Low SHBG Last updated: Jul 17, 2008

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  Low SHBG  
 

 
Conditions that suggest it | Contributing risk factors | Other conditions that may be present | Recommendations

 
 

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.

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.

Lab Values
  Elevated Cortisol Levels
 Modest reductions in SHBG levels may be encountered in individuals with Cushing's syndrome.

Metabolic
  Problem 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
  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.

Lab Values - Hormones
  Very/moderately low SHBG

Counter-indicators:
  Elevated SHBG
 
 

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 amylose content, can raise SHBG levels via lowered insulin levels. However, starches should generally be restricted when trying to lower insulin levels.

Drug
  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.

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).

Lab Tests/Rule-Outs
  Test Sex Hormone Binding Globulin (SHBG)
 
 


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

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GLOSSARY

Acne:  A chronic skin disorder due to inflammation of hair follicles and sebaceous glands (secretion glands in the skin).

Androgen:  Any steroid hormone that increases male characteristics.

Chronic:  Usually Chronic illness: Illness extending over a long period of time.

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.

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.

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.

Estrogen:  One of the female sex hormones produced by the ovaries.

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.

Hypothyroidism:  Diminished production of thyroid hormone, leading to low metabolic rate, tendency to gain weight, and sleepiness.

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.

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.

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.

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.