Sex Hormone Binding Globulin (SHBG)#

SHBG (sex hormone binding globulin) is a protein produced by the liver. It binds tightly to sex hormones - especially testosterone, and to a lesser extent estradiol and dihydrotestosterone (DHT). Once bound to SHBG, those hormones cannot enter cells or have a biological effect.

In a typical adult man, about 60 to 70% of testosterone is bound to SHBG, about 30% is loosely bound to albumin (another blood protein), and only 1 to 4% circulates freely. The free fraction plus the albumin-bound fraction together are sometimes called "bioavailable testosterone" - the portion the body can actually use.

Total testosterone is the sum of all testosterone in the blood:

• Testosterone tightly bound to SHBG (not available to cells)
• Testosterone loosely bound to albumin (available to cells)
• Free testosterone (available to cells)

When SHBG is unusually high or low, total testosterone alone can be misleading. That is why SHBG is often measured with testosterone in cases of suspected testosterone deficiency.

Calculated free testosterone is an estimate of the bioavailable testosterone in your bloodstream, calculated from total testosterone, SHBG, and albumin using a published formula. It is more clinically useful than measuring free testosterone directly, because direct measurement of free testosterone is technically difficult and often inaccurate at most Canadian labs.

SHBG is most useful when:

• A man has clear symptoms of testosterone deficiency (low libido, fatigue, erectile dysfunction, depressed mood, reduced muscle mass) but his total testosterone is in the low-normal range. A high SHBG can explain symptoms despite a "normal" total testosterone.
• A man has a high total testosterone but no signs of androgen excess - a high SHBG can explain this.
• A woman is being evaluated for hyperandrogenism (acne, hirsutism, irregular periods), as in PCOS. A low SHBG with normal or high total testosterone often points to insulin resistance and PCOS.
• Someone is being evaluated for liver disease, thyroid disease, or metabolic syndrome - SHBG levels reflect liver protein production and metabolic status.

• As a stand-alone test without testosterone. SHBG by itself rarely guides care.
• For monitoring testosterone replacement therapy at routine visits, unless calculated free testosterone is being tracked.

• Morning blood draw. Testosterone and SHBG follow a daily rhythm; both are best measured in the morning, ideally before 10 AM.
• Fasting is generally preferred when testosterone and SHBG are drawn together, because fasting helps with the accompanying metabolic panel (glucose, lipids) and reduces variability.
• Stop high-dose biotin (vitamin B7) for at least 72 hours before testing - biotin interferes with many hormone assays, including SHBG and testosterone.
• Avoid testing during acute illness or within 2 weeks of recovering from an illness - illness lowers testosterone temporarily.
• Two separate morning draws are needed to confirm low testosterone before starting testosterone replacement therapy. SHBG should be drawn with each.

• Age (SHBG naturally rises with age in men)
• Liver disease
• Overactive thyroid (hyperthyroidism)
• HIV
• Hepatitis or other inflammatory liver conditions
• High estrogen states (estrogen-containing birth control, pregnancy, hormone replacement therapy)
• Anti-seizure medications
• Low body weight or anorexia
• High caffeine or fibre intake (modest effects)

• Obesity, especially central (abdominal) obesity
• Type 2 diabetes and insulin resistance
• Polycystic ovary syndrome (PCOS)
• Underactive thyroid (hypothyroidism)
• Nephrotic syndrome (a type of kidney disease causing protein loss)
• Anabolic steroid use, including supraphysiological testosterone doses
• Long-term corticosteroid use (oral steroid pills, used for autoimmune or inflammatory conditions)
• Some progestins
• Cushing's syndrome (excess cortisol)

When SHBG is high, more testosterone gets locked to the SHBG protein and less is bioavailable. A man can have a "normal" total testosterone but still have symptoms of testosterone deficiency. The calculated free testosterone (or bioavailable testosterone) will be lower than expected for his total.

This is why clinicians treating suspected low testosterone often look at SHBG and calculated free testosterone together, not total testosterone alone.

When SHBG is low, more testosterone is bioavailable for any given total testosterone. A man can have a "low" total testosterone but a normal calculated free testosterone, and therefore no clinical androgen deficiency. In women, a low SHBG with normal testosterone often points to underlying insulin resistance or PCOS, even when total testosterone is in range.

• Lose excess abdominal weight. Reducing visceral fat raises SHBG and tends to improve free-testosterone balance.
• Address insulin resistance. Improving insulin sensitivity through diet, exercise, and (when needed) medical management raises SHBG.
• Treat underactive thyroid if present.
• Reduce alcohol intake.
• Stop anabolic steroids if you are using them. Anabolic steroids suppress SHBG and damage natural testosterone production.

Estrogen-containing birth control pills raise SHBG, often substantially. This is normal and expected. If SHBG is being interpreted for a clinical question (such as androgen excess), your clinician will factor this in. Total testosterone may look misleadingly low because so much is bound to SHBG.

In a man, this combination is most often seen with obesity, type 2 diabetes, or both. The total testosterone may look low because of low SHBG, not because of true androgen deficiency. The calculated free testosterone may actually be normal. Weight loss, improving insulin sensitivity, and addressing sleep apnea (if present) often improve testosterone in this setting, often more effectively than testosterone replacement.

Usually no. Most guidelines (including the Endocrine Society) recommend treating testosterone deficiency only when both:

1. Symptoms are consistent with low testosterone, and
2. Two morning samples show low total testosterone (and usually low calculated free testosterone)

If the calculated free testosterone is normal, the symptoms are most likely from another cause - weight, sleep, depression, medications, or another condition - and testosterone replacement is unlikely to help.

Most provincial health plans do not cover SHBG as a routine test. It is typically billed as an uninsured test through TeleTest. The lab will collect the fee at the time of your visit. TeleTest will order SHBG as an insured test only when there is a documented clinical indication that meets provincial billing rules.

Costs vary by lab. Contact your local lab for current pricing, or see your TeleTest booking confirmation.