---

Until 2002 mainstream physicians routinely
prescribed conventional hormone replacement
therapy (HRT) in order to alleviate
menopausal symptoms, such as hot flashes,
mood swings, decreased sexual desire,
vaginal dryness, and difficulty sleeping, as
well as to prevent heart disease and
osteoporosis. In 2002 more than 160,000
women participated in the Women’s Health
Initiative (WHI), the results of this
landmark study identified grave dangers
associated with conventional hormone
replacement therapy in women.
This conventional HRT therapy caused
dangerous consequences including
A 26% increased risk of breast cancer,
A 29% increased risk of heart attack,
A 41% increase in risk for strokes,
And a doubling in risk for blood clots
relative to the untreated group.
Moreover, women receiving conjugated equine
(horse-derived) estrogen experienced a six-
fold increased risk for uterine cancer.
Only a small sub-group of women, those under
60 years of age who had undergone a
hysterectomy (surgical removal of the
uterus), experienced a reduction in breast
cancer risk when using estrogen without
medroxyprogesterone acetate (MPA), a
synthetic progestogen (Rossouw et al 2002;
Grady et al 2002; Hulley et al 2002; Azoulay
2004; Moskowitz 2006; Ragaz 2010).

After the devastating results of this large
Up to 70% of women taking HRT stopped, and
women’s trust in the mainstream medical
establishment declined significantly Given
these substantial risks of conventional HRT,
many women began to seek natural
alternatives to hormone replacement (Roumie
2004; Schonberg 2005). This frightening Data
from the study also forced many physicians
to discourage the use of conventional HRT
for the prevention of osteoporosis and
cardiovascular disease in aging women
(Sharma 2003, Azoulay 2004).

Though many mainstream physicians were
shocked by the results of the WHI study,
Functional and Integrative wholistic
physicians were not The hormones utilized in
the WHI study consisted of oral equine
(horse) estrogen and a synthetic
progestogen, both of which differ in
chemical structure from the hormones a
woman’s body produces naturally. Functional
and Integrative wholistic physicians has
discouraged the use of conventional HRT for
many years and has instead recognized the
value of bioidentical HRT, which uses
hormones that are exactly the same as those
naturally produced in women. Bioidentical
HRT is associated with far fewer side
effects than conventional HRT and there is
intriguing evidence that it may reduce the
risk of certain cancers (Holtorf 2009).

Moreover, supplementation with
scientifically studied vitamins and natural
plant extracts can help promote healthy
metabolism of female hormones and complement
the actions of bioidentical HRT.
What is Conventional HRT?

As women age their sex hormone levels
decline. The thought of traditional
physician was that HRT replacement should
reverse troubling menopausal symptoms, which
include increased risk of heart attack and
cancer (Wren 2009; Lenfant 2010; Lee 2010).
While the original understanding of
menopause and the logic of HRT were
theoretically correct, modern science is
showing that the true story of HRT is much
more complex (Sitruk-Ware 2007). Early views
did not do justice to the finely tuned
hormonal symphony that is conducted
throughout a woman’s life.

The hormonal concerto is a tightly regulated
masterpiece it is therefore impossible to
consider estrogen and progesterone
replacement in isolation from other
hormones. All steroid hormones are created
from cholesterol in a hormonal cascade. The
first in the cascade is pregnenolone, which
is subsequently converted into other
hormones, including dehydroepiandrosterone
(DHEA), progesterone, testosterone, and the
various forms of estrogen. These hormones
are interrelated, yet each performs unique
physiological functions. Biologically sound
hormone replacement should focus on a
woman’s total hormone balance, and not only
on estrogen and progesterone.

The importance of balance cannot be
overstated. Mainstream physicians are just
now beginning to recognize the importance of
hormonal state called estrogen dominance
(Turgeon 2006), a term used to characterize
the relative imbalance between excess
estrogen and insufficient progesterone.
Estrogen dominance is associated with many
of the conditions that confront modern
Western women, such as fibrocystic breast
disease (Kubista 1990), and cancer (Bentrem
2003; Bradlow 1995; Papaconstantinou 2000).
Estrogen dominance can occur in any woman,
but perimenopausal women, who typically
experience a more rapid decline in
progesterone relative to estrogen, are
especially at risk (Fauser and Van Heusden
1997).

Conventional HRT makes use of non-
bioidentical hormones that differ chemically
from those naturally produced by a woman’s
body. Furthermore, the relative levels of
the female hormones administered in
conventional HRT are also different (Turgeon
2006; Chlebowski 2010).


For instance, conjugated equine estrogen
(CEE), as the name implies, is obtained from
the urine of pregnant mares (horses)
(Bhavnani 2003). CEE is usually given in
combination with progestin, a chemical
compound modified for the purpose of
appearing structurally similar to natural,
bioidentical progesterone, but which, in
fact, is not the same. These structural
differences between conjugated equine
estrogens and chemical progestins, and the
hormones that women’s bodies produce
naturally explain many of the adverse
affects associated with conventional HRT.

Another major problem with conventional HRT
is the ratio of estrogens. Specifically, an
approximate ratio of estrogens in Premarin®
is about 75% estrone, up to 15% equilin (a
potent horse estrogen), estradiol, and at
least two other equine estrogens. These are
substantially different from the ratios
observed naturally in a woman’s body (Wright
1999).

Causes of Estrogen Dominance

Beginning in perimenopause and continuing
through menopause, the production of
progesterone tends to decline more rapidly
than that of estrogen. If the ratio between
progesterone and estrogen is unbalanced
favoring excess estrogen, a woman may become
susceptible to an increased risk of
fibrocystic breast disease and other health
risks (Kubista 1990; Lee and Hopkins 1996).

Factors contributing to estrogen dominance
include:
Exposure to estrogen-mimicking chemicals
found in herbicides, pesticides, and
petrochemicals (for example BPA, or
bisphenol A) and PCB’s (polychlorinated
biphenyl’s), used in some cosmetics, glue,
plastic, and other modern materials (Tapiero
2002)
Obesity, as well as increased intake of
excess calories from simple sugars, fiber-
deficient refined grains, and trans­-fat from
partially hydrogenated vegetable oil
Estrogen dominance is often associated with
symptoms such as food cravings, bloating,
weight gain, fatigue, mood swings,
depression, cyclical migraine headaches,
lack of sexual desire, menstrual cramps,
short cycles, heavy menstrual bleeding, hair
loss, fibroids, and endometriosis.
Is possible Cancer Risk a legitimate Reason
to Deprive Aging Women of healthy aging and
Natural Hormone balancing?

Hormones like estrogen and testosterone
affect cell growth and proliferation; this
heightens the concern about the possibility
of increase in the cancer risk in this
population. This fear about cancer
development is an important reason why more
aging women chose not to restore their
hormonal levels to more youthful levels.
Does that mean aging women should simply
accept the sex hormone deficiencies they
face as a part of “normal� aging?

To better clarify the association between
sex hormone restoration and the increased
risk of cancer risk I have reprinted a chart
showing women’s breast cancer risk by age
(Simone 2005). If estrogen caused breast
cancer, then we would expect to see very
high rates of breast cancer in young women
of childbearing age, with a dramatic
decrease in breast cancer after menopause;
this simply is not the case. Clearly aging
and not proper bio-identical hormonal
restoration is the primary cause of breast
cancer.

Risk of Developing Breast Cancer by Age
By age 25:      1 in 19,608
By age 30:      1 in 2,525
By age 40:      1 in 217
By age 45:      1 in 93
By age 50:      1 in 50
By age 55:      1 in 33
By age 60:      1 in 24
By age 65:      1 in 17
By age 70:      1 in 14
By age 75:      1 in 11
By age 80:      1 in 10
By age 85:      1 in 9
The reason cancer risk increases with aging
is that the genes that help regulate healthy
cell growth can mutate. In fact, mutations
in cells’ regulatory genes are an underlying
cause of cancer (Haber 2000). The concern is
that breast cells with mutated regulatory
genes may be more vulnerable to estrogen’s
growth stimulating effects.

Information on nutrients that complement
bioidentical HRT and may combat these age-
related genetic mutations is provided in
this protocol in the section entitled
“Anticancer Nutrients to Complement
Bioidentical HRT.�

Estrogen Explained

To fully appreciate the complexity of HRT,
it is important to understand the various
forms of estrogen and their effects in the
body. The estrogen family include smore
than 15 forms of estrogen naturally created
in a woman’s body (Taioli, 2010). These
include the three major players Estrone is
the criminal and cancer promoter, Estradiol,
and Estriol is the cancer police.

Each of these estrogens has particular
functions.
Estradiol (E2), the predominant form in
reproductive-age non-pregnant females,
primarily aids in the cyclic release of eggs
from the ovaries for potential fertilization
and preparation of the uterus for pregnancy.
Estradiol also has beneficial effects on
heart, bone, brain and colon. Reduction in
the level of estradiol causes common
menopausal symptoms such as hot flashes and
night sweats.
Estrone (E1), produced in the ovaries but
also generated in fat cells, is another
relatively potent form of estrogen, and is
the dominant estrogen in postmenopausal
women.
Estriol (E3) is secreted in large quantities
during pregnancy by the placenta; however,
it is a comparatively weak estrogen, and the
form of estrogen least associated with
hormone-related cancers. In Europe and
Japan, estriol is frequently used for HRT
(Head 1998; Kano 2002, Moskowitz 2006,
Holtor 2009).

The three estrogens convert into many
metabolites. Estrone, for example, may
convert into three different forms:

2-hydroxyestrone
4-hydroxyestrone
16-alpha-hydroxyestrone
Scientists have identified 2-hydroxyestrone
as a “good,� or chemoprotective estrogen,
while 16-alpha-hydroxyestrone and 4-
hydroxyestrone have been associated with the
development of cancer (Bradlow 1996; Muti
2000). The relationship between 2-
hydroxyestrone and 16-alpha-hydroxyestrone
is sometimes expressed as the 2:16 ratio
(Taioli 2010).

By increasing the ratio of 2-hydroxyestrone
to 16-alpha-hydroxyestrone, it may be
possible to reduce the risk of estrogen-
related cancers (Bradlow 1986; Taioli 2010).

3,3’-Diindolylmethane (DIM) and indole-3-
carbinole (I3C), found in appreciable
concentrations in cruciferous vegetables,
favorably affect estrogen metabolism and
help to optimize the 2:16 ratio. A placebo-
controlled, double-blind study of women at
increased risk for breast cancer found that
four weeks of supplementation with I3C
promoted favorable changes in the urinary
estrogen metabolite ratio of 2-hydroxy-
estrone to 16-alpha-hydroxyestrone (Wong
1997; Dalessandri 2004).

Estrogen Receptors and a Closer Look at
Estriol

As mentioned previously, estriol (E3) is the
form of estrogen least associated with
cancer. Estriol’s protective effects become
apparent when examining the differing
actions that each of the three primary
estrogens exerts upon the estrogen
receptors. On breast cells there are two
distinct classical estrogen receptors that
bind estrogens,
Estrogen receptoralpha
And estrogen receptorbeta.
In addition, there is one non-classical
estrogen receptor, GPR30 (Paruthiyll 2004;
Paech 1997; Katzenellenbogen 2000; Nilsson
200; Wang 2010).
The binding of estrogen hormones to estrogen
receptor alpha promotes breast cell
proliferation, which can exacerbate the
spread of existing breast cancer.
Conversely, the binding and activation of
estrogen receptor betaattenuates breast cell
proliferation and may slow the development
of a cancerous tumor (Helguero 2005; Bardin
2004; Isaksson 2002; Weatherman 2001).
Estrone and estradiol preferentially bind to
and activate estrogen receptor alpha,
thereby explaining the proliferative effects
of these two hormones (Zhu 2006; Rich 2002).
Estriol, on the other hand, binds to and
activates estrogen receptor beta (Zhu 2006;
Rich 2002). This critical fact helps to
explain estriol’s “anti-estrogenic�
activity, which led a noted researcher in
hormone replacement therapy to state, “This
unique property of estriol, in contrast to
the selective ER [estrogen receptor] alpha
binding by other estrogens, imparts to
estriol a potential for breast cancer
prevention, while other estrogens [estrone
and estradiol], would be expected to promote
breast cancer… Because of its differing
effects on ER alpha and ER beta, we would
expect that estriol would be less likely to
induce proliferative [potential cancerous
growth] changes in breast tissue and to be
associated with a reduced risk of breast
cancer� (Holtorf 2009).

Moreover, groundbreaking research has
revealed that the non-classical estrogen
receptor, GPR30, mediates proliferation of
breast cancer cells independently of the two
classical estrogen receptors. Estradiol
strongly binds to and activates GPR30,
driving proliferation. Estriol, on the other
hand, acts as an antagonist of GPR30, though
it has a much lower affinity for GPR30 than
does estradiol (Wang 2010; Lappano 2010).
Many carcinogenic toxins, including
bisphenol A (BPA) and polychlorinated
biphenyl’s (PCB’s), promote the growth of
breast cancer cells by functioning as
agonists of GPR30 (Wang 2010).

Significantly, the traditional breast cancer
drug tamoxifen, which blocks the activity of
the classical estrogen receptors, fails to
suppress the cancer-promoting effects of
GPR30. It is by this mechanism that some
estrogen receptor positive breast cancers
become drug-resistant. In fact, tamoxifen
has been shown to stimulate the growth of
drug-resistant breast cancer cells via
activation of GPR30 (Ignatov 2010).

Estriol, through its estrogen receptor
modulatory capacity, combats the
proliferative effects of estrone and
estradiol (Melamen 1997; Wang 2010). These
scientific findings highlight the importance
of emphasizing estriol in any bioidentical
hormone replacement program intended to
restore youthful hormone balance and guard
against breast cancer development.

Age-Related Hormone Decline is dangerous

By the time a woman enters menopause, she
may have already experienced two decades of
hormonal imbalance. After menopause, when
sex hormone levels decrease significantly,
aging women are at increased risk of major
diseases, including the following:
Heart disease Rates of heart disease in
postmenopausal women gradually climb until
they equal the rates typically seen among
men. According to the Centers for Disease
Control and Prevention (CDC), heart disease
is the leading killer of American women (CDC
2006). A number of negative changes in
cardiovascular health are provoked by
menopause, including elevations in blood
pressure, low-density lipoprotein (LDL)
cholesterol, total cholesterol, and
triglycerides. At the same time, high-
density lipoprotein (HDL) cholesterol levels
drop significantly. Elevated levels of
homocysteine, C-reactive protein, and
interleukin-6 (an inflammatory cytokine) are
all associated with estrogen deficiency
(Cushman 2003; Davison 2003; Dijsselbloem
2004). Estrogenic activities are vital for
maintaining integrity of the vascular
endothelium, where atherosclerotic changes
begin (Arnal 2009). Finally, lack of
estrogen replacement in the postmenopausal
state may predispose women to forms of
cardiac muscle disease that are only now
beginning to be understood (Kuo 2010).
Osteoporosis Hormone deficiencies are
clearly associated with bone loss and
osteoporosis, beginning as early as the
third decade of life. By the time women
reach 50, they are at significantly
increased risk of an osteoporotic bone
fracture. Estrogen deficiency results in
increased production of pro-inflammatory
cytokines, which cause increased bone
breakdown and inflammation (Weitzmann and
Pacifici 2006). Combined estrogen and
androgen therapy increases bone mineral
density (BMD), and has been shown to
increase BMD more than estrogen therapy
alone (Notelovitz 2002).
Alzheimer’s and dementia Loss of hormones is
associated with neuronal degeneration and
increased risk of dementia, Alzheimer’s
disease, and Parkinson’s disease (Amtul
2010; Rocca 2008). Estrogen stimulates
degradation of beta-amyloid protein, noted
to accumulate in the brain of Alzheimer’s
disease patients, by up-regulating
production of protective proteins (Liang
2010). Deficiencies in pregnenolone and
DHEA, which are both neuroprotective
hormones, are also linked to reduced memory
and brain cell death associated with
Alzheimer’s disease (Vallée 2001; Yao 2002).
These two hormones play an important role in
regulating neurotransmitter systems that are
involved in learning, stress, depression,
addiction, and many other vital functions
(Vallée 2001).

Progesterone’s Balancing Act

Estrogen is only part of women hormonal
story. Progesterone is equally important. In
a healthy young woman, progesterone serves
as a counterweight to estrogen. While
estrogen builds up during the first half of
a menstrual cycle, progesterone levels do
not start rising until the middle of the
cycle. Progesterone’s job is to prepare the
uterus for implantation with a healthy
fertilized egg and to support the early
pregnancy. If no implantation occurs,
progesterone levels drop and another cycle
begins.

Studies have shown that progesterone has
anti-proliferative effects on at least two
different types of breast cancer cells, as
well as leukemia cells (Formby 1998; Hayden
2009; Hilton 2010). Breast cancer is 5.4
times more common in pre-menopausal women
with low progesterone than in pre-menopausal
women who have favorable progesterone levels
(Cowan 1981). Data suggest that while
natural, bioidentical progesterone does not
increase breast cancer risk, synthetic
progestins used in conventional HRT do raise
the risk. (Campagnoli 2005).

Natural progesterone has also demonstrated
neuroprotective properties. For example, one
study called for more attention to
progesterone as a “potent neurotrophic agent
that may play an important role in reducing
or preventing motor, cognitive, and sensory
impairments [in both men and women].� (Stein
2005)

Progesterone deficiency has also been linked
to migraine (Colson et al 2005).
Bioidentical Hormone Replacement Therapy

Bioidentical hormone formulations in doses
tailored to individual patients can be
obtained from a compounding pharmacy after a
physician’s prescription has been submitted.
The use of bioidentical estrogens has been
utilized extensively in Europe and Japan for
several years (Kano et al 2002).
Estriol has shown beneficial effects in
women at risk for cardiovascular
disease.Japanese scientists found that a
group of menopausal women treated with
estriol for 12 months had a significant
decrease in both systolic and diastolic
blood pressure (Takahashi 2000). Another
placebo-controlled study demonstrated that
estriol replacement for 30 weeks improved
flow-mediated dilation, a measure of
arterial relaxation (Hayashi 2000). Estriol
accomplishes these effects by strongly
activating nitric oxide signaling systems
and stabilizing atherosclerotic plaques
(Kano 2002).
Estriol may further reduce cardiovascular
risk through its beneficial effects on lipid
profiles. One Japanese study found that
estriol prevented a postmenopausal rise in
total cholesterol, and did not induce the
elevated triglyceride levels, a side effect
frequently seen after treatment with
conventional estrogen therapy (Itoi 2000).
Estriol, in combination with a statin drug,
can reduce carotid artery intima-media
thickness, a measure of atherosclerosis, in
postmenopausal women with elevated blood
lipids (Yamanaka 2005).
Estriol also increases bone mineral density,
a vital parameter in post-menopausal women
at risk for osteoporosis. In one study,
women treated with estriol exhibited an
increase in bone mineral density and
improved climacteric symptoms with no
increased risk of endometrial hyperplasia
(Minaguchi 1996). In a second study,
researchers treated postmenopausal and
elderly women with estriol and 1,000 mg/day
of calcium lactate versus 1,000 mg/day of
calcium lactate alone. Bone mineral density
significantly increased in women who
received estriol, while those who did not
take estriol experienced a decrease in bone
mineral density (Nishibe 1996). In a summary
statement, the researchers wrote, “the
acceleration of bone turnover usually
observed after menopause was prevented by
treatment with E3 [estriol].� (Nozaki 1996)
Estriol also supports sexual and urinary
health. For example, one study showed that
estriol-treated women reported a 68%
reduction in symptoms of incontinence, a
significant result compared with just 16% of
women in the placebo group (Dessole 2004).
Women with recurrent urinary tract
infections experienced a 91% reduction in
infections following treatment with an
intravaginal estriol cream, compared with
placebo recipients (Raz 1993). Another study
demonstrated that locally administered
estriol therapy significantly increased the
number of blood vessels surrounding the
urethra, thereby improving its ability to
keep urine in the bladder until urination is
desired (Kobata 2008). The addition of
estriol to standard therapy for prevention
of urinary tract infections reduced the
number of recurrences 11-fold, and the days
of antibiotic therapy more than 12-fold in
another study (Davidov 2009).
Stress incontinence refers to intermittent
loss of urine with pelvic floor stress from
laughing, coughing, etc. Pelvic floor muscle
exercises are effective in reducing stress
incontinence, and studies suggest that
estriol adds substantially to the beneficial
effect (Ishiko 2001).
Estriol can offer relief for women suffering
from atrophic vaginitis, the symptoms of
which include vaginal dryness, vaginal
burning, and painful intercourse. After 4
weeks of treatment with an intravaginal
estriol cream, researchers noted,“atrophy of
vaginal epithelium and chronic vaginitis
stopped or significantly decreased… The
subjective complaints relating to the
estrogen deficiency (vaginal burning and
dryness, itching, dyspareunia [painful sex]
and urinary dysfunctions) ceased. Side-
effects and complications during the
treatment were not found.� (Koloszar 1995)
More objective improvements to vaginal
dryness and acidity have been demonstrated
in recent studies (Chollet 2009).
Topical estriol creams applied to the face
and neck can also reduce many of the
symptoms of aging skin, such as dryness and
wrinkling. Animal studies demonstrate that
estriol cream promotes collagen production
and enhances the elasticity of treated skin
(Ozyazgan 2005).
Studies have also shown estriol to be
effective in the treatment of menopausal
symptoms. In one investigation of women
given varying doses of estriol for six
months, vasomotor symptoms of menopause,
such as hot flashes, decreased. The
improvements were found to be dose-
dependent. There were no detrimental effects
on uterine or breast tissue (Tzingounis
1978). Other studies have shown similar
results, with up to 71% of patients
reporting elimination of hot flashes and
sweating, and 21% reporting substantial
reduction (Lauritzen 1987).

Progesterone complements and balances the
impact of estrogen in aging women. Combined
with estrogen, progesterone substantially
improved the amount of time women with a
history of heart attack or coronary artery
disease could work out on a treadmill before
reducing blood flow to the heart. Use of
non-bioidentical progesterone produced no
effect (Rosano 2000). Another mechanism by
which progesterone enhances cardiovascular
health is its ability to maintain or even
increase HDL levels in women receiving
estrogen replacement therapy (Bernstein and
Pohost 2010; Ottosson 1985; Jensen 1987).

Progesterone has a major role in relieving
menopausal symptoms as well. Four head-to-
head studies comparing progesterone to non-
bioidentical progestin reported that women
experienced greater satisfaction, improved
quality of life, and fewer side effects when
they were switched from non-bioidentical
progestin to progesterone (Hargrove 1989;
Montplaisir 2001; Ryan 2001; Lindenfeld
2002). In a landmark study at the Mayo
Clinic, the beneficial effects of
progesterone compared to nonbioidentical
progestin included a 30% reduction in sleep
problems, a 50% reduction in anxiety, a 60%
reduction in depression, a 25% reduction in
menstrual bleeding, a 40% reduction in
cognitive difficulties, and a 30%
improvement in sexual function. 80% of women
in the study reported overall satisfaction
with the bioidentical progesterone
formulation (Fitzpatrick 2000).
What You Need to Know: Bioidentical Hormones

Non-bioidentical hormones are chemically
different from hormones naturally produced
within the body. The use of non-bioidentical
estrogen and synthetic progestin in the
Women’s Health Initiative trial was
associated with the risk of breast cancer,
heart attack, venous blood clot and stroke.
Non-bioidentical, oral conventional hormone
replacement therapy is associated with an
increase the risk of uterine cancer.
Bioidentical hormones have the same
molecular structure as the hormones produced
naturally within the body. The body does not
distinguish between supplemental
bioidentical hormones and the hormones
produced within the body. As a result,
bioidentical hormones are properly utilized,
and are able to be naturally metabolized and
excreted from the body.
Current literature suggests that
bioidentical progesterone is associated with
a decreased risk of breast cancer.
A scientific literature review suggests that
bioidentical progesterone may be superior to
non-bioidentical, synthetic progestogens
(progestins) in treating menopausal
symptoms. Estriol (see below) is also highly
effective in the treatment of menopausal
symptoms.
Research on bioidentical progesterone has
shown beneficial effects on cardiovascular
health, including decreasing the risk of
blood clots, protecting against
atherosclerosis, and maintaining healthy HDL
levels.

Three major types of estrogen are produced
naturally in a woman’s body: estriol,
estrone, and estradiol.
Estriol has been shown to improve bone
density, promote youthful skin, and enhance
sexual and urinary health.
Beyond Estrogen and Progesterone: The
Complete Hormonal Picture

In addition to estrogen and progesterone, it
is also important to monitor levels of the
hormones Pregnenolone, DHEA, and
testosterone. Ideal bioidentical HRT goes
beyond the mere suppression of symptoms
caused by declining ovarian hormone levels.
The real goal of Life Extension’s approach
to female hormone restoration is to restore
hormones to youthful levels. Such an
approach has wide-ranging benefits
throughout the body and significantly
enhances physical and psychological well-
being.

DHEA is a natural steroidal hormone secreted
by the adrenal gland, the gonads, and the
brain (Maninger 2009). Although women
usually have less DHEA than men, both sexes
lose DHEA over time, suggesting that its
decline is age-related (Labrie 2010). Peak
levels are typically reached when women are
in their third decade of life, after which
they begin to lose approximately 2% per
year. Decreased levels of DHEA are
associated with cancer, diabetes, lupus, and
psychiatric illness (Genazzani and Pluchino
2010). Low levels of DHEA are also
associated with higher levels of insomnia,
pain, and disability (Morrison et al 2000).

DHEA has been shown to improve mood,
neurological functions, immune functions,
energy, feelings of well-being, and the
maintenance of muscle and bone mass (Kenny
2010; Weiss 2009). A combination of DHEA and
pregnenolone has been shown to improve
memory (Ritsner 2010). DHEA may also improve
insulin sensitivity and lower triglyceride
levels (Genazzani 2010; Casson 1995).

AWAREmed Health and Wellness Resource Center
suggests that maturing women strive to keep
their DHEA-sulfate (DHEA-s) levels in a
range of 250 – 380 µg/dL in order to promote
optimal health and vitality.

Testosterone levels in women also gradually
decrease with age (Schneider 2003). Loss of
testosterone affects libido, bone and muscle
mass, vasomotor symptoms, cardiovascular
health, mood, and well-being (Simon 2001;
Watt 2003). Testosterone therapy, in
conjunction with estrogen therapy, has been
shown to improve quality of life, vigor,
mood, ability to concentrate, bone
mineralization, libido, and sexual
satisfaction (Al-Azzawi 2010; Simon 2001;
Braunstein 2002; Cameron 2004). This
combination therapy also helps reduce hot
flashes, sleep disturbances, night sweats,
and vaginal dryness (Guillermo 2010).
Because DHEA converts into testosterone, it
is possible to raise testosterone levels
with DHEA (Cameron 2004; Schneider 2003).

Studies also suggest that testosterone, in
the context of hormone restoration, may
prevent or reduce estrogenic cancer risk in
the treatment of women with ovarian failure
(Dimitrakakis 2003; Zhou 2000). In addition,
testosterone is effective in the treatment
of decreased libido in women (Guillermo
2010).

AWAREmed Health and Wellness Resource Center
encourages females to maintain a total
testosterone level of 35-45 ng/dL and a free
testosterone level of 1 – 2.2 pg/mL.

Pregnenolone levels also decline with age.
As the initial hormone in the overall
steroid hormone cascade, pregnenolone is
derived from cholesterol. As is the case
with other hormones, a significant reduction
begins when women reach their early thirties
(Havlikova 2002). Pregnenolone deficiencies
have been associated with diminished brain
function and dementia (Mellon 2007).

Aging women should attain a pregnenolone
blood level of 130 -180 ng/dL for optimal
performance.

It is very important that women have their
hormone levels checked before beginning bio-
identical hormone restoration therapy. To
ensure safe and adequate levels, testing
should occur one month after commencing HRT,
and then again after two more months. Those
women who wish to enhance their sexual
desire and have already tried DHEA and
pregnenolone therapy, should talk to their
physician about options that may include
small amounts of testosterone. Women should
always consult a physician before beginning
HRT, especially if they have had a hormone-
responsive cancer (e.g., breast or
endometrial) or are at high risk (e.g., have
a first-degree relative with breast cancer).

Moving Forward with Bioidentical HRT

Given the wealth of data demonstrating the
superiority of bioidentical HRT, a noted
researcher in hormone replacement therapy
proclaimed, “Physiological data and clinical
outcomes demonstrate that bioidentical
hormones are associated with lower risks,
including the risk of breast cancer and
cardiovascular disease, and are more
efficacious than their… animal-derived [non-
bioidentical] counterparts. Until evidence
is found to the contrary, bioidentical
hormones remain the preferred method of
HRT.� (Holtorf 2009)

Compounded prescription bioidentical
estrogen formulas include Bi-Est and Tri-
Est. Bi-Est consists of estradiol and
estriol, while Tri-Est contains estradiol,
estrone, and estriol (Taylor 2001). Bi-Est
typically consists of 80% estriol and 20%
estradiol. Tri-Est usually contains 80%
estriol, 10% estradiol, and 10% estrone. In
some situations these proportions do not
meet the needs of every woman. For example,
the proportions observed naturally in
reproductive age women were 90% estriol, 7%
estradiol, and 3% estrone (Wright 1999). In
these cases a prescription is tailored to
the needs of the patient by an experienced
physician, and is based upon the results of
hormone tests and assessment of symptoms.

A comprehensive hormone restoration program
should also include progesterone, DHEA,
pregnenolone, and perhaps testosterone.

There are two differing philosophies
regarding the dosing of hormones. The first
encourages using the lowest possible dose
that will ameliorate the symptoms. This is a
very conservative approach that may appeal
to some women and their treating physicians.
This approach is also unlikely to cause a
menopausal woman to generate bleeding
associated with a menstrual cycle. It is,
however, unlikely to bring hormones back to
the levels Life Extension would consider
optimal.

The second approach involves significantly
higher hormone dosages. The idea here is
that a woman needs to “trick� her brain into
thinking she is still of reproductive age.
According to this strategy, the goal is to
achieve levels that mimic the hormonal
fluctuations of a menstruating young woman,
thereby restoring the menstrual cycle.