FEMALE HORMONE REPLACEMENT

HRT for Postmenopausal Women, and PhARMA Profits First

Home
HRT the smart choice for post menopausal women
10 reasons for HRT
Estrogen lowers breast cancer death rate
Breast Cancer Survival up with subsequent HRT
Setting the record straight with journal articles on HRT
HRT for Postmenopausal Women, and PhARMA Profits First
More Setting the Record Straight
HRT Studies, much fewer heart attacks, etc.
Breast-Firmer-HRT
Cholesterol profile improved by Estradiol
Increased libido (sex drive)
More More setting the record right
healther skin with HRT
Bioidentical Hormone therapy advice
HRT benefits journals
Choice of progestagen component in HRT affects incidence of Breast cancer
HRT & Heart Benefits--etc.
22% muscle loss prevented with testosterone
Arthritis effective treatment HRT
Testosterone, Sex Drive, Feeling Better, etc--Mayo Clinic
Testosterone improves sexual desire and sex
FDA Article on Menopause and HRT
Bioidentical Hormone therapy advice
Prempro settlement $330M
alcohol and higher estradiol and testosterone levels in postmenopausal women

Backdrop:  1) The FDA has always been headed by those with proven track records, usually executives of Big PhARMA. 2) That it creates for the public a fašade of supervision through mostly limited regulatory actions such as black-box warnings and belatedly having a drug withdrawn from the market.  3) That pharmaceutical ads are a major source of revenue for the corporate press and medical journals (neither of them see the raw data and thus can never properly review the evidence for the articles they publish).  4) The Pharmaceutical industry is about profits; their research is profit driven, and thus when there is a conflict between an older off-patent drug and a less effective patented drug, the public suffers.  5)  The marketing departments of Big PhARMA dominate the production of medical opinions.  6) The majority of HRT population studies are flawed because they fail to distinguish the types of conjugated HRT.  7) The issue of salubrious & pernicious properties of HRT is further clouded by the trend over the last 4 decades to reduce the hormone dosage--which is supported by evidence for women of child-bearing age, but not for post-menopausal women.      

12/23/11 last edited jk

Journal articles below support these findings, more at http://healthfully.org/fhr/

What to take:  topical* Estradiol 2 mg[1], plus Progesterone 100 mg

Journals--DECREASED:    Alzheimer’s 83%,     Heart attacks 32%    Coronary Heart Disease 50% 

Colorectal Cancer 20%    Breast Cancer 0%    Thrombosis 8%      Osteoporosis Fractures 90%

Firmer breasts    Healthier thicker skin (48% more collagen) and less hair loss, improved cognitive function, reduces & prevents arthritic join destruction, and general feeling of well being with increased libido. 

Estradiol (E2, 17B-esteradiol) the natural predominant sex hormone in females.  A number of common supposedly bioequivalent modification of esteradiol including its acetate, cyprionate, and ethinyl estradiol (commonly used ingredient in combined oral contraceptive pill).  Esterfied Estrogen is considered bioequivalent to estradiol.  Progesterone (P4, pregn-4-3n3-3,20-dione) the natural hormone of the class called either progestogen.    

 

Avoid MPA synthetic progestogen (used with Equine (horse) Estrogen (in Prempro)--WHI study

WHI study found INCREASED:  Heart attacks 23%    blood clots 29%     breast cancer 29%   Alzheimer’s 50%

                    DECREASED:    Colorectal cancer 37%        vertebral fractures 40%

In HRT, some synthetic progestogens are very inferior to the natural hormone progesterone

Terms:  conjugated equine estrogen = conjugated estrogen = Premain (PREgnant MAres urINe).

Medroxyprogesterone = MPA, an artificial progestin in Provera, a synthetic form of the natural hormone progesterone. 

Prempro a monthly supply of pills by Wyeth Laboratory (now Pfizer) which contains Premain 0.625 mg and Provera 2.5 mg.  Opposed estrogen is plus a progestogen.  The progestogen can be either cycled given the last 7 days of a 28 day cycle, or found in every pill.  Unopposed means no such cycling, just estrogen. Prempak C is the British name for Prempro.  Progestin is a synthetic progestogen.

Estradiol, is the sex hormone present in females, and is widely marketed in various forms and preparations including ethinylestradiol, the most common estrogen in combination oral contraceptive pills.  Esterfied estrogen is bio-equivalent to estradiol. Pfizer (who bought out Merck the maker of Prempro) has in Feb 2011 settled suit over breast cancer, to pay $330M, $150,000 per person.

 

           

ADVICE ON HRT (preventing age related ailments follow menopause)

SUMMARY BY JK



[1] *         The higher dose 2 mg  (compared to 1 or 0.5 mg) is recommended because of the various positive health consequences of estrogen--a trend established by the misuse of the WHI Study.  Because of the skin barrier, the dose is higher than those of pills or transdermal patch.  A very competitive pricing is available from a compounding pharmacy, {Medical Plaza Pharmacy of Foothill Ranch (949-586-6337) whose service is excellent, approximately $105 for a 90 day supply}.  Recent changes in the market place as to availability, has made esterfied estrogen more costly than estradiol.  For best results spread as far a possible over skin.  Add a few drops of water to hand to facilitate spreading, and thereby improve absorption.   Oral formulas are available such as Fernhrt (norethindrone acetate .5 mg and ethinyl estradiol 2.5 mgc).  Norethindrone might not be biologically equivalent to progesterone.   

 

Even in well designed studies there are limits of entailment, and these limits are often shoved aside by a press more concerned with ratings than the truth, and with pleasing advertisers.  For example both New Week and Time Magazines--two of the best sources in the popular press for medical news published articles advising the discontinuation of HRT (hormone replacement therapy) for women based on the WHI (Women’s Health Initiative 1991-2002, see bottom of page for details) study that showed an increased incidents of breast cancer (had been known for over 4 decades) and a surprising increase in cardiac events.  What was known and not considered, the financial

gains for Big PhARMA for getting women off of generic HRT (a topic developed below).  Major defects in the WHI studies were not given proper press. 

In an effort to right the record Dr Robert Langer, UCSD Professor of Medicine, spoke in November of 2002 before an audience of medical students about the WHI study, which he was involved in (the talk was broadcasted on UCSD channel in December).  He used for both his introduction and summation the articles in Time and Newsweek about WHI, especially the conclusions they drew.  It provided an avenue for him to discuss other studies and limits

upon conclusions that could be drawn from the WHI, limits violated by these two magazines.  Times article The Truth about Hormones, 7/22/02, was short on truth, so too the Newsweek article.  They noted that one portion of the study was stopped because of health consequences from the use of Prempro, but failed to note the large body of research which showed very significant benefits for other forms of estrogen used with progesterone or used estrogen unopposed.  Doctor Langer discussed these alternatives, among other things.     

Time's article failed for 4 major reasons and numerous minor ones.  First and fundamental failure was that the very study was designed to fail because it used a combo of hormones (equine estrogen & MPA) were known prior to be atypically ineffective (see “Setup to Fail” below for details). Second the results for Prempro (the hormone combination of equine estrogen and medroxyprogesterone) cannot be generalized to other HRTs, namely esterified estrogen alone and estrogen with progesterone.  Third the increased risk in breast cancer was caused by MPA (medroxyprogesterone--see article below).  And fourth, since the study was of menopausal women, it could not be applied to postmenopausal women or the effects of such women using long-term HRT.  For example for post menopausal women using good HRT for 10 years reduced Alzheimer’s disease 83%, also breast cancer and thrombosis (supporting studies below).  These limits of the WHI study and more were brought before the audience at UCSD by Doctor Langer.

With distant glasses a look at the performance of the pharmaceutical industry reveals that they replace inexpensive off-patent drugs with new patented, expensive drugs, especially for health issues which can produce what the industry terms “a block buster.”   This has been done over and over again.  One block buster, the treatment for osteoporosis with the class of drugs bisphosphonates, has as a competitor the much more effective estrogen.  The near elimination of the use of estrogen to prevent & treat osteoporosis has produced billions in profits.  Significant profits are also derived from treating other age related conditions that would have been less frequent if a different HRT was used then Prempro.  This is a serious abuse of trust.  Other examples corporate greed occurs with the replacing of diuretics with patented drugs for the control of blood pressure, and the use of aspirin as an arthritic medication.  This website contains a detailed examination of the COX-2 inhibitors such as VIOXX and the efforts of Merck to keep it adverse consequences hidden (an estimated 55,000 deaths and 125,000 strokes and heart attacks prior to its being pulled).  As the article below “Setup to Fail” argues the choice of drugs for the WHI was done knowingly.   

There is a large body of research on HRT, which help put the WHI in proper perspective.  For HRTs other than Prempro by Wyeth the results depend on the progestogen used.  With progesterone there was no increase (see French study below).   With Prempro there is a significant increase in blood clots, heart attacks, breast cancer, and Alzheimer’s disease. For all HRTs with progesterone there is a decrease in the rate of colon cancer, heart attacks, osteoporosis, and Alzheimer’s disease (see page 1).  Given these differences in HRT, it speaks poorly of the FDA that Prempro is still available and widely used.  Of particular importance was a study that compared statins to either estrogen or estrogen and prostaglandin.  Statins are given to women with high levels of cholesterol and low-density lipoproteins.  These women had done just as well if given either estrogen or estrogen and progesterone instead of a statin in improving their lipid profile.  Since statins have some serious side effects and none of the additional benefits of estrogen, estrogens should be the treatment of choice.  Unfortunately, the Prempro therapy does not confer these benefits. 

There are 3 immediate reasons for HRT therapy.  One is the control of hot flashes.  Second are cosmetic and psychological reasons:  the skin remains suppler, breasts firmer, memory improved, and less depressions.  All these effect self-esteem and thus quality of life.  Third is sexual performance:  the control of vaginal dryness and the wall of the vagina is thicker.  Medical intervention for social and psychological benefits is common in our society. 

There are many older long-term benefits (well beyond the scope of the WHI) that show very significant reduction of Alzheimer’s, of atherosclerosis, of heart attacks, of osteoporosis, of colon cancer, no increase in breast cancer, and a reduction of THROMBOSIS with esterfied estrogen with progesterone (see studies below, and on this website http://healthfully.org/fhr/).  When one adds to this the cosmetic and sexual advantages plus the managing of hot flashes, the choice is crystal clear.  Because of its common usage as contraception for over 50 years, the use of female hormones has been the best studied of all drugs. There is enough data available to put to rest any of the Big PhARMA generated uncertainties over HRT treatment.  

Because of the complexities of issues and the limited time that health professional have to review studies and keep abreast of new treatments, they look to “opinion makers” and follow accepted practices.  Medical societies such as the American Heart Association also receive significant “donations” from Big PhARMA; the same for medical schools. The industry selects directly or indirectly researchers for their studies, and thus who will become “opinion makers”.   We have corporate medicine.  The harm done is incredible.  Millions of women have died early because they have discontinued (or not started) HRT due to incorrect coverage in the popular press and the role of Big PhARMA in changing the once very common practice of managing the side effects of menopause and post menopause, and of treating & preventing osteoporosis with HRT. 

Every aspect of medical science and treatment has been compromised by corporate medicine.  This website along with worstpill.org attempt to address the misinformation--BY JK.

  http://healthfully.org/imagelib/sitebuilder/layout/spacer.gif^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Setup to Fail:

http://www.nature.com/news/2010/100907/full/news.2010.453.html#comment-id-13486  Published in the highly acclaimed science journal Nature September 2010

Prempro  (Premphase) is conjugated Estrogens (.625 mg) & Medroxyprogesterone acetate (2.5 mg)----jk emphasis:

  • 2010-09-09 12:24:18 AM    Posted by: Anna Michaels, PhD     #13486

 Millions of women took a mix of the hormones oestrogen  and progesterone called Prempro.

Is Nature ignorant of the vital fact that Prempro contains no progesterone, but instead the artificial progestogen Provera? The other component is Premarin (conjugated estrogen), which is a very uncertain, patent mixture of substances from the urine of pregnant mares. Whilst that in no way invalidates the main point of the report, or the research, indeed the it makes the need for clear statements and open scientific evidence absolutely clear, it completely invalidates all the material in the report generalising about HRT, because Prempro is totally unrepresentative of any other product used for HRT purposes.

Provera (artificial progestogen) has crucially different effects to the natural hormone progesterone. And Premarin has different effects to the natural hormone estradiol.    The literature has detailed those, and explained them, over many years. Much of it was known before the NIH chose to use Prempro in its intended landmark study.

Using a study of the effects of Prempro to attack the entire use of HRT has, through needless fear, caused millions of women to forgo considerable benefits of HRT using better products.

This point has been repeatedly made by endocrinologists. Why does Nature not know it?--END OF ARTICLE.

This published comment appeared in a section on the pervasive practice of pharmaceutical companies hiring companies that specializes in ghost writing.  These companies produce books, journal articles, news releases, lecture materials with the supposed review of these materials by the researchers whose name appears thereon or who gives the lecture--jk. 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Hormone Hysteria ---Scientific American, Dennis Watkins, 9/2003, edited by jk http://www.scientificamerican.com/article.cfm?id=hormone-hysteria

Postmenopausal women have for decades relied on estrogen supplements to control the hot flashes, memory loss, osteoporosis and other ailments that can occur when their bodies no longer produce the compound. But hormone replacement therapy (HRT) is no longer considered the best way to treat menopause, ever since a report last year found that women receiving a certain type of HRT were at increased risk for dangerous side effects, such as breast cancer. Many health professionals have concluded that altering a woman's physiology will always increase risks over time. But a handful of respected scientists are calling for another look at HRT, arguing that not all therapies are created equal.

… A RESEARCH STATES:  "I think that it borders on a tragedy that Premarin and Provera were chosen as the only HRT treatments."   {AS JK STATED ABOVE IT IS THE PROSTOGLANDIN in Provera & Premarin that caused the serious side effects}   Another researcher finds that hat Provera--and no other progestin--blocks the mechanisms that allow estrogen to fight the brain's immune response to Alzheimer's. This immune response wears away at brain cells and causes them to leak neurotransmitters such as glutamate, which overloads and kills neurons. "It's basically as if someone were to open your mouth and shove down gallons" of soft drink, Brinton explains. "It's caustic, and you can't metabolize it enough."

{After the usual journalistic waffling, the Scientific American articles gets to the issue}  For many scientists, a critical question yet remains: To what extent do the results of the initiative study apply to other forms of hormone replacement? "We cannot be sure whether other hormone combinations will have the same effects," Rossouw cautions, "but in my opinion we should assume they do until proven otherwise." But neuroendocrinologist Bruce S. McEwen of the Rockefeller University is unequivocally critical of the study: "I think that it borders on a tragedy that Premarin and Provera were chosen as the only HRT treatments."

A growing number of researchers believe that Provera is a poor substitute for progesterone. For example, medroxyprogesterone will bind in the breasts to progesterone receptors, which causes breast cells to divide after puberty and during the menstrual cycle, and also to glucocorticoid receptors, which causes cell division during pregnancy. This double-barreled assault on breast cells, explains C. Dominique Toran-Allerand, a developmental neurobiologist at Columbia University, probably led to the high rates of breast cancer in the study. "With Provera you are activating two receptors involved with cell division in the breast," she says, "and that's the culprit, not estrogen."

In addition, recent research shows that Provera interferes with estrogen's ability to prevent memory loss and dementia. "Estrogen is able to protect neurons against toxic assaults that are associated with Alzheimer's disease," notes Roberta Diaz Brinton, a neuroscientist at the University of Southern California. Using in vitro studies of several types of progestin, she found that Provera--and no other progestin--blocks the mechanisms that allow estrogen to fight the brain's immune response to Alzheimer's. This immune response wears away at brain cells and causes them to leak neurotransmitters such as glutamate, which overloads and kills neurons. "It's basically as if someone were to open your mouth and shove down gallons" of soft drink, Brinton explains. "It's caustic, and you can't metabolize it enough." 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Past long-term estrogen use decreases Alzheimer’s disease in older women (83% for over 10 years)

December 2002 report of NAMS (North American Menopause Society)

Zandi PP, Carlson MC, Plassman BL, et al, for the Cache County Memory Study Investigators. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County study. JAMA 2002;288:2123-2129.

Use of hormone therapy is associated with a reduced risk of Alzheimers disease (AD), especially use for longer than 10 years, according to results from this prospective observation al study conducted in Cache County (Logan, Utah). A total of 1,889 women (mean age, 74.5 years) were enrolled. A similarly aged group of men (n = 1,357) served as controls. History of hormone therapy use (either estrogen alone or estrogen plus a progestogen), as well as intakes of calcium and multivitamin supplements, were assessed at baseline. After 3 years of follow-up, 88 women (4.7%) and 35 men (2.6%) had developed AD. Women aged 80 and older had more than twice the rate of AD as men of that age (hazard ratio [HR], 2.11; 95% CI, 1.22-3.86). Overall, hormone therapy significantly reduced the risk of AD by 41% compared with nonusers (95% CI, 0.36-0.96). Hormone use for at least 10 years resulted in a 69% reduction in risk (95% CI, 0.17-0.86), which was statistically the same as the risk for matched males. When the results were assessed by current and former hormone use, current use (72% unopposed estrogen) was not associated with decreased AD risk unless the duration of treatment exceeded 10 years. For former users, 3 or more years of use significantly reduced the AD risk, with more than 10 years use reducing the risk by 83% (95% CI, 0.01-0.80). No similar effects were seen with either calcium or multivitamin use.

NOTE:  the results are based taking the best combination, other studies using different combinations obtain lower results and those with Prempro no benefit. A earlier (1999) NAMS meta-study, not separating types of HRT or duration of usage found a 29% reduction--jk. 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Molecualr Pharmacology, April 1, 1997 vol. 51, no. 4, 535-541

Neuroprotection against Oxidative Stress by Estrogens: Structure-Activity Relationship

Abstract

Oxidative stress-induced neuronal cell death has been implicated in different neurological disorders and neurodegenerative diseases; one such ailment is Alzheimer’s disease. Using the Alzheimer’s disease-associated amyloid β protein, glutamate, hydrogen peroxide, and buthionine sulfoximine, we investigated the neuroprotective potential of estrogen against oxidative stress-induced cell death. We show that 17-β-estradiol, its nonestrogenic stereoisomer, 17-α-estradiol, and some estradiol derivatives can prevent intracellular peroxide accumulation and, ultimately, the degeneration of primary neurons, clonal hippocampal cells, and cells in organotypic hippocampal slices. The neuroprotective antioxidant activity of estrogens is dependent on the presence of the hydroxyl group in the C3 position on the A ring of the steroid molecule but is independent of an activation of estrogen receptors.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

8% Reduced Risk of Thrombosis with Esterfied Estrogen Only

Esterified Estrogens and Conjugated Equine Estrogens and the Risk of Venous Thrombosis

JAMA (the Journal of the American Medical association) 2004;292(13):1581-1587. doi: 10.1001/jama.292.13.1581

At http://jama.ama-assn.org/content/292/13/1581.abstract

  1. Nicholas L. Smith, PhD; Susan R. Heckbert, MD, PhDRozenn N. Lemaitre, PhD; Alex P. Reiner, MD, MPH;
  2. Thomas Lumley, PhD; Noel S. Weiss, MD, DrPH; Eric B. Larson, MD, MPH; Frits R. Rosendaal, MD;
  3. Bruce M. Psaty, MD, PhD
1.      Rosendaal).
  1. Corresponding Author: Nicholas L. Smith, PhD, Cardiovascular Health Research Unit, 1730 Minor Ave, Suite 1360, Seattle, WA 98101 (nlsmith@u.washington.edu).

Abstract

Context:  Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds.

Objective:  To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers.

Design, Setting, and Participants  This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis between January 1995 and December 2001 and controls were matched on age, hypertension status, and calendar year.

Main Outcome Measure:  Risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. Current use was defined as use at thrombotic event for cases and a comparable reference date for controls.

Results:  Five hundred eighty-six incident venous thrombosis cases and 2268 controls were identified. Compared with women not currently using hormones, current users of esterified estrogen had no increase in venous thrombotic risk (odds ratio [OR], 0.92*; 95% confidence interval [CI], 0.69-1.22). In contrast, women currently taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen users, current users of conjugated equine estrogen had a higher risk than current users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated equine estrogen users, increasing daily dose was associated with increased risk (trend P value   = .02). Among all estrogen users, concomitant progestin use was associated with increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13-2.26).  * Not “no increase” but rather reduces 8%--jk.

Conclusion:  Our finding that conjugated equine estrogen but not esterified estrogen was associated with venous thrombotic risk needs to be replicated and may have implications for the choice of hormones in perimenopausal and postmenopausal women.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^


Decrease in breast cancer found for the use of estrogen and progesterone compared to those who never used HRT; the same risk if estrogen and dydrogesterone, and a marked increase with estrogen and progestins such as with Prempro (NAMS study above).  This failure to consider adequately consider other combinations that that in Prempro entails that the WHI study has limited scope--jk.    

From Wikipedia  Women’s Health Initiative WHI study (the one used to get women off of HRT)

The Women's Health Initiative (WHI) was initiated by the National Institutes of Health (NIH) in 1991. The objective of this women's health research initiative was to conduct medical research into some of the major health problems of older women. In particular, randomized controlled trials were designed and funded that address cardiovascular disease, cancer, and osteoporosis.

Study components

There are actually 4 different randomized interventions and a separate observational-only cohort in the WHI. All 4 of the randomized components overlap with each other to some extent (and a few even overlap with the observational study). The 4 interventions and their abbreviated terminology are:

Estrogen-progestin versus placebo

This phase studied estrogen, specifically conjugated equine estrogen, plus progestin (Prempro, Wyeth) compared to placebo (the "WHI-E+P" trial), among healthy postmenopausal women.

This trial found that, compared with placebo, women receiving equine estrogen plus progestin experienced:[1]

The trial was ended early in 2002 when the researchers found that the subjects with estrogen plus progestin had a greater incidence of coronary heart disease, breast cancer, stroke, and pulmonary embolism than the subjects receiving placebo.[2] Hormone replacement therapy use declined in the U.S. and around the world, followed by a decline in breast cancer.[3]

Conjugated estrogen versus placebo

This trial studied estrogen, specifically conjugated equine estrogen (Premarin, Wyeth), alone versus placebo (the "WHI-CEE" trial) in women with prior hysterectomy.

The trial was conducted among women with hysterectomy so that estrogen could be administered without a progestin. In women with a uterus, a progestin is needed to counteract the risk of endometrial cancer posed by unopposed estrogen.

Major results of this study were than, compared with placebo, women receiving {equine} estrogen alone experienced:[1]

  • no difference in risk for myocardial infarction
  • an increased risk of stroke
  • an increased risk of blood clots
  • an uncertain effect on breast cancer risk
  • no difference in risk for colorectal cancer
  • a reduced risk of fracture
  • {with esterifed estrogen all of the above categories are significantly more favorable--jk}

Calcium and vitamin D versus placebo

This trial compared calcium plus vitamin D versus placebo ("WHI-CalcVitD"). This had 2 major papers arise from it in NEJM 2006, and one in May 2007 in the Archives of Internal Medicine [1]:

  • CRC endpoint
  • Fracture endpoint

Non-intervention cohort

The non-interventional observational cohort study ("WHI-OS") observed 93,000 women drawn from the same national clinical coordinating centers (many epidemiology studies conducted within this observational component of the WHI).

The WHI Postmenopausal Hormone Therapy Trials were part of the effort to address the high risk of cardiovascular disease in older women. By the early 1990s, many physicians had come to interpret results from previous clinical trials and studies using experimental animals as indicating that administration of an estrogen supplement to postmenopausal women would lower the incidence of cardiovascular disease. Two hormone clinical trials were designed and conducted:

The estrogen that was administered in the WHI studies was conjugated equine estrogen (CEE). This consists of a mixture of estrogens isolated from horse urine (Premarin). The CEE was administered orally. Both studies were randomized, placebo-controlled studies. Half the women were given an inactive placebo rather than hormone(s). Both studies were terminated early because a reduction in cardiovascular disease was not observed for most women and some women had dangerous side-effects. In particular, an increased risk of dangerous blood clotting is associated with oral administration of CEE. A review of the observational and WHI estrogen trial results describes potential explanations for the conflicting results.

In addition, co-administration of MPA (medroxyprogesterone acetate, a type of progestin) with CEE was associated with a slightly increased risk of breast cancer. Some benefits of using an estrogen supplement such as reduced risk of bone fractures were confirmed by these studies. However, for the older postmenopausal women who were recruited for this study, the undesirable side-effects of treatment generally were greater than the health benefits. Based on the results of these studies, CEE and MPA are no longer given to women in order to try to prevent cardiovascular disease in older women. Younger postmenopausal women seeking relief from conditions such as hot flashes, sleep disturbance and urinary/vaginal atrophy are still candidates for hormone replacement therapy. Alternatives to orally administered CEE and MPA are being increasingly used by women since the termination of the WHI studies. For example, other forms of estrogen (such as esterified estrogens) or topical administration of estradiol may reduce the risk of blood clotting compared to that for oral CEE.[4]

Finally, the low fat dietary pattern trial of the WHI yielded conflicting and controversial results. However, the WHI trial has been argued as unnecessary by many scientists, who already knew a full decade ago that total fat intake is not related to cardiovascular risk nor postmenopausal breast cancer risk.

WIKIPEDIA ON HRT:

Wikipedia, the best single source on evidence-based, scholarly, information on drugs, diseases, conditions, and treatments confirms my research.  On their estrogen articles:  Estrogen and other hormones are given to postmenopausal women in order to prevent osteoporosis as well as treat the symptoms of menopause such as hot flushes, vaginal dryness, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating. Fractures of the spine, wrist, and hips decrease by 50–70% and spinal bone density increases by ~5% in those women treated with estrogen within 3 years of the onset of menopause and for 5–10 years thereafter.

Before the specific dangers of conjugated equine estrogens were well understood, standard therapy was 0.625 mg/day of conjugated equine estrogens (such as Premarin). There are, however, risks associated with conjugated equine estrogen therapy. Among the older postmenopausal women studied as part of the Women's Health Initiative (WHI), an orally administered conjugated equine estrogen supplement was found to be associated with an increased risk of dangerous blood clotting. The WHI studies used one type of estrogen supplement, a high oral dose of conjugated equine estrogens (Premarin alone and with medroxyprogesterone acetate as PremPro).[29]

In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated equine estrogens. Hormone replacement therapy has favorable effects on serum cholesterol levels, and when initiated immediately upon menopause may reduce the incidence of cardiovascular disease, although this hypothesis has yet to be tested in randomized trials. Estrogen appears to have a protector effect on atherosclerosis: it lowers LDL and triglycerides, it raises HDL levels and has endothelial vasodilatation properties plus an anti-inflammatory component.

Enter supporting content here

Teddy Roosevelt's advised that, "We must drive the special interests out of politics. The citizens of the United States must effectively control the mighty commercial forces which they have themselves called into being. There can be no effective control of corporations while their political activity remains."