What are the likely causes and recommended evaluation for a male adult with yellow semen, reduced ejaculate volume, sudden erectile dysfunction, a high‑normal total testosterone level and elevated sex‑hormone‑binding globulin?

Evaluation and Management of Yellow Semen, Reduced Volume, and Sudden Erectile Dysfunction with Elevated SHBG

Understanding Your Hormone Profile

Your total testosterone of 40 nmol/L (approximately 1154 ng/dL) appears elevated, but your extremely high SHBG of 95 nmol/L is binding most of this testosterone, likely leaving you with low bioavailable testosterone despite the high total level—this explains your sudden erectile dysfunction. 1

Your presentation requires urgent evaluation because:

• Yellow semen with reduced volume suggests possible infection, inflammation of the seminal vesicles or prostate, or ejaculatory duct pathology 2
• Sudden-onset ED in the context of high SHBG indicates that free testosterone is likely severely reduced despite normal-to-high total testosterone 1, 3
• High SHBG (>50 nmol/L) can cause symptomatic hypogonadism with normal total testosterone, occurring in 17.2% of ED patients 1

Immediate Diagnostic Workup Required

Essential Laboratory Tests

Calculate your free testosterone immediately—this is critical because total testosterone alone is misleading with SHBG this elevated 1, 3:

• Free testosterone <6.5 ng/dL (or <225 pmol/L) confirms biochemical hypogonadism despite your elevated total testosterone 1
• Measure LH to distinguish primary testicular dysfunction from secondary hypogonadism 2
• Check thyroid function (TSH, free T4) as hyperthyroidism directly increases SHBG production and can cause both ED and elevated SHBG 1
• Obtain fasting glucose/HbA1c and lipid panel, as ED is a cardiovascular risk marker 2

Semen Analysis and Infection Workup

Visual analysis of ejaculate for red or yellow discoloration, microbiological testing, semen analysis, urinalysis, and urine culture are essential first steps 2:

• Yellow semen may indicate infection (prostatitis, seminal vesiculitis), pyospermia, or prolonged abstinence 2
• Reduced ejaculate volume (<1.5 mL) suggests ejaculatory duct obstruction, seminal vesicle pathology, or retrograde ejaculation 2
• Post-ejaculatory urinalysis is indicated if volume is very low to diagnose retrograde ejaculation 2

Imaging Studies

Transrectal ultrasound (TRUS) should be performed as first-line imaging 2:

• TRUS detects abnormalities in 82-95% of men with hemato/pyospermia and seminal tract pathology 2
• Evaluates for seminal vesicle cysts, ejaculatory duct obstruction, prostatic calcifications, or prostatitis 2
• Can guide transperineal aspiration if seminal vesicle pathology is identified 2

Understanding the SHBG-Testosterone-ED Connection

In men over 60 years, elevated SHBG prevalence increases steeply, with 52.5% having elevated SHBG and 26.3% having normal total testosterone but low free testosterone 1:

• Ageing is the primary driver of elevated SHBG in most cases (74.2% of normal TT/low FT patients) 1
• Only 12.9% of patients with normal TT/low FT have identifiable causes like hyperthyroidism, liver disease, or HIV 1
• Patients with normal TT/low FT are significantly older (mean 65.6 vs 56.8 years) and have higher SHBG (78.5 vs 52.4 nmol/L) 1

Critical Management Principles

What NOT to Do

Never start exogenous testosterone therapy if you desire fertility—it will completely suppress spermatogenesis through negative feedback, causing azoospermia that can take months to years to recover 2:

• Testosterone replacement is contraindicated until fertility goals are addressed
• Even with low free testosterone, exogenous testosterone will worsen fertility

Treatment Algorithm Based on Free Testosterone Results

If free testosterone is low (<6.5 ng/dL):

1. Treat underlying causes first 1:

   • Correct hyperthyroidism if present (normalizes SHBG and improves sexual function)
   • Optimize metabolic health and achieve healthy body weight
   • Address any liver disease

2. For erectile dysfunction management 2:

   • PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are first-line therapy even with low free testosterone 2
   • Provide proper dosing instructions: take on empty stomach, allow adequate time for absorption (30-60 minutes for most agents)
   • Titrate dose to maximize efficacy 2
   • Testosterone treatment may improve response to PDE5 inhibitors in men with low-normal or low testosterone 3

3. Consider testosterone therapy only after addressing fertility concerns 3:

   • Testosterone is more likely to improve erectile function with severe hypogonadism
   • Most effective when free testosterone is well below normal range
   • May be combined with PDE5 inhibitors for synergistic effect

Addressing the Semen Abnormalities

If infection/inflammation is identified:

• Appropriate antibiotic therapy based on culture results
• Anti-inflammatory treatment if indicated
• Repeat semen analysis after treatment completion 2

If ejaculatory duct obstruction is confirmed:

• Transurethral resection of ejaculatory ducts may be considered
• TRUS-guided aspiration for diagnostic and potentially therapeutic purposes 2

Important Caveats

Current screening guidelines for hypogonadism in ED are inadequate 1:

• Total testosterone alone misses 17.2% of men with biochemical hypogonadism 1
• This percentage increases to 26.3% in men over 60 years 1
• Free or bioavailable testosterone measurement is essential in conditions that alter SHBG levels, particularly in elderly men 3

ED is a cardiovascular risk marker 2:

• ED predicts future cardiac events as strongly as smoking or family history of MI 2
• Communicate this risk to your primary care provider for appropriate cardiovascular evaluation 2

Psychological factors may be contributing 2:

• Sudden-onset ED suggests possible psychogenic component 2
• Consider referral to mental health professional to reduce performance anxiety and integrate treatments 2
• Presence of morning/nocturnal erections suggests (but doesn't confirm) psychogenic contribution 2

Next Steps Summary

1. Calculate free testosterone immediately using total testosterone, SHBG, and albumin 1, 3
2. Obtain thyroid function tests, LH, and metabolic screening 1
3. Perform semen analysis with microbiological testing and urinalysis 2
4. Schedule TRUS to evaluate seminal tract pathology 2
5. Start PDE5 inhibitor therapy for ED while awaiting complete workup 2
6. Address any identified infections or reversible causes of elevated SHBG 2, 1
7. Consider testosterone therapy only after fertility assessment and if free testosterone is confirmed low 3