The Change
How to Preserve Health and Prevent Disease

Some feel change is good. Others feel change is bad. Change is inevitable and it's happening right now. Even if you are on the right tract, if you stand still long enough the train will hit you.

Menopause is the "Change of Life." There are many options to turn to on this journey. We will discuss how to stay on the right tract.

The ovaries stop producing estrogen during menopause. A host of predictable consequences occur including:
  1. Perimenopausal symptoms like hot flashes and mood swings.
  2. Vaginal dryness with increased risk of UTI and Dyspareunia.
  3. Loss of bone/Osteopenia/Osteoporosis and attendant risk of fracture.
  4. Higher risk of Colon Cancer due to the diminished Estrogen level.
  5. Skin cells lose their elasticity and youthful appearance.
  6. The hair can become dryer and thinner.
With other endocrine glands, like the thyroid, for example, we always replace the deficient hormone with drugs like Synthroid when the gland stops making its own hormone. So why would we ever think of not replacing the hormone made by the ovaries, Estrogen, when this endocrine organ begins to fail?

Menopause is viewed by some as a natural change of life and not a disease state. It sounds good on first glance to turn away from expensive doctor prescribed pharmaceutical drugs with their long list of potential harmful and annoying side effects. The uninformed look at the problem as simplistically as menopause has side effects and so does the doctor prescribed treatments. So since both are bad (have side effects), maybe it is better to go with the "natural" way as it appears safer and in the short run is cheaper.

The more informed ask the question how bad or how good for what condition and in my particular individual case what is the best course of action. The quantitative review reveals much more data than the qualitative one of good vs bad. So we recommended ERT (Estrogen Replacement Therapy) for women when their ovaries stop making Estrogen (Ovary Hormone) and we began to study the effects. Preliminary data were encouraging that it helped prevent heart attack and stroke. It was always known to increase the risk of breast cancer. But it was felt that the net result was to save more lives with its use.

In America, the majority (62%) of postmenopausal women already chose not to use HRT to treat their menopause. This data was before the 2002 WHI (Women's Health Initiative) study was published. Some groups already look at the cessation of menstruation as no more of a disease entity as the beginning of it (menarche). Their main fear is that of Breast Cancer. The fear is many times greater than the actual event. It makes sense that estrogen should be related to Breast Cancer. Observational studies have shown that the more estrogen a woman has for more years, the higher the resultant risk of developing Breast Cancer.

On July 17, 2002, JAMA, the Journal of the American Medical Association, published the WHI (Women's Health Initiative), the results of which will make postmenopausal women and their doctors think harder about why to use combination HRT (Hormone Replacement Therapy) for how long, in which women, and with what other concomitant treatments.

The WHI was the first randomized trial to directly address whether Prempro (combination of Premarin-estrogen and Provera-progestin) has a favorable or unfavorable effect on CHD (Coronary Heart Disease) incidence and on overall risks and benefits in primary prevention in a predominantly healthy cohort of women. In the past, there have been other trials that made HRT appear good. In 1996, the PEPI trial (Postmenopausal Estrogen/Progestin Intervention) showed us that if a woman has a uterus, she will need the progestin, Provera to stop the Premarin from increasing the risk of uterine cancer. There have been studies in other primates, observational studies, and secondary prevention trials in women who already have heart disease that show HRT has a favorable effect on Cholesterol. It was found to lower the bad LDL-C 12.7% and raise the good HDL-C 7.3%. It should follow that lowering the cholesterol should translate to fewer heart attacks. This data goes along with that found in the PEPI trial and the HERS trial (Heart and Estrogen/progestin Replacement Study). In HERS, 2,763 post-menopausal with CHD (Coronary Heart Disease) were given Prempro (Wyeth Ayerst) vs. Placebo (dummy sham pill). There was an increase in risk of CHD the first year only, but no overall risk long-term. So, their cholesterol levels improved, but their hearts got worse for some unclear reason.

WHI was first conceived in 1991 and began enrolling research volunteers in its different arms between 1993 and 1998. In the Prempro combo arm, there were 16,608 subjects, 8,506 in the Prempro group and 8,102 in the Placebo group. It was supposed to be an 8.5 year study, but it was terminated early by the DSMB (Data Safety Monitoring Board) at the end of 5.2 years due to the excess risk of Breast Cancer in the Prempro group compared with the Placebo group. Other risk factors that were trending elevated included: Heart Disease, Stroke, Blood Clots (Pulmonary Embolism and Phlebitis).

Cases per 1,000 women per year
  1. Breast Cancer: 3.8 (HRT), 3.0 (Placebo), +26% (Difference)
  2. Heart Disease: 3.7 (HRT), 3.0 (Placebo), +23% (Difference)
  3. Stroke: 2.9 (HRT), 2.1 (Placebo), +38% (Difference)
  4. Blood Clots: 2.6 (HRT), 1.3 (Placebo), +100% (Difference)
  5. Hip Fracture: 1.0 (HRT), 1.5 (Placebo), -33% (Difference)
  6. Colon Cancer: 1.0 (HRT), 1.6 (Placebo), -37% (Difference)
So, the DSMB (Data and Safety Monitoring Board) concluded that the evidence for an increased risk of CHD, Stroke, and Blood Clots outweighed the possible benefits from decreasing Hip Fractures and Colon Cancer over the average 5.2 year follow-up period and the Prempro arm was discontinued. The Premarin alone arm continued in women who have had a hysterectomy and The National Institutes of Health announced in March 2004 preliminary findings from the estrogen-alone study arm which showed the estrogen therapy:
  1. Decreased the risk of Hip Fracture.
  2. Did not increase the risk of Breast Cancer.
  3. No effect of Coronary Artery Disease.
  4. Increased the risk of Stroke.
Combination Estrogen and Progestin Therapy
During the past year, for every 10,000 women taking Prempro, one would expect to find:
  • 7 more CHD events
  • 8 more invasive Breast Cancers
  • 8 more Strokes
  • 8 more Pulmonary Embolisms (Blood Clots)
  • 6 fewer Colorectal Cancers
  • 5 fewer Hip Fractures
From the above, you can see there will be 31 extra bad events per year for each 10,000 women on Prempro and a simultaneous 11 fewer bad events. This leaves an excess of 20 more women experiencing a harmful event. This is why the results are big news and why the study was stopped early. Now, what should practicing physicians and the 38% of postmenopausal women taking HRT do as we enter the "post-HRT era"? Well, keep in mind that the absolute excess risk attributable to Prempro was low. The majority of women didn't have any adverse events (side effects). However, the whole purpose of healthy women taking long term estrogen/progestin therapy is to preserve health and prevent disease. The results of WHI provide strong evidence that the opposite is happening in the long term users even if the absolute risk is low.

So exactly what to do in regards to HRT (Hormone Replacement Therapy) is in more questionable and controversial. We at the Concierge Care Club teach women to preserve health and prevent disease as follows:
  1. Recognize menopause is a disease state. Menarche is an inevitable normal consequence of becoming an adult woman, but menopause is an abnormal state that occurs from the ovary failing to produce estrogen.
  2. We assumed replacing exactly what the ovary used to make when it was functioning with bioidentical hormones would be a good long term solution. As with most medical treatments, there are risks, benefits and alternative procedures. The key is to educate the woman so that they understand what is good and what is bad about HRT.
  3. Menopause hurts. That is, the Perimenopausal hot flashes and sweats interfere with ADL (activities of daily living). This should be treated.
  4. The really bad effects of HRT worsen with time. We at the Concierge Care Club feel 5 years is a reasonable length of time to be exposed to HRT and limit the harmful side effects of: Breast Cancer, MI, Stroke and Blood Clots.
  5. Stopping HRT abruptly will make acute Perimenopausal symptoms. As soon as the Estrogen level falls you begin to feel as if it were day one of your menopause. Wean off the HRT can prevent this. It is reasonable to take as long as you need to gradually wean off of HRT. Keep in mind the longer you are on it and the higher the dose, the greater the chance of side effects. However using a small dose of Premarin like the 0.3mgm dose for 5-10 years should be relatively safe. It is reasonable to take Premarin for Perimenopausal symptoms and continually try to wean it off.
  6. Customize your HRT to your specific goals and risk factors:
    1. CHD (Coronary Heart Disease) Risk: If you have high cholesterol and a positive family history for premature heart disease, you would want to take less HRT than if CHD were not a concern. Instead of HRT, stress the use of low fat diet, regular exercise, and cholesterol lowering drugs like statins.
    2. Osteoporosis: Even though it's clear that HRT works well for this indication, there are other alternatives that appear not to share the same side effects. Calcium supplements; bisphonates like Fosamax, Actonel and Boniva; SERMS like Evista and weight bearing exercise can all favorable effect risk of Osteoporosis without raising the risk of breast cancer.
    3. Colon Cancer: HRT will lessen the risk of colon cancer. Even though the women in WHI on Estrogen experienced less Colon Cancer, one can diminish her risk by:
      1. Getting a colonoscopy.
      2. Fecal occult blood testing.
      3. Eating fruits and vegetables.
      4. Regularly exercising at the Ritz Carlton gym.
    4. Healthy Skin: HRT is good for your skin. When you take less or stop it, the skin will begin to get worse. Skin cells lose their elasticity and youthful appearance when the estrogen level falls with menopause. The hair can become dryer and thinner. Alternatives include:
      1. Creams and moistures available for sale here at the Ritz.
      2. Cosmetic surgery.
    5. Breast Cancer: The more estrogen you have for the more years, the greater the chance of breast cancer. The lowest risk would be if you had the ovaries removed (oopherectomy) prior to menarche. This is not reasonable. Even though HRT does indeed raise the risk of developing invasive Breast Cancer, things a woman can do to limit the risk include:
      1. Mammography
      2. Regular GYN visits.
      3. Breast self-exam. (Tell about a bad HMO that charges women for a annual breast self exam. They charge a flat rate!)
    6. Stroke or CVA (Cerebrovascular Accident): As the estrogen level falls, the blood vessels age and become less flexible, leading to a buildup of plaque. This can cause a Stroke. HRT can help this, but its tendency to promote blood clots looks like it causes more Strokes than it prevents. Blood pressure control and not smoking are big things that one can do to limit risk of Stroke.
    7. Alzheimer's disease: Even though some studies show HRT may help, there are other treatments available, like: Aricept, Exelon and Reminyl. If you are very concerned about Alzheimer’s disease, HRT will be god if you can remenber to take it.
    8. Hot Flashes: HRT is great for hot flashes. This is the main reason to use it now. The dose should be the smallest number of milligrams for the least number of years that helps you control hot flashes. Short-term HRT is the way to go for 5 years or so, and then wean down the dose and stop as symptoms of hot flashes allow. Other treatments for the sweating and flushing include:
    9. Natural plant-based estrogen, including: Black Cohosh, Soy Products, and Wild Yams. These may provide some relief. But you have to check the reliability of the alternative medicines and the estrogen in them may also be harmful.
    10. Vaginal Dryness: HRT is great for this. When the vaginal tissue is deprived of estrogen, it loses its suppleness and becomes dry and irritated. Itching discomfort and dysparunia can result. Options include:
      1. Vaginal creams.
      2. Flexible hormonal rings.
      3. Vitamin E, both orally and topically.
    11. Mood swings: HRT is good for this, also. The drop in estrogen can cause Mood Swings that are manifested by: irritability; depression; and insomnia. Tiredness can cause changes in personality. Options include:
      1. Short term HRT.
      2. Relaxation exercises.
      3. Meditation.
      4. Massage can help. Also available at the Ritz.
      5. In more severe cases, antidepressants like Prozac can be useful.
In conclusion, the possibilities of these small absolute risks must be balanced against the severity of the woman's symptoms and the benefits of the treatments. It's obvious that in the years after 2002, less than 38% of postmenopausal women will be taking HRT. If you already had a hysterectomy and you don't have a uterus, you might benefit from staying on the Premarin alone as this appears safer than the combination therapy. Meanwhile doctors that believe "primun non nocere" (first do no harm) and patients who fear even small risks of drugs are going to have to deal with this brave new post-HRT world!

Sincerely:
Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
Member, SIMPD (Society for Innovative Medical Practice Design) www.ConciergePhysicians.com
PI (Principal Investigator), DSI (Drug Study Institute)
Board Certified Internist, JPMC (Jupiter Preventive Medicine Center)
DABIM (Diplomat American Board of Internal Medicine)
FACP (Fellow American College of Physicians)
CPI (Certified Physician Investigator) by the APPI (Academy of Pharmaceutical Physicians and Investigators)
CCTI (Certified Clinical Trial Investigator) by the ACRP (Association of Clinical Research Professionals)
CCI (Certified Clinical Investigator) by the DIA (Drug Information Association)
CCRC (Certified Clinical Research Coordinator) by the ACRP (Association of Clinical Research Professionals)
CCRP (Certified Clinical Research Professional) by SoCRA (Society of Clinical Research Associates)
IRB Member, Jupiter Medical Center
Ethics Committee Member, Jupiter Medical Center
Member, ARENA (Applied Research Ethics National Association)
Member, PRIM&R (Public Responsibility in Medicine and Research)
Member: The American College of Preventive Medicine
Member, ACPM (American College Preventive Medicine)
Founder, CertifiedResearchers.com
Member: The American College of Preventive Medicine