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
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.
Estrogens increase liver manufacture of SHBG. Androgens decrease it. A lack of estrogens can effectively increase available blood androgens.
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.
Elevated Cortisol Levels
Modest reductions in SHBG levels may be encountered in individuals with Cushing’s syndrome.
Problem Caused By Being Overweight
SHBG levels respond to extreme changes in body weight, decreasing in obese patients.
Adult Acne
Low levels are often found in cases of acne vulgaris.
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
Prescription Drug Side-Effects
Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.
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.
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 Progesterone or Estrogen Dominance
Elevated estrogen levels stimulate SHBG production, increasing levels in the blood.
Very/moderately low SHBG
Counter Indicators
Elevated SHBG
Low SHBG suggests the following may be present
Prescription Drug Side-Effects
Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.
Recommendations for Low SHBG
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 amylose content, can raise SHBG levels via lowered insulin levels. However, starches should generally be restricted when trying to lower insulin levels.
Conventional Drugs / Information
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.
Diindolylmethane DIM / Indole 3 Carbinol IC3
Aromatase inhibitors like DIM (diindolylmethane), Indole 3 carbinol, and chrysin should be avoided, as they will enhance any preexisting androgen / estrogen dominance.
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).
Key
| Weak or unproven link |
| Strong or generally accepted link |
| Proven definite or direct link |
| Very strongly or absolutely counter-indicative |
| May do some good |
| Likely to help |
| Highly recommended |
| Reasonably likely to cause problems |
Glossary
Androgen
Any steroid hormone that increases male characteristics.
Estrogen
One of the female sex hormones produced by the ovaries.
Testosterone
The principal male sex hormone that induces and maintains the changes that take place in males at puberty. In men, the testicles continue to produce testosterone throughout life, though there is some decline with age. A naturally occurring androgenic hormone.
Steroid
Any of a large number of hormonal substances with a similar basic chemical structure containing a 17-carbon 14-ring system and including the sterols and various hormones and glycosides.
Hormones
Chemical substances secreted by a variety of body organs that are carried by the bloodstream and usually influence cells some distance from the source of production. Hormones signal certain enzymes to perform their functions and, in this way, regulate such body functions as blood sugar levels, insulin levels, the menstrual cycle, and growth. These can be prescription, over-the-counter, synthetic or natural agents. Examples include adrenal hormones such as corticosteroids and aldosterone; glucagon, growth hormone, insulin, testosterone, estrogens, progestins, progesterone, DHEA, melatonin, and thyroid hormones such as thyroxine and calcitonin.
DHT
Dihydrotestosterone - a highly active form of testosterone, which influences many aspects of manly behavior, from sex drive to aggression. The conversion from testosterone to DHT is driven by an enzyme called 5-alpha reductase, which is produced in the prostate, various adrenal glands, and the scalp.
Hypothyroidism
Diminished production of thyroid hormone, leading to low metabolic rate, tendency to gain weight, and sleepiness.
Acne
A chronic skin disorder due to inflammation of hair follicles and sebaceous glands (secretion glands in the skin).
Enzymes
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Protein
Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.
Insulin
A hormone secreted by the pancreas in response to elevated blood glucose levels. Insulin stimulates the liver, muscles, and fat cells to remove glucose from the blood for use or storage.
Chronic
Usually Chronic illness: Illness extending over a long period of time.
Diabetes Mellitus
A disease with increased blood glucose levels due to lack or ineffectiveness of insulin. Diabetes is found in two forms; insulin-dependent diabetes (juvenile-onset) and non-insulin-dependent (adult-onset). Symptoms include increased thirst; increased urination; weight loss in spite of increased appetite; fatigue; nausea; vomiting; frequent infections including bladder, vaginal, and skin; blurred vision; impotence in men; bad breath; cessation of menses; diminished skin fullness. Other symptoms include bleeding gums; ear noise/buzzing; diarrhea; depression; confusion.