In an adult male with a total testosterone of approximately 40 nmol/L and SHBG of approximately 99 nmol/L, is this hormonal profile likely causing his erectile dysfunction?

Your Hormonal Profile Is Unlikely to Be the Primary Cause of Your ED

With a total testosterone of 40 nmol/L (approximately 1154 ng/dL), you have normal—even high-normal—testosterone levels that should not cause erectile dysfunction. However, your extremely elevated SHBG of 99 nmol/L is binding most of your testosterone, potentially reducing your free (bioactive) testosterone to levels that could contribute to ED 1, 2.

Understanding Your Hormone Results

Your total testosterone of 40 nmol/L converts to approximately 1154 ng/dL, which is well above the threshold for hypogonadism (300 ng/dL or 10.4 nmol/L) 1, 2. However, SHBG binds testosterone and renders it biologically inactive—only free testosterone can enter tissues and exert physiological effects 3, 4.

The critical issue is that your SHBG of 99 nmol/L is markedly elevated (normal range approximately 10-50 nmol/L) 1, 5. This creates a situation called "functional hypogonadism" where total testosterone appears normal or high, but free testosterone is low enough to cause symptoms including erectile dysfunction 3, 4.

Why This Matters for Erectile Function

• Testosterone facilitates erections by acting as a vasodilator of penile arterioles and cavernous sinusoids 6, 7
• A minimal level of testosterone is required for complete effect of PDE5 inhibitor therapy (like Viagra or Cialis), explaining why some men fail these medications when bioavailable testosterone is low 6, 7
• Higher SHBG independently predicts erectile dysfunction risk, even after adjusting for total testosterone 8
• Men with both low free testosterone and high SHBG have the highest ED risk (4.6-fold increased risk) 8

Essential Next Steps

1. Measure Your Free Testosterone

You must measure calculated free testosterone by equilibrium dialysis or using a validated formula (Vermeulen method) to confirm whether you have functional hypogonadism 2, 5. Total testosterone alone misses approximately half of hypogonadism diagnoses when SHBG is elevated 3, 5.

• In one study of men presenting with ED, 17.2% had normal total testosterone but low free testosterone, and 74.2% of these men were over 60 years old 5
• Among men over 60 with ED, 26.3% had normal total testosterone but low free testosterone 5

2. Investigate Causes of Your Elevated SHBG

Common causes of elevated SHBG include 1, 3:

• Hyperthyroidism (check TSH, free T4)
• Hepatic disease (check liver function tests)
• Medications: anticonvulsants, estrogens, thyroid hormone
• Aging (SHBG increases with age)
• Smoking
• HIV/AIDS

3. Calculate Your Free Testosterone Index

The free testosterone index (total testosterone/SHBG ratio) is more predictive of hypogonadal symptoms than total testosterone alone 3. Using your values:

• Free testosterone index = 40 nmol/L ÷ 99 nmol/L = 0.40
• A ratio <0.3 indicates functional hypogonadism in men with cirrhosis 2
• Your ratio of 0.40 is borderline and requires formal free testosterone measurement to clarify

Treatment Algorithm Based on Free Testosterone Results

If Free Testosterone Is Confirmed Low:

1. First-line: Address reversible causes of elevated SHBG 3

   • Treat hyperthyroidism if present
   • Discontinue SHBG-elevating medications if possible
   • Optimize metabolic health and body composition

2. Second-line: PDE5 inhibitors (sildenafil, tadalafil, vardenafil) remain first-line for ED regardless of testosterone status 1, 3

   • These medications work even with low testosterone, though response may be suboptimal 6, 7

3. Third-line: Consider testosterone replacement therapy if free testosterone remains low after addressing reversible causes 2, 3

   • Testosterone replacement can convert over half of PDE5 inhibitor non-responders into responders 7
   • Transdermal testosterone gel 1.62% at 40.5 mg daily is preferred first-line formulation 2
   • Monitor free testosterone levels 2-3 months after initiation 2

If Free Testosterone Is Normal:

Your ED is likely due to other causes 1:

• Vascular disease (most common cause in men over 40)
• Diabetes and metabolic syndrome
• Medications (antihypertensives, antidepressants)
• Psychological factors (anxiety, depression, relationship issues)
• Neurological conditions

Critical Pitfalls to Avoid

• Do not assume your testosterone is "fine" based on total testosterone alone—with SHBG of 99 nmol/L, you may have functional hypogonadism despite high total testosterone 3, 5, 4
• Do not start testosterone therapy without first measuring free testosterone—you may not need it if free testosterone is normal 2, 5
• Do not ignore other ED causes—even if you have low free testosterone, ED is often multifactorial and requires comprehensive evaluation 1
• Do not use testosterone therapy if you desire fertility preservation—it causes azoospermia and requires alternative treatment with gonadotropins 2

Bottom Line

Your total testosterone is normal-to-high, but your markedly elevated SHBG may be sequestering most of it in an inactive bound form, potentially causing functional hypogonadism that contributes to ED 3, 4, 8. Measure your free testosterone by equilibrium dialysis or calculated method to determine if this is truly contributing to your erectile dysfunction 2, 5. If free testosterone is low, address reversible causes of elevated SHBG first, then consider PDE5 inhibitors with or without testosterone replacement 3, 7. If free testosterone is normal, your ED is likely due to other causes requiring standard ED evaluation and treatment 1.