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Estrogens - Activity / Concentration in Tissues

Estrogen concentration/activity in tissues

Many factors determine estrogen concentration/activity in a particular tissue

Estrogen's affinity (binding strength) for components of that tissue, relative to its affinity for the blood

Sex hormone-binding carriers

Potency of different estrogenic compounds

Comparative strengths of ESTRADIOL /ESTRONE/ESTRIOL

Activation/inactivation of estrogen receptors.   Estrogens (like all steroid hormones) readily diffuse across cell membranes, where they bind with estrogens receptors. This leads to the production of specific proteins that express the effect of estrogen upon the target cell.

Estrogen Receptors

(1) Inactivated by PROGESTERONE

(2) Activated by many physical and chemical conditions

Xenoestrogens -“Endocrine Disruptors”

Plasma, total, or free Estrogen concentrations.

Circulating Levels of estrogen

External estrogen dose

Estrogen HRT is NOT necessary

Tissue activity of enzymes which convert androgens to estrogens;

-   Aromatase, the main enzyme that converts androgens to estrogens can be found in all parts of the body:

•  Fat and skin.   Major sources of estrogen, especially in older people, since aromatase activity increases with aging;

•   Also fibroblasts, smooth muscle cells, breast and endometrium (uterine lining), pancreas, liver, brain, bone, more.

-   Aromatase activity (and therefore estrogen production) is affected by many factors:

•  Aromatase activity is increased ▲  by aging, and under the influence of PROLACTIN, CORTISOL, prostaglandin, and the pituitary hormones FOLLICLE STIMULATING HORMONE and GROWTH HORMONE.

•  Aromatase activity is inhibited ▼ by:  PROGESTERONE , thyroid hormones, aspirin, and high altitude.

-   Aromatase activity is involved in breast cancer, endometriosis, uterine cancer, lupus, gynecomastia.   Also many other diseases

•  Aromatase in mammary tissue appears to increase estrogen receptors and cause breast neoplasia.   Independently of ovarian estrogen

Tekmal, et al., 1999

Enzymes affecting Steroid Production /Activity

Metabolic clearance of estrogen.    A healthy liver combines estrogen with glucuronic acid (“sugar acid”) to make it water-soluble for elimination. In the 1940's, the Biskindsdemonstrated some causes of liver impairment that decrease its ability to excrete estrogen, including:

-    A dietary protein deficiency

-    Hypothyroidism.   Prevents the liver from attaching glucuronic acid to estrogen, and so increases the body's retention of estrogen, which in turn impairs the thyroid gland's ability to secrete thyroid hormone. Hypothyroidism often results from nutritional protein deficiency.

Estrogen Elimination

Activity of beta-glucuronidase, sulfatase and other enzymes determine whether estrogen is in water-soluble (inactive) or oil-soluble (active) form.    Water-soluble estrogen must be made oil-soluble to be able to enter cells and exert its effects through their lipid membranes.

-    Sulfatase

•   Sulfatase.     Attaches sulfuric acid, and also several other enzymes modify the activity /solubility of estrogens.

•   Sulfatase activity is inhibited by: antiestrogenic hormones. (E.g. PROGESTERONE )

•   Sulfatase also releases estrogen in tissues

-    Beta-glucuronidase (found in inflamed tissue).   Normally, the healthy liver combines estrogen with glucuronic acid to make it water-soluble for elimination. However, if it passes through inflamed tissue, the large amounts of beta-glucuronidase there remove glucuronic acid, converting inactive estrogen-glucuronides into active estrogen, which accumulates in tissue

•   Beta-glucuronidase activity is increased ▲  by: Inflammation.

•   Beta-glucuronidase activity is inhibited by PROGESTERONE (in some tissues), and maybe more so with aging

Cristofalo VJ & Kabakjian J (1975) Mech. Ageing Dev. 4, 19-28.

•   Breast cancer treatment uses glucaric acid - which inhibits beta-glucuronidase; also glucuronic acid tends to inhibit the intracellular release of estrogen by beta-glucuronidase.

•   Glucuronidase - converts water-soluble estrogen glucuronides into oil-soluble forms by attaching glucuronic acid.

Estrogen Transport and Availability

PROGESTERONE prevents tissue from concentrating estrogen

-   PROGESTERONE antagonizes the effect of estrogen.    By reducing estrogen receptor levels. PROGESTERONE also acts indirectly, by its antagonizing action against PROLACTIN, it prevents PROLACTIN from stimulating the formation of estrogen receptors

-    Tissue/plasma ESTRADIOL (E2) ratio varies with PROGESTERONE presence - ranging from 20.36 in early follicular phase to 1.45 in mid-luteal phase when PROGESTERONE level is high.

-    During pregnancy, tissue estrogen decreases as blood PROGESTERONE increases;

-    PROGESTERONE production sharply decreases in aging allowing tissues to concentrate estrogen even with low serum estrogen - similar to follicular phase of menstrual cycle.

-    In postmenopausal women, the tissue E2 concentration is not significantly lower than in menstruating women in follicular phase

Akerlund, et al., 1981

-    An excessive estrogen presence is causing an hormonal imbalance (referred to as Estrogen Dominance), especially with PROGESTERONE.      One must consider not only the absolute level of a hormone but also its relative ratios with other hormones, including ESTRADIOL, PROGESTERONE , TESTOSTERONE, CORTISOL and thyroid hormones. A “sea”of estrogen “look-alikes”have infiltrated our lives today, having an estrogenic effect that is manifesting as a wide range of health problems by causing hormonal imbalance, especially with PROGESTERONE . E.g. infertility/miscarriage, menopausal symptoms, PMS, fibrocystic breasts, ovarian cysts, hirsutism, uterine fibroids, reproductive organ cancers in men and women, enlarged prostate, osteoporosis, depression/anxiety, water retention, inflammation, and much more . Healthy women without breast cancer have saliva-tested PROGESTERONE levels routinely 200-300 times greater than saliva ESTRADIOL level. Compare this to women with breast cancer, who have a saliva PROGESTERONE / ESTRADIOL ratio considerably less than 200 to 1. When you consider the many functions of PROGESTERONE . which are being suppressed by excess estrogen, you can understand why just about every aspect of health is affected. A so-called estrogen dominance problem is addressed by first reducing estrogen exposure, attending to other important factors involved with hormone imbalance* and then possibly, by supplementing PROGESTERONE .

Xenoestrogens -“Endocrine Disruptors”


Reduce Body's Estrogen levels

Estrogen dominance treatment 1-2-3



Attend to Diet, Lifestyle & Emotional State

N E W  S T A R T S

C-Reactive Protein - Reliable Inflammation Marker
hot flame


Chronic low-level inflammation (CLII) involved in almost all health problems

How to treat CLII

Pulsed Electromagnetic Field Therapy (PEMFT)


       "The medical kit of the future"

The Body Electric

General electrotherapy health benefits.   Used systemically and/or locally at specific problem areas of the body, its effective application has many benefits:

Detoxification Wellness / Healthy aging Pain relief 
Relief from insomnia Immune system restoral Anti-Inflammatory
Maximizes cellular energy production Accelerated tissue /bone
/scar healing
Stress Reduction
Muscle relaxation / rehabilitation Increased blood oxygen
/ circulation

There are several reasonably affordable electrotherapy devices available for personal use. The following electrotherapies are those that have received a significant amount of positive feedback:

Cranial Electrotherapy Stimulation (CES) applies specific frequency patterns to the head area, with the following benefits:

Balances neurotransmitters Relieves pain Treats depression
Substance abuse withdrawal Relieves insomnia Relieve stress / anxiety
Anti-Inflammatory Fibromyalgia +++