Hypogonadism in the Elderly Male

PATHCHAT Edition No. 34
Please contact your local Ampath pathologist for more information.

Author: Dr. David Haarburger, MBBCh, MMed (Chem Path), FCPath (Chem)

Testosterone Biochemistry

🔹 What is Testosterone?

• Testosterone is the primary male sex hormone produced mainly by Leydig cells in the testes in response to luteinizing hormone (LH).
• Small amounts are secreted by the adrenal glands.
• Plays a critical role in male reproductive development and promotes secondary sexual characteristics, such as:
  • Muscle and bone mass increase.
  • Body hair growth.
  • Prevention of osteoporosis (via conversion to estradiol).

✅ Testosterone Circulation & Bioavailability:

• 44% to 65% is bound to sex hormone-binding globulin (SHBG) (not bioavailable).
• 33% to 50% is bound to albumin (low affinity, bioavailable).
• 2% is unbound (free testosterone, fully bioavailable).

🔹 Diurnal Variation:

• Testosterone levels peak early in the morning and decline throughout the day.
• Peak and trough values can differ by more than 30%.

📌 Testosterone declines with age, leading to potential late-onset hypogonadism (LOH).

Age-Related Changes in Testosterone

✅ Physiological Effects of Ageing on Testosterone:

• Increased fat mass.
• Reduced immune function and bone mineral density.
• Loss of muscle mass and strength.
• Changes in mood, depression, irritability.
• Reduced libido and sexual function.

🔹 Testosterone Decline with Age:

• Serum testosterone peaks at 25–30 years of age.
• Declines gradually at 1% per year from age 30 onward.
• Sex hormone-binding globulin (SHBG) increases with age, reducing bioavailable testosterone.
• Free testosterone decreases by 2%–3% per year.
• Luteinizing hormone (LH) increases at a rate of 1% per year, suggesting both primary (testicular) and secondary (pituitary) hypogonadism.

📌 Despite declining testosterone, most elderly men remain eugonadal and asymptomatic.

Late-Onset Hypogonadism (LOH)

🔹 Definition:

• LOH is a clinical and biochemical syndrome associated with ageing, characterized by:
  1. Symptoms of androgen deficiency.
  2. Low serum testosterone levels.

✅ Prevalence of Biochemical Hypogonadism:

• 20% of men over 60 years old.
• 30% of men over 70 years old.
• 50% of men over 80 years old.

🔹 Important Considerations:

• Not all men with low testosterone levels have clinical hypogonadism.
• There is little correlation between symptoms and testosterone levels.
• Chronic conditions can mimic hypogonadism symptoms.

📌 Diagnosis of LOH requires both symptoms AND biochemical evidence.

Guidelines for Diagnosing & Managing LOH

✅ Endocrine Society 2010 Guidelines Summary:

✔ Diagnosis:

• LOH should only be diagnosed in symptomatic men with confirmed low testosterone.
• Symptoms include:
  • Reduced libido, erectile dysfunction, fatigue.
  • Loss of muscle mass, osteoporosis.
  • Depressed mood, poor concentration.

✔ Testing Protocol:

• Measure morning total testosterone levels as the initial test.
• Confirm diagnosis with a repeat test.
• Free or bioavailable testosterone should be measured if total testosterone is borderline low.
• Measure serum LH and FSH to differentiate primary vs. secondary hypogonadism.

✔ Who Should NOT Be Screened?

• Routine screening for LOH in the general population is not recommended.

✔ Androgen Replacement Therapy (ART):

• Recommended for symptomatic men with confirmed LOH.
• Aims to improve:
  • Sexual function.
  • Sense of well-being.
  • Bone mineral density.
• Prostate health should be assessed before starting ART.
• Contraindications:
  • Prostate or breast cancer.
• Monitor patients at 3–6 months after ART initiation, then annually.

Recommended Testosterone Levels for Diagnosing LOH

🔹 Cut-off values vary by platform:

✔ Roche Platforms:

• Overt hypogonadism:
  • Total testosterone < 8 nmol/L.
  • Free testosterone < 180 pmol/L.
• Hypogonadism unlikely:
  • Total testosterone > 12 nmol/L.
  • Free testosterone > 250 pmol/L.

✔ Beckman Platforms:

• Overt hypogonadism:
  • Total testosterone < 6.1 nmol/L.
  • Free testosterone < 170 pmol/L.
• Hypogonadism unlikely:
  • Total testosterone > 10 nmol/L.
  • Free testosterone > 210 pmol/L.

📌 If total testosterone is borderline, free testosterone measurement can provide additional clarity.

Goals of Androgen Replacement Therapy (ART)

✅ ART aims to:

• Restore testosterone to normal levels.
• Improve quality of life and symptoms of LOH.

🔹 Expected Benefits of ART:

• Moderate improvements in libido, erectile function, and sexual satisfaction.
• Increase in lean muscle mass, reduction in fat mass.
• Modest increase in bone mineral density.
• Possible improvements in obesity and insulin resistance.

📌 The impact of ART on muscle strength, functional capacity, and cardiovascular risk remains uncertain.

Risks & Monitoring of ART

✅ Potential Risks:

• Erythrocytosis (increased red blood cells).
• Gynaecomastia.
• Increased aggression or mood swings.
• Liver abnormalities.
• Uncertain long-term effects on prostate cancer risk.

✅ Follow-Up Protocol:

• Evaluate patients at 3–6 months post-treatment initiation, then annually.
• Monitor for symptom improvement and adverse effects.

Conclusion

✅ LOH is a clinical and biochemical syndrome that affects a subset of elderly men.
✅ Testosterone testing should be reserved for symptomatic men.
✅ ART is beneficial for select cases but should be monitored carefully for adverse effects.
✅ More research is needed to assess the long-term benefits and risks of ART in ageing men.