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HRT concise summary--jk

Natural HRT Benefits;  Mare’s urine estrogen with MPA, the tragic differences (10/13/12)--jk

 The reason why women’s health precipitously declines after menopause

The long-term use of NATURAL estradiol (estrogen) and progesterone has been shown to DECREASE the risk of:    Alzheimer’s 83%,   Heart attacks 32%, Coronary Heart Disease 50%, Colorectal Cancer 46%, Breast Cancer 0%, Thrombosis 8%,, Osteoporosis Fractures 90%, Macular degeneration 65%, reduces & prevents arthritic join destruction, firmer breasts, Healthier skin (less wrinkles, thicker, 48% more collagen), reduces hair loss, improves cognitive function, less depression and mental illness, and a general feeling of well-being with increased libido. These claims are referenced below and at http://healthfully.org/fhr/.


Backdrop:  1) The Pharmaceutical industry (hereafter referred to by their trade organization PhARMA) is about profit maximization; public service is their hype.  2) What follows assumes that you have read the 2-page account of the state of Marketing Science and Misinformation”.  In that paper you will find out that PhARMA totally dominates medicine:  research, the  production of information for physicians and the public, the setting up of treatment protocols, and the FDA from the top- down.  Money talks:  the medical journals and media are “PhARMA friendly, as is also our 2-party system.


Estrogen Basics:  Estrogens are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones.  Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal. The name comes from the Greek οἶστρος (oistros), literally meaning "gadfly" but figuratively sexual passion or desire,[1] and the suffix -gen, meaning "producer of".  Estrogens are synthesized in all vertebrates[2] as well as some insects.[3]  Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors which in turn modulate the expression of many genes.[4] Additionally, estrogens have been shown to activate a G protein-coupled receptor, GPR30.[5]   The three major naturally occurring estrogens in women are estrone (E1), estradiol (E2), and estriol (E3).  Estradiol (E2) is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect.  Estrone is secreted by the ovary, adipose [fat] tissue, and placenta.  As a sulfate it acts as a reservoir that can be converted as needed to estradiol.  During menopause, estrone is the predominant circulating estrogen.  Estriol during pregnancy is the predominant circulating estrogen in terms of serum levels.   Though estriol is the most plentiful of the three estrogens it is also the weakest.  Thus, estradiol is the most important estrogen in non-pregnant females who are between the menarche and menopause stages of life.   A 4th type of estrogen called estetrol (E4) is produced only during pregnancy.  All of the different forms of estrogen are synthesized from androgens, specifically testosterone and androstenedione, by the enzyme aromataseFollicle-stimulating hormone (FSH) stimulates the ovarian production of estrogens by the granulosa cells of the ovarian follicles and corpora lutea.  Some estrogens are also produced in smaller amounts by other tissues such as the liver, adrenal glands, and the breasts.   Androstenedione has weak androgenic activity [muscle building] and is the predominant precursor for the more potent androgens such as testosterone as well as estrogen.   Among estrogen’s over 2-dozen bodily functions are those of lowering the remodeling threshold, thus preventing osteoporosis.  Estrogen prevents cardiovascular disease by lowering cholesterol levels, and by reducing inflammation and oxidative damage to VLD [bad cholesterol].  Inflammation and oxidative damage are causal factors for cognitive decline, Alzheimer’s disease and other conditions.  Estrogens circulate in the blood in association with proteins including sex hormone binding globulin and albumin (50-80%), and a significant portion is in the form of a sulfate.  It is distributed in most tissues, especially the breast, uterine, vaginal, and has a high affinity of adipose tissue.  Estrogens are metabolized in the liver and excreted as metabolites by the kidney.  Estradiol during menopause sharply declines; but the levels of total and free testosterone, as well as dehydroepiandrosterone sulfate (DHEAS) and androstenedione appear to decline gradually with age. The limited effectiveness of plant type estrogens is due to their lower bio-activity and first-pass metabolism by the liver. Progesterone belongs to a class of hormones called progestogens, and is the major naturally occurring human progestogen. The recognition of progesterone's ability to suppress ovulation during pregnancy spawned a search for a similar hormone that could bypass the problems associated with administering progesterone (low bioavailability when administered orally and local irritation and pain when applied to the skin).  A progestin is a synthetic[1] progestogen that has progestational effects similar to progesterone.[2] The two most common uses of progestins are for hormonal contraception (either alone or with an estrogen), and to prevent endometrial hyperplasia [excess tissue in the uterus] from unopposed estrogen in hormone replacement therapy.   [Progestins is in HRT  to lower the risk of uterine cancer.]   In mammals, progesterone, like all other steroid hormones, is synthesized from pregnenolone, which in turn is derived from cholesterol  in a very complex bio-system (Wikipedia).  Synthetic plant and horse estrogens are inferior to evolved human natural hormones.  The synthetics progestin MPA in Prempro HRT is much worse than progesterone.  As for other synthetic progestins, little is known about their side effects.  What follows is setting the record straight by distinguishing natural versus Prempro, then list of journal links to estrogen’s benefits.    

Bad Press:  Prempro, one of the first HRTs[1], has been marketed since 1942 by Wyeth Laboratory (bought out by Pfizer in 2009).  It has been and still is the best-selling HRT.   A supposedly definitive study of HRT was done by the FDA’s drug research branch, National Institute of Health (NIH) (with undoubtedly a nod from PhARMA).  The Women’s Health Initiative (WHI) knowingly selected the worst formulation of HRT, Prempro .  NIH had the results of the Hormone Estrogen Replacement Study (HERS ) completed in 1998  used Prempro; moreover, the medical literature had numerous disappointing results for Prempro when compared to natural HRT formulas.  Prempro consists of an estrogen cocktail derived from pregnant mare’s urine to which is added the synthetic progestogen MPA.  (The tragic treatment and slaughter produced from collecting urine for estrogen was broadcast by Frontline.)   “Pregnant mare’s estrogens are the weak estrone (>50%), and the two mare estrogens, equilin (15-25%) and equilenin….  It is not clear if estrogens such as equilin, that are foreign to the human body, likely have effects that are significantly different from the human estrogens like estradiol[2]MPA, the synthetic progestin used in Prempro, blocks most of the beneficial effects of estrogen--the natural progesterone doesn’t.  Using Prempro, the WHI found that compared to a placebo there was increased incidents:  heart attacks 29%, breast cancer 26%, pulmonary embolism 113%, strokes 41%, total deaths 15%, all cancers 3%; reduced incidents: hip fractures 34%  and colon cancer 37%.   (Compare this to the benefits of natural estradiol with progesterone listed at the top of the first page.)  The press made the most of these results (undoubtedly with a nod from their biggest advertiser[3]).  HRT sales plummeted with this assault.  The estrogen only arm of WHI had better results; more proof that adding MPA causes the harm.  But equine (horse) estrogen is clearly inferior to estradiol in other studies.  Pfizer in 2010 settled a suit over breast cancer for $330 million or $150,000 per person.  Yet Prempro is still on the market (thank you FDA) and still first in sales.  The NIH along with PhARMA deliberately failed to distinguish the natural HRT from Prempro.  Based on the WHI, NIH issued this warning: “…increased risk of myocardial infraction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women… Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman”.  The warning is placed on all packages of HRT—not just Prempro.  I suspected the worst of NIH and PhARMA having followed in the journals HRT and the birth control pill since the early 70s.  My doubts were confirmed when attending a lecture in 2002 given at UCSD by Professor Robert Langer.  He explained to a large medical audience that the WHI results can only be validly applied to Prempro.  Over 50 years of research were not overturned; but physicians and the public were tragically misled by the press, PhARMA, and the NIH

[1] DES (diethylstilbestrol) an non-steroidal estrogen with was first made in 1938; Like Fleming’s penicillin, DES also discovered in England) was not patented because Dodds felt scientists were working for the pubic, and it was considered too important to deny cheap availability.  Animal studies had in the 1930’s exposed DES side effects; but the industry relied upon human trials, and the FDA on Sept. 19, 1942 approved DES, though they were aware of animal studies.  DES was marketed under 200 brand names.   Numerous claims were made such as producing healthier babies and preventing miscarriages.   In 1971 DES was found to cause a rare vaginal cancer.  Later studies found other health consequences in the daughters and sons of mothers given DES, but and it remained available until the in 1997 when Eli Lilly stopped making and  marketing DES.   DES is another example of an unnatural product having health consequences hidden for decade-- like Prempro--mainly because of it is not in PhARMA’s financial interest to uncover and publish side effects.   DES was also the standard initial treatment advanced prostate cancer for over 40 years

[2] Equilin blocks E1 and E2 receptors and thus would like reduce the effectiveness of natural estrogens.  Though Prempro is still the world’s leading HRT, no follow-up research was done on this evidence by Wythe--for financial reasons.  

[3] Huge profits were made by reducing the sales of the off-patent HRT.  Osteoporosis became a major health problem. The sales of drugs to treat osteoporosis, heart attacks, depression, and Alzheimer’s disease all dramatically increased over the next decade. 

^^^^^^^ Setting the record straight findings for natural HRT --  see also http://healthfully.org/fhr/  ^^^^^^^^^

Set Up to Fail was published in the highly acclaimed science journal, Nature, 09/09/2010:  “Prempro contains no progesterone, but instead the artificial progestogen Provera [MPA].  The other component is Premarin (conjugated estrogen), which is a very uncertain, patent mixture of substances from the urine of pregnant mares…. [MPA] has crucially different effects. Prempro is totally unrepresentative of any other product used for HRT purposes…. . 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”.

"I think that it borders on a tragedy that Premarin and Provera [the 2 compounds in Prempro] were chosen as the only HRT treatments [for the WHI Study]”.  Another researcher finds that Provera [MPA]--and no other progestin--blocks the mechanisms that allow estrogen to fight the brain's immune response to Alzheimer's….  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."  “Medroxyprogesterone [MPA] in Provera you are activating two receptors involved with cell division in the breast," she says, "and that's the culprit, not estrogen [for increased breast cancer]."  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…. 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.”  Hormone Hysteria, Scientific American Sept. 2003.

Cardiovascular disease (CVD) “Women lose their relative protection … 14% higher total cholesterol, 12% higher triglycerides, and 27% higher LDL cholesterol; 7% lower HDL…. Estrogen-replacement therapy has been shown to decrease CAD morbidity and CAD mortality …. In a meta-analysis … the relative risk for CAD in postmenopausal subjects taking estrogen was 0.56 compared with postmenopausal subjects not taking estrogen”.  Braunwald, Heart Disease: a Textbook of Cardiovascular Medicine 5th Ed.1997 p 1142”.  That is a 44% reduction--another study found a 50% reduction in CHD after HRT; its mechanism.  CVD is the number one cause of death. Another found 56 deaths vs. 26 for placebo

Breast cancer:  No increased of risk:  “The association of estrogen-progestogen combinations with breast cancer risk varied significantly according to the type of progestogen: the relative risk was 1.00 (0.83–1.22) for estrogen–progesterone [all natural, also in and].”  The same is mention in the Scientific American article above.


Colon cancer: the reduction among current users RR = 0.55… users of 11 years or more RR of 0.54 [46% lower, also].” Benefits found for “esophagus, stomach, peptic ulcer disease, gallbladder, irritable bowel syndrome, colon,” etc.

 Alzheimer’s disease reduced 83% with  long-term HRT.  This is because estrogen is neuro-protective, it inhibits oxidative damage.  Progesterone also limits damage and is used in a large dose following trauma “to limit central nervous system damage.”

Thrombosis:  an 8% reduction in risk of with Esterfied Estrogen while those on Prempro had a 65% elevated risk JAMA 04,  “Cases and controls, whose average age was 65 years, did not differ significantly on matching variables or on current use of exogenous estrogen (5.1% of cases versus 6.3% of controls).”  A 23% reduction with estrogen is significant!

Breast density measured for women on HRT.  The difference has been repeatedly noted on mammograms

Healthier skin American Journal of Clinical Dermatology, Studies of postmenopausal women indicate that estrogen deprivation  is associated with dryness, atrophy, fine wrinkling, poor healing, epidermal thinning, declining dermal collagen content, diminished skin moisture.  The decrease was preventable by the use of hormone replacement therapy. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women,  Conclusions: HRT with the mentioned regimes improved parameters of skin ageing.


Osteoporosis:   “Esterified estrogens produced significant increases in bone mineral density (lumbar spine, hip).   54.2% greater spinal mineral.  “1 of 4 white women over the age of 60 had spinal compression fractures associated with osteoporosis.  One woman of 5 will fracture a hip by the age of 90”   Bone gain from long-term HRT.

Rheumatoid Arthritis:  “Transdermal HRT was well tolerated, increased well-being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA.”

Osteoarthritis: When both incident and progressive radiographic knee OA cases combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5).    

Macular degeneration, age related. HRT resulted in a 36% reduction and other eye pathologies 

Sexual Satisfaction:HRT improves sexual function in the orgasm, lubrication and pain domains …”

Mood elevation and depression: Numerous molecular and clinical studies have implicated estrogen in modulating brain function including that related to mood.”  Fluctuations in estrogen occur naturally throughout the reproductive years and can be associated with disruptions in mood.  Estrogen inhibits the re-uptake of the neural transmitter serotonin 

10 Reasons for HRT:  Menopause Int.  Vol. 16 No 1, pp. 44-46.  Given the above, consider the harm PhARMA has done to women.

RECOMMENDATIONS:  Compounded as a skin lotion, the higher dose 2 mg or more of estradiol is recommended because of the various positive health consequences of estrogen increase with dose, plus progesterone.  Skin lotion absorption is about 10-20%. Excellent mail service is available from Medical Plaza Pharmacy (949-586-6337, $105 for a 90 day supply).  To spread the lotion as far a possible, add a few drops of water to hand; this improves absorption.  After looking at a list of over 50 formulas of HRT, compared to the older formulas such as in the Danish Study (sequential 2 mgs estradiol and 1 mg of norethisterone), The current pill formulas are of too low for me to recommend them. This lower dose is consistent recommendation of the FDA for lower dose and shorter usage.  Avoid Tibolone, which blocks estrogen.  A patch is also available; however, it too is a lower dose, and possible causes skin irritation.      


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