What is the primary treatment for hypogonadism?

Primary Treatment for Hypogonadism

Testosterone replacement therapy is the primary treatment for hypogonadism in men who have confirmed low testosterone levels on two separate morning measurements and are not concerned about fertility. 1, 2

Diagnostic Confirmation Required Before Treatment

• Two separate morning total testosterone measurements below 300 ng/dL must be documented, along with clinical symptoms of hypogonadism, before initiating any treatment. 1, 3

• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to classify hypogonadism as primary (elevated LH/FSH indicating testicular failure) or secondary (low/normal LH/FSH indicating hypothalamic-pituitary dysfunction). 1, 2

• For obese men or those with borderline low total testosterone, measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) levels for more accurate assessment. 1

• Obtain baseline hemoglobin/hematocrit and PSA (in men over 40 years) before starting treatment. 4

First-Line Treatment: Transdermal Testosterone

Transdermal testosterone preparations (gels or patches) are the recommended first-line treatment for men without fertility concerns, targeting testosterone levels between 350-750 ng/dL. 4, 1, 2

• Testosterone gel 1.62% starting dose is 40.5 mg applied once daily in the morning to shoulders and upper arms, with dose adjustments between 20.25-81 mg based on serum levels. 3

• Transdermal preparations provide more stable testosterone levels compared to injectable forms and avoid the fluctuations that can occur with injections. 1

• Critical safety warning: Children must avoid contact with unwashed or unclothed application sites due to risk of virilization from secondary exposure. 3

Alternative Treatment: Injectable Testosterone

• Injectable testosterone (cypionate or enanthate) may be used as an alternative when transdermal preparations are not suitable, though it causes more fluctuating testosterone levels and injection site discomfort. 1, 5

• Injectable testosterone is indicated for both primary hypogonadism (testicular failure) and hypogonadotropic hypogonadism (gonadotropin or LHRH deficiency). 5

Treatment for Men Desiring Fertility

Exogenous testosterone is absolutely contraindicated in men who desire current or future fertility because it suppresses spermatogenesis and can cause oligospermia or azoospermia. 4, 1, 2

• Human chorionic gonadotropin (hCG) at 500-2500 IU administered 2-3 times weekly is the first-line treatment for men with secondary hypogonadism who wish to preserve fertility. 1, 2

• hCG stimulates endogenous testosterone production while preserving testicular function and spermatogenesis. 4

• Follicle-stimulating hormone (FSH) may be added after testosterone levels normalize on hCG if additional stimulation is needed. 2

• Recovery of sperm production after cessation of testosterone therapy can take months or even years, making prevention of suppression critical. 2

Monitoring Protocol

• Check testosterone levels at 14 days and 28 days after starting treatment or following dose adjustment to guide titration. 3

• Target testosterone range is 350-750 ng/dL, with dose adjustments based on pre-dose morning levels: decrease dose if >750 ng/dL, maintain if 350-750 ng/dL, increase if <350 ng/dL. 3

• Monitor hematocrit regularly to detect erythrocytosis, particularly with injectable testosterone formulations. 1, 2

• Assess PSA and lipid profile periodically during treatment. 1

• Evaluate sexual symptoms and overall response at 3 months initially, then periodically thereafter. 4

Absolute Contraindications

• Active or treated breast cancer is an absolute contraindication to testosterone therapy. 4, 1

• Severe uncontrolled heart failure remains a contraindication, though recent evidence suggests testosterone therapy appears safe for cardiovascular health in men 45-80 years with confirmed hypogonadism. 1

• Current desire for fertility is a contraindication to exogenous testosterone use. 4, 2

Expected Benefits on Morbidity and Quality of Life

• Testosterone replacement therapy improves sexual function and libido, which directly impacts quality of life. 1, 2

• Treatment increases lean body mass, decreases body fat, and improves bone mineral density, reducing fracture risk and osteoporosis-related morbidity. 6, 1

• Benefits include enhanced muscle strength and reduced symptoms of frailty, particularly important for older hypogonadal men. 6

• Improvements in insulin sensitivity occur in hypogonadal men with type 2 diabetes mellitus and metabolic syndrome. 6

Special Considerations

• For obese patients with secondary hypogonadism, weight loss through diet and exercise can improve testosterone levels and should be attempted before pharmacological intervention. 2

• The dogma against treating men with severe lower urinary tract symptoms or untreated obstructive sleep apnea has been challenged by recent level 1 evidence, though caution is still warranted. 6

• Effects on quality of life, well-being, and erectile dysfunction have been inconsistent across studies, so expectations should be managed appropriately. 6