What is the initial treatment for hypoandrogenism?

Initial Treatment for Hypoandrogenism

The initial treatment for hypoandrogenism should be testosterone replacement therapy (TRT) in most cases, with the exception of men who desire fertility preservation, for whom selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or human chorionic gonadotropin (hCG) should be used instead. 1

Diagnosis Confirmation

Before initiating treatment, hypoandrogenism should be confirmed by:

• Morning serum testosterone levels (before 10 AM) on two separate occasions
• Target diagnostic threshold: total testosterone <300-350 ng/dL
• Assessment of free testosterone in obese patients
• Evaluation of secondary causes (pituitary/hypothalamic disorders)

Treatment Options Based on Patient Goals

For Patients Without Fertility Concerns:

1. Testosterone Replacement Therapy (TRT):

   • Provides small but significant improvements in sexual functioning and overall quality of life 1
   • Increases lean body mass, reduces abdominal fat, improves insulin sensitivity 1
   • Available formulations:
     • Topical gels (1.62% testosterone)
     • Intramuscular injections
     • Transdermal patches
     • Target testosterone levels: 450-600 ng/dL (middle tertile of normal range) 1

2. Monitoring During TRT:

   • Testosterone levels: 4-6 weeks after initiation, then every 3-6 months
   • Hematocrit/hemoglobin: Monitor for polycythemia
   • PSA: Monitor for prostate-related events
   • Cardiovascular risk factors

3. Contraindications for TRT 1:

   • Prostate cancer
   • Male breast cancer
   • Desire for fertility in near future
   • Severe obstructive sleep apnea
   • Uncontrolled congestive heart failure
   • Hematocrit >54%

For Patients With Fertility Concerns:

1. First-line: Selective Estrogen Receptor Modulators (SERMs) 1:

   • Clomiphene citrate: Starting dose 25 mg every other day
   • Target testosterone levels: 450-600 ng/dL
   • Preserves and may improve sperm parameters

2. Alternative Options:

   • Aromatase inhibitors (anastrozole, letrozole): Particularly useful in men with elevated estradiol levels 1
   • Human Chorionic Gonadotropin (hCG): Particularly effective for hypogonadotropic hypogonadism 1, 2
     • Dosing: 500-1,000 USP Units three times weekly for three weeks, then twice weekly for three weeks

Special Considerations

For Female Hypoandrogenism:

• Less well-studied than male hypoandrogenism
• Common symptoms include reduced sexual desire, arousal, vaginal vasocongestion, reduced pubic hair, bone mass, muscle mass 3
• Treatment options are limited as FDA has not approved androgen supplementation for women 3
• For premenopausal women with hypogonadism, estrogen replacement with progesterone should be offered 4

For Hypoandrogenism Related to Chronic Liver Disease:

• Treat hypogonadism with hormone replacement therapy 4
• For men: transdermal testosterone (after discussion of theoretical risks of hepatocellular carcinoma) 4
• For women: transdermal HRT (estrogen only if no uterus, otherwise combined/sequential or combined/continuous HRT) 4

Risks and Side Effects of Treatment

Testosterone Therapy:

• Suppression of spermatogenesis (critical consideration for men of reproductive age) 1, 5
• Polycythemia (increased hematocrit) 6
• Peripheral edema 5
• Emotional lability 5
• Potential cardiovascular effects 5
• Sleep apnea exacerbation 5
• Gynecomastia 5

SERMs and Other Fertility-Preserving Options:

• Generally fewer side effects than TRT
• May not address all symptoms of hypogonadism as effectively as TRT

Common Pitfalls to Avoid

1. Diagnosing hypogonadism based on a single testosterone measurement
2. Failing to measure free testosterone in obese patients
3. Overlooking secondary causes of hypogonadism
4. Initiating TRT in men desiring fertility without discussing fertility implications
5. Not monitoring for adverse effects, particularly hematocrit elevation
6. Using testosterone for "age-related hypogonadism" without structural or genetic etiology

Treatment Algorithm

1. Confirm diagnosis with two morning testosterone measurements
2. Assess fertility desires:
   • If fertility desired: Use SERMs, AIs, or hCG
   • If fertility not a concern: Consider TRT
3. Rule out contraindications to chosen therapy
4. Initiate treatment with appropriate dosing
5. Monitor response at 4-6 weeks and adjust dosing as needed
6. Continue monitoring every 3-6 months for efficacy and side effects

By following this treatment approach, patients with hypoandrogenism can experience significant improvements in symptoms while minimizing risks associated with therapy.