What is the treatment for secondary hypogonadism?

Treatment of Secondary Hypogonadism

For men with secondary hypogonadism not seeking fertility, transdermal testosterone gel 1.62% at 40.5 mg daily applied to shoulders and upper arms is the first-line treatment. 1

Initial Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with specific biochemical criteria:

• Obtain two separate morning total testosterone measurements showing levels <300 ng/dL 1
• Measure LH and FSH to confirm secondary hypogonadism (characterized by low or inappropriately normal gonadotropins with low testosterone) 1, 2
• In obese patients, measure free testosterone by equilibrium dialysis, as they may have low total testosterone due to reduced sex hormone-binding globulin but normal free testosterone 1
• Rule out reversible causes including medications affecting the hypothalamic-pituitary axis, acute illness, obesity, and metabolic disorders 1

Treatment Algorithm Based on Fertility Goals

For Men NOT Seeking Fertility

Testosterone replacement therapy is the treatment of choice: 1, 3

• First-line: Transdermal testosterone gel 1.62% at 40.5 mg daily to shoulders and upper arms 1
• Alternative: Intramuscular testosterone cypionate or enanthate 50-400 mg every 2-4 weeks for patients preferring less frequent dosing or when cost is a concern 1, 3
• Testosterone enanthate is FDA-approved for hypogonadotropic hypogonadism (congenital or acquired) due to gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury 3

For Men Seeking Fertility Preservation

Gonadotropin therapy is mandatory, and testosterone is absolutely contraindicated: 4, 1

• First-line: hCG 500-2500 IU subcutaneously or intramuscularly 2-3 times weekly to stimulate testosterone production 1, 5, 6
• hCG is FDA-approved for selected cases of hypogonadotropic hypogonadism in males 5
• Add FSH if needed after testosterone levels normalize on hCG to optimize spermatogenesis 1, 6
• The combination of FSH and hCG for 12-24 months promotes testicular growth in almost all patients, spermatogenesis in approximately 80%, and pregnancy rates around 50% 6
• Aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), or combinations may also be used for infertile men with low serum testosterone 4

Critical pitfall: Exogenous testosterone suppresses spermatogenesis and can cause azoospermia that may take months to years to reverse after cessation 4, 1

Lifestyle Modifications

Weight loss and exercise should be implemented alongside pharmacologic treatment:

• Weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism by improving testosterone levels and normalizing gonadotropins 1
• Combining lifestyle changes with testosterone therapy yields better outcomes than lifestyle alone in symptomatic patients 1
• Physical activity shows similar benefits, with results correlating to exercise duration and weight loss 1

Monitoring Requirements

Initial Monitoring (2-3 months after starting treatment):

• Testosterone levels 1
• Hematocrit 1
• PSA in men over 40 years 1

Ongoing Monitoring (every 6-12 months once stable):

• Same parameters as initial monitoring 1
• Assess for lower urinary tract symptoms and perform prostate examination 1

Expected Benefits

Testosterone replacement therapy provides multiple benefits:

• Sexual function: Improves libido and erectile function, particularly in mild ED 1
• Combining testosterone with PDE5 inhibitors can improve erectile function in more severe ED 1
• Quality of life: Improves vitality and mood, although evidence is limited 1
• Metabolic improvements: Fasting glucose, insulin resistance, triglycerides, and HDL cholesterol 1
• Other benefits: Improved muscle mass, strength, bone density, and well-being 4

Absolute Contraindications

Never prescribe testosterone to:

• Men actively seeking fertility (can cause azoospermia requiring months to years to reverse) 4, 1
• Men with active or treated male breast cancer 1
• Eugonadal men (normal testosterone levels), even if symptomatic 1

Special Considerations

For men with diabetes and symptomatic hypogonadism (decreased sexual desire, erectile dysfunction), screening with morning serum testosterone is recommended 4. In men with total testosterone levels close to the lower limit, further testing with LH and FSH levels may be needed to distinguish between primary and secondary hypogonadism 4.