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HRT Women, Natural Benefits

    Natural HRT Benefits vs. Mare’s Urine Estrogen with MPA--the tragic differences 5/23/16—jk

The reason why women’s health precipitously declines after menopause http://healthfully.org/rc/id2.html

The long-term use of NATURAL estradiol (estrogen) and progesterone has been shown to DECREASE the risk of:  Alzheimer’s 83%, Heart attacks 51%, Coronary Heart Disease 50%, Colorectal Cancer 46%, Breast Cancer 72%, 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, increased libido & improves cognitive function, mental health, and extends life.. These claims are referenced below and at http://healthfully.org/fhr/.  WARNING: Avoid E2 antagonist (block action of estradiol), & E1, E3, E4; phytoestrogens, and most progestins; take Natural HRT (NHRT) estradiol plus progesterone.   

 

Backdrop:  1) The Pharmaceutical industry’s (pharma) prime goal is the maximization of profits; public service is their hype.  I call this tobacco ethics.  2) Know how broken the system is:  thus read Marketing Science, on the FDA , how doctors are their pawns, and watch Prof. Angell.  The attack on HRT follows the pattern of eliminating an off-patent drug that reduces profits, in this case prevents chronic conditions (above).  By convincing doctors and women that estrogen is dangerous, when they get breast or cervical cancer, they can put her for life on a drug that blocks estrogen.    Estrogen Basics:  Estrogens [Wikipedia] are a group of related compounds named for their importance in the estrous cycle of humans and 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, and the suffix -gen, meaning "producer of".  Estrogens are synthesized in all vertebrates as well as some insects.  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.  The three major naturally occurring estrogens in women are (E1) estrone, (E2) estradiol, and (E3) estriol.  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; while Estriol is during pregnancy 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 aromatase.  Follicle-stimulating hormone (FSH) stimulates the ovarian production of estrogens by the granulosa cells of the ovarian follicles and corporalutea.  Some estrogens are also produced in smaller amounts by the liver, [the brain & fat cells] adrenal glands, and the breasts.  Androstenedione has weak androgenic activity [muscle building] & 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 LDL.  Inflammation and oxidative damage are causal factors for cognitive decline, arthritis, Alzheimer’s disease and other conditions.  Estrogens circulate in the blood in association with proteins including sex hormone binding globulin and albumin (50-80%), & a significant portion is in the form of a sulfate.  It is distributed in most tissues, especially the breast, uterine, vagina, and has a high affinity to 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) & androstenedione decline gradually with age.  Progesterone (P4) is the most important of a class of hormones called progestogens.  [Wiki lists 12 major effects of progesterone.  They are structurally similar to the estrogens.]  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 orally bioavailability, except in oil].  A progestin is a synthetic  progestogen that has progestational effects similar to progesterone.  The two most common uses of progestins are for hormonal contraception (either alone or with an estrogen), and to prevent endometrial hyperplasia [excess growth in the uterus] from unopposed estrogen in hormone replacement therapy.  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“ (Wiki 2009, more, journal articles).                                                         

 

 ^^^^^^ Setting the record straight Prempro vs. natural HRT --  for  more    ^^^^^^^  

 

 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) UK completed in 1998 which used Prempro; moreover, earlier studies singled out (medroxyprogesterone) MPA as the cause for the  increased risk of breast cancer (Goodman & Gilman 2006, 1552).   Prempro consists of an estrogen cocktail derived from pregnant mare’s urine to which is added the synthetic progestin MPA.  (The cruel treatment of mares and subsequent slaughter was broadcast by Frontline.)  “Pregnant mare’s estrogens are the weak estrone (>50%), and the two mare estrogens, equilin (15-25%) and equilenin….  Mare (equine) estrogens such as equilin, that are foreign to the human body, have been shown, when compared to other studies, to have effects that are significantly worse than the natural 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%.”   “MPA antagonizes this athero-protective effect [on coronary arteries]” at 1997.  Though “all causes of mortality were not effected”, the press highlighted risks for HRT (undoubtedly with a nod from their biggest advertiser[3]), & HRT sales plummeted.  The equine estrogen only arm of WHI had better results; more proof that adding MPA causes the harm.   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 & pharma) and still first in sales.  Based on the WHI, NIH issued this warning on all HRTs: “…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…”  The warning is placed on all packages of HRT, and it is accepted as correct by most doctors.  My doubts were confirmed when attending a lecture on the WHI given in 2002 at UCSD by Professor Dr. Robert Langer.  He explained to a large medical audience that the WHI Prempro results cannot be validly applied to other HRT formulas.  Over 50 years of research was not overturned; rather physicians and the public were tragically misled by the press, pharma, guidelines, and the NIH.  This is another example of regulatory capture.  Tobacco ethics guides pharma. 

CONFIRMATION: Set Up to Fail was published in the highly acclaimed science journal, Nature, 09/09/2010:  Is Nature ignorant of the vital fact that 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…. [equine estrogens] have 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.   Why does Nature not know it?--END OF ARTICLE.



[1] First was DES (diethylstilbestrol) a non-steroidal estrogen developed in 1938.  Like Fleming with penicillin, DES was not patented because Dodds felt that scientists were working for the pubic, and it was too important to deny cheap availability by patenting.  Animal studies had in the 1930’s exposed DES serious side effects; but the industry relied upon human trials, and the FDA on Sept. 19, 1942 approved DES though aware of the more reliable 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 40 fold increase in cervical & vaginal cancers.  Later studies found several internal genital abnormalities in the daughters and sons of mothers given DES.  26 years later In 1997 Eli Lilly stopped making and  marketing DES.   DES was also the standard treatment for advance prostate cancer for over 40 years.  The other early blockbuster HRT Prempro with the progestin MPA has been shown to increase the rate of growth of breast cancer.  So too does nonrethisterone and dienogest, but progesterone induces apoptosis, at.

[2] Equilin blocks E1 and E2 receptors and thus would reduce the effectiveness of natural estrogens.  Though Prempro and Premarin (just equine estrogen) are still the world’s leading HRT and ERT, no follow-up research was done because the financial incentive is to hide side effects. 

[3] Pharma’s  assault on HRT is driven by their profits for chronic conditions arising from osteoporosis, depression, arthritis,  Alzheimer’s disease and the assorted illnesses and conditions related to atherosclerosis especially  heart attacks, strokes, and  hypertension; an example of tobacco ethics.

 

"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….  Bruce S. McEwen Neuroendocrinologist 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."  “With 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 breast cancer].”  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.

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---- BENEFITS OF HRT ---

Cardiovascular disease (CVD) & MI: “estrogen lowered … 37% LDL …, extends life 2.1 years,” Braunwald, Heart Disease 5th Ed, 97, p 1708.  “HRT decreases CAD morbidity and CAD mortality … was 0.56 compared to subjects not taking estrogen” Braunwald 1142; another 50%, 16 vs 33, reduction in CHD.  Estradiol blocks oxidation of LDL to prevent atherosclerosis.  Estradiol completely reverses the effects induced by OX-LDL on the DDAH/ADMA/NO pathway,” Avoid MPA and LNG (levonorgestrel).   Another study found 26 MI deaths for estradiol vs. 56 for placebo (115%).  A meta-study found and a 50% reduction of Coronary Heart Disease.  Lowers hypertension risk.  Two AHA studies explain mechanisms of cardio arteries protection and Wiki,  also,   Angina pain is associated with low estrogen, treated.   Calcification of arteries is strongly associated with MI.  HRT lower calcification of coronary arteries—at, using Prempro.

Cholesterol effects, percentage of reduction in LDL with E 37%, with E +PA 46% (E is equine estrogen and PA is medroxyprogesterone Braunwald, Table 51-2).  Estrogen is held to significantly protect LDL from oxidation at . “E2 at a concentration of 1 μmol/L inhibited LDL oxidation by 37% to 62% at the various concentrations of copper” at. Oxidized LDL in the tunica media of the artery is held to by pharma to be the major cause for atherosclerosis and CVD.   

Breast cancer risk decreased:  73% less for estradiol:   “in breast cancer 10 in treated group v 17 in control group.”   HRT after & also during breast cancer greatly increases survival, also ratio 0.28--results would be better with progesterone. “MPA (in Prempro) increases the risk of breast cancer” some progestins increase risk.  Contrary to pharma, estradiol  progesterone doesn’t  increase risk,  and when given following breast cancer over  2/3rd fewer deaths at 15 years HRT, and  also, also, same for uterine cancer.   HRT also prevent skin cancer.

Colon cancer: the reduction among current users RR = 0.55… users of 11 years or more RR of 0.54 [46% lower, also].” Estrogen and progesterone have beneficial effects for “esophagus, stomach, gallbladder, and intestines.”

Breast cancer survival:  Cancers in women who use HRT are often less advanced, and lower mortality has been reported in those who use HRT than in nonusers… The association of HRT with lower proliferation rate and smaller tumor size was exclusively caused by ER-positive tumorsat.  After diagnosis 72% higher survival: “The risk of death was lower among the HRT survivors; odds ratio 0.28…” at,  Also, breast cancer mortality rate of 5 per 1000 person years in HRT users compared to 15 in nonusers, at.  For negative results, pharma used the progestin MPA (WHI study); other progestins could be similar; however, “progesterone combined with estradiol induces apoptosis [cancer cell death]” at. 

Alzheimer’s disease with past long-term HRT, 7 vs 30 control. Estrogen is neuro-protective by inhibiting oxidative damage.  Progesterone is also neuro-protective:  used in large doses following trauma “to limit central nervous system damage.”  Again MPA in WHI study increased risk of dementia, 40 cases of dementia versus 21 in the placebo group, at.

Parkinson’s disease,” loss of estrogen resulted in decrease neuron density in the substantia nigra (structure of brain damaged by Parkinson’s disease), and restoration of estrogen in increased density” at, and.  Again MPA exacerbates condition & risk, at.  Pharma of course does junk science to show that HRT does not affect the course of the disease. 

Cognitive Function: “There are plausible biological mechanisms by which estrogen might lead to improved cognition.”

 

Longevity:  Telomere numbers of units on the end of DNA are essential for cell longevity and functionality—see Wiki.  It has been shown both in animal and human studies that treatment with estradiol lengthens through action on telomerase the number of telomere units, see careful matched study of HT therapy, and, and, and, for animals.  This action on telomerase in part explains the many benefits from estradiol. 

Programed death through menopause is to remove elderly women from the community, thus the precipitous decline in health of women after menopause.  To slow this process requires the taking of natural HRT.

Macular degeneration, and hearing:  HRT resulted in a 36% reduction and other eye pathologies.  Hearing better.

NAFLD:  Non-alcoholic fatty liver disease is also more common among men than women in all age groups until age 60, where the prevalence between sexes equalize. This is due to the protective nature of estrogen,” Wiki.— for diet's role.

Obesity & Diabetes:  the drop of estradiol increases LPL  which regulates weight, distribution of fat, and activity.  Gary Taubes, Good Calories, Bad Calories, 398, Taubes Why we Get Fat, 90-91, and Wade at,  In Obese estrone +40% at. Weight related issues (metabolic syndrome, insulin resistance, & diabetes) are associated with drop in estradiol, at.   

Osteoporosis: “Bone loss increases after menopause due to lower levels of estrogen.,. [causes removal of ovaries” Wiki  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, also; estradiol's role. Numerous journal articles hold that progesterone work with estradiol to increase remodeling of bone, at, and, and.  

Rheumatoid Arthritis (RA):  “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 RAalso, & lowers RA CVD deaths.

Osteoarthritis (OA): When both incident and progressive radiographic knee OA cases combined, “current ERT [estrogen only replacement therapy] use had a 60% decreased risk compared with never use”.    Progesterone most important.

Sarcopenia age related loss of skeletal muscle mass with age is associated with low level of estrogen & testosterone in 22.6% in older postmenopausal women not receiving estrogen or TTT.   TTT prevents and reverses sarcopenia, and.      

 

Skin healthier American Journal of Clinical Dermatology & more hair, hair, hair.    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 HRT.” “The mean collagen content in the skin was … found to be 48% greater”, slows skin aging,  also, and less skin cancer, 2008.

Urinary Tract Infections Recurrent (UTI), also urinary urgency, urogenital & vaginal atrophy are associated with low estrogen in post-menopausal women.  A meta-analysis of 8 quality studies found the placebo group 2.5 times more likely to have a subsequent UTI. Topical administration most effective; however for vaginal atrophy estradiol tablets.

Venus Thrombosis:  an 8% reduction in risk of with esterfied estrogen while those on Prempro had a 65% elevated risk JAMA 04, and; a 23% reduction exogenous estrogen (5.1% of cases versus 6.3% control cohort).

Sexual Satisfaction: prevents vaginal atrophy, HRT improves sexual functionbetter, estradiol & testosterone, &.

Mood elevation and depression: “Numerous molecular and clinical studies have implicated estrogen in modulating brain function including that related to mood,” treatment of mood disorders and depression no additional weight gain.

10 Reasons for HRT:  Menopause Int. & Oncology:  Both list the above benefits, and the latter advises HRT for survivors of breast cancer because of “a 70% reduction in the risk of death” during the 15 years, also.

 

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

 

RECOMMENDATIONS:  take natural HRT (NHRT) at dose comparable to the Danish study (Trisekvens sequential 2 mg estradiol with a progestin).  NHRT is part of nature’s clock.  NHRT sets the body’s clock to premenopausal and thereby reduces the rise for age-related chronic conditions.  Their lack causes the precipitous decline after menopause.  Life extension with long-term NHRT is over 4 years.  True to profits-first, corporate tobacco ethics, pharma offers 1) HRT in too low a dose; 2) synthetic estrogens, horse estrogen, and synthetic progesterone (progestins) of questionable value and safety; 3) human estrogens estrone (E1), Estriol (E3), estetrol (E4) which are less bioactive and they block some of the action of estradiol, the best estrogen; 4) the other progestins could be like MPA and block some of the benefits of estradiol.   For hot flashes, NIH guidelines include a major tranquilizer (SSRI) or an estrogen blocker such as Tamoxifen.  My wife takes 50 mg progesterone micronized in oil capsule[1] with 2 mg estradiol prepared by a compounding pharmacy.  Alternate, which she once took, is topical lotion of 8 mg of estradiol + 100 mg progesterone (absorption is 10%).   The use of sequential treatment with progesterone used for the last 10 days is probably as good or better, but unfortunately the evidence is thin.  Some doctors favor the sequential treatment because it duplicates the body’s natural cycle.  If concerned about muscle strength, add 10 mg of testosterone in lotion to reverse sarcopenia, androgen deficiency, & to improve libido without reduction in estradiol.  For lotion, moisten skin then apply as widely as possible over the torso and face and rub it in.  Tell your physician you are aware of risks and are convinced of benefits of NHRT outweigh risk, then give him a copy 2010 journal article.  Tell him you observed the benefits in a friend & a relative and want the same.   Most doctors will comply.  Beware of hormone balancing; some doctors are milking the insurance.  The evidence for sequential HRT is weak and it has a lower compliance because of vaginal bleeding—at 1997.  For more on Why Natural HRT.   Avoid “bio-identical” plant estrogens and progesterones—they aren’t identical to human sex hormones.  These hormones occupy receptors with uncertain action and possible block benefits like MPA, and have low bio-availability.   There is a lack of quality clinical trials on them.[2]  The youthful free-serum estradiol level is > 300 pmol/L, or > 80 pg/mL.  Estrogen is involved in both weight regulation and fat distribution.  Low estrogen entails for most a gain in unhealthy visceral (adnominal) fat.  Reset you bio-clock with NHRT, fix your diet, learn about the corruption caused by pharma (on YouTube), and why doctors are their pharma’s pawns.  For testimonials and more on osteoporosis, link.



[1] Prometrium is marketed in dose of either 100 or 200 mg of progesterone micronized in oil. 

[2] There is no evidence that the human body can convert its active ingredient.  For example diosgenin, the plant steroid, is chemically converted to produce several steroid and sold as natural, see Wiki, and for more on progesterone, Dr. Lee.  

 


              ^^^^^^^^^^^^^^^^^^  Non-technical summation    ^^^^^^^^^^^^^^^


Natural Estrogen (Estradiol) with progesterone NHRT:  What every woman should be taking because of the numerous, major health benefits, benefits that would slash pharma’s profits.  Of the 4 natural estrogens only estradiol (E2) has major health benefits.  Two--estriol (E3) and estetrol (E4)--are found in pregnant women and block estradiol.  Big pharma being against hormone replacement therapy (HRT) markets ineffective products including those containing estriol and estetrol, and estradiol at too low a dose & with inferior progestins such as in the best-selling Prempro.  Prempro, a combination of estrogen derived from pregnant mare’s urine and the progestin MPA.  The biological effects of mare’s estrogens are different than human estrogen and MPA blocks most of the positive effects of estrogen.  Thus the results of the major WHI study funded by the FDA apply only for Prempro[1].  Nevertheless he FDA warns that HRT has only one valid medical use, to manage hot flashes, and should be used at the lowest dose for the shortest time.  Thus pharma has used marketing science & guidelines to overturn 4 decades of positive results for HRT:  Alzheimer’s 83%, Heart attacks 51%, Coronary Heart Disease 50%, Colorectal Cancer 46%, Breast Cancer 73%, Thrombosis 8%, Macular Degeneration 65%, osteoporosis fractures 90%, & prevents arthritic join destruction, firmer breasts, healthier skin (less wrinkles, thicker, 48% more collagen), reduces hair loss, improved cognitive function, less depression and mental illness, and a general feeling of well-being with increased libido.  These results occur because estrogen & progesterone receptors set the body to “premenopausal” maintenance.  Through their many functions, these hormones are part of nature’s clock for death in the 7th decade.  The lack of estradiol & progesterone is the reason for the precipitous decline in health of women after menopause.  Life extension with long-term NHRT is over 4 years, and twice that with a natural diet.  Progesterone (P4), the major natural occurring progestogen, is similar to estrogen and works together.  It has numerous benefits, while some of the artificial progestins are clearly harmful (such as stimulating the growth of breast cancer), and none have been adequately researched as to side effects.  Like testosterone, a very similar hormone, at higher dose, more benefits.  A sufficient dose is available only from a compounding pharmacy (2 mg of estradiol plus 100 mg of micronized progesterone) in a capsule; or you can use a lotion obtained in a dose of 4 mgs estradiol plus 100 mg of progesterone per application (there is a 15% absorption rate with topical hormones).  Apply widely as possible over the torso, back, shoulders, underarms, and face using water and rubbing it in to promote better absorption. Ideal free-serum estradiol level is 200-500 mol/L.  Plant sources for HRT are not natural and are metabolized by the liver on first pass from the digestive system.  These hormone mimics fail to perform well and have adverse consequences (see MPA above).  Mimic can occupy sites that estradiol would go to and block their action, one of which is the control of appetite.  Doctors who follow the Wiley Protocol are other methods of hormone balancing for post menopause women are milking the insurance and patient, and it lacks convincing scientific evidence. In Europe excellent results have been obtained with sequential Trisekvens; Novo Nordisk, Denmark, though with greater side effects (nausea, break-through bleed), thus low compliance. Since ovulation is not possible sequential NHRT lacks benefits (see Natural HRT, below).  Keep it simple, and send the message to your cells that you are premenopausal. 




[1]   Prempro has been the leading selling HRT since the mid 40s in the US, and it still is.  The issues with MPA and mare’s urine estrogens has been known for decades by scientist including those in the FDA as inferior of the other HRT & natural HRT.  Because of birth control pills, HRT, and the possibility that an estrogen would protect men—as it does women—from cardiovascular disease, there has been thousands of published articles on the estrogen and progesterone family of hormones.   Unfortunately the FDA acts to promote products for pharma while minimally regulating in the public’s interest—see Consumer Report’s article, and also. 



Why Natural HRT, which estrogens, higher dose, and non-sequential


There are 4 superior choices for natural hormone replacement therapy (NHRT).   1) that of estradiol and progesterone; 2) a sequential uses of those hormone to mimic the women’s premenopausal cycle;  3) to take all 3 natural estrogens plus progesterone[1], and 4) to take them sequentially.  What is the evidence to support these choices?  Unfortunately, dispositive quality evidence is lacking:  no long-term clinical trials; nor are there short-term clinical trials.  The reason is simple, the profit margin in insufficient on off patent drugs to justify such trials.  Products natural to the body cannot be patented (with a few exceptions).  Contributing factor:  in the golden age of medicine, when there was still significant amount of university ran and clinical trials with just mere funding by pharma, progesterone was available only as a topical cream (not orally active).  Today that has changed, and like CoQ10 it is available in an oil based capsule micronized.  For these reasons the evidence for NHRT is mainly anecdotal.  The second source for evidence is population studies (epidemiological), but nearly all of them have a major flaw, they gather the evidence from all women on HRT, independent of formulation.  A few epidemiological studies separate women according to type of products, & a few clinical trials are for one product.[2]  These provide evidence suggestive that 1 of the 4 choices could be better. 


So why do I favor # 1), non-sequential progesterone with estradiol?  First, estradiol has been used in a number of preparations with excellent results.  In the French epidemiological study (EN3) estrogen showed no increase in breast cancer; & Prempro the greatest increase (due to the progestin MPA).  E3N study supports the use with estrogen with progesterone and not a progestin.  Second progesterone and estradiol work together in the body, thus to use a synthetic form, called a progestin, has consistently resulted in lower benefits—see MPA example above.  Third, for those using a better progestins, their results were superior to using only estradiol, ethinyl estradiol, and esterified estrogen[3], this favors the combination NHRT. Fourth those who used estradiol and testosterone (common in Europe in the 1980-90s) instead of synthetic progestin had very good results; this also supports the use of progesterone.   Fifth, there is no clinical evidence supporting comparable benefits from the other forms of estrogen comparable to those from estradiol; this supports the use of estradiol.  Sixth, the laboratory work testing with estradiol indicates that it is the most important of the 4 estrogens.  Seventh in the Danish study of the sequential high-dose (tri-cyclic) Trisekvens[4] (a product only available in Europe), the results were excellent.  Eight, compliance issue because of mild side effects of nausea and break-through bleeding like those of a menstrual period.  Ninth, the paucity of evidence supporting for postmenopausal women a need for having cyclic hormones[5].   Tenth, cyclic NHRT would cost more and is less convenient to take.  Eleventh, if I in recommended sequential, some woman would find a doctor who charges many times more for monitoring blood hormone levels and providing a custom balanced hormone cocktail based on her blood work.  This lacks sound science.  Conclusion:  Thus recommend #1, NHRT of estradiol with progesterone from a compounding pharmacy, 2 mg estradiol and 100 mg of micronized progesterone in oil as a capsule. 




[1] Dr. Jonathan V. Wright in Natural Hormone Replacement (1997) recommends all 3 hormones.

[2] Note, the large trials government funded trials (HERS and  WHI) are designed to show HRT as dangerous, since pharma opposes for business reason HRT.

[3] Esterified estrogen and ethinyl estradiol are commonly used instead of estradiol because of longer half-life--still available. They are  derivatives of estradiol, of which for esterified estrogen there are over 30--a way for pharma to obtain patents of exclusivity.  I consider these 2 equivalent to estradiol, though some of these forms must be inferior.   

[4]  The women in the treated group with an intact uterus started treatment with 2 mg synthetic 17-β-estradiol for 12 days, 2 mg 17-β-estradiol plus 1 mg norethisterone acetate for 10 days, and 1 mg 17-β-estradiol for six days (Trisekvens; Novo Nordisk, Denmark). http://www.bmj.com/content/345/bmj.e6409?etoc= .  “Because of break-through bleeding with sequential Trisekvens, non-sequential combined HRT form of Trisekvens was better received.” At.  

[5] Over 95% of HRT products are not sequential and the literature does not indicate an associated problems.  Nor are the benefits exceptional favorable from sequential Nordisc compared to the best of epidemiological studies. 



Why the higher dose of estradiol?  This is comparable to that used in Trisekvens which had excellent results.  In the 1960s through the 1980s the higher dose of estradiol was the norm, and during that period the numerous benefits were uncovered in epidemiological studies; thus higher dose is better.  Second, in men higher dose testosterone[1] has significantly greater health benefits, more evidence for a higher dose of estradiol.  Third, pharma in their opposition to these healthful hormones recommends the lowest dose, still more evidence that the higher is better.   


Why natural?  The goals is to restore youthful benefits and avoid age related conditions, thus to restore hormones to youthful levels.  Natural products have evolved to work in the body through receptors and complex feedback systems; thus synthetic chemicals don’t function as well.  Natural hormones have lower risk of side effect (for which the reporting system is broken)[2].  Of the over 100 synthetic hormones, there is no evidence that they work better, and only one has very good results in a clinical trial—unfortunately the Danish product is not licensed in the US. 


Why not branded drugs for HRT?  With the support of the NIH, pharma opposes HRT since 1990s, thus current products have various issues:  1) dose is too low for most of the healthful benefits; viz. not equivalent to 2 mg of estradiol.  Fernhrt has only .25 mcg of ethinyl estradiol (1/8th the recommended 2 mg).  Estragyn (estrone) is a 0.1 gm vaginal cream; but estrone is far less bioactive than estradiol, and the absorption rate is under 25%.  2)  A number of products are not estrogen, but estrogen antagonists (they occupy estrogen receptors on the cells and thus block estradiol’s action).  Tamoxifen is one of several estrogen antagonists marketed as HRT.  3) Estrogens with harmful progestins: Femhrt has the progestin norethindrone acetate, and Prempro has the progestin MPA.  4) Use less bioactive estrogens such as estrone, estriol, derivatives of the estrogens, and mare’s estrogen in Premarin.  5) For hot flashes several tranquilizers of the SSRI and dopamine agonist types have been approved, and many more are used off-label. 


Problem of finding a doctor who will prescribe HRT as recommended.  Be prepared with an answer when your doctor suggests that you try something else first.  You can refer to books, such as Natural Hormone Replacement (the Amazon reviews has good material). Ask him to read an article in Menopause Internal Journal which I have pasted with link.  Refer to the experience of friends, or other articles you have read.  And you can simply tell him that the 40 years of positive journal literature was not overturned by the flaw Women’s Health Initiative Study (WHI) which used estrogen from mare’s urine along with MPA as a progestin, which has been known to block some of the benefits of estrogen and increase risk for breast cancer. 


Nearly all doctors have fallen for the anti-HRT myths:  promotes breast cancer, and benefits aren’t worth the risks.  As argued at HRT, this is false for NHRT and most formulations of HRT.  Thus to get HRT or NHRT long-term (not just for hot flashes) requires a physician who is willing to do what once was the norm before 2002.  The earlier studies on HRT were not wrong.  I about 3/4th of doctors will write a prescription for NHRT for their regular patient after lecturing on the risks and a referral for a mammogram.[3]  He is protecting himself from possible litigation.  Copy this 2010 journal article Ten Reasons to be Happy About Hormone Replacement Therapy: A Guide for Patients to MS word and print it.  Read it before seeing him, and give him a copy.  These hormones are part of nature’s clock for us to die in the 7th decade.  The low estradiol & progesterone is the reason for the precipitous decline in health of women after menopause.  Sending a message to your body that you are premenstrual; it is worth the effort to jump through a few of pharma’s hoops. 


Progestins are of uncertain effects:  The use of progestins, in particular medroxyprogesterone acetate, in treating post-menopausal symptoms have been associated with increased risk of blood clots[45] and breast cancer in a study carried out by the Women's Health Initiative. While the study did not involve dydrogesterone, it is possible, but not certain, that it too increases these risks.[46]   [The blood clots a key risk factor for MI, explains why with Prempro used in the WHI) there was no reduction in MI—while with other formulas of HRT the reduction is 35% or greater.  The WHI has a second flaw in that of 55% equine estrogen, which is of uncertain consequences, thus the estrogen alone arm of the study is applies only to Premarin —jk.]  https://en.wikipedia.org/wiki/Dydrogesterone


 


^^^^^^^^^^^^^^^^^    http://www.sciencedirect.com/science/article/pii/S0378512203003463    


Abstract


Our in vitro results indicate that not all progestogens act equally on breast cancer cells. Some progestogens (medroxyprogesterone acetate (MPA), norethisterone acetate (NETA) and dienogest) alone or combined with estradiol (E2) stimulate proliferation of breast cancer cells, while others (dihydrodydrogesterone (DHD), the active metabolite of dydrogesterone, tibolone and progesterone (Prog)) alone or combined with estradiol induce apoptosis [prevents cancer].  Further pharmacological and clinical studies should be initiated to evaluate these findings in vivo.


 


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The women in the treated group with an intact uterus started treatment with 2 mg synthetic 17-β-estradiol for 12 days, 2 mg 17-β-estradiol plus 1 mg norethisterone acetate for 10 days, and 1 mg 17-β-estradiol for six days (Trisekvens; Novo Nordisk, Denmark). http://www.bmj.com/content/345/bmj.e6409?etoc= .  “Because of break-through bleeding with sequential Trisekvens, non-sequential combined HRT form of Trisekvens was better received.” At.  



[1]  Testosterone is structurally the same as estradiol but for one group on the molecule.  In the body women convert some of their estradiol to testosterone so that there level is about 1/10 that of a man’s.  Men convert some of their testosterone to estradiol.  

[2] Progestins are of uncertain effects:  The use of progestins, in particular medroxyprogesterone acetate, in treating post-menopausal symptoms have been associated with increased risk of blood clots[45] and breast cancer in a study carried out by the Women's Health Initiative. While the study did not involve dydrogesterone, it is possible, but not certain, that it too increases these risks.[46]   [The blood clots a key risk factor for MI, explains why with Prempro used in the WHI) there was no reduction in MI—while with other formulas of HRT the reduction is 35% or greater.  The WHI has a second flaw in that of 55% equine estrogen, which is of uncertain value, thus the estrogen alone arm of the study is applies only to Premarin —jk.]  https://en.wikipedia.org/wiki/Dydrogesterone

[3]  Men have a similar problem in obtaining a testosterone of sufficient dose, which entails using a compounding pharmacy. 


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http://en.wikipedia.org/wiki/Medroxyprogesterone_acetate

The Women's Health Initiative investigated the use of MPA and conjugated equine estrogens compared to placebo. The study was prematurely terminated when previously unexpected risks were discovered, specifically the finding that though the all-cause mortality was not affected by the hormone therapy, the benefits of the hormone replacement therapy (reduced risk of hip fracture, colorectal and endometrial cancer and all other causes of death) were offset by increased risk of coronary heart disease, breast cancer, strokes and pulmonary embolism. MPA increases the risk of breast cancer, dementia and thrombus when used in combination with conjugated equine estrogens to treat the symptoms of menopause.[3] 

MPA is associated with an increase in depression.  MPA may cause adrenal suppression and interfere with carbohydrate metabolism but does not cause diabetes. MPA can cause weight gain, worsen diabetes mellitus and edema (particularly of the face).   MPA may cause reduced bone density


For hormone replacement http://healthfully.org/fhr/; for women health issues http://healthfully.org/highinterestmedical/.  Both library of journal articles and more.

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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment.