Treatment of Secondary Hypogonadism

Diagnostic Confirmation

The European Association of Urology recommends confirming the diagnosis of secondary hypogonadism with two separate morning total testosterone measurements showing levels <300 ng/dL 1, 2
Measure LH and FSH to confirm secondary hypogonadism, characterized by low or inappropriately normal gonadotropins with low testosterone 3
Free testosterone by equilibrium dialysis should be measured in obese patients, as they may have low total testosterone due to reduced sex hormone-binding globulin but normal free testosterone 3
Rule out reversible causes, such as medications affecting the hypothalamic-pituitary axis, acute illness, obesity, and metabolic disorders 1

The European Urology guidelines recommend testosterone replacement therapy as the treatment of choice for men with secondary hypogonadism who are not seeking fertility 1, 2
First-line formulation is transdermal testosterone gel 1.62% at 40.5 mg daily, applied to shoulders and upper arms 1, 4
Alternative formulations include intramuscular testosterone cypionate or enanthate 50-400 mg every 2-4 weeks, for patients preferring less frequent dosing or when cost is a concern 4
For men seeking fertility preservation, gonadotropin therapy is mandatory, and testosterone is absolutely contraindicated 1, 2
Start with hCG 500-2500 IU subcutaneously or intramuscularly 2-3 times weekly to stimulate testosterone production, and add FSH if needed to optimize spermatogenesis 1, 2

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

Initial monitoring should include testosterone levels, hematocrit, and PSA in men over 40 years, 2-3 months after starting treatment 1, 4
Ongoing monitoring should include the same parameters as initial monitoring, every 6-12 months once stable 4
Assess for lower urinary tract symptoms and prostate examination 1

Testosterone replacement therapy can improve libido and erectile function, particularly in mild ED 1, 2
Combining testosterone with PDE5 inhibitors can improve erectile function in more severe ED 1, 4
Testosterone replacement therapy can also improve quality of life, vitality, and mood, although the evidence is limited 2, 4
Metabolic improvements, such as fasting glucose, insulin resistance, triglycerides, and HDL cholesterol, can also be expected 3, 4

Testosterone should never be prescribed to men actively seeking fertility, as it can cause azoospermia that may take months to years to reverse 1, 2, 4
Testosterone is also contraindicated in men with active or treated male breast cancer, and in eugonadal men (normal testosterone levels), even if symptomatic 1, 4