are a group of related 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
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
across the cell membrane. Once inside the cell, they bind to and
activate estrogen receptors which in turn modulate the expression
of many genes.
Additionally, estrogens have been shown to activate a G protein-coupled receptor, GPR30. 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; 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
(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 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 LDL [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 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
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, except in oil). A progestin is a synthetic
that has progestational effects similar to progesterone.
The two most common uses of progestins are for hormonal contraception (either alone or with
and to prevent endometrial hyperplasia [excess tissue 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 (Wikipedia). Synthetic plant and horse estrogens are
inferior to evolved human hormones. The
synthetics progestin MPA in Prempro is much worse than progesterone. As for
other synthetic progestins, several increase
cancer risk, and others lack literature including other side effects. What
follows are 3 sections: setting the
record straight by comparing natural HRT to Prempro; then a list of HRT’s
benefits supported by links to articles; last are recommendations.
record straight Prempro & natural HRT -- for more http://healthfully.org/fhr/
Press: Prempro, one of the first
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 which 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 (medroxyprogesterone). (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…. 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.” 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 using the natural
estradiol with progesterone listed at the top of the first page.) The press
made the most of the WHI results (undoubtedly with a nod
from their biggest advertiser).
HRT sales plummeted with this assault.
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) and still first in
sales. Based on the WHI, NIH issued
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…” The
warning is placed on all
packages of HRT, and it is accepted as correct by most doctors. My doubts about
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 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, and the NIH.
Up to Fail was published in the highly acclaimed science journal, Nature,
Nature ignorant of the vital fact
that Prempro contains no progesterone, but instead
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”. Why does Nature not know it?--END OF ARTICLE.
"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."
[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. ------
BENEFITS Cardiovascular disease (CVD) & MI: estrogen lowered by 20% cholesterol, 37% LDL (bad cholesterol)
and raised by 14% HDL 14%, extends life
2.1 years, Braunwald, Heart Disease …, 5th Ed, 1997, p 1708 tables.
“Estrogen-replacement therapy decreases CAD
morbidity and CAD mortality … was 0.56 compared to subjects not taking estrogen”
[a 44% reduction] Braunwald supra 1142.
Another study found a 50% reduction in CHD. Estradiol blocks
oxidation of LDL to prevent atherosclerosis. “Estradiol completely
effects induced by OX-LDL on the DDAH/ADMA/NO pathway,” Avoid MPA and LNG (levonorgestrel). Another study found 26 deaths for
estradiol vs. 56 for placebo, -115%. A
meta-study found and a 50% reduction of Coronary
AHA study explains
mechanisms of cardio protection. Angina
pain (cardiac syndrome X) associated
with low estrogen, treated.
cancer 73% using estradiol:
“in breast cancer (10 in treated group v 17
group).” HRT after & also during breast cancer
survival, also ratio 0.28--results would be better with
progesterone. “MPA (Prempro)
increases the risk of breast cancer” other progestins increase risk. Contrary
to PhARMA estradiol reduces risk and increases survival, and when given following breast cancer 2/3rd
fewer deaths at 15 years HRT, and same for uterine
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.”
reduced 83% with long-term HRT.
This is because estrogen is neuro-protective, it inhibits oxidative damage. Progesterone also limits damage; thus it is used in large doses
following trauma “to limit central nervous
Venus Thrombosis: an 8% reduction in risk of with
Esterfied Estrogen while those on Prempro had a 65% elevated risk JAMA 04, Cases and controls, , 23% reduction exogenous
estrogen (5.1% of cases versus 6.3% of controls
Breast density measured for women on HRT. The
difference has been repeatedly noted on mammograms.
American Journal of Clinical
& more hair, hair, hair.
postmenopausal women indicate
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
to be 48% greater.
Conclusions: HRT improved skin ageing.
“Esterified estrogens produced
in bone mineral density (lumbar spine, hip).
greater spinal mineral. “1
of 4 white
women over the age of 60 had spinal compression fractures associated with
woman of 5 will fracture a hip by the age of 90” Bone gain from long-term HRT; estradiol's
Rheumatoid Arthritis (RA): “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.”
both incident and progressive radiographic knee OA
cases combined, “current ERT [estrogen replacement therapy] use had a 60% decreased risk compared with never use.”
degeneration, age related. HRT resulted in a 36% reduction and other eye pathologies.
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 were clearly superior.
Satisfaction: “HRT improves sexual function in the orgasm, lubrication and pain
Mood elevation and depression: “Numerous molecular and
clinical studies have implicated estrogen in
modulating brain function including that related to mood,” and for treatment of mood disorders
10 Reasons for HRT:
Menopause Int. & Oncology: Both list the above benefits,
and the latter advices HRT for breast cancer patient survivor that they take
HRT because of “a 70% reduction in the risk
of death” during the 15 years.
to the loss of skeletal muscle mass with age and is associated with low level
of estrogen or TTT (testosterone). Sarcopenia
in older postmenopausal women not receiving estrogen or TTT. TTT prevents and
reverses sarcopenia, and.
Since the various health benefits are dose dependent, a dose
comparable to the Danish study (sequential
2 mg estradiol and 1 mg of norethisterone), Noretheisteone simulates
growth of breast cancer. All commercial products have a progestin. Thus
USE natural progesterone 100
mg micronized in oil capsule with 2 mg estradiol prepared in
a compounding pharmacy, or a lotion4-8 mg of estradiol + 200 mg progesterone
because skin absorption is 10-15%. Bio-activity decreases
with age. To improve absorption, mix ¼ tsp of
lotion with tablespoon of water and apply with fingers over upper torso,
(especially underarms, breasts and face).
Progesterone lowers risk of uterine cancer and has other benefits. Add
10 mg testosterone to avoid sarcopenia, loss of muscle mass, and to reverse androgen deficiency and improves libido.
In the 1980s testosterone was safely used in some HRT.
of doctors who do hormone balancing; it is not based on science. Post-menopausal
do not have hormone cycle—pre
do. There are no heads on studies to
prove the benefits of sequential HRT or balancing. If sequential, 200 mg progesterone 12 days
of a 28 day cycle. Ideal
free-serum estradiol level is 7-9 pg/mL.
For excellent mail-service and price use Coast
Compounding Pharmacy (760-433-6263), Dieter Steinmetz. JK since 2003 uses compounded lotion
testosterone (not orally active) as described above.