Clinical Applications
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HORMONE BALANCE CLINICAL APPLICATIONS © 2014 SpectraCell Laboratories, Inc. All rights reserved. DOC 502 12.14 Visit us at www.spectracell.com or call us at 800.227.LABS (5227) HORMONES 101 Steroid Hormones • Dehydroepiandrosterone sulfate (DHEAS) • Androstenedione • Testosterone • Estradiol (E2) • Estrone (E1) • Estriol (E3) • Progesterone Peptide Hormones • Sex hormone binding globulin (SHBG) • Luteinizing hormone (LH) • Follicle stimulating hormone (FSH) • Prolactin Hormone Biosynthesis Pathway DHEAS → Androstenedione → Testosterone or Estrogens Dehydroepiandrosterone sulfate (DHEAS) DHEA is the most abundant sex hormone in the body, with levels typically around 20 times that of any other steroid hormone. Produced primarily in the adrenal gland, it circulates the body in the form of DHEAS (sulfated form), and it is the major precursor hormone to androstenedione and subsequently estrogen and testosterone. DHEA has important functions unrelated to its role as a precursor to other sex hormones such as enhancing immunity to viruses (by increasing natural killer cell activity), alleviating autoimmune conditions, cancer prevention, bone health, cognitive function (via its role in the calming neurotransmitter GABA) and improving insulin sensitivity (by inhibiting glucose-6-phosphate dehydrogenase, the enzyme responsible for fat accumulation). Levels of DHEAS, which is synthesized through a series of reactions from cholesterol, peak when a person is in their mid 20’s and gradually decline in later decades of life. Increasing DHEAS levels may eventually increase levels of downstream sex hormones (testosterone and estrogen, but not necessarily progesterone) and the clinical effects are similar. In addition, the effects of DHEAS may depend on the levels of other hormones. For example, in premenopausal women, DHEAS seems to have a protective effect against hormone related cancers (breast, ovarian, uterine), while in postmenopausal women, if estrogen levels are low, DHEAS may contribute to growth of rogue cells in hormone sensitive tissues. Women with PCOS often have elevated levels of DHEAS. Low levels may be indicative of adrenal dysfunction (also called hypoadrenalism, adrenal insufficiency and sometimes adrenal fatigue) since DHEAS is produced in the adrenal cortex. Very small amounts are produced in the ovaries so women with adrenal insufficiency will have low DHEAS levels. However, men with adrenal fatigue may have normal DHEAS levels since more of it is produced by the testes than the ovaries. Small doses of DHEA do not appear to have a negative feedback effect on hormones secreted by the pituitary (LH, FSH or prolactin). People taking glucocorticoid medications (hydrocortisone, prednisone, etc) for allergies or to reduce inflammation will typically have low levels of DHEAS because glucocorticoids suppress the adrenal glands and therefore suppress DHEAS synthesis. DHEAS may also increase the efficacy of thyroid hormone and studies suggest it increases growth hormone in those with normal pituitary function. Since both excess and deficiency of this hormone is associated with various disease conditions, it is best evaluated in the context of other hormones with overall hormonal balance being the key therapeutic goal. Androstenedione Androstenedione is a precursor hormone to testosterone and estrogen. Its precursor is DHEA, so much of originates from the adrenal glands, although androstenedione is also manufactured in the ovaries or testes. Androstenedione is converted by fat cells into estrogens via the enzyme aromatase and converted into testosterone via the enzyme 17β hydroxysteroid hydrogenase. Testosterone and androstenedione occur in equilibrium in the body, meaning that when there is an increase in either, the body will make more of the other. Androstenedione synthesis is regulated by adrenocorticotropic hormone (ACTH). High levels of this hormone in women can cause the development of male characteristics such as deepening voice or hirsutism (excess body or facial hair). Women with polycystic ovary syndrome (PCOS) typically have high levels of androstenedione. Although much less common, tumors of the adrenal gland can also result in unusually high levels of androstenedione. Testosterone Testosterone is the most potent circulating sex steroid. Produced primarily in the testes in men and the ovaries in women, it is most often clinically associated with increased muscle mass, enhanced libido, bone health and a general sense of well being. Levels in healthy women are 5-10% of the levels found in healthy men. Testosterone that is bound to SHBG is biologically inactive. Symptoms of excess testosterone in women are increased facial hair (hirsutism), acne and polycystic ovary syndrome, while excess testosterone in males often manifests behaviorally (aggressiveness, hyperlibidio, etc.) Symptoms of low testosterone in either sex include low libido, decreased muscle mass and depression. Only free, unbound testosterone is biologically active. Since the amount of SHBG profoundly affects testosterone’s influence on the body, it should be evaluated in the context of other hormones. For example, testosterone can be aromatized (chemically changed) into estradiol. Similarly, luteinizing hormone and follicle stimulating hormone both regulate the production of testosterone. Estradiol (E2) Considered the primary female sex hormone, estradiol (E2) is one of the three major circulating hormones known collectively as estrogens – estrone (E1) and estriol (E3) being the other two. Estradiol is by far the most active of the three estrogens. It is 10 times stronger than estrone and 80 times stronger than estriol, meaning it has a strong affinity for estrogen receptors in tissue around the body and thus exerts a potent biological and clinical effects. It is considered an end-point hormone in that estradiol generally acts directly on biological tissue and does not convert into other hormones, versus precursor hormones like progesterone or androstendione, which are used to make other hormones. In women, estradiol is manufactured primarily in the ovaries before menopause and in the adrenal glands after menopause. In men, small amounts of E2 are produced in the testes. An enzyme called aromatase can also convert testosterone into estradiol in both men and women. Since this enzyme is found primarily in adipose tissue (fat cells), overweight women and men may have excess estradiol relative to other hormones like testosterone. In premenopausal women, estrogen levels fluctuate throughout the menstrual cycle peaking around ovulation. Estrogens are considered heart protective because they increase good cholesterol (high density lipoprotein, or HDL), improve smooth muscle tone in blood vessels and promote vasodilation, which expands arteries to allow healthy blood flow throughout the circulatory system. Estradiol prevents bone loss, thus lowering risk of osteoporosis, and improves collagen formation which results in younger looking skin. Estradiol also prevents loss of cognitive function as we age and increases the immune response. However, estrogen also exerts a strong proliferative (overgrowth of tissue) effect on hormone sensitive tissue such as the breast, ovary and uterus. Excess estrogen, especially when progesterone is relatively low, can increase risk of breast, ovarian and uterine cancer as well as conditions associated with tissue proliferation that may not be cancerous such as uterine fibroids , fibrocystic breast disease, or breast tenderness that occurs during periods. In men, estrogen plays a role in maintaining healthy sperm. Low levels of estrogen can cause thinning skin, vaginal dryness, urinary tract infections or brain fog. Excess estrogen manifests clinically as premenstrual related symptoms such as breast tenderness, endometriosis, weight gain, acne or depression or menopause related symptoms such as hot flashes and memory loss. When not balanced by appropriate levels of progesterone, normal levels of estrogen can manifest clinically as excess estrogen, and this condition is often referred to as estrogen dominance. Unopposed estrogens are exogenous estrogens that are not balanced (not opposed) with appropriate levels of progesterone, which selectively balances estrogen’s biological activity. High estrogen levels may also indicate a need to improve estrogen detoxification, which is critical to reducing breast cancer risk. High levels may also indicate insulin resistance since insulin causes the ovaries to decrease SHBG, which then allows more estrogens into circulation. Several nutrients affect both estrogen levels and estrogen metabolism. Estrone (E1) Estrone (also called E1) is one of the three major estrogens – the others being estradiol (E2) and estriol (E3). It is the most common estrogen in postmenopausal women. When a woman enters menopause, estrone becomes dominant because the ovaries have stopped producing estradiol. In premenopausal women, E2 is the predominant estrogen and in pregnant women E3 is the predominant estrogen. Estrone can convert easily into estradiol in the liver and can also be converted back to estrone. Estrone is also made in the adrenal glands or by a conversion of androstenedione via the enzyme aromatase in fat cells, so women who have had their ovaries removed or postmenopausal women (with low ovarian hormone output) can still secrete high levels of estrone. In addition, estrone can convert into a dangerous metabolite called 4-hydroxyestrone which plays a role in initiating breast cancer. Estrone has major