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Estrogen and Progesterone Replacement after Menopause
Can be Both Safe and Highly Beneficial

     Every woman at or approaching menopause should become familiar with this information to avoid putting their future health and well-being unjustifiably at the mercy of drug manufacturers.

    A large amount of published scientific research shows both safety and substantial benefit from menopausal hormone replacement with estrogen, often combined with progesterone (HRT), after menopause.

     Recent claims of risk from menopausal hormone replacement apply mostly to  synthetic progestin (Provera®, combined with estrogen in PremPro®, and generically named medroxy-progesterone acetate). This is a substance unnatural to the human body and has long been known to be associated with health risks. Safety of natural, bioidentical hormones, which can be specially compounded by a pharmacist, are  rarely reported in the media.

     Scientific evidence supporting the safety and benefits of menopausal hormone replacement is summarized below. This is not about alternative medicine. These references are taken from main-stream medical journals. Read the data yourself, and make your own decisions. Link to a long list of published scientific references.

     A review of published scientific studies stated that hormone replacement (HRT) after menopause resulted in a 50% decreased incidence of atherosclerotic heart disease and a 28% decreased risk of death from heart disease, a 50% decreased risk of hip fracture from osteoporosis, and with NO significant increased risk of breast cancer. The authors performed complex statistical analysis of previously published studies (meta-analysis). They reported an overall decrease in death rate from breast cancer in women receiving HRT.

Bluming AZ. Hormone replacement therapy: Benefits and risks for the general postmenopausal female population and for women with a history of previously treated breast cancer. Semin Oncol 1993; 20(6):662–74. 

     In 2001, a similar literature review  reported that HRT in menopause produced a 34% decrease in colon cancer and between 20% to 60% reduction in Alzheimer’s disease.

Burkman RT, Collins JA, Greene RA. Current perspectives on benefits and risks of hormone replacement therapy. Am J Obstet Gynecol 2001; 185(2 suppl):S13–23

     A 1994 analysis relative to a group of 10,000 women concluded that health benefits of estrogen replacement far exceeded any risk. Of 10,000 women taking estrogen for 25 years after menopause (compared to women who did not), 574 deaths could be prevented with an increase of approximately 4 years of quality life.

Gorsky RD, Koplan JP, Peterson HB, Thacker SB. Relative risks and benefits of long term estrogen replacement therapy: A decision analysis. Obstet Gynecol 1994; 83(2):161–6. 

     A 1998 report concluded that up to 99% of postmenopausal women would benefit from taking HRT with a decreased death rate and improved longevity. The authors wrote, "Hormone replacement therapy should increase life expectancy for nearly all postmenopausal women, with some gains exceeding 3 years."

Col NF, Eckman MH, Karas RH, et al. Patient-specific decisions about hormone replacement therapy in postmenopausal women. JAMA 1997;277(14):1140–7.

In another study, approximately 500 women who belonged to the Kaiser Permanente health system in California were followed for 17 years. Two hundred and thirty-two women on menopausal hormone replacement were compared with two hundred and twenty-two women who used hormones for less than one year during that same period. The death rate from all causes was reduced by 44% in women on estrogen. This reduction in death rate included  breast cancer deaths.

Ettinger B, Friedman GD, Bush T, Quesenberry CP Jr. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol. 1996 Jan;87(1):6-12.

     In 2006 a study at Harvard Medical School concluded that women who begin HRT soon after menopause experience a 30% reduction in coronary heart disease. This study contradicts previous conclusions from 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.

     Recent reports have cast doubt on the above listed studies and other studies like them. Frightening warnings about heart disease and breast cancer related to HRT have suddenly appeared. Why might that be? Is it possible that the pharmaceutical industry is attempting to discredit generic hormones from which they derive no profit? After all, the patents on commonly prescribed HRT have long since expired. Medical journals depend for their very existence on drug company advertising. Clinical research is largely funded by the big drug companies. Doctor's are being aggressively targeted with marketing for newer, patented, expensive, and highly profitable hormone substitutes, alleged to provide partial benefits without the alleged risk of commonly prescribed generics. How much is coincidence?

     To understand how this might be done, you must understand a bit about statistical risk and how it can be can be distorted in a frightening manner. Assume, for instance, that 3% of people who eat sugar develop cavities, compared with only 2% of people who don’t eat sugar. The difference is only 1%. That is not very much and, if true, might be an acceptable risk for people who enjoy eating sweets. In relative terms, the increased risk is 50%. In real terms the increased risk is 1%. If reported as 50% increased relative risk (RR 1.5), it can appear  more alarming than the actual increase would justify.

     To better understand relative risk  (RR), look at the table  below. A "RR" of 1.0 is average, a RR of 2.0 is twice average, for a 100% increase, etc.

Table of breast cancer risk in am image

    Using RR as a determining factor, the use of an electric blanket would cause close to 400% increase in breast cancer. Abdominal obesity would increase breast cancer by 230%. Taking an antibiotic would double the risk of breast cancer. Estrogen alone (in the absence of a uterus) would actually reduce the incidence of breast cancer by 25%. The addition of a synthetic progestin (not natural progesterone), might increase the risk of breast cancer by approximately 1% per year of use, compared to women who do not take HRT (20% relative increase using RR figures). That was one sensationalistic interpretation of the Women's Health Initiative.

Link to scientific references numbered in the table above.

     Bear in mind that associated risk factors often do not imply cause and effect. For example, the wearing of skirts is associated very strongly with the occurrence of breast cancer. It would be absurd, however, to suggest that if women wore only slacks they would avoid breast cancer. This is known as the "post hoc ergo propter hoc," (after-it-therefore-because-of-it) fallacy of reasoning. Nevertheless, routine medical practices are sometimes based on similar fallacious reasoning.

    The Women’s Health Initiative study (WHI) was interrupted in 2002 because of  alleged increase in the risk of breast cancer—despite the fact that the measured increase was barely statistically significant and occurred only in the group that received a synthetic progestin, not bioidentical progesterone. On statistical analysis, the difference in breast cancer between the treated and placebo groups was so small it could have been entirely caused by random chance alone, totally unrelated to HRT. The statistical analysis showed only borderline significance.

Sterne JA, Davey Smith G. Sifting the evidence-what’s wrong with significance tests? BMJ 2001; 322(7280):226–31

     Massive media coverage resulted, with frightening headlines alleging that hormone replacement causes breast cancer. Fear sells! Frightened women all over the world abruptly stopped their hormones, suffering all the symptoms of sudden menopause and increasing their risk for many age-related conditions known to be forestalled or prevented by HRT.

    There were serious flaws in that WHI study. Forty-two percent of the hormone treated women were known to have stopped taking hormones. Eleven percent of the placebo group actually took hormones during the study.

     Women in the WHI who took HRT and were subsequently diagnosed with breast cancer had a better prognosis, and higher cure rate than women who did not take hormones.

     Even accepting the worst possible interpretation of the WHI, a 50-year-old woman on HRT (including the synthetic progestin) for 10 years would have at most a 4% risk of breast cancer. Without HRT, and without the synthetic progestin, her risk would still be 2%. In other words, assuming a worst-case interpretation, using a synthetic hormone substitute, a woman on HRT for 10 years has a 96% chance of remaining free of breast cancer compared with 98% for those not taking HRT.

Santen RJ, Pinkerton J, McCartney C, Petroni GR. Risk of breast cancer with progestins in combination with estrogen as hormone replacement therapy. J Clin Endocrinol Metab 2001; 86(1):16–23.

     Careful analysis of the WHI data shows that the alleged risks were not associated with natural bioidentical hormones, but with the synthetic progestin, medroxy progesterone acetate (brand name Provera®, combined with estrogen in a product named Prempro®)

     A more recent report alleged that the use of estrogen increased the risk for Alzheimer's-like dementia. The results were later found to be insignificant, after women who suffered from early Alzheimer's symptoms prior to receiving HRT were excluded from the data. Other studies show just the opposite.

    All this, of course, has created a feeding frenzy amongst trial lawyers, who now have a license to sue any doctor for malpractice if he has prescribed postmenopausal HRT, regardless of whether or not HRT is related to breast cancer or another medical problem. Lawyers are now soliciting patients on the internet. After all, some women will get breast cancer unrelated to treatment, and with no treatment at all. Massive media coverage with distorted and  misleading statistics has made it impossible to select a jury member not already biased and exposed to misleading media reports that HRT causes breast cancer and a myriad of other serious problems. Doctors are running scared (already paying outrageous malpractice insurance premiums), and are refusing to prescribe HRT. Women are confused, frightened, suffering and being subjected to increased risks that could be prevented with HRT.

To quote from a recent article published in the medical journal, Geriatrics:

"Recent reports attributing a significant increased risk of breast cancer development, cardiac events, and Alzheimer's disease to the administration of estrogen-progestin hormone replacement therapy (HRT) require critical review, not blind acceptance. An appreciation of the numbers used to generate these conclusions, the abundance and strength of the studies that do not support them, the small size of the effect reported, even if arguably valid, and the persisting reported benefit of HRT on longevity should alert clinicians to the risks of accepting these studies as guidelines for patient management. The additional report from this same group that HRT has no effect on health-related quality of life deserves a good laugh, not serious consideration. Bluming, AZ. Hormone replacement therapy: The debate should continue. Geriatrics November 2004, 59:11; 31-38

Link to a more lengthy article on the benefits of post-menopausal HRT.

    Note: The above statements do not apply to those few women with a very strong family history, or some other cause for an unusually high risk for breast cancer.


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

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