Sex Hormone Binding Globulin (SHBG)

Overview

Sex Hormone Binding Globulin (SHBG), also known as Sex Steroid Binding Protein (SBP), Testosterone-Estradiol Binding Globulin, or TeBG, is a glycoprotein produced by the liver. Its main role is to bind sex hormones such as testosterone, dihydrotestosterone (DHT), and estradiol with varying affinities, thereby controlling the amount of free (biologically active) hormone circulating in the bloodstream.

SHBG is crucial for hormonal balance as it regulates the bioavailability of sex hormones to target tissues. It has high affinity for DHT, medium affinity for testosterone and estradiol, and low affinity for hormones like estrone, androstenedione, and dehydroepiandrosterone.

Production of SHBG is regulated by a balance of androgens, estrogens, thyroid hormones, insulin, and dietary factors. It also binds divalent cations such as calcium and zinc, which can influence its affinity for hormones. Clinically, SHBG levels are measured to evaluate conditions related to androgen excess, androgen deficiency, fertility issues, and metabolic or liver disorders.

Symptoms

Abnormal SHBG levels—whether too high or too low—affect the balance of active sex hormones, producing various symptoms:

1. Low SHBG (high free testosterone):
   1. Low sex drive in men
   2. Erectile dysfunction
   3. Fertility issuesIn women: Hirsutism (excess facial/body hair), deepening of voice, acne, irregular menstrual cycles, or amenorrhea
   4. Weight gain and metabolic issues
2. High SHBG (low free testosterone):
   1. Symptoms of hypogonadism (low testosterone)
   2. Fatigue and low energy
   3. Reduced muscle mass and strength
   4. Infertility
   5. In women: Signs of estrogen dominance such as irregular cycles or acne

These symptoms often prompt SHBG testing alongside testosterone and estradiol measurements.

Causes

Abnormal SHBG levels may be due to various physiological and pathological factors:

1. Causes of Low SHBG:
   1. Type 2 diabetes
   2. Polycystic Ovary Syndrome (PCOS)
   3. Cushing’s syndrome
   4. Obesity or overweight
   5. Hyperthyroidism
   6. Old age
   7. Use of anabolic steroids or excessive steroid medications
2. Causes of High SHBG:
   1. Hyperthyroidism
   2. Hypogonadism
   3. Androgen insensitivity
   4. Liver cirrhosis or other chronic liver conditions
   5. Hyperprolactinemia
   6. Eating disorders
   7. Birth control pills and hormone replacement therapy
   8. Certain medications and drug therapies

Risk Factors

Individuals more likely to experience abnormal SHBG levels include:

1. Men with Testosterone Disorders: Low libido, erectile dysfunction, or suspected hypogonadism.
2. Women with Hormonal Imbalances: Those with PCOS, hirsutism, or infertility.
3. Individuals with Metabolic Conditions: Patients with type 2 diabetes, obesity, or insulin resistance.
4. People with Thyroid or Liver Disorders: Since SHBG production is influenced by thyroid hormones and liver function.
5. Elderly Individuals: SHBG levels naturally fluctuate with aging, impacting sex hormone bioavailability.
6. Patients on Hormone Therapy: Including contraceptives, hormone replacement, or anabolic steroids.

Prevention

While abnormal SHBG levels cannot always be fully prevented, proactive health measures can help minimize risks and maintain hormonal balance:

1. Regular Health Check-ups:
   1. Monitor hormone levels in individuals with fertility issues, metabolic syndrome, or unexplained hormonal symptoms.
   2. SHBG testing can be combined with testosterone and estradiol assessments for better diagnostic accuracy.
2. Sample Collection Guidelines:
   1. Collect 3 mL blood in a plain (red-capped) or lithium heparin (green-capped) tube.
   2. Serum or plasma should be separated early and sent to the lab for accurate results.
3. Lifestyle Modifications:
   1. Maintain a healthy weight through balanced diet and exercise.
   2. Manage blood sugar levels to prevent insulin resistance and diabetes.
   3. Avoid unnecessary steroid or anabolic drug use.
4. Managing Underlying Conditions:
   1. Treat thyroid dysfunction, liver disease, and metabolic disorders promptly.
   2. Adjust hormone therapies under medical guidance to avoid altering SHBG levels.
5. Monitoring During Puberty and Aging:
   1. SHBG levels naturally vary across Tanner stages and throughout adulthood. Monitoring these variations ensures better management of reproductive health.