A low SHBG level means that more of the total testosterone is bioavailable and not bound to SHBG.

Decreases in SHBG are seen with:

- Obesity

- Polycystic ovary syndrome

- Hypothyroidism

- Steroid use

- Cushing disease

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IN WOMEN:

Many conditions of mild-to-moderate androgen excess in women, particularly polycystic ovarian syndrome, are associated with low sex hormone-binding globulin (SHBG) levels. Most of these women are also insulin resistant and many are obese. A defect in SHBG production could lead to bioavailable androgen excess, in turn causing insulin resistance that depresses SHBG levels further. There are rare cases of SHBG mutations that clearly follow this pattern. SHBG levels are typically very low in these individuals. However, in most patients, SHBG levels are mildly depressed or even within the lower part of the normal range. In these patients, the primary problem may be androgen overproduction, insulin resistance, or both. A definitive cause cannot be usually established. Any therapy that either increases SHBG levels (e.g., estrogens or weight loss), reduces bioactivity of androgens (e.g., androgen receptor antagonists, alpha-reductase inhibitors), or reduces insulin resistance (e.g. weight loss, metformin, peroxisome proliferator-activated receptor [PPAR] gamma agonists), can be effective.

Improvement is usually associated with a rise in SHBG levels, but bioavailable or free testosterone levels should also be monitored.

The primary method of monitoring sex-steroid or antiandrogen therapy is direct measurement of the relevant sex-steroids and gonadotropins. However, for many synthetic androgens and estrogens (e.g., ethinyl-estradiol) clinical assays are not available. In those instances, rises in SHBG levels indicate successful anti-androgen or estrogen therapy, while falls indicate successful androgen treatment.

SHBG is also produced by placental tissue and therefore values will be elevated during pregnancy. In patients with known insulin resistance, "metabolic syndrome," or high risk of type 2 diabetes (e.g., women with a history of gestational diabetes), low SHBG levels may predict progressive insulin resistance, cardiovascular complications, and progression to type 2 diabetes. An increase in SHBG levels may indicate successful therapeutic intervention.

What are normal SHBG levels?
The normal ranges for SHBG concentrations in adults are:

Males: 10 to 57 nanomoles per liter (nmol/L)
Females (nonpregnant): 18 to 144 nmol/L

Men typically have lower SHBG levels than women. However, a man’s SHBG level will usually increase with age as his testosterone levels drop.

Pregnancy usually raises SHBG levels. They typically return to normal after childbirth.

A high SHBG level means that it is likely that less free testosterone is available to the tissues than is indicated by the total testosterone test. This may be seen in:

-Liver disease

-Hyperthyroidism

-Eating disorders like anorexia nervosa

-Corticosteroids or estrogen use (hormone replacement therapy or oral contraceptives

-Pregnancy

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Increased SHBG in men may be associated with symptoms of low testosterone levels (=hypogonadism) because less testosterone is available to the body's tissues. The Endocrine Society professional guidelines recommend measuring total testosterone in the initial screen for testosterone deficiency. If abnormal, the test is repeated on another day. If repeat results are low-normal and/or if SHBG is abnormal, they recommend one of the following:

- Measure bioavailable testosterone (using ammonium sulfate precipitation or SHBG). 

- Calculate free testosterone from total testosterone and SHBG 

- Measure free testosterone (using a method called equilibrium dialysis) 

In women, small amounts of testosterone are produced by the ovaries and adrenal glands. 

Even slight increases in testosterone production can disrupt the balance of hormones and cause symptoms such as irregular or missed menstrual periods, infertility, acne, and excess facial and body hair (hirsutism). These signs and symptoms and others are often seen with polycystic ovary syndrome (PCOS), a condition characterized by an excess production of male sex hormones (androgens). SHBG and testosterone testing may be useful in helping to detect and evaluate excess testosterone production and/or decreased SHBG concentrations and in evaluating women suspected of having PCOS.

Thyrotoxicosis (an excess of thyroid hormone in the body) increases SHBG levels. In situations when assessment of true functional thyroid status may be difficult (e.g., patients receiving amiodarone treatment, individuals with thyroid hormone transport-protein abnormalities, patients with suspected thyroid hormone resistance or suspected inappropriate thyroid-stimulating hormone [TSH] secretion such as a TSH-secreting pituitary adenoma), an elevated SHBG level suggests tissue thyrotoxicosis, while a normal level indicates euthyroidism or near-euthyroidism. 

In patients with gradual worsening of thyrotoxicosis (e.g., toxic nodular goiter), serial SHBG measurement, in addition to clinical assessment, thyroid hormone, and TSH measurement, may assist in the timing of treatment decisions. Similarly, SHBG measurement may be of value in fine-tuning suppressive TSH therapy for patients with nodular thyroid disease or treated thyroid cancer. Results are not definitive in the short-term in patients receiving drugs that displace total thyroxine (T4) from albumin.

Patients with anorexia nervosa have high SHBG levels. With successful treatment, levels start to fall as nutritional status improves.    

What are normal SHBG levels?
The normal ranges for SHBG concentrations in adults are:

Males: 10 to 57 nanomoles per liter (nmol/L)
Females (nonpregnant): 18 to 144 nmol/L