What is sex hormone binding globulin?

Sex Hormone Binding Globulin, or SHBG, is a protein produced by the liver that plays a vital role in regulating your body's sex hormones, particularly testosterone, dihydrotestosterone (DHT) and oestrogen. SHBG binds to these hormones and controls how much hormone is available for your body to use. We often measure SHBG to check for hormone imbalances that can cause issues such as polycystic ovarian syndrome (PCOS), irregular periods and infertility in women or low libido and problems with erections in men.

What does SHBG do?

Most (about 98%) testosterone and oestrogen circulates in your bloodstream “bound” to two proteins - albumin and sex hormone binding globulin. Only a small fraction (about 2%) is unbound or “free”. However, it’s this free hormone that’s actually “bioavailable” to have an effect on your cells. So, you can think of SHBG as a “mop” soaking up testosterone and oestrogen and preventing them from having an effect.

In this way, SHBG acts as a sex hormone regulator, releasing more when your body needs them and locking them away when their levels are too high. For instance, during puberty in males, less SHBG is produced because the body needs more free testosterone to stimulate development of male characteristics.

Why do you need the SHBG test?

Doctors often check SHBG levels when investigating hormone-related symptoms.

For men, we would check SHBG when investigating signs of low testosterone such as low sex drive, mood changes, erectile dysfunction and loss of muscle mass. If the SHBG level is high, the level of free testosterone available to your body may be low. This can cause a problem even if your total testosterone level is ok.

In women, SHBG levels are important when investigating PCOS, irregular periods and fertility problems. In PCOS, we tend to see lower SHBG levels and high levels of testosterone.

What are the normal SHBG ranges by age and sex?

The levels of SHBG depend on a person’s sex, age and the presence of certain health conditions. Therefore, the normal ranges for SHBG levels differ across age groups between men and women, as shown in the table below.

SHBG levels also increase 5 to 10 fold in pregnancy. This may be to protect the mother from the effects of androgens produced by the foetus.

What are the symptoms of low SHBG?

Low SHBG levels usually mean that there are higher levels of bioavailable androgens and oestrogens. The androgenic effects are most pronounced because SHBG binds more easily to androgens than oestrogens.

Symptoms of low SHBG in women

If SHBG levels are low in women, they might experience symptoms related to higher levels of bioavailable testosterone such as:

• Male pattern facial and body hair (hirsutism)
• Acne
• Deepening of the voice
• Mood changes
• Irregular periods
• Infertility

Symptoms of low SHBG in men

Low SHBG levels in men will result in higher levels of free testosterone. Many men wouldn’t notice any symptoms as they have high levels of testosterone to begin with. However, if free testosterone levels got very high, they might notice:

• Acne
• Headaches
• Mood changes
• Infertility

What are the causes of low SHBG?

Your genes play a major role in your SHBG level and account for about 50% of the variation we see between individuals^{1, 2}. However, there are some non-genetic factors that can result in a low SHBG:

• Obesity: obesity is associated with low SHBG levels. Fat cells produce hormones and inflammatory markers that suppress production of SHBG in the liver³.
• PCOS: polycystic ovarian syndrome is associated with insulin resistance, obesity, and increased levels of androgens (or male hormones) which can cause lower levels of SHBG⁴.
• Insulin resistance: insulin resistance results in high levels of circulating insulin. In turn, high insulin suppresses SHBG production. Low SHBG is also associated with a high risk of developing type 2 diabetes⁵.
• Hypothyroidism: an underactive thyroid gland produces less thyroid hormones and this is linked to reduced SHBG production.
• Metabolic dysfunction-associated fatty liver disease (MAFLD): deposition of fat in the liver reduces its ability to produce SHBG.
• Testosterone replacement therapy (TRT): TRT typically leads to lower SHBG levels. When you have a lot of testosterone in circulation, the body signals the liver to produce less SHBG.

How to increase your SHBG

In general, the best way to increase SHBG level is to treat the cause of low SHBG if that’s known. Otherwise, some other factors that can increase your SHBG levels are:

• Regular exercise: exercise increases the levels of SHBG and dihydrotestosterone. Moderate to vigorous intensity exercise for at least one hour a day for 6 days a week raised the levels of SHBG significantly in one study ⁶.
• Weight loss: If you are overweight or obese, losing weight can help to increase your levels of SHBG⁷.
• Increase dietary fibre: a high-fibre and low-sugar diet is associated with increased SHBG levels according to a study done in menopausal women⁸.
• Drink coffee: in one large, observational study of postmenopausal women, drinking two or more cups of coffee a day was associated with a higher SHBG level⁹.

What happens if your SHBG level is too high?

As we’ve seen above, a low SHBG level is associated with obesity, metabolic syndrome and insulin resistance. It shouldn’t come as a surprise then that in general, higher SHBG levels are associated with a lower risk of diabetes and heart disease^{10, 11}.

However, it’s still possible for SHBG levels to be too high, resulting in low levels of bioavailable testosterone and oestrogen.

Symptoms of high SHBG in women

High SHBG levels in women would be expected to lower bioavailable testosterone and oestrogen, causing symptoms such as:

• mood changes
• irregular periods
• reduced sex drive
• lower bone and muscle mass

Symptoms of high SHBG in men

In men, a high SHBG level would result in a low level of free testosterone, causing symptoms of low testosterone:

• low energy
• reduced sex drive
• erectile dysfunction
• difficulty putting on muscle

What are the causes of high SHBG?

The common causes of high sex hormone binding globulin include:

• Pregnancy: because of the hormonal changes in pregnancy, the levels of SHBG increase, particularly in the second and third trimesters.
• Advanced liver disease: although fatty liver disease can reduce SHBG production, severe liver disease (cirrhosis) can actually cause high SHBG levels. This is because cirrhosis causes a reduction in total testosterone production. Testosterone usually inhibits SHBG production but this negative feedback is lost in cirrhosis leading to high levels. Furthermore, oestrogens tend to increase SHBG production and serum oestrogen is higher in people with cirrhosis¹².
• Hyperthyroidism: an overactive thyroid gland produces more thyroid hormones which stimulates the liver to produce more SHBG¹³.
• Medications: the oral contraceptive pill, hormone replacement therapy and antiepileptic medications can all increase SHBG levels^{14, 15}.
• Anorexia: severe calorie restriction affects the production of most hormones, including SHBG.

How to lower your SHBG level

If the cause of high SHBG is known, it’s best to address this first. However, one lifestyle factor that has been shown to lower SHBG levels is increasing protein intake, particularly in older men¹⁶. High protein intake may therefore increase bioavailable testosterone levels which is beneficial for muscle mass and metabolic health.

How do I prepare for an SBG test?

In most cases, you don’t need any special preparation for the SHBG test. However, high-dose biotin supplementation can interfere with the assay used to measure SHBG levels. This can cause falsely low results. It’s best to stop high-dose biotin supplements for a few days before checking your SHBG level.

What should you do if you have abnormal SHBG levels?

We don’t tend to measure SHBG on its own, rather we would test it alongside other hormones such as testosterone and oestradiol. We would then put together the whole picture to determine what to do next if you have abnormal SHBG levels.

For example, we might suggest further testing to look at the levels of pituitary hormones, LH and FSH, which control testicular and ovarian hormone production. It might also be necessary to check your thyroid and liver function as these can influence SHBG production.

A lot of the time, an abnormal SHBG level is a sign that other areas of your health could be improved, such as your nutrition and exercise regimen.