What are the ways to lower Sex Hormone-Binding Globulin (SHBG) levels?

How to Lower SHBG Levels

To lower SHBG levels, address the underlying causes first—particularly obesity, insulin resistance, and metabolic syndrome—as these are the most effective interventions, while pharmacological options like glucocorticoids, growth hormone, or androgens should only be used when clinically indicated for other conditions, not solely to reduce SHBG. 1, 2

Primary Strategies to Lower SHBG

Address Metabolic Factors (First-Line Approach)

• Weight loss and obesity management are the most effective interventions, as obesity (particularly central/abdominal obesity) is strongly associated with lower SHBG levels 2, 3
• Improve insulin sensitivity through lifestyle modifications, as insulin resistance directly suppresses SHBG production 2, 3, 4
• Optimize calorie intake and energy balance, as these factors independently regulate SHBG levels beyond just steroidal effects 3

Identify and Treat Underlying Medical Conditions

• Evaluate and correct hyperthyroidism if present, as thyroid hormone increases SHBG; treating hyperthyroidism will lower elevated SHBG 5, 1, 2
• Assess for and manage liver disease, as hepatic dysfunction can elevate SHBG levels 1, 2
• Review medications that may increase SHBG, including anticonvulsants, estrogens, and thyroid hormone replacement 1, 2
• Consider HIV testing in appropriate clinical contexts, as HIV/AIDS is associated with elevated SHBG 1, 2

Pharmacological Approaches (Use Only When Clinically Indicated)

Important caveat: These medications should never be used solely to lower SHBG, but only when clinically indicated for other conditions 1

• Glucocorticoids (such as prednisone) can lower SHBG levels 2, 3
• Growth hormone decreases SHBG 1, 2
• Testosterone or anabolic androgenic steroids suppress SHBG production 1, 2, 6
• Danazol causes marked dose-dependent suppression of SHBG, though this is typically used for endometriosis, not SHBG management 6

Clinical Context: When SHBG Lowering May Be Relevant

In Males with High SHBG and Low Free Testosterone

• Measure morning total testosterone along with free testosterone or calculate the free testosterone index (total testosterone/SHBG ratio) to accurately assess androgen status 5, 1, 2
• A free testosterone index <0.3 indicates hypogonadism 1, 2
• Testosterone replacement therapy may be appropriate in symptomatic men with documented low free testosterone, even if total testosterone is normal, with benefits including improved sexual function, well-being, muscle mass, and bone density 5, 2
• TRT can normalize free testosterone levels and may reduce elevated SHBG levels 2

Monitoring During Treatment

• Reassess testosterone (total and free) and SHBG levels after 3-6 months of any intervention 2
• For patients on testosterone replacement, monitor hematocrit/hemoglobin, PSA, and assess for urinary symptoms, sleep apnea exacerbation, and gynecomastia 2

Common Pitfalls to Avoid

• Do not use medications solely to lower SHBG without a clear clinical indication for that medication 1
• Do not overlook metabolic factors like obesity and insulin resistance, which are often more important than steroidal factors in SHBG regulation 3, 4
• Avoid relying solely on total testosterone measurements when SHBG is abnormal, as this can miss functional hypogonadism 1, 2
• Remember that growth factors (IGF-I, EGF, TGF-alpha) and insulin are important determinants of SHBG production and may explain changes not attributable to sex steroids alone 4