Why am I experiencing loss of libido and erectile dysfunction despite elevated total testosterone and high sex hormone‑binding globulin (SHBG) (≈99 nmol/L, total testosterone ≈43 nmol/L) – could low free testosterone or a genetic factor be responsible?

Understanding Your Sudden Loss of Libido and Erectile Dysfunction Despite High Total Testosterone

Your symptoms are almost certainly caused by low free (bioavailable) testosterone due to your markedly elevated SHBG (99 nmol/L), not by your total testosterone level. Although your total testosterone appears high at 43 nmol/L (≈1,240 ng/dL), the extremely elevated SHBG is binding most of it, leaving insufficient free testosterone to drive libido and erectile function. 1, 2

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Why This Happens: The Free Hormone Hypothesis

• Only free (unbound) testosterone is biologically active and can enter tissues—including brain centers that regulate sexual desire and the penile tissues required for erections. 1, 2

• SHBG acts as a gatekeeper: it binds testosterone tightly, rendering it biologically inactive. Your SHBG of 99 nmol/L (reference range 7–50 nmol/L) means the vast majority of your circulating testosterone is locked up and unavailable. 1, 2

• The free testosterone index (total testosterone ÷ SHBG × 100) predicts hypogonadal symptoms better than total testosterone alone. A ratio < 30 (or total testosterone/SHBG < 0.3) reliably identifies functional hypogonadism—meaning you have androgen deficiency symptoms despite seemingly normal or high total testosterone. 1

• In men presenting with erectile dysfunction, 17.2% have normal total testosterone but low calculated free testosterone, and this pattern is frequently missed by screening protocols that measure only total testosterone. 3

• Among men over 60 years, the prevalence of normal total testosterone with low free testosterone rises to 26.3%, because SHBG increases steeply with aging. 3

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Why Symptoms Appeared Suddenly This Year

• Aging is the primary driver: SHBG rises progressively with age, and the prevalence of elevated SHBG increases sharply after age 60. 1, 3

• Your total testosterone production may have declined slightly year-over-year (a normal age-related change), but because your SHBG simultaneously increased, the drop in free testosterone became severe enough to cross the symptomatic threshold. 1, 3

• Functional hypogonadism from elevated SHBG causes symptomatic androgen deficiency even when total testosterone appears normal or high, leading to low libido and erectile dysfunction. 1

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Confirming the Diagnosis

You need to measure calculated free testosterone to confirm functional hypogonadism. 1, 3, 2

• Gold standard: free testosterone by equilibrium dialysis coupled with LC-MS/MS, though this is rarely available in routine clinical practice. 2

• Practical alternative: calculated free testosterone using the Vermeulen formula (requires total testosterone, SHBG, and albumin). This is the currently preferred method and avoids the inaccuracy of direct immunoassay measurements. 1, 2

• Diagnostic threshold: calculated free testosterone < 6.5 ng/dL (≈225 pmol/L) or a free androgen index < 30 confirms functional hypogonadism. 1, 3

• Repeat testing on a second morning (8–10 AM) is mandatory to confirm the pattern, as single measurements can be misleading. 1

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Investigating Reversible Causes of Elevated SHBG

Before considering testosterone replacement, address any reversible causes of elevated SHBG: 1

• Hyperthyroidism: excess thyroid hormone stimulates hepatic SHBG synthesis. Check TSH and free T4; treatment of hyperthyroidism normalizes SHBG. 1

• Chronic liver disease or cirrhosis: hepatic dysfunction raises SHBG production. Obtain liver function tests (ALT, AST, bilirubin, albumin). 1

• Medications that raise SHBG: anticonvulsants (phenytoin, carbamazepine), oral estrogens, and supratherapeutic thyroid hormone. Review your medication list and discontinue offending agents when feasible. 1

• HIV infection: suboptimal antiretroviral therapy or HIV-associated wasting can elevate SHBG. If applicable, optimize ART. 1

• Physiological aging: aging modestly raises SHBG, but treatment is warranted only when free testosterone is demonstrably low. 1

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Treatment Options If Free Testosterone Is Confirmed Low

First-Line: Optimize Reversible Factors

• Treat hyperthyroidism, discontinue SHBG-elevating medications, and optimize metabolic health (weight loss if obese, regular exercise, management of diabetes or metabolic syndrome). 1

Second-Line: Testosterone Replacement Therapy

If free testosterone remains low after addressing reversible causes, testosterone replacement therapy is indicated. 1

• Expected benefit: small-to-moderate but statistically significant improvement in sexual function and libido (standardized mean difference ≈ 0.35), representing a clinically meaningful benefit. Evidence strength: moderate-quality randomized data. 1

• Limited benefit: little to no impact on physical functioning, energy, vitality, depressive symptoms, or cognitive performance. 1

• Preferred formulation: transdermal testosterone gel (e.g., 1.62% gel, 40.5 mg daily) provides stable day-to-day levels and lower risk of erythrocytosis compared with injectable preparations. 4, 1

• Alternative formulation: intramuscular testosterone cypionate or enanthate (100–200 mg every 2 weeks) is more economical but carries higher risk of erythrocytosis. 4

• Monitoring: measure testosterone levels (targeting mid-normal 500–600 ng/dL), free testosterone, and SHBG at 2–3 months, then every 6–12 months once stable. Monitor hematocrit at each visit; withhold treatment if > 54%. 4, 1

Adjunctive Therapy for Erectile Dysfunction

• PDE5 inhibitors (sildenafil, tadalafil, vardenafil) remain first-line for erectile dysfunction regardless of testosterone status. 1

• A minimal level of testosterone is required for complete effect of PDE5 inhibitor therapy, explaining why some men fail sildenafil or other ED medications when testosterone is low. 5

• Combining PDE5 inhibitors with testosterone therapy improves outcomes in men with low testosterone. 4

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Why Genetic Factors Are Unlikely

• Genetic polymorphisms in the SHBG gene do influence baseline SHBG levels, but they do not explain a sudden change in symptoms over one year. 2

• Aging, hyperthyroidism, liver disease, and medications are far more common and clinically relevant causes of elevated SHBG than genetic variants. 1, 3

• If you have no identifiable reversible cause (normal thyroid, normal liver function, no offending medications), then age-related SHBG elevation is the most likely explanation. 1, 3

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Critical Pitfalls to Avoid

• Do not rely on total testosterone alone to exclude hypogonadism when SHBG is elevated; approximately half of diagnoses are missed without measuring free testosterone. 3, 2

• Do not assume you are "fine" because total testosterone is high; functional hypogonadism from elevated SHBG causes real symptoms despite normal or elevated total testosterone. 1, 3

• Do not start testosterone replacement without first confirming low free testosterone on repeat testing and investigating reversible causes of elevated SHBG. 1

• Do not expect testosterone therapy to improve energy, physical function, or mood; the primary benefit is sexual function and libido. 1

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Recommended Diagnostic Algorithm

1. Obtain calculated free testosterone using the Vermeulen formula (requires total testosterone, SHBG, albumin) on a morning blood draw (8–10 AM). 1, 2

2. Repeat the test on a second morning to confirm the pattern. 1

3. Check TSH, free T4, liver function tests (ALT, AST, bilirubin, albumin), and review medications to identify reversible causes of elevated SHBG. 1

4. If free testosterone is < 6.5 ng/dL (or free androgen index < 30) on both occasions and reversible causes are addressed or absent, initiate testosterone replacement therapy. 1, 3

5. Monitor free testosterone, SHBG, hematocrit, and symptom response at 2–3 months, then every 6–12 months. 4, 1