Management of High Sex Hormone-Binding Globulin (SHBG) and Low Free Testosterone

Diagnostic Approach

Free testosterone is a better indicator of gonadal status than total testosterone, particularly when SHBG levels are abnormal 1
Measure morning total testosterone, free testosterone or calculate free testosterone index (total testosterone/SHBG ratio) to assess hypogonadism 1
A ratio of total testosterone/SHBG (free testosterone index) <0.3 indicates hypogonadism 2
Measure LH and FSH to determine primary vs. secondary hypogonadism 3

Hepatic disease/liver cirrhosis, aging, hyperthyroidism, medications (anticonvulsants, estrogens, thyroid hormone), smoking, and HIV/AIDS can increase SHBG levels 4, 5

Address underlying causes such as liver disease, metabolic factors, thyroid disorders, and medication review to manage high SHBG and low free testosterone 4, 5, 6, 7
Consider testosterone replacement therapy (TRT) for men with persistent symptoms and confirmed low testosterone despite addressing underlying causes 1, 3, 8
TRT can normalize free testosterone levels and may reduce elevated SHBG levels, but monitor hemoglobin/hematocrit and PSA before and during therapy 8

TRT suppresses spermatogenesis and should be avoided in men desiring fertility, consider selective estrogen receptor modulators instead 3, 8, 9

Reassess testosterone (total and free) and SHBG levels after 3-6 months of treatment, and monitor for side effects of TRT 8
Adjust treatment based on symptom response and laboratory values 3, 8

The European Association of Urology notes that several factors can lower SHBG levels, including obesity, insulin resistance, high-dose glucocorticoids, growth hormone, testosterone, and certain medications 10
The American Academy of Family Physicians recommends considering the effect of glucocorticoids, such as prednisone, on SHBG levels 10, 11
The American Academy of Family Physicians also notes that certain anticonvulsants and androgens, such as testosterone, can lower SHBG levels 10, 11
The American Academy of Family Physicians states that obesity, particularly central or abdominal obesity, is associated with lower SHBG levels 11
The European Association of Urology and the American Academy of Family Physicians agree that polycystic ovary syndrome (PCOS) is associated with low SHBG levels 12, 11

The American Academy of Family Physicians notes that Cushing's syndrome and acromegaly are endocrine disorders associated with low SHBG levels 11

The American Academy of Family Physicians recommends measuring both total and free testosterone, or calculated free testosterone index, when evaluating testosterone status, especially when SHBG levels may be abnormal 11