Understanding Low SHBG in the Context of Testosterone Therapy
Low SHBG (15.7 nmol/L) does not indicate impaired testosterone "conversion"—it reflects increased metabolic clearance and tissue delivery of testosterone, commonly driven by obesity, insulin resistance, or metabolic syndrome. 1
What Low SHBG Actually Means
SHBG is a binding protein, not an enzyme—it does not "convert" testosterone. Instead, it regulates how much testosterone circulates in the free (bioavailable) form versus the protein-bound (inactive) form. 2, 3
Key Physiological Points:
- Low SHBG increases free testosterone availability because less testosterone is tightly bound, allowing more to circulate as free or albumin-bound (bioavailable) testosterone. 2, 4
- Common causes of low SHBG include obesity, insulin resistance, metabolic syndrome, type 2 diabetes, hypothyroidism, and exogenous testosterone or anabolic steroid use. 1
- Your patient's low SHBG (15.7 nmol/L) is likely driven by metabolic factors (obesity, insulin resistance) or by the exogenous testosterone itself, which suppresses hepatic SHBG production. 1
Interpreting the Testosterone Panel
Total Testosterone = 692 ng/dL
- This is mid-normal and appropriate for testosterone replacement therapy (target 450–600 ng/dL). 5, 6
Free Testosterone = 214 pg/mL
- This value appears elevated for a man with total testosterone of 692 ng/dL, because low SHBG allows more testosterone to circulate unbound. 2, 4
- Low SHBG artificially elevates free testosterone relative to total testosterone. 2, 4
- This is not a "conversion" problem—it reflects increased bioavailability of testosterone due to reduced binding capacity. 2, 3
DHEA-S = 263.7 µg/dL
- DHEA-S is produced by the adrenal glands and does not aid in diagnosing hypogonadism or assessing testosterone metabolism. 7
- Functional medicine targets of 350–500 µg/dL for men are not evidence-based. DHEA-S declines naturally with age and does not require supplementation in the absence of adrenal insufficiency. 7
- Do not supplement DHEA based on this value alone—it is irrelevant to testosterone therapy outcomes. 7
Clinical Implications of Low SHBG on Testosterone Therapy
1. Low SHBG Increases Free Testosterone Exposure
- With low SHBG, a given total testosterone level yields higher free testosterone than expected. 2, 4
- This means your patient is receiving adequate—or even supraphysiologic—free testosterone exposure despite a mid-normal total testosterone. 2, 3
2. Low SHBG Does Not Indicate "Poor Conversion"
- Testosterone does not "convert" via SHBG. SHBG is a carrier protein, not an enzyme. 2, 3
- The low SHBG reflects metabolic factors (obesity, insulin resistance) or suppression by exogenous testosterone. 1
3. Low SHBG May Increase Metabolic Clearance
- Low SHBG is associated with faster testosterone metabolism and clearance, which can cause fluctuations in testosterone levels between injections. 8
- This may explain why some patients with low SHBG experience symptom recurrence before their next injection. 8
Addressing the Low SHBG: Treatment Algorithm
Step 1: Optimize Metabolic Health
- Weight loss through calorie restriction and regular exercise is first-line therapy for obesity-associated low SHBG and secondary hypogonadism. 5
- Target 5–10% body weight reduction, which can increase SHBG and improve endogenous testosterone production. 5
- Optimize diabetes control if present: intensify therapy with GLP-1 receptor agonists or SGLT2 inhibitors, which provide cardiovascular benefits and improve insulin sensitivity. 5
Step 2: Consider Switching Testosterone Formulation
- If the patient experiences symptom recurrence before the next injection (due to rapid clearance from low SHBG), switch from injectable testosterone to transdermal gel. 5, 6
- Transdermal testosterone provides more stable day-to-day levels and avoids the peaks and troughs seen with injections, which may be exaggerated in men with low SHBG. 5, 6
Step 3: Monitor for Erythrocytosis
- Low SHBG increases free testosterone exposure, which may increase the risk of erythrocytosis (hematocrit >54%). 5
- Monitor hematocrit at each visit—withhold testosterone if >54% and consider phlebotomy in high-risk cases. 5
Step 4: Reassess DHEA-S—Do Not Supplement
- DHEA-S does not aid in diagnosing hypogonadism or assessing testosterone therapy outcomes. 7
- Functional medicine targets of 350–500 µg/dL are not evidence-based. 7
- Do not supplement DHEA unless adrenal insufficiency is confirmed. 7
Common Pitfalls to Avoid
1. Do Not Interpret Low SHBG as "Poor Conversion"
- SHBG is a binding protein, not an enzyme—it does not "convert" testosterone. 2, 3
- Low SHBG increases free testosterone availability, not decreases it. 2, 4
2. Do Not Supplement DHEA Based on Functional Medicine Targets
- DHEA-S does not aid in diagnosing hypogonadism or assessing testosterone therapy outcomes. 7
- Functional medicine targets are not evidence-based. 7
3. Do Not Ignore Metabolic Factors Driving Low SHBG
- Obesity, insulin resistance, and metabolic syndrome are the primary drivers of low SHBG. 1
- Weight loss and metabolic optimization are first-line therapies. 5
4. Do Not Overlook Erythrocytosis Risk
- Low SHBG increases free testosterone exposure, which may increase the risk of erythrocytosis. 5
- Monitor hematocrit at each visit—withhold testosterone if >54%. 5
Summary Algorithm
- Low SHBG increases free testosterone availability—it does not indicate "poor conversion." 2, 4
- Optimize metabolic health: weight loss, exercise, and diabetes control are first-line therapies. 5
- Consider switching to transdermal testosterone if symptom recurrence occurs between injections. 5, 6
- Monitor hematocrit at each visit—withhold testosterone if >54%. 5
- Do not supplement DHEA based on functional medicine targets—it is not evidence-based. 7