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 Elevated SHBG
Problem Caused By Being Underweight
SHBG levels respond to extreme changes in body weight, increasing in individuals with anorexia nervosa.
Risk factors for Elevated SHBG
Hyperthyroidism
Elevated levels of SHBG may be observed with hyperthyroidism. This results in a decrease in bioavailable testosterone.
Protein Deficiency
A study published in 2000 examined the relationship between diet and sex hormone binding globulin (SHBG), and found that diets low in protein in elderly men [40-70 years old] may lead to elevated SHBG levels and decreased testosterone availability. The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass, and contribute to the loss of bone density. [J Clin Endocrinol Metab. 2000 Jan; 85(1):293-6]
Prescription Drug Side-Effects
Elevated levels of SHBG may be observed during administration of drugs, such as phenytoin, that promote hepatic enzyme induction.
Elevated Testosterone Level, Male
Numerous studies have shown that total testosterone (free+SHBG bound+albumin bound) correlates with SHBG levels. As SHBG levels rise, testosterone is believed to partition out of the free and albumin bound phases into the SHBG phase. Testosterone bound tightly to SHBG is less subject to the action of metabolic enzymes. Hence the increase in SHBG bound testosterone leads to a decrease in the metabolic clearance rate of testosterone, with a corresponding increase in total plasma testosterone.
Elevated Testosterone Level, Female
Elevated testosterone levels are associated with higher levels of SHBG.
Elevated SHBG
Cirrhosis of the Liver
Elevated levels of SHBG may be observed with hepatic cirrhosis.
Liver Detoxification / Support Requirement
The liver is responsible for removing excess estrogen and SHBG, so any compromise in liver function (such as that caused by heavy alcohol consumption, for example) can exacerbate hormonal imbalances.
Natural estrogen use
Elevated SHBG suggests the following may be present
Cirrhosis of the Liver
Elevated levels of SHBG may be observed with hepatic cirrhosis.
Recommendations for Elevated SHBG
Fish Oil / Krill
A Japanese study examined how the essential fatty acids EPA and DHA (found in high concentrations in fish) affected SHBG levels in men 43 to 88 years of age. After controlling for other variables, the researchers concluded that both EPA and DHA decreased levels of SHBG in middle-aged and elderly men. [Nutr Canc. 2000;38(2):163-67]
Nettle (Urtica urens)
Nettle root, as a highly concentrated extract, has shown to be effective at binding to SHBG and therefore permiting more free testosterone to circulate in the the system. It also acts as a 5-alpha reductase inhibitor. This is the enzyme, responsible for the conversion of testosterone to dihydrotestosterone (DHT), a more potent form of the male sex hormone, which causes prostate enlargement. A methanol extract of nettle can also reduce SHBG levels, which has the effect of elevating free testosterone in the blood stream.
Conventional Drugs / Information
SHBG’s may be lowered by two of the artificially generated progesterones, norgestrel and norethisterone.
Key
| Weak or unproven link |
| Strong or generally accepted link |
| Proven definite or direct link |
| May do some good |
| Likely to help |
| Highly recommended |
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.
Anorexia Nervosa
An eating disorder characterized by excess control - a morbid fear of obesity leads the sufferer to try and limit or reduce their weight by excessive dieting, exercising, vomiting, purging and use of diuretics. Sufferers are typically more than 15% below the average weight for their height/sex/age and typically have amenorrhea (if female) or low libido (if male). 1-2% of female teenagers are anorexic.
Hyperthyroidism
An abnormal condition of the thyroid gland resulting in excessive secretion of thyroid hormones characterized by an increased metabolism and weight loss.
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.
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.
Metabolism
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.
Cirrhosis
A long-term disease in which the liver becomes covered with fiber-like tissue. This causes the liver tissue to break down and become filled with fat. All functions of the liver then decrease, including the production of glucose, processing drugs and alcohol, and vitamin absorption. Stomach and bowel function, and the making of hormones are also affected.