the medications and the subject is not well taught in medical school and in specialty residency programs. The senior medical students or young physicians who rotate through my practice admit that their instruction programs have minimally addressed the subject regarding sex steroid metabolism, pathology and treatment of hormone deficiency in the menopausal woman. They tell me that what they learn in my office is totally new to them.

For example, during my fellowship in Endocrinology (1969-1970) we learned in depth the biochemistry, the pharmacology and different ways of treating patients with hormone deficiency. Our scientific program directed by Dr. Virendra Mahesh was among the first to study hormone receptors. Then, we could find in Dr. Greenblatt’s office the perfect field for the application of our lessons. As said earlier, we were seeing in his practice many, many women who were consulting for symptoms that could be related to menopause. The endocrinology Fellows published a lot of scientific papers on the subject and they all, without exception, became enthusiastic prescribers of estrogen therapy. Being good disciples, they spread the word and practiced what they learned wherever they went.

A few years later, following my fellowship, during my residency in obstetrics and gynecology (1973-1976), I found out that the subject of menopause was poorly covered. There was much more emphasis placed on surgical and obstetrical techniques, pathology, infections and management of complications. We were very well trained on all matters except on menopause. The chapter existed in our textbooks but it was overlooked, ignored or very briefly covered. In fact, I don’t recall seeing any questions regarding this particular subject on our specialty board exams. It was not my business, but several personal observations tell me that some of my professors did not treat their wives’ menopausal miseries. I believe that this lack of concern is still prevalent in most teaching programs. As a result, many physicians specialized in women’s health care shy away from treating menopause or give very small doses of hormone for a short term that are inefficient. When I ask them why, they tell me that they don’t want to get sued because of a potential poor outcome or fear of any complications and, without shame, say that they’d rather practice a defensive medicine than take any chances. To which I retort: “After forty-five years of medical practice, I, or my associates, have never been sued for providing hormonal treatments and most of the outcomes have been excellent.”

So, if obstetricians and gynecologists are not well trained in hormonal replacement therapy (HRT), how could we expect family physicians or PCPs to know better? I would say the same thing about general surgeons or cancer specialists who certainly know a lot about their specialty but ignore the detrimental effects of hormone depletion and show no compassion for women suffering from menopausal symptoms. This will be also discussed later in this chapter.

It’s very simple. There are several endocrine glands and their excess or insufficiencies have to be treated. For some of them it’s a matter of life or death.If the pancreas does not function properly, insulin treatment is indispensable. Thyroid medication is necessary to reverse hypothyroidism. If the adrenals are not working, cortisone is lifesaving. Then, if “males” testicles are not producing enough testosterone –“Low T”– they need to receive male hormone in the form of, patches or injections and amazingly, PCPs do not hesitate to treat them and insurances are usually prompt to cover male treatments. So, why make such a fuss about replacing the “females” loss of hormone? Is it because there are so many of them and the cost would be too high or is it because of the fear of adverse effects, which are, as we will see, so minimal?

Vacuum Effect

In the meantime, many women seeking relief from their miseries–which can happen to be unbearable–have to face physicians –PCPs or Ob-Gyns— who refuse to treat them or want to prescribe small doses that have no chance to satisfy their patients. There is a whole industry out there, that is ready to exploit this flagrant vacuum or gap in traditional medicine. Through word-of-mouth or the web, menopausal women can obtain what they need and many of them seek help the best way they can. It’s not always the best solution but it’s better than nothing or what their personal physicians were offering to alleviate their problems.

The most commonly encountered solution comes from a “Compounding Pharmacist” who advertises on TV, gives lectures, checks the hormone levels via saliva and prescribes products that can be purchased over-the-counter through a magical cream formulated with several hormonal components. It’s not cheap because the ladies buy tickets for the lectures, pay about $200 for the saliva test with results given on a fancy sheet with colored curves. And there is an additional expense for the tailored cream that will have to be renewed every three months.

One of my new patients who was dissatisfied with the results from the compounded drug admitted that she had to pay a total of $450, not covered by her insurance. In my office, she received a complete comprehensive medical exam. A simple blood work was ordered and a relatively inexpensive but efficient “FDA approved” medication containing a natural estrogen –estradiol patches–was prescribed. Her insurance covered consultation, blood work and medicine and she was soon very satisfied with the results of her treatment. There is a need for compounding pharmacists and in my practice, I have often prescribed drugs that needed to be compounded. For the first twenty years that I practiced medicine in this country, I deplored the absence of compounding pharmacists in the USA. After the early 1990’s, the American pharmacy schools resumed teaching drug compounding, an art that had disappeared or had been forgotten. Nowadays, there are a great number of pharmacists advertising for their compounding abilities. We can find them in every city and there are at least six of them in Augusta. They can advise and dispense a very useful service. However, they don’t have the ability or the expertise to provide a comprehensive medical treatment.

The saliva tests are extensive, expensive and despite their apparent complexity, are predictable; therefore unnecessary. Even more interesting is the fact that when the results are received, the patients are always told that they are very low in progesterone. Why bother measuring progesterone, a hormone that cannot be produced anyway by menopausal women since it’s the hormone of pregnancy. The term “progesterone” originates from “progestation.” It’s a waste of time unless there is another reason like, I guess, an excuse for ordering a progesterone cream which can be sold over-the-counter, without medical prescription.

Some older Ob-Gyns who don’t want to deliver babies anymore have tried to convert their office into a “hormonal practice.” Unfortunately, like many of their colleagues, they have been poorly trained on the subject and instead of completing their learning and practicing sound medical endocrinology, they associate themselves with a network of compounding pharmacists and saliva testing labs.

Some other physicians are associated or employed by Wellness Centers. They can be found on the web and they usually promote their services with appealing advertisements like: “Avoid the Roller Coaster! Optimize today! Regain energy & strength! Heighten mental clarity! Increase quality of life! Feel younger & happier! Age healthier!” They also use some expressions like “life revitalization,” “youth renewal,” “rejuvenation,” always using the word “bioidentical hormone,” a marketing term rather than a scientifically meaningful one. It sounds better than “natural hormone,” which, actually, is the real scientific term. I was told that they charge about $2,500 per year, to be paid in advance, that include three blood works and four pellet injections. In their commercials, they sound like peddlers selling snake oil, giving a bad reputation to a good cause. It’s a shame that many menopausal ladies have to obtain relief of their illness in “pop-up” clinics. All of these services should legitimately be provided by the patients’ PCPs or their gynecologists.

Finally, some menopausal women seek relief of their symptoms with herbal medicine. Black cohosh, red clover, chaste-tree berry, dong quay, evening primrose, ginkgo, ginseng and licorice are among the most popular herbs. They can also try “phytoestrogens,” compounds that naturally occur in plants. They’re found in a wide range of plant foods. A plant-based diet –especially when soy is included — can be rich in natural phytoestrogens. They are ineffective unless taken in very large amounts, making their use cumbersome and impractical.

Fake News

We cannot count how many times we’ve heard or read journalists; news casters, speakers or other supposedly well-educated people start a sentence with the following statement: “Since estrogen causes breast cancer…” It is announced without ambiguity and the listener or the reader is to accept it as an empirical statement, based on subjectivity rather than pure logic or scientific demonstration. In metaphysics, it would be called a dogma or a principle laid down by an authority as incontrovertibly true, without any possible discussion. Indeed, in some studies synthetic estrogen has been linked to an increase in breast cancer due to prolonged exposure; however, the data were considered inconclusive. There are other studies — with either synthetic or natural estrogen–not as much publicized, that have shown a decreased incidence in breast cancer. The bottom line is that there is no obvious causal effect. There is an exaggerated fear of cancer provoking a national phobia for estrogen treatments.

Undoubtedly, estrogen stimulates the breast tissue as it does all female reproductive organs. Therefore, estrogen receptors are found everywhere in the mammary glands. So, if a woman is found to have a breast cancer, she should not receive any estrogen that could stimulate the cancer as it energizes all breast tissue. But it doesn’t mean that it’s the spark that initiated the cancerous process. In the US, one in eight women will eventually be diagnosed with breast cancer in their lifetime, the most significant factor being aging. Most cases occur in the patients’ 70’s or 80’s. Whether or not a woman has used a hormone treatment the ratio is the same. Breast cancer deaths have been declining since 1990 thanks to early detection, better screening and increased awareness. When counseling patients I usually compare the breast tissue with logs in a fire place and estrogen with oil. You can throw as much oil as you wish on the logs and it will not start a fire. Now, if the logs are on fire, any addition of oil will feed the fire. This is why we make sure that all patients on hormone therapy have a yearly mammogram and perform monthly self-breast examination.

Here, I would like to briefly mention that there is a small subset of breast cancers that do not arise from estrogen dependent mammary tissue. They are generally more aggressive, difficult to treat and the most lethal. Flawed from the start, the Women’s Health Initiative (WHI) research has deprived menopausal women of hormone therapy (HRT) that could have helped. It did not make any sense because they didn’t use a natural hormone. They used an estrogen manufactured with pregnant mare’s urine (Premarin). If it was used in association with a synthetic (not natural) progesterone (Prempro), there was an increased breast cancer risk. But estrogen-alone decreased breast cancer risk, an effect that became statistically significant over the total follow-up time of 13 years. In other words, we received a lot of alarming proclamations for nothing. In addition, the authors of the study made no mention of the patients’ weights; which is a serious error, knowing that being overweight or obese definitely increases the risk of breast cancer. The long-term national study, which was initiated in 1991, has misguided and poisoned the medical literature and trend of thought.

Large epidemiological studies in Western European countries where medicine is socialized allow for easier tracking of many participants over many years. In the E3N Women Prospective study, tens of thousands of women are being followed over many years. In January 2008, with eight years of follow up, data was released from E3N showing that women using natural (a.k.a. bioidentical) hormones still had the same risk as women using no HRT of any kind. However, women using synthetic HRT (extracted from pregnant mare urine) had a slightly higher risk of breast cancer. The conclusion of the study was that, “when both duration of use and the last period of use were analyzed together, no significant increase in breast cancer incidence was observed in any of the four subgroups considered,” and, “From internal analysis, there was no significant increase in the risk of breast cancer related to natural hormones.”

Opinion Readjustment

Hormone therapy has received such a bad press from an alarmist and poorly informed news media that many physicians have remained uncertain about prescribing hormone therapy for menopausal women. It prompted an American Society of Reproductive Medicine (ASRM) workshop in November 2005. It convened a multidisciplinary group of healthcare providers to discuss the risks and benefits of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women who were suffering from menopausal symptoms. It focused on peri-menopausal and menopausal women. The conclusion was that “symptomatic women should be offered the option of hormone therapy. There is clear evidence that it improves vasomotor and urogenital symptoms and provides benefits to many women with sexual dysfunction and psychological disturbances related to estrogen deficiency. Taken together, the beneficial effects of hormone therapy for many women far outweigh the risks and provide an overall improvement in the quality of life. Thus, the fears of hormonal therapy in this setting do not seem to be justified. All hormone therapy should be individualized. This involves prescribing the regimen and dosage according to individual needs.” I rest my case.

Reassessment of a Medical Bias

Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. Unfortunately, some medical opinions have been forged with minimal knowledge and studies. They can be so deeply ingrained in some of our colleagues’ brains that we are sometimes facing the task of Sisyphus in Greek mythology. He was forced to roll an immense boulder up a hill only for it to roll down again when it neared the top, ad infinitum.

Surgeons and oncologists deal directly with the victims of breast cancer. They are often prompt to blame hormone whether the patient has recently taken hormonal treatments or has not taken any hormone since she took oral contraceptives for one or two years at the beginning of her reproductive life. It has become an obsession. I don’t argue with the fact that a patient who has just been diagnosed or is treated for breast cancer should discontinue estrogens because we know that the breast tissue is stimulated by estrogen. It makes sense, but it doesn’t mean that estrogen caused the problem.

Once the cancer is treated and considered as cured, the patients who continue to suffer with the menopausal miseries request the relief of their symptoms which can generally be achieved by resuming HRT. Surgeons and oncologists persist in being adamant about forbidding prescription of estrogen. Indeed, they have for a long time been permanently contraindicated for women who had a history of breast cancer. A prominent and very experienced gynecologist oncologist from Charleston, SC, Dr. William Creasman, has reviewed several studies regarding the effects estrogen has on the breast. His conclusions were that HRT may be of benefit to women recovering from breast cancer. “There have been several retrospective as well as case-controlled and cohort studies demonstrating that HRT can be given to the post-breast cancer patient without a negative impact on survival. The retrospective studies show very low recurrences and death rates.” Also, he noted that there are fewer recurrences and mortality compared with match controls. Dr. Creasman’s publications can be found in the scientific literature or on Google Search.

Final Thoughts

The fears of hormonal therapy do not seem to be justified. Its beneficial effects for many women far outweigh the risks and provide an overall improvement in the quality of life. There are very few side effects and they can be easily controlled. There are very few contra-indications: liver disease, blood clots, stroke or heart attack and obviously a breast cancer while being treated. But when the cancer treatment is over, the patient should be able to resume HRT.

Scientific studies have proven that estrogen stimulates the production of collagen, which consists of 75% of the body’s natural protein and is located in every part of the body (skin, hair, nails, bones, muscles, blood vessels and brain).

Women are now living in a different world. Many of them at the time of menopause occupy an important position in society. Some are business executives; some others are engineers, doctors, lawyers or judges. Hormone replacement will preserve energy, good judgment and good memory that are needed to accomplish their task. The ratio of women to men in the US Congress and Senate is 23 to 100. They need to compete with men for jobs and performances. If they are menopausal and not on HRT, they have a significant disadvantage because most men continue to produce testosterone for the rest of their lives.

Many of our patients who return to our office once, twice or three times a year –depending on the type of treatment they are following—are grateful for the fact that their life quality has been strikingly improved after being on hormonal replacement. When they are willing to talk about their experience, I ask them to tell their story to the students or young physicians who are shadowing me. There are a lot of different stories and they are often very interesting and touching. For example, a few of them relate being healed from a severe depression that could not be relieved by psychiatric treatments. Some other patients thank us for saving their marriages. Our nurse practitioner, Aprile Melton, who — after practicing for thirty years in our clinic has an extensive experience in hormonal evaluation and treatment– claims that we are probably more efficient in the prevention of mid-life divorces than any marriage counselor.

No medication other than estrogen can provide a better protection from bone loss. All our patients who are in their sixties or seventies and have been faithfully following their hormone therapy, have a near-perfect bone density. They have a strong spine and do not exhibit the “widow’s or dowager’s hump” that we see so often in aging women.

With the outcry engendered by the feminist cause, we could think that the topic would have hit the headlines. But surprisingly, the women’s rights movement has remained relatively silent on the subject. Nevertheless, the feminist discussion of menopause revealed a larger women’s health agenda namely, the unyielding belief that women should retain control of their bodies and participate fully in the decision-making efforts regarding their health. All women, whether feminist or not, could ultimately better control their lives.

In conclusion, hormone therapy is not a fountain of youth, as claimed by some, but it definitely improves life quality and slows the aging process. Presently, many practicing physicians stir –by ignorance or misguided received information– the fear of estrogens. Consequently, a large segment of our society is being deprived of proper care. The medical schools should attribute more importance to the teaching of the menopausal drama and its treatment.

estrogen-therapy

Curve showing the effect of estrogen on bone loss by evaluating the metacarpal mineral content. An early treatment will prevent osteoporosis. A late treatment will stop the bone loss but will not make the bone recover its original mineral content.

A drawing showing the progressive deformity in menopausal women who are not receiving hormonal replacement.