What is the likelihood of a sexually transmitted disease (STD) in a male patient with sudden onset of low libido, erectile dysfunction (ED), semen changes, and possible testicular atrophy, with laboratory results showing low testosterone levels, elevated Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), and abnormal Sex Hormone-Binding Globulin (SHBG)?

STD is Extremely Unlikely – This Presentation Indicates Primary Hypogonadism with Elevated SHBG

The clinical picture strongly suggests primary testicular dysfunction (hypergonadotropic hypogonadism) rather than a sexually transmitted infection. The laboratory values—elevated LH (7.5 IU/L) and FSH (9.5 IU/L) with low total testosterone (45 nmol/L ≈ 1300 ng/dL appears high, but with SHBG of 95 nmol/L, the bioavailable testosterone is severely reduced)—indicate testicular failure, not an infectious process 1.

Why STD is Not the Diagnosis

• STDs do not cause the hormonal pattern observed here. Sexually transmitted infections do not elevate gonadotropins (LH/FSH) or SHBG in this manner 1.
• The constellation of symptoms—low libido, ED, semen changes, and testicular atrophy—with elevated gonadotropins indicates primary testicular failure, not infection 1.
• STD screening should still be performed as routine practice (gonorrhea, chlamydia, syphilis, HIV), but these would not explain the endocrine abnormalities 1.

Understanding the Actual Problem: High SHBG Masking Severe Hypogonadism

• The markedly elevated SHBG (95 nmol/L, normal 7-50 nmol/L) is binding most of the testosterone, rendering it biologically unavailable 1.
• Free testosterone measurement by equilibrium dialysis is essential to determine true androgen status, as total testosterone can be misleadingly normal or high when SHBG is elevated 1.
• The elevated LH and FSH with low bioavailable testosterone confirms primary testicular failure (hypergonadotropic hypogonadism) 1.

Causes of Elevated SHBG to Investigate

Common causes that must be ruled out include 1:

• Hyperthyroidism – check TSH and free T4
• Hepatic disease – check liver function tests, consider viral hepatitis screening, assess for cirrhosis 1
• HIV infection – perform HIV testing 1
• Medications – anticonvulsants, estrogens, thyroid hormone 1
• Aging and smoking – contributory factors 1

Diagnostic Algorithm

Step 1: Confirm hypogonadism with free testosterone

• Obtain morning (8-10 AM) free testosterone by equilibrium dialysis on two separate occasions 1
• Calculate free androgen index (total testosterone ÷ SHBG) as alternative 1

Step 2: Identify cause of elevated SHBG

• TSH, free T4 (hyperthyroidism) 1
• Comprehensive metabolic panel, liver function tests 1
• HIV testing 1
• Medication review 1

Step 3: Determine etiology of primary hypogonadism

• Karyotype testing is mandatory given testicular atrophy and elevated FSH—screen for Klinefelter syndrome (47,XXY) and other chromosomal abnormalities 1
• Consider hemochromatosis screening (iron saturation, ferritin) as this causes both testicular failure and can elevate SHBG through liver involvement 2
• Testicular ultrasound to assess for structural abnormalities 3

Step 4: Rule out secondary causes if indicated

• If prolactin elevation suspected (decreased libido), check serum prolactin 1
• MRI sella turcica only if secondary hypogonadism features emerge 1

Critical Pitfalls to Avoid

• Do not assume normal total testosterone means adequate androgen status when SHBG is elevated – the free fraction determines biological activity 1.
• Do not start testosterone replacement before genetic testing – karyotype and Y-chromosome microdeletion analysis must be completed first if fertility is a consideration 1.
• Do not overlook treatable causes of elevated SHBG – correcting hyperthyroidism or hepatic disease may partially restore androgen bioavailability 1.
• Testosterone replacement will further suppress already-elevated gonadotropins and worsen testicular atrophy – address underlying causes first 1.

Management Based on Etiology

If hyperthyroidism or hepatic disease is identified:

• Treat the underlying condition first, as SHBG may normalize and improve testosterone bioavailability 1
• Reassess hormonal status after 3 months of treatment 1

If primary hypogonadism is confirmed with no reversible cause:

• Testosterone replacement therapy is indicated once free testosterone is confirmed low on repeat testing 1
• Choose transdermal preparations (gel/patch) for stable levels, or intramuscular injections for convenience 1
• Avoid testosterone if fertility is desired – refer to reproductive endocrinology for alternative strategies 1, 3

If Klinefelter syndrome or other genetic abnormality is diagnosed:

• Genetic counseling is essential 1
• Testicular sperm extraction may be possible in 20-50% of Klinefelter cases if fertility desired 1