Hypogonadism in men: Updates and treatments.

Hypogonadism affects a significant proportion of men, with prevalence increasing with age and comorbidities.

• Hypogonadism affects approximately 2% to 6% of men overall, but prevalence increases with age.
• Prevalence rises to 20% in men ages 60 to 69 years and up to 50% in men ages 80 years and older.
• Men with obesity, diabetes, and other comorbidities are at higher risk for hypogonadism.
• The condition is considered underdiagnosed and undertreated in clinical practice.

Hypogonadism presents with nonspecific symptoms that span multiple organ systems.

• Primary symptoms include sexual dysfunction, fatigue, and decreased strength or muscle mass.
• Additional symptoms may include decreased libido, erectile dysfunction, depressed mood, and reduced bone density.
• The nonspecific nature of symptoms contributes to underdiagnosis.
• Symptoms overlap with those of other common conditions, complicating diagnosis.

Diagnosis of hypogonadism requires measurement of serum testosterone levels in symptomatic men.

• Total testosterone levels below 300 ng/dL are generally used as a diagnostic threshold.
• Testing should be performed in the morning due to diurnal variation in testosterone levels.
• At least two separate low testosterone measurements are recommended to confirm diagnosis.
• Free testosterone measurement may be useful when total testosterone is borderline or when sex hormone-binding globulin abnormalities are suspected.

Multiple formulations of testosterone replacement therapy are available, each with distinct administration routes and clinical profiles.

• Available formulations include intramuscular injections, transdermal gels and patches, subcutaneous pellets, and buccal and nasal preparations.
• Intramuscular testosterone cypionate or enanthate is typically administered every 1 to 2 weeks.
• Transdermal formulations provide more stable testosterone levels compared to intramuscular injections.
• Subcutaneous pellets are implanted every 3 to 6 months and offer a long-acting option.
• Choice of formulation depends on patient preference, cost, adherence, and clinical considerations.

Testosterone therapy carries significant risks that require close monitoring.

• Known risks include erythrocytosis, worsening of sleep apnea, acne, and potential cardiovascular effects.
• Testosterone therapy suppresses endogenous testosterone production and spermatogenesis, causing infertility.
• Hematocrit should be monitored, and therapy should be withheld if hematocrit exceeds 54%.
• Testosterone therapy is contraindicated in men with prostate cancer, breast cancer, or those desiring fertility.
• Patients require regular follow-up including monitoring of testosterone levels, hematocrit, and prostate-specific antigen (PSA).

Testosterone replacement therapy is associated with improvements in symptoms and quality of life in hypogonadal men.

• Treatment improvements include increased libido, improved sexual function, enhanced mood, increased muscle mass, and decreased fat mass.
• Bone mineral density may improve with testosterone therapy in hypogonadal men.
• Benefits are more clearly demonstrated in men with unequivocally low testosterone levels.
• Patients treated for hypogonadism may experience improvement of symptoms and quality of life.

Alternative therapies exist for men with hypogonadism who wish to preserve fertility.

• Clomiphene citrate, a selective estrogen receptor modulator, can stimulate endogenous testosterone production while preserving spermatogenesis.
• Human chorionic gonadotropin (hCG) can also be used to stimulate testosterone production and maintain fertility.
• These alternatives are particularly relevant for younger men with secondary hypogonadism who wish to father children.
• Clomiphene is used off-label for this indication.