Womens Health

The Livers Role in Hormone Balance

Everything we breathe, ingest, or
absorb through the skin gets into
the blood stream and eventually
passes through the liver. Because
the liver is the bodys primary
detoxifier, keeping it healthy is
critical to your overall health, including proper metabolism and
function of your hormones.

Liver Function
As unglamorous as it sounds,
the liver operates somewhat like
a sewage treatment plant. The
liver takes everything we put
into our bodieswhether it is
swallowed, inhaled or absorbed
through the skinand filters
it. The livers filtration process
separates the nutrients that the
body needs for energy and all of
its other functions and prepares
to dispose of that which the body
does not need, such as metabolic waste, toxins and excess
substances.

n Storing vitamins and minerals, such as iron

n Storing sugars as fuel (glycogen) for future use
n Helping to maintain fluid
and electrolyte balance
n Creating serum proteins that
act as hormone carriers
n Creating immune substances,
such as gamma globulin
n Filtering blood, regulating
blood clotting, and storing
extra blood for quick release
n Manufacturing testosterone
and the estrogen hormones
n Regulating sex hormone
levels and eliminating excess
hormones.

n Oily, processed foods

n Man-made chemicals including preservatives, pesticides,
and lead from paints or
gasoline
n Alcohol and drugs
(therapeutic or otherwise)
n Excess hormones.
Health problems can also occur if the nutrients that the liver
needs to process toxins or excesses are in limited supply. Like a

Liver

Specific liver functions include:

n Converting fats, proteins and
carbohydrates to energy and
nutrients
n Creating bile to break down
fats and eliminate fat-soluble
toxins and excess substances,
including excess hormones
n Removing harmful chemicals, bacteria, and excesses
n Metabolizing drugs and
breaking down alcohol

Health problems can arise when

we put things into our body,
both consciously and unconsciously, that are toxic or build
up an excess or toxicity over
time, such as:

Stomach
Gall
Bladder

Small
Intestine
Bile
Duct

The liver breaks down and metabolizes everything we swallow, inhale or absorb through the skin. It filters out the harmful toxins or excesses, and makes
nutrients, hormones, and other substances available to the rest of the body.
Continued on Page 2

sewage treatment plant that is

short staffed, if these nutrients
are in short supply, the liver
cannot process as quickly or
as thoroughly as needed. If the
liver becomes overburdened
because of insufficient nutrients, the toxins or waste build
up and the excess can escape
back into the body, leading to
serious health concerns.

Hormone
Metabolism
The liver plays a vital role in
the bodys use of hormones,
both those that are produced
naturally in our bodies as well
as those hormones that are
introduced via hormone
therapies. It acts as a hormone
processor, manufacturing and/
or regulating some hormone
levels, and directing various
hormones to perform their
proper function in other parts
of the body. But when the body
experiences a hormone excess
(whether produced by the body
or introduced by hormone therapy), the liver may not be able
to process the hormone(s) as
quickly or efficiently, causing a
hormone imbalance.

Estrogen Hormones
Of primary concern for womens health is the livers role in
regulating the sex hormones,
primarily the estrogen hormones. This is a consideration
for women undergoing hormone therapy, whether it is
conventional hormone replacement therapy (HRT), typically
consisting of synthetic hormones that are not biologically
identical to human hormones,

Maintaining liver health is central to

maintaining hormone balance, which in
turn helps to maintain overall health.
or a biologically-identical hormone therapy (BHT).
Researchers are gaining new
insight into how estrogens are
metabolized and the effects of
that metabolism. They found
that estrogens break down into
estrogen metabolites that have
varying levels of estrogenic
activity, and that the stronger
the estrogenic effect, the greater
the risk of developing estrogenrelated cancer.

Phase I and Phase II

Pathways
The liver metabolizes hormones and other substances
using two primary phases
known as the Phase I and
Phase II pathways.
During Phase I, some hormones or substances are metabolized directly, but often they
are converted into intermediate
forms, which are then further
metabolized in Phase II.
Cumulatively, these two phases of biological transformation
are how the liver provides the
body with nutrients and supports the excretion of excess or
toxic substances in the urine,
liver bile (see box on page 4), perspiration and exhaled air.

The pathways depend on a

large number of nutrients, including enzymes and amino
acids, and their availability
(or lack thereof) seems to have
a significant influence on the
metabolic outcome. For example, the Phase I pathway is
the main metabolic pathway
for the estrogen hormones. In
premenopausal women, the
ovaries produce estrogen, primarily estradiol, most of which
the body converts to estrone,
and eventually estriol. The liver
then metabolizes the remaining
estradiol and the converted estrone, breaking it down further,
and excreting the excess from
the body.
Some researchers and practitioners now believe that the livers
ability to metabolize estrone
is the key to understanding
estrogen-related cancer risk.
During Phase I metabolism,
estrone is converted into
various metabolites including 2-hydroxyestrone, a very
weak estrogen, and 16-alphahydroxyestrone, a very potent
estrogen. If the conversion
process favors the stronger
form(s) rather than the weaker
form(s), then tissue that has an
abundance of estrogen receptors, such as the breasts and
Continued on Page 3

uterus, may be more vulnerable

to excessive estrogen activity,
potentially leading to the formation of fibroids or the stimulation
of estrogen-sensitive cancers.
Phase I processing can be affected by many factors, including
extreme overload, the effects of
alcohol or drugs, a lack of nutrients, or interference from other
substances. For example, grapefruit juice can slow down the
enzymes in Phase I, potentially
altering hormone balance. And,
many prescription drugs are
metabolized in Phase I, which
can also interfere with the livers
ability to handle the estrogen
hormones. On the other hand,
Indole-3-carbinol (I3C), a phytonutrient derived from cruciferous vegetables (e.g., broccoli,
cauliflower, cabbage and brussels sprouts), stimulates enzymes
that promote the metabolism
of estrogens into milder forms,
potentially reducing the risk of
estrogen-dependent cancers.

Free Radicals
Each reaction in the Phase I
pathway produces an intermediate form called a free radical.
As you have probably heard,
free radicals can be very damaging to body tissues if they are
not quickly neutralized by antioxidants. Nutrients such as vitamins C and E, minerals such as
selenium, and other substances
such as lipoic acid and glutathione are antioxidants that help
protect against free radicals.
The intermediate forms produced in Phase I are in a highly
reactive state until they are fully
converted in Phase II.

During Phase II, a process

known as conjugation begins, in
which nutrients such as amino
acids are combined with hormones and other substances, to
convert them to water-soluble
compounds that can be excreted
efficiently in the urine or stool.
Of the various types of conjugation that may occur in Phase II,
the following are most relevant
to hormone metabolism:
n Methylation, also known as
methyl metabolism, is the
process in which small parts
of molecules, called methyl
groups, are passed from one
molecule to another. Once estrogens are methylated, they
can be easily excreted.
In order for the liver to
have an adequate supply of
methyl groups available, an
adequate intake of vitamins
B6 (e.g., whole grains and
legumes) and B12 (primarily from animal products),
and folic acid (such as from
green leafy vegetables) are
necessary.
An over-the-counter dietary
supplement known as SAMe
(s-adenylmethionine) is
also a rich source of methyl
groups and sulfur.
n Sulfation is the process in
which sulfur groups are
added to estrogen or other
molecules to prepare them
for easy excretion. Adequate
amounts of foods containing
sulfur should be in the diet,
including egg yolks, garlic,
onions and brussels sprouts.
Animal protein is another
important source of sulfur.
n Glucuronidation is another
process by which estrogens
can be conjugated. This type

of conjugation may be affected by the condition of the

intestines. If the intestines
have an abundance of abnormal bacteria, an enzyme produced by these bacteria may
cut off the conjugated part
from the estrogen.
The estrogen that would
have been excreted is then reabsorbed back into the body,
allowing even estrogens produced by the body to build
up to excessive levels.
The supplement calcium
D glucarate (also found in
fruits and vegetables) can
render the enzyme inactive
and prevent this buildup.
n Gluthathione conjugation is
the process in which glutathione, another sulfur-containing molecule, is added to
estrogen for easy excretion.
Foods such as avocado, walnuts and asparagus are rich
in glutathione, and vitamin
C stimulates the body to produce more of it.
Glutathione depletion can be
due to a lack of the essential
nutrients and amino acids
(found in fresh fruits, vegetables, fish and meats) that
are needed to synthesize it.
Glutathione deserves special
mention as a crucial detoxifier
because it also behaves as an antioxidant in Phase I. Glutathione
neutralizes the free radicals produced in the Phase I reactions,
and combines with them to produce water-soluble compounds
that can be excreted.
Glutathione is also needed for
the detoxification of alcohol.
Studies have shown that even a
small amount of alcohol intake
can increase estrogen levels in
Continued on Page 4

the blood because alcohol

competes for the available
glutathione, preventing
estrogen excretion.
Smoking is also known to
deplete glutathione levels, as
do chronically stressful conditions such as infections or
inflammatory disorders.

Sex HormoneBinding Globulin

To regulate sex hormones,
the liver also produces special
proteins (binding globulins)
that chaperone the hormone molecules throughout
the body. If the hormone level
is too high, the protein also
inactivates the bodys own
hormone production as part
of its chaperoning duty.
Sex hormone-binding globulin (SHBG) is stimulated by
estrogen in the blood stream.
However, as the body produces more SHBG, it is more
attracted to testosterone than
it is to estrogens. In the case
of women who have been
treated only with estrogens
after a hysterectomy, it is
therefore predictable that testosterone activity is limited
due to the increase in SHBG
stimulated by this overbalance of estrogen. A consequence of this is a decrease
in sexual interest, mental
zest, and the bodys ability to
maintain muscle mass.

Hormone Delivery
As mentioned earlier, most
drugs are metabolized during Phase I. However, the
delivery method is key.
Orally administered drugs,

Liver Bile
Bile is a complex fluid secreted by the liver for the digestion and
absorption of fats and fat-soluble substances. Bile is stored in the
gall bladder (see figure on page 1), where it then flows through the
bile duct to the small intestine, from which it is eventually eliminated in stool.
Many fat-soluble toxins, including excess estrogen hormones,
are eliminated from the body into the intestines with the aid of
bile. However, some women, such as those on birth control pills,
may have difficulty eliminating excess estrogens, and this may be
linked to an inhibited bile flow. Methionine, found in an over-thecounter dietary supplement called SAMe, has been shown to improve bile flow, thereby helping to reduce excess estrogen levels.

including birth control pills

and other hormones, are absorbed through the digestive
tract and at least partially
metabolized by the liver and
excreted before they can be
made available to the rest of
the body. This is known as
first-pass effect. Avoiding
the first-pass effect is not intended to protect the liver,
but to provide greater absorption of the hormones.
Delivery methods that avoid
the first-pass effect include
creams or gels applied to the
skin, suppositories or inserts
administered in the rectum or
vagina, and lozenges or drops
delivered under the tongue in
the mouth (not swallowed).
In addition, oral gelatin capsules that contain micronized
powdered hormones mixed
with edible oils also avoid
the first-pass effect because
the fat is taken up directly
into the lymphatic system.
To illustrate the difference
that the delivery mechanism
can make, refer back to the
role of SHBG in hormone
balance and consider this: a

study showed that orally

administered conjugated
estrogens (not in edible oil)
transfer to the liver quickly,
triggering the liver to release
SHBG, whereas a skin patch
containing estradiol did not
trigger the SHBG release,
primarily because the patch
released the hormone more
slowly. From that study
we can infer that the influx
of estrogen and resulting
SHBG spike from conjugated
estrogens (not in edible oil)
can have a negative effect
on other hormones, whereas
estradiol absorbed through
a skin patch would not have
that same effect.

Maintaining a
Healthy Liver
The liver is responsible for
literally hundreds of functions that affect the entire
body, including regulating
hormones. Maintaining a
healthy liver is central to
maintaining hormone balance, which in turn helps to
maintain overall health.
Continued on Page 5

Liver function and hormone

balance are intimately connected. Liver function has a
critical effect on hormones
and, at the same time, is affected by hormonesthe ones
produced in the body as well
as those used as therapy. The
liver can be protected by using bioidentical hormones, by
not taking excessive levels of
hormones, by ensuring that
the liver has adequate nutrients available for processing
hormones, and by avoiding
other chemicals that compete
for liver function. Healthy
liver function is the under
pinning of hormone balance.
One of the best ways to
achieve and maintain good
overall health is to be kind
to your liver. This includes
reducing the burden on the
liver whenever possible, and
providing adequate supplies
of nutrients to assist with
detoxification.
Liver stress can be reduced
by avoiding overeating and
heavy alcohol use. Other
ways to reduce liver burden
are to eliminate processed
foods, high-fat foods, and
those with preservatives or
other additives from your
diet, and to drink plenty of
water to facilitate elimination of toxic and excess substances. Reducing exposure to

Are you overweight?

Healthy liver
function is the

Do you engage in heavy

alcohol or tobacco use?

Do you have high expo-

sure to chemicals such as

herbicides or pesticides?

underpinning

Are you on hormone ther-

of hormone

Have you been diagnosed

balance.

Have you been diagnosed

toxic chemicals such as pesticides and herbicides in your

home, yard and workplace
will also reduce the burden
on the liver and promote
liver health.
As discussed previously,
the liver is dependent upon
many nutrients to complete
its job of breaking down and
detoxifying any excess and
toxins. To promote healthy
liver function, we must en
sure that those nutrients
are available with a proper
diet and/or supplementation, when necessary or
appropriate.
If you are wondering if your
liver function is up to par,
ask yourself the following
questions:

apy, or other prescription

drugs?
with gallstones?

with a liver disease?

If you answered yes to any

of these questions, discuss
your liver health with your
healthcare practitioner. We
are fortunate in that the liver
is quick to heal itself, if we
give it the chance to do so.

References
The references used in researching and writing this
newsletter include:
n The Secrets to Great Health
by Jonn Matsen, ND;
Goodwin Books, Ltd.;
North Vancouver, BC;
1998.
n Natural Therapy for Your
Liver, Second Edition, by
Christopher Hobbs, Lac;
Avery Publishing; New
York, NY; 2002.

We are fortunate in that the liver is quick to heal itself,

if we give it the chance to do so.

Continued on Page 6

n Natural Hormone Balance for

Women by Uzzi Reiss, MD, OB/
GYN; Pocket Books; New York,
NY; 2001.

n Literature Review by Alan R.

Gaby, MD; Townsend Letter for
Doctors & Patients, November
2004.

n Encyclopedia of Natural Medicine,

2nd Edition, by Michael Murray,
ND, and Joseph Pizzorno; Prima
Publishing; Rocklin, CA; 1998.

n Long-term effects of continuous

oral and transdermal estrogen
replacement therapy on sex hormone binding globulin and free
testosterone levels by Serin IS, et
al; European Journal of Obstetrics,
Gynecology, & Reproductive
Biology, December 2001.

n Methyl Magic: Maximum Health

through Methylation by Craig
Cooney, PhD; Andrew McMeel
Publishing; Kansas City, KS; 1999.

n Absorption of oral progesterone

is influenced by particle size
by Joel T. Hargrove, MD, et al.;
American Journal of Obstetrics and
Gynecology, October 1989.

n The Lark Letter by Susan Lark,

MD; ASP-ACI PHI Acquisitions,
LLC, and PH OPCO, LLC;
Potomac, MD; January 2005.
n Cabbages et al. and Cancer Risk,
Sex Hormones, and Sex Hormone
Metabolites by Jonathan Wright,
MD; Townsend Letter for Doctors &
Patients, May 2000.

Connections is a publication of Womens International Pharmacy, which is dedicated to the

education and management of PMS, menopause, infertility, postpartum depression, and other
hormone-related conditions and therapies.
This publication is distributed with the understanding that it does not constitute medical
advice for individual problems. Although material is intended to be accurate, proper medical
advice should be sought from a competent healthcare professional.

Publisher: Constance Kindschi Hegerfeld, Executive VP, Womens International Pharmacy

Co-Editors: Michelle Davenport and Carol Petersen, RPh, CNP; Womens International Pharmacy
Writer: Kathleen McCormick, McCormick Communications, Inc.
Illustrator: Amelia Janes, Midwest Educational Graphics
Copyright December 2011, Womens International Pharmacy. This newsletter may not be reproduced or distributed without the permission of Womens International Pharmacy.
For more information, please visit www.womensinternational.com or call (800) 279-5708.
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