How can sex hormone binding globulin (SHBG) levels be lowered?

How to Lower Sex Hormone Binding Globulin (SHBG)

The most effective approach to lowering SHBG is to identify and treat the underlying condition causing its elevation, with insulin resistance, obesity, and certain medications being the primary modifiable factors that decrease SHBG levels. 1

Primary Strategy: Address Underlying Causes

The key to lowering SHBG is treating the root cause rather than targeting SHBG directly. 1 Common conditions that elevate SHBG include:

• Hyperthyroidism - Correcting thyroid dysfunction will normalize SHBG 1
• Hepatic disease - Managing liver disease appropriately addresses elevated SHBG 1
• Certain medications - Review and potentially discontinue medications that increase SHBG (anticonvulsants, estrogens, thyroid hormone) 1
• HIV/AIDS - Consider HIV testing in appropriate clinical contexts 1

Metabolic Interventions That Lower SHBG

Weight Management and Insulin Resistance

Obesity and insulin resistance are the most clinically relevant factors that decrease SHBG levels. 2, 3

• Increased body mass index (BMI) inversely correlates with SHBG - as BMI increases, SHBG decreases 3, 4
• Insulin directly inhibits hepatic SHBG synthesis, making insulin resistance a powerful SHBG-lowering mechanism 2
• Low SHBG levels are found in obese patients regardless of androgen status 3
• In type 2 diabetes patients with metabolic syndrome, SHBG levels progressively decline as metabolic syndrome components accumulate 5

Caloric Intake and Energy Balance

• Increased calorie intake and positive energy balance reduce SHBG production 3
• These factors may be more relevant than sex steroids alone in certain conditions 3

Growth Factors That Suppress SHBG

Growth factors significantly decrease SHBG production at the hepatic level: 6

• Insulin-like growth factor I (IGF-I) decreases SHBG levels (p<0.01) 6
• Epidermal growth factor (EGF) reduces SHBG production 6
• Transforming growth factor alpha (TGF-alpha) lowers SHBG 6
• IGF-I can blunt the SHBG-stimulating effects of thyroid hormone 6

Pharmacological Approaches

Medications that decrease SHBG should only be used when clinically indicated for other conditions, not solely to lower SHBG: 1

• Glucocorticoids decrease SHBG levels 1
• Testosterone or anabolic androgenic steroids lower SHBG 1
• Growth hormone reduces SHBG production 1

Important Caveat

Androgens present a paradox: while they suppress SHBG in vivo, they can stimulate SHBG production in vitro, suggesting complex regulatory mechanisms beyond direct hormonal effects. 6

Clinical Context: When SHBG Lowering Matters

In Polycystic Ovary Syndrome (PCOS)

• Low SHBG is characteristic of PCOS and contributes to increased free testosterone 2, 1
• Insulin resistance is the primary driver of low SHBG in PCOS patients, even in non-obese individuals 2

In Type 1 Diabetes

• SHBG is decreased in young females with type 1 diabetes 4
• Insulin dose, BMI, and HbA1c have significant independent inverse influences on SHBG (r²=0.77, p<0.001) 4
• Better glycemic control (lower HbA1c) may paradoxically increase SHBG 4

Factors That Regulate SHBG Beyond Steroids

SHBG regulation is complex and multifactorial: 7, 3

• The liver is the primary peripheral organ producing SHBG 7
• SHBG production varies throughout the life cycle, with marked decreases during prepubertal and pubertal periods that cannot be explained by sex steroids alone 3, 6
• Bone age and developmental stage influence SHBG independently of androgens 3

Critical Clinical Pitfall

Do not attempt to lower SHBG pharmacologically without addressing the underlying metabolic or endocrine disorder. 1 SHBG serves as a marker of metabolic health, and artificially suppressing it without treating insulin resistance, obesity, or other root causes provides no clinical benefit and may mask important diagnostic information. 7, 5