Can SHBG Be Lowered? Evidence-Based Answer
No, the claim that SHBG cannot be lowered is false—SHBG levels can be reduced through multiple interventions including weight loss, insulin reduction, certain medications, and potentially specific nutritional factors. 1, 2
Primary Factors That Lower SHBG
Obesity and Insulin Resistance
- Weight loss is the most clinically validated intervention for lowering SHBG, particularly in obese individuals where SHBG concentrations are negatively correlated with body mass index (BMI) and central adiposity 3
- Insulin directly inhibits SHBG synthesis and secretion by hepatocytes, making insulin reduction a key mechanism for increasing SHBG 3, 4
- A three-week low-fat diet (<10% calories) plus daily exercise increased SHBG from 18 ± 2 to 25 ± 3 nmol/L (p < 0.01) while decreasing insulin from 222 ± 30 to 126 ± 21 pmol/L 5
- Calorie restriction results in reduction of serum insulin followed by an increase in SHBG, though an isocaloric low-fat diet without calorie restriction has no significant effect 3
Pharmacological Interventions
- Medications that decrease SHBG include growth hormone, glucocorticoids, and testosterone or anabolic androgenic steroids, though these should only be used when clinically indicated for other conditions, not solely to lower SHBG 2
- Androgens of both glandular and peripheral origin have the capacity to lower SHBG plasma levels 6
Medical Conditions That Lower SHBG
- Hypothyroidism 2
- Acromegaly 2
- Cushing's disease 2
- Polycystic ovary syndrome (PCOS), particularly in obese women with truncal obesity and hyperinsulinemia 3
Clinical Context: Why Lowering SHBG Matters
In Obesity-Related Hypogonadism
- Men with obesity frequently have low total testosterone due to low SHBG concentrations, but may have normal free testosterone levels 7
- When evaluating low total testosterone in men with obesity, measuring morning serum free testosterone is essential to distinguish true hypogonadism from SHBG-mediated changes 7
- Obese women with PCOS have lower SHBG and reciprocally higher free testosterone levels compared to lean counterparts, contributing to greater prevalence of hirsutism 3
Monitoring Requirements
- Any intervention that lowers SHBG should be monitored for free and total testosterone levels 1
- Monitor for symptoms of androgen excess or deficiency when using SHBG-lowering interventions 1
- Bone health markers should be monitored if SHBG-lowering interventions are used chronically 1
Important Caveats and Pitfalls
Lack of Long-Term Data
- The absence of long-term data beyond one week is a major limitation for many interventions, including whether SHBG reduction persists beyond 7 days 1
- The body may develop compensatory mechanisms over time, and there are safety concerns with chronic suppression of SHBG 1
Not All Hyperandrogenic States Show SHBG Correlation
- In adult hyperandrogenic patients, SHBG levels are significantly lower than controls but not always inversely correlated with androgen levels 6
- In precocious adrenarche, SHBG inversely correlates with BMI or bone age but not with androgens, suggesting other factors may be more relevant than steroids in SHBG regulation 6
Nutritional Factors Are Often More Important Than Steroids
- Nutritional factors may be more important than sex steroids in regulating SHBG in women, with SHBG concentrations negatively correlated with BMI and indices of central adiposity 3, 8
- Several factors including calorie intake, energy balance, and growth factors (beyond steroids) are involved in plasma SHBG regulation 6
- Each regulating factor may act to different extents depending on life cycle periods 6