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Estrogen

Estradiol

Estradiol is the most potent estrogen of a group of endogenous estrogen steroids which includes estrone and estriol. In women estradiol is responsible for growth of the breast and reproductive epithelia, maturation of long bones and development of the secondary sexual characteristics. Estradiol is produced mainly by the ovaries with secondary production by the adrenal glands and conversion of steroid precursors into estrogens in fat tissue.

During the early part of the menstrual cycle, estradiol levels remain nearly constant. This is followed by a rapid increase reaching a peak the day before or the day of the Leutinizing Hormone (LH) surge (ovulation). It is generally believed that the rise in estradiol is the factor which triggers LH release. Following ovulation there is a drop in estradiol followed by a second rise which corresponds with the formation of the corpus luteum.

At menopause, estrogen concentrations in the body fall to low levels. This decrease is often accompanied by vascular instability (hot flashes and night sweats), a rise in incidence of heart disease, and an increasing rate of bone loss (osteoporosis), Estrogen replacement for alleviation of menopausal symptoms or to prophylax against heart disease and osteoporosis has become very common.

Estradiol levels are used to assess fertility, amenorrhea and precocious puberty in girls. Measurement of estrogen levels is also useful to monitor and titrate replacement therapy especially when the endpoints are long term health (reduction in heart disease and osteoporosis) rather than the immediate relief of symptoms.


Estrone

Estrone is one of the three naturally occurring estrogens, the others being estradiol and estriol. Estrone is produced primarily from androstenedione originating from the gonads or the adrenal cortex. In premenopausal women, more than 50% of the estrone is secretd by the ovary. In prepubertal children, men and non-supplemented postmenopausal women the major portion of estrone is derived peripheral tissue conversion of androstenedione. Interconversion of estrone and estradiol also occurs in peripheral tissue. Bioassay data indicate that the estrogenic action is much les than estradiol. Estrone is a primary estrogenic component of several pharmaceutical preparations, including those containing conjugated and esterified estrogens. In premenopausal women estrone levels generally parallel those of estradiol. After menopause estrone levels increase, possibly due to increased conversion of androstenedione to estrone.


Estriol

Estrol is one of the three major naturally occurring estrogens, the others being estradiol and estrone. Estriol is produced almost exclusively during pregnancy and is the major estrogen produced in the normal human fetus. During pregnancy the production of estriol depends on an intact maternal-placental-fetal unit. Fetal-placental production of estriol leads to a progressive rise in maternal circulating levels reaching a late-gestational peak several orders of magnitude greater than non-pregnant levels. Estriol has been suggested to be less carcinogenic than estradiol and estrone in animal studies. It has been shown that at doses effective for the relief of postmenopausal symptoms, estriol does not induce endometrial proliferation to the extent as the other estrogens. Topical estriol has also been used for the relief of postmenopausal genital atrophic changes and urinary incontinence.

Estrogen metabolism

Monitoring estrogen metabolism is the next step in patient care and prevention of diseases. The goal of estrogen metabolism monitoring is to assess and reduce potential risk of disease as much as possible by monitoring which estrogen metabolites are being produced, the relationship between the metabolites, and how replacement therapy effects these metabolite levels.

The three most prevalent metabolites of estradiol and estrogen are 2 (OH) estrone, 4 (OH) estrone and 16 alpha (OH) estrone. 2 (OH) estrone are considered protective as they have been found to be powerful antioxidants, protecting against iron induced lipid peroxidation. 4 (OH) estrone is considered a free radical generator and increased levels may induce the production of super oxide free radicals. 16 (OH) estrone is considered genotoxic and may be important in predicting cancer of the breast. The ratio between 2 (OH) and 16 (OH) estrone is considered an important indicator of cancer risk with increase levels of 16 (OH) being beneficial in preventing breast cancer.

Perimenopause

Perimenopause is the time leading up to and immediately following menopause and literally means "surrounding menopause". Technically, menopause is an event that occurs twelve months after a women's last menstrual cycle. Generally occurring during a women's forties, perimenopause can begin as early as age 35 and can last anywhere from 2 - 7 years.

Over a rather lengthy period of time sex steroids hormones first begin to fluctuate, then fluctuate wildly, and then decline causing a number of physiological changes and symptoms. Ranging from subtle to dramatic, these often unexpected physical and emotional changes, such as hot flashes, insomnia, decreased libido and mood swings can be disconcerting. Symptoms of perimenopause are highly individual as you will see from the following chart.

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Natural hormone replacement

A number of methods available for treating menopausal symptoms are considered "natural". They include maintaining a healthy lifestyle through diet, exercise and stress reduction; the use of herbal medicines like dong quai, black cohosh and licorice; and the use of phytoestrogen (plant) products which contain flavones. While many women find these natural therapies helpful, they are not the same as natural hormone replacement therapy (HRT).

Natural hormones are derived from chemical precursors found in plants. Soybeans and wild yams are the most commons sources of these chemicals. For a soy or yam precursor to be converted into a hormone, it must be done in a laboratory. Therefore, natural hormones, like their synthetic and animal-derived counterparts, can be pharmaceutical compounds.

Natural hormones are identical in molecular structure to the hormones the body makes, thus they are called bio-identical. When a bio-identical hormone circulates through your system and binds with a receptor, the fit is the same as if your body had produced that hormone.

Animal-derived and synthetic hormones are similar to human hormones, but they do not have the same molecular structure. When one of these binds with its receptor, the fit is not exact, sometimes resulting in side effects.

For many years conventional HRT has consisted of a standard prescription of hormones - most commonly 0.625 mg of premarin (animal-derived) and 2.5 mg. of provera (synthetic). Premarinis a combination of estrogens derived from the urine of pregnant mares. Provera is synthesized in the laboratory from natural progesterone, than modified for reasons of product patenting. Synthetic hormones have been shown to increase the risk of breast cancer.
Natural hormone replacement consists of bio-identical estrogens, the most common being Tri-est which consists of estradiol, estrone, and estriol in a 10-10-80% and Bi-est which consists of estradiol and estriol in a 20-80% formulation both of which are designed to match the body's natural ratio. Natural progesterone creams are also available in a variety of strengths.

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