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Sex hormone-binding globulin (SHBG) is a glycoprotein synthesized by the liver. Circulating androgen and estrogen concentrations influence SHBG synthesis. The regulation of SHBG synthesis, combined with SHBG's higher affinity for testosterone, impacts bioavailable testosterone levels.
SHBG binds up to 98 percent of the steroid hormones in the blood including 5a-dihydrotestosterone (DHT), testosterone and androstenediol with particularly high affinity, and estradiol and estrone with slightly lower affinity
Male and female children have similar SHBG concentrations until the onset of puberty, when SHBG levels begin decreasing more rapidly in males than in females. Levels are higher in women than in men, due to the higher ratio of estrogens to androgens in women. Levels are especially elevated during late pregnancy and in women taking oral contraceptives.
True androgen status can be assessed either by measuring free testosterone or by calculating the ratio of total testosterone to SHBG, known as the free androgen index (FAI).
Conditions that suggest Low SHBG:
Hormones Hirsutism Because SHBG is often low in women with hirsutism, free testosterone is elevated while the total testosterone concentration is normal. This means the free testosterone portion is responsible for increased male characteristics. Just an increase in free testosterone with no increase in total testosterone can produce significant consequences.
Hypothyroidism Modest reductions in SHBG levels may be encountered in individuals with hypothyroidism.
Hyperprolactinemia Modest reductions in SHBG levels may be encountered in individuals with hyperprolactinemia.
Lab Values
Elevated Cortisol Levels Modest reductions in SHBG levels may be encountered in individuals with Cushing's syndrome.
Metabolic
Problems Caused By Being Overweight SHBG levels respond to extreme changes in body weight, decreasing in obese patients.
Skin-Hair-Nails
Adult Acne Low levels are often found in cases of acne vulgaris.
Uro-Genital
Polycystic Ovary Syndrome (PCOS) Low levels are often found in cases of polycystic ovary syndrome. SHBG is low in about 50% of cases.
Risk factors for Low SHBG:
Drug Side Effects Prescription Drug Side-Effects Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.
Environment / Toxicity
General Detoxification Requirement Aromatase is the enzyme that converts androgen to estrogen. Aromatase is an important target of some environmental chemicals. Some of these compounds inhibit aromatase activity, resulting in a decrease in the level of estrogen or an increase in the level of androgen in cells. Environmental chemicals can also modify the expression of aromatase in various tissues, resulting in a change in the ratio between androgen to estrogen. The compounds that inhibit aromatase or suppress aromatase expression will behave as antiestrogens or androgen-like compounds in vivo. On the other hand, compounds that increase aromatase expression or enhance aromatase activity (or stability) may function as anti-androgens or estrogen-like compounds.
Hormones
High Testosterone Level, Male
High Testosterone Level, Female Elevated testosterone causes SHBG synthesis to decrease, lowering its level in the blood.
Low Progesterone or Estrogen Dominance Elevated estrogen levels stimulate SHBG production, increasing levels in the blood.
Lab Values - Hormones
Very/moderately low SHBG
Counter-indicators:
Elevated SHBG
Laboratory Test Needed
Elevated Insulin Levels Research has discovered that sex hormone binding globulin (SHBG), a relatively unknown blood protein, is a reasonably good indicator of insulin resistance. Low levels of SHBG are consistently linked to high levels of insulin in the body. Sustained high levels of insulin are, in turn, associated with the development of the chronic diseases such as high blood pressure, diabetes and coronary heart disease.
Low SHBG suggests the following may be present:
Drug Side Effects Prescription Drug Side-Effects Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.
Recommendations for Low SHBG:
Diet Weight Loss As weight loss will improve insulin resistance, and insulin resistance can be measured by low SHBG, weight loss should help normalize low SHBG levels.
Gluten-free Diet Substituting rice for wheat, which generally has a lower amylase content, can raise SHBG levels via lowered insulin levels. However, starches should be restricted when trying to lower insulin levels.
Drug
Conventional Drugs Selection of an OC formulation that maintains increases in SHBG may be important in minimizing androgenic effects in general, and especially important in hyperandrogenic women, who may benefit most from reductions in levels of free testosterone.
SHBG's may be lowered by two of the artificially generated progesterones, norgestrel and norethisterone. If you are a woman who may be susceptible to androgenetic alopecia, that is, hereditary hair loss (female pattern baldness), or you have a naturally low SHBG level, you should avoid any contraceptive pills or hormone replacement therapy that contains synthetic progesterone.
Extract
Not recommended:
DIM (di-indolmethane)/I3C (Indole-3-Carbinol) Aromatase inhibitors like DIM, Indole 3 carbinol, and chrysin should be avoided, as they will enhance any preexisting androgen / estrogen dominance.
Hormone
Estrogen Replacement The use of estrogen to increase SHBG and hence reduce biologically free testosterone may lessen acne and hirsutism. This mechanism is commonly operative in women with Polycystic Ovarian Syndrome. With estrogen replacement, estrogen levels are higher and liver production of SHBG increases. With pregnancy or some birth control pills, you will have high SHBG, and you will have high levels of circulating hormones, but they will be mostly bound (including testosterone).
Although this article was primarily written for women, all the info is also applicable to men.
SHBG binds up to 98 percent of the steroid hormones in the blood including 5a-dihydrotestosterone (DHT), testosterone and androstenediol with particularly high affinity, and estradiol and estrone with slightly lower affinity
Male and female children have similar SHBG concentrations until the onset of puberty, when SHBG levels begin decreasing more rapidly in males than in females. Levels are higher in women than in men, due to the higher ratio of estrogens to androgens in women. Levels are especially elevated during late pregnancy and in women taking oral contraceptives.
True androgen status can be assessed either by measuring free testosterone or by calculating the ratio of total testosterone to SHBG, known as the free androgen index (FAI).
Conditions that suggest Low SHBG:
Hormones Hirsutism Because SHBG is often low in women with hirsutism, free testosterone is elevated while the total testosterone concentration is normal. This means the free testosterone portion is responsible for increased male characteristics. Just an increase in free testosterone with no increase in total testosterone can produce significant consequences.
Hypothyroidism Modest reductions in SHBG levels may be encountered in individuals with hypothyroidism.
Hyperprolactinemia Modest reductions in SHBG levels may be encountered in individuals with hyperprolactinemia.
Lab Values
Elevated Cortisol Levels Modest reductions in SHBG levels may be encountered in individuals with Cushing's syndrome.
Metabolic
Problems Caused By Being Overweight SHBG levels respond to extreme changes in body weight, decreasing in obese patients.
Skin-Hair-Nails
Adult Acne Low levels are often found in cases of acne vulgaris.
Uro-Genital
Polycystic Ovary Syndrome (PCOS) Low levels are often found in cases of polycystic ovary syndrome. SHBG is low in about 50% of cases.
Risk factors for Low SHBG:
Drug Side Effects Prescription Drug Side-Effects Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.
Environment / Toxicity
General Detoxification Requirement Aromatase is the enzyme that converts androgen to estrogen. Aromatase is an important target of some environmental chemicals. Some of these compounds inhibit aromatase activity, resulting in a decrease in the level of estrogen or an increase in the level of androgen in cells. Environmental chemicals can also modify the expression of aromatase in various tissues, resulting in a change in the ratio between androgen to estrogen. The compounds that inhibit aromatase or suppress aromatase expression will behave as antiestrogens or androgen-like compounds in vivo. On the other hand, compounds that increase aromatase expression or enhance aromatase activity (or stability) may function as anti-androgens or estrogen-like compounds.
Hormones
High Testosterone Level, Male
High Testosterone Level, Female Elevated testosterone causes SHBG synthesis to decrease, lowering its level in the blood.
Low Progesterone or Estrogen Dominance Elevated estrogen levels stimulate SHBG production, increasing levels in the blood.
Lab Values - Hormones
Very/moderately low SHBG
Counter-indicators:
Elevated SHBG
Laboratory Test Needed
Elevated Insulin Levels Research has discovered that sex hormone binding globulin (SHBG), a relatively unknown blood protein, is a reasonably good indicator of insulin resistance. Low levels of SHBG are consistently linked to high levels of insulin in the body. Sustained high levels of insulin are, in turn, associated with the development of the chronic diseases such as high blood pressure, diabetes and coronary heart disease.
Low SHBG suggests the following may be present:
Drug Side Effects Prescription Drug Side-Effects Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.
Recommendations for Low SHBG:
Diet Weight Loss As weight loss will improve insulin resistance, and insulin resistance can be measured by low SHBG, weight loss should help normalize low SHBG levels.
Gluten-free Diet Substituting rice for wheat, which generally has a lower amylase content, can raise SHBG levels via lowered insulin levels. However, starches should be restricted when trying to lower insulin levels.
Drug
Conventional Drugs Selection of an OC formulation that maintains increases in SHBG may be important in minimizing androgenic effects in general, and especially important in hyperandrogenic women, who may benefit most from reductions in levels of free testosterone.
SHBG's may be lowered by two of the artificially generated progesterones, norgestrel and norethisterone. If you are a woman who may be susceptible to androgenetic alopecia, that is, hereditary hair loss (female pattern baldness), or you have a naturally low SHBG level, you should avoid any contraceptive pills or hormone replacement therapy that contains synthetic progesterone.
Extract
Not recommended:
DIM (di-indolmethane)/I3C (Indole-3-Carbinol) Aromatase inhibitors like DIM, Indole 3 carbinol, and chrysin should be avoided, as they will enhance any preexisting androgen / estrogen dominance.
Hormone
Estrogen Replacement The use of estrogen to increase SHBG and hence reduce biologically free testosterone may lessen acne and hirsutism. This mechanism is commonly operative in women with Polycystic Ovarian Syndrome. With estrogen replacement, estrogen levels are higher and liver production of SHBG increases. With pregnancy or some birth control pills, you will have high SHBG, and you will have high levels of circulating hormones, but they will be mostly bound (including testosterone).
Although this article was primarily written for women, all the info is also applicable to men.
