Treatment of Male Hypoandrogenism
Testosterone replacement therapy (TRT) is the first-line treatment for confirmed male hypogonadism, with the specific formulation selected based on patient preference, cost, and pharmacokinetic considerations. 1
Diagnostic Confirmation
Before initiating treatment, proper diagnosis is essential:
- Confirm hypogonadism with morning total testosterone measurements (between 8-10 AM) on at least two separate days 2
- Determine if primary (testicular) or secondary (hypothalamic-pituitary) hypogonadism by measuring LH and FSH levels 2
- For secondary hypogonadism, consider additional testing including serum prolactin, iron saturation, pituitary function tests, and MRI of the sella turcica 2
Treatment Options
1. Lifestyle Modifications (First Step)
- For functional hypogonadism associated with obesity and metabolic disorders, weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism 1
- Physical activity shows similar benefits, with results correlating to exercise duration and weight loss 1
- While lifestyle changes are essential, combining these with TRT may yield better outcomes in symptomatic patients 1
2. Testosterone Replacement Therapy
Injectable Testosterone
- Starting dose: 100-200 mg every 2 weeks or 50 mg weekly intramuscularly 2
- Peak serum levels occur 2-5 days after injection, returning to baseline 10-14 days after injection 1
- Advantages: low cost and high peak serum levels 1
- Disadvantages: pain of injection, frequent medical visits, and "roller coaster" effect of fluctuating testosterone levels 1
Transdermal Preparations (Gels/Patches)
- First-line option providing stable day-to-day testosterone levels 2
- Skin reactions are more common with patches (up to 66%) compared to gel (5%) 1
- Apply daily to clean, dry skin of shoulders, upper arms, or abdomen
Target Levels and Monitoring
- Target testosterone levels in the mid-normal range (450-600 ng/dL) 2
- Monitor testosterone levels 2-3 months after treatment initiation and after any dose changes, then every 6-12 months once stable 2
- For injectable testosterone, measure levels midway between injections 2
3. Gonadotropin Therapy
- For secondary hypogonadism patients seeking fertility, gonadotropin therapy is standard 1
- Combines human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) 1
- Maintains testosterone levels while preserving fertility 1
Monitoring and Safety
Regular Monitoring Schedule
- Hematocrit: TRT can cause erythrocytosis (dose-dependent: 2.8-17.9%) 2
- Prostate health: PSA and digital rectal examination every 6-12 months 2
- Cardiovascular risk factors: lipid profile and blood pressure 3
- Bone density in men with osteoporosis or fracture risk 2
Contraindications for TRT
- Active or treated male breast cancer 1
- Desire for fertility in the near term 1
- Prostate cancer 4
- Hematocrit >54% 2
- Severe untreated sleep apnea 4
- Uncontrolled heart failure 4
Expected Benefits
- Improved sexual function (libido and mild erectile dysfunction) 1
- Increased lean muscle mass and reduced body fat 2
- Improved sense of well-being and energy levels 2
- Improved bone density and reduced fracture risk 2
- Small but significant improvements in quality of life 2
Special Considerations
- Erectile Dysfunction: TRT is first-line for hypogonadal patients with mild ED; for more severe ED, consider combination with PDE5 inhibitors 1
- Fertility: TRT suppresses spermatogenesis and is contraindicated in men seeking fertility 1
- Cardiovascular Risk: Evidence is inconclusive regarding cardiovascular outcomes with TRT; patients should be informed of possible risks 3
- Prostate Health: Recent evidence suggests TRT does not increase prostate cancer incidence 1
By following this treatment approach and monitoring protocol, most men with hypoandrogenism can achieve symptomatic relief and improved quality of life while minimizing potential adverse effects.