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Sex Hormone Binding Globulin (SHBG) is an important protein that helps in reproduction and puberty. There are many factors that help regulate SHBG. Read below to learn more about this protein and its effects on the body.



Sex Hormone Binding Globulin (SHBG) is a glycoprotein encoded by a single gene on the short arm of chromosome 17 in humans (R).

The liver produces SHBG and circulates throughout the body (R).

The production of SHBG fluctuates throughout the life cycle. Metabolic and hormonal factors primarily influence its production (R).

The difference in SHBG levels can also be due to genetic differences (R).

SHBG is the primary plasma transport protein for sex steroid hormones estrogen and androgen (R1, R2).

SHBG can control the plasma distribution, metabolic clearance rate, and bioavailability of the sex steroid to the target tissues (R1, R2).

Insulin is a suppressor of hepatic SHBG production (R).

SHBG in Adulthood


In adults, plasma SHBG levels vary between people (R).

The variance can be due to a number of factors, such as endocrine and metabolic rates. The differences could also be inherited (R).

Mutations, such as polymorphism, can cause variation as well (R).

For example, a common SNP that results in a D327N substitution increases the half-life of SHBG in blood and increase SHBG levels (R).

SHBG levels are higher in women than men. SHBG levels in men are about 50% of that in women (R).

The occupancy of steroid-binding sites in SHBG is different between the two sexes as well (R).

During pregnancy, SHBG levels increase 10-fold in women due to increased SHBG production in the liver (R).

Roles of Sex Hormone Binding Globulin

1) SHBG Aids Reproduction


Sex steroids or their immediate precursors are produced in the gonad, adrenal glands, and placenta and are transported to their target tissues in the blood via steroid-binding proteins (R).

Sex Hormone Binding Globulin is one of such steroid-binding proteins and binds to biologically active androgen and estrogen with high affinity (R).

During mid to late pregnancy, SHBG levels in the maternal plasma increase 5- to 10- fold (R).

The increase in the SHBG levels is to protect the mother from the fetal sex steroids and prevent excess androgen in the placenta (R1, R2).

2) SHBG Helps Regulate Puberty

SHBG levels start low in newborn babies and increase in infants of both sexes until puberty (R).

After puberty, SHBG starts to decline (R).

SHBG levels decline more in boys than in girls (R).

The reason for this might be due to androgens that suppress SHBG levels (R).

This allows for an increase in free testosterone levels in the blood, which is necessary for maturation of accessory sex organs and physical stature in boys (R).

3) SHBG Might Protect Against Diabetes


There is a relationship between testosterone levels and Type 2 Diabetes Mellitus (T2DM) (R).

In men, low testosterone levels are correlated with diabetes while in women, high testosterone levels are correlated with diabetes (R).

Women with diabetes had significantly lower SHBG levels compared to individuals without diabetes (R).

However, men with diabetes had only slightly lower SHBG levels than non-diabetic controls (R).

The relationship between SHBG levels and T2DM may seem to be the result of SHBG altering the bioavailability of the sex hormones (R).

Regulation of SHBG

There is a large variation in SHBG levels among individuals (R).

There are many factors that affect SHBG levels in the blood of an individual (R).

In most cases, the mechanism by which these factors affect the SHBG levels are unknown (R).

Factors that Increase Level of SHBG in Blood:

  • Estrogens
  • Pregnancy
    • During pregnancy, SHBG levels increase 10-fold in women due to increased SHBG production in the liver (R).
  • Weight Loss
    • Weight loss is associated with a decrease in testosterone levels and an increase in SHBG levels (R).
  • Alcoholic Cirrhosis
    • Alcohol damages the testes, which results in increased levels of luteinizing hormone, which in turn increases estradiol levels and decrease SHBG levels (R).
  • HepB and C infections
    • SHBG levels are significantly lower in patients with Hepatitis B or C infection (R).
  • Growth Hormone Deficiency
    • Patients with growth hormone deficiency have lower serum on SHBG-bound testosterone concentrations (R).
  • Hyperthyroidism
    • SHBG levels increase drastically in hyperthyroidism (R).
    • The increase in SHBG levels is caused by stimulation of SHBG gene expression by thyroid hormone (R).
    • SHBG levels normalize when hyperthyroxinemia is treated (R).

Factors that Decrease Level of SHBG in Blood:

  • Androgens
    • Exogenous testosterone, a type of Androgen, has shown to decrease serum SHBG levels (R).
  • Obesity
    • Studies link low levels of SHBG with obesity (R).
  • Insulin
    • Experiments suggest that insulin suppresses SHBG production in liver (R).
  • Growth Hormone
    • Continuous subcutaneous infusion of the growth hormone decreases serum concentration of SHBG (R).
    • Acromegaly (condition of having too high growth hormone levels) patients have lower SHBG levels (R).
  • Carbohydrates
    • In response to a monosaccharide, SHBG levels are lowered (R).
  • Metabolic Syndrome (R)
    • SHBG levels are low in children and adults with MetS (R).
    • MetS is a combination of metabolic risk factors such as obesity, hypertension, and impaired glucose metabolism (R).
  • Cushing’s Syndrome
    • SHBG levels are lower in patients with Cushing’s Syndrome (R).
  • Type 2 Diabetes Mellitus (R)
  • Polycystic Ovary Syndrome
    • SHBG levels are lower in patients with polycystic ovary syndrome, which results in higher amount of active androgen (R).
  • Congenital Adrenal Hyperplasia
    • Female patients with congenital adrenal hyperplasia have lower SHBG levels (R).


  • The first is that Sex Hormone Binding Globulin directly participates in the delivery of steroid ligands to specific target cells (R).
  • Secondly, SHBG itself acts as a ligand for a receptor (R).
  • In women, only about 18% of the steroid-binding sites are occupied at serum concentrations, whereas about 56% of the sites are occupied by men (R).
  • However, studies suggest that the relationship between SHBG and T2DM is independent of sex hormone levels (R).
  • The exact mechanism by which SHBG influences risk of diabetes is unclear. However, SHBG and glucose metabolism impairment are linked together (R).

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  • msmetzger

    I don’t agree: [insidetracker]

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