Subject: Menopausal Hormones: Friend or foe?

From: Jean

Message: 

Reply from Dr. Bazos:

Dear Jean:

Your question is informative, extremely relevant and important to so many females. Before I answer your specific concerns I feel it important to give some definitions and some historical background to provide an understanding as to why this controversial topic has become so complicated.

These changes that women undergo are related to aging and to estrogen depletion. At this time, usually between 48 - 52 years old, their ovaries become depleted of follicles and stop making estrogen. In your case, Jean, menopause was created by your doctors after it was decided to surgically remove your uterus for painful heavy fibroids. If my math is correct this operation was done when you were about 46 years old. I have concerns as to why both of your ovaries were also taken out at that time. Presumably these ovaries were also felt to be 'diseased'. If you do not know for sure, then you are entitled to an explanation from your gynecologist as to why this was done.

You are taking Premarin which is the most commonly prescribed form of female menopausal estrogen hormone replacement. For the remainder of this discussion I will refer to menopausal hormones as estrogen hormone replacement therapy or HRT for short. Now Jean, I wish to review some of the advantages and disadvantages of taking estrogen as you have illustrated in your question.

BENEFITS OF ESTROGEN HORMONE REPLACEMENT THERAPY (HRT)
a. Treatment of Vasomotor flushes (hot flushes)
You made no mention Jean of any hot flushes. Presumably, you were started on estrogen immediately following your surgery and hence never experienced this symptom. These 'hot flushes' are the predominant symptom of postmenopausal woman that brings menopausal women to doctor’s offices. Our best understanding of what causes these flushes is an abrupt estrogen withdrawal phenomenon.

Estrogens are the best agent we as physicians have for providing rapid relief of these vasomotor hot flushes.

b. Treatment of Vaginal Dryness
I presume the "improvement in your private life" refers to this prevention of vaginal dryness. Vaginal dryness is a symptom of genital atrophy. In my experience I have seen that couples as they age can maintain and will maintain an active sex life as long as they are both physically healthy.  Women with genital atrophy will present to their doctors office with pain with intercourse, on entry, as opposed to pain with intercourse on deep penetration, which is more consistent with pelvic inflammatory disease. Pain with intercourse is termed 'dyspareunia'. I was taught by my learned-elders that "dyspareunia is better than no pareunia". If we doctors can rid these women of this symptom of genital atrophy, it would certainly help you couples a great deal with your "private" sex lives. In the past we were reluctant to ask patients about this and patients would feel unease discussing it with us. Your question Jean bears testament to this fact, in that you made no mention of your sex life, rather termed it your "private" life.

c. Prevention of Heart disease, A Historical Overview
O.K. Jean, put the coffee on and get out your bifocals. This is where it starts to get confusing. First of all let me point out that there is no long term randomized clinical trial with estrogens showing that it prevents heart disease. That is no long-term randomized trial without physician bias. So, Jean, you have asked the question: Do estrogens reduce risk for heart disease? And the answer is, it depends on the year the question is asked. In the 1950's everybody thought estrogens prevent heart disease, with the book "Feminine Forever". Sure enough clinical trials were done at that time giving estrogens to men at risk and low and behold what happened? More of these men died of heart attacks, strokes and blood clots. But those with metastatic prostate cancer lived longer with their cancer and rather died of heart disease while receiving estrogens. The message was clear: Estrogens were not safe for men. Then came the 70's and what were we seeing. Young women on the birth-control pill (BCP) were dying of heart attacks and blood clots. Mind you the dose of the BCP was almost 3 times the lowest dose you could prescribe now. So we've learned to lower the dose of estrogen in BCP. We later learned that this heart risk increases exponentially if you smoke as well as take the BCP. So what happened? Well, in the early 1970's, the BCP data suggested it was not felt to be safe for women. What a mess this created for Gloria Steinham, abortion clinics, women's activists, everyone had a field day. Then in the 80's the clinical studies suggested that estrogen replacement therapy was not only safe but actually reduced the risk for heart attacks. However, the physicians treating women in the 1980's may have been biased by data from the 1970's. If we dissect those studies done at that time we see that these women were a biased population who were wealthier, had more Pap smears, more blood tests, exercised more and ate healthier and of course hence lived longer with a lower incidence of heart disease. During this decade the healthiest, most educated, most sophisticated and wealthier patients were receiving estrogens and hence of course lived longer. These were selected self-patients. Then came the 90's. Long-term studies were done which concluded that you have to take estrogens for at least 17 years to have a significant reduction in the mortality of heart disease. This puts things in perspective. Then in 1998 came a prospective trial out of JAMA, which showed that estrogens actually increased the risk for heart disease in a high-risk population in the first year, but then ultimately caused a reduction over the long term. This study actually showed that if you went on hormones, and you don't have a heart attack in the first year, then you had a decreased heart risk after that. Well that's great, try explaining that to someone: I got some good news.... but first the bad news.

Now what if you already had a heart attack and wish to take estrogen for protection. Then I would suggest giving you a very low dose estrogen alone initially to get the full beneficial effect before I would start any combination progestin to reduce the risks for endometrial hyperplasia (a potential precursor to cancer).

We know that if you lower LDL cholesterol, you lower the risk of a heart attack. We know that HDL cholesterol, if it's very low, is a risk factor for heart attack and triglycerides; if they are high, are risk factors for heart attack; and fibrinogen, if it's high, is a risk factor for heart disease.

We don't know exactly how estrogens prevent heart disease. Ten years ago, the teaching was it was related to the lipid profile. This is too simplistic. It's probably because estrogens prevent atherosclerosis by serving as an antioxidant and we also know that estrogen is a very potent vasodilator. There are many different ways how estrogens might prevent heart disease.

d. Treatment and Prevention of Osteoporosis
Jean, you were correctly told that estrogens would make your bones stronger. Over 2 million Canadians suffer from either osteoporosis (weak and brittle bones) or low bone mass (osteopenia), which puts them at risk for pain and disability associated with fracture. Fractures of the hip, spine (vertebrae) and forearm (wrist) are the most common. Risk factors for osteoporosis hip fractures include: females, estrogen deficiency, elderly, thinness, cigarette smokers, previous fractures, and a family history.
- Vertebral (age 50-60)
- Hip (age 70+)
There is clinical based evidence to support the use of estrogens for prevention of osteoporosis and/or active treatment of osteoporosis. Enough said on this topic as I am preparing a more extensive discussion on osteoporosis.

e. Prevention of Cognitive Deficiency and Alzheimer's Disease
You made no direct mention of this in your question with the exception of "I feel great while taking them," Jean. Alzheimer's disease is present both in men and women. Alzheimer's is more prevalent in women than in men. The prevalence approximately doubles with every five years of advancing age. Perhaps Alzheimer's is related to estrogens. Women are running out of estrogens in their later years after 70; therefore, they may be losing their protection and getting Alzheimer's. Retrospective studies have shown that the longer you are on estrogens, the greater the reduction in risk for Alzheimer's disease. But again if these particular studies are analyzed, we see both patient and physician selection bias as we did in the heart studies mentioned above. A more recent multicenter large population double-blind randomized (PEPI TRIAL) carefully analyzed cognition, forgetfulness, concentration and distraction amongst placebo and estrogen patients and found no difference in these 2 populations. Further studies have shown no difference between women who got estrogens and placebo on psychometric testing.

Then came a startling study, which suggested an association between hot flashes and brain cell (neuronal) loss. "It is hypothesized that the hot flush may result in an irreversible loss of neurons such that the women who enter their 70's and 80's with a history of hot flushes have a decrease in neuronal reserve and thus are more likely to express Alzheimer's Disease at an earlier age." This was naturally all hyped-up and sensationalized in women's magazines, Time, and most of the lay media.

When you really go into this study and other similar ones in great detail you will see that there is no evidence that women with hot flushes will be destroying neurons in their brains to affect cognition and hence predispose them to Alzheimer's Disease. Rather, women with a lot of hot flushes may not be sleeping well and this may affect their concentration, but they're not destroying their neurons.

So what do I think of all this? If I had to sum up the role of estrogens in preventing Alzheimer's disease, I'd have to say that yes there are retrospective studies that suggest estrogens might prevent the disease, but these studies are not randomized. Remember that women who are better educated and eat better and exercise more are less at risk for Alzheimer's disease and maybe those are the women who take estrogens in the first place, especially the better-educated women. When you put all this together, if a patient of mine wants to take estrogens to prevent Alzheimer's disease, I'll say, "Okay, but I'm not convinced of the data."

O.K. Jean. Now let us examine your concerns as to the risks or as you put it "foes" of taking estrogens.

RISKS OF ESTROGEN HORMONE REPLACEMENT THERAPY (HRT)
a. Endometrial Cancer
This does not apply to you, Jean, because you had a hysterectomy (your uterus was surgically removed), but must be mentioned for completeness as to educate other women who may be taking estrogen in their menopause. This is no longer a major concern with the advent of progestin. Yes, any postmenopausal women with her ovaries have a significant increase risk of endometrial cancer if given estrogens without progestins. Simply giving combination therapy of progestins, either continuous low dose or cyclic higher dose will prevent the development of endometrial cancer. Endometrial cancer is not the key issue.

b. Breast Cancer
You are right on the money with your major concern, Jean. Breast cancer is by far the biggest concern in postmenopausal women; far more than heart disease (unless there is a very overwhelming family history), osteoporosis, Alzheimer's disease and cosmesis (vaginal dryness, skin aging).

The main concern about estrogen replacement therapy that worries me the most for which we still don't have enough data is whether or not estrogens are associated with breast cancer.

As far as I'm concerned Jean, I tend to be a little more conservative than some of my colleagues. I am concerned that estrogens might increase the risk for breast cancer after many years of use. Somewhere after 5 to 7 years of estrogen, the risk of breast cancer goes up in some women. We don't know who those women are, and have no easy of identifying them.

The 'cancer-meter' starts ticking after age 50. If a woman goes through premature menopause at age 40, using estrogen for 5 years does not increase the risk. After age 50, more than 5 to 7 years of use, I believe the evidence suggests that the risk goes up.

If you look just at the numbers and statistics without any emotions, then it's a no brainer. You would see that the number of lives saved from heart disease or osteoporotic hip fractures completely outweighs lives potentially lost due to breast cancer or endometrial cancer, assuming you're not using a progestin.

If you look at the emotional aspects of this dilemma, because breast cancer becomes a major problem for patients and a major concern and it happens at a different age, then the numbers change quit a bit.

Now, Jean, all the hype in the lay-media began in January 26, 2000 with the controversial article in the very respected and prestigious Journal of the American Medical Association (JAMA). This study showed a slight increased risk of breast cancer associated with long-term use of estrogen, as well as somewhat greater risk of breast cancer diagnosis with combination estrogen-progestin use compared to estrogen alone. Unfortunately, the results as presented in this study only add to the complexity and uncertainty surrounding the issue of breast cancer and hormone replacement therapy (estrogen). Because the subjects were surveyed over the past 20 years, they could have been on higher doses and different regimens of estrogen-progestin than are commonly prescribed today. These results, therefore, may not be reflective of current low-dose therapies."

At this time, the Society of Obstetricians and Gynecologists of Canada (SOGC) believes it is essential to restate the facts on the risks of hormone replacement therapy within the appropriate context.

In 1998, the Society of Obstetricians and Gynecologists of Canada (SOGC) published a consensus on Menopause and Osteoporosis, which was based on the best scientific evidence available. This study shows that, based on a then recent meta-analysis of over 50 epidemiological studies published on the risk of breast cancer with hormone replacement therapy, current users of estrogen, or those who ceased one to four years previously, had a small increased relative risk of breast cancer. The combined analysis reported no increased risk for estrogen users of less than five years. For women who had used estrogen for five years or longer, the average relative risk of breast cancer increased by approximately two percent per year of use. This reported relative risk for breast cancer with estrogen would account for an excess of two, six or 12 cases per 1,000 estrogen users after five, ten or 15 years of use, respectively. Within five years of discontinuation of estrogen use, the increased relative risk virtually disappeared.

In fact, the risk of developing breast cancer increases by 60% if alcohol consumption exceeds 2 drinks per day, by 60% if a woman does not exercise, by 2.8% for each year menopause is delayed and by only 2.3% by year of use of hormone replacement therapy. Age is also a risk factor.

It is therefore important to note that the increased risk as reported is therefore extremely small, particularly when compared with other known risk factors.

Canadian women who have reached menopause are at a greater risk of developing other diseases, such as cardiovascular disease, if they don't take hormone replacement therapy. Heart disease is the number one killer of women in this age group. Hormone replacement therapy not only protects women after menopause from developing heart disease, but also provides protection against osteoporosis (which afflicts one in four women over the age of 50), as well as colorectal cancer.

The SOGC recommends that women should discuss the potential benefits and risks of hormone replacement therapy with their health care provider based on their individual health needs and personal risk factors for such things as cancer, osteoporosis and heart disease. The SOGC further states that a woman may not need to take hormone replacement therapy indefinitely, and should reassess her needs with her health care provider on a regular basis.

SUMMARY
So where does that leave us, Jean, with regards to your particular situation?

Firstly, let me address your question as to the beneficial effects of estrogens and heart disease. The point I've been trying to make above, Jean, with all this is that I have always told my patients when they say they want to take estrogens to prevent heart disease that there are so many studies in the literature suggesting that estrogens prevent heart disease, that I actually believe it. But, I also tell these patients that there are no randomized trials and that we may be dealing with self-selection and with physician bias. I never promise my patients that estrogens will actually prevent heart disease. Rather, I say the data is suggestive of it but we have to wait for the National Institute of Health: Women's Health Initiative Study (W.H.I.S), a randomized, double-blind, clinical trial which is studying benefits or risks of estrogen and progestin on the bone, heart, breast and other tissues. This large study along with its definitive answers to these controversial questions will be completed by 2006.

There are so many studies, that I truly believe estrogens cut down the risk of heart disease. I don't know if it cuts it down as high as 70%, as some studies suggest, but even if it cuts it own to 10% which the most scrutinous studies suggest, then this is still very significant in that heart disease is the number one killer of both men and women.

Now, Jean, let me respond to your more important question as to the current evidence-based medical risks of estrogens and breast cancer.

What you have to consider, Jean, is that you must ask yourself the following paramount question:

Jean, you and many similar women are faced with that decision -- it's so personal, that you alone must make it for yourself. All we doctors can do is give you the information and help you put it all together in some meaningful manner to help you make the decision for yourself.

Now, Jean, if you do decide to stop your estrogen, don't stop the estrogen cold turkey, because the hot flushes will promptly occur. Rather, wean them down slowly over time. I would recommend cutting them down to 6 pills a week for 2 weeks, then 5 pills a week for 2 weeks, and so on.

If on the other hand, you decide to remain on estrogen, then you must perform regular breast self-examinations and also have a regular annual mammogram. This is good preventative advice regardless of what you decide.

There is no right or wrong answer, rather I have attempted in keeping with the health coach philosophy to gather, organize and present to you the relevant evidence-based studies and guide you to ask the right question. I look forward to revisiting this question again with you in 2006 after the anticipated W.H.I.S. study is completed.

Until then I wish you a "private" peachy Norma-Jean life and hope you never become a Blue-Jean baby.