Initial Androgen Testing and Treatment
Begin with a morning fasting total testosterone measurement using liquid chromatography tandem mass spectrometry (LC-MS/MS) in a certified laboratory, and only proceed with treatment if you confirm unequivocally low levels on repeat testing along with consistent clinical symptoms. 1, 2, 3
Diagnostic Algorithm
Step 1: Initial Clinical Assessment
History must specifically evaluate:
- Sexual dysfunction (decreased libido, erectile dysfunction) 4
- Physical changes (decreased muscle mass, increased body fat, gynecomastia) 4
- Mood and cognitive symptoms (fatigue, depression, decreased concentration) 2, 3
- Body habitus and secondary sex characteristics including hair distribution and breast development 4
Physical examination must include:
- Measurement and palpation of testes (normal adult testicular length is 4-5 cm) 4
- Presence and consistency of vasa deferentia and epididymides 4
- Assessment of body hair distribution and gynecomastia 4
- Digital rectal examination for prostate assessment 4
Step 2: Laboratory Testing Sequence
Initial test:
- Morning (before 10 AM) fasting total testosterone using LC-MS/MS in a laboratory certified by an accuracy-based benchmark 1, 3
Confirmation testing (mandatory before diagnosis):
- Repeat morning fasting total testosterone on a separate day 2, 5, 3
- If total testosterone is near the lower limit of normal (typically 264-300 ng/dL), measure free testosterone using equilibrium dialysis or calculate using an accurate formula 1, 3
Additional endocrine evaluation when indicated:
- Serum follicle-stimulating hormone (FSH) if sperm concentration <10 million/mL or other clinical findings suggest endocrinopathy 4
- Prolactin and thyroid function if hypogonadotropic hypogonadism suspected 4
Step 3: Determine Etiology
Primary hypogonadism indicators:
Secondary (hypogonadotropic) hypogonadism indicators:
- Low testosterone with low or inappropriately normal FSH 4
- History of pituitary/hypothalamic disease, trauma, or radiation 6
Treatment Initiation
Absolute Contraindications to Testosterone Therapy
Do not start testosterone if any of the following are present:
- Breast or prostate cancer 2, 5, 3
- Palpable prostate nodule or induration 2, 5, 3
- PSA >4 ng/mL (or >3 ng/mL in high-risk men including African Americans or those with first-degree relatives with prostate cancer) without urological evaluation 5, 3
- Hematocrit >50% 2, 5, 3
- Untreated severe obstructive sleep apnea 2, 5, 3
- Uncontrolled heart failure (Class III-IV) 2, 3
- Myocardial infarction or stroke within the last 6 months 3
- Planning fertility in the near term 4, 3
Treatment Selection for Confirmed Hypogonadism
For men NOT pursuing fertility:
- Testosterone enanthate 200 mg intramuscularly every 2 weeks OR 300 mg every 3 weeks 6, 7
- Target mid-normal testosterone range (400-700 ng/dL) during treatment 2, 5, 3
For men with hypogonadotropic hypogonadism pursuing fertility:
- Human chorionic gonadotropin (hCG) 500-2500 IU subcutaneously 2-3 times weekly as first-line therapy 4
- Add FSH injections after testosterone normalizes on hCG if needed 4
- Never use exogenous testosterone in men desiring fertility as it suppresses spermatogenesis and may cause prolonged azoospermia lasting months to years after discontinuation 4
Monitoring Protocol
During first year of testosterone therapy:
- Symptoms and adverse effects at 3-6 months 2, 5, 3
- Serum testosterone and hematocrit at 3-6 months, then annually 2, 5, 3
- Digital rectal examination and PSA at 3-6 months, then annually 4, 3
Ongoing monitoring:
- Bone density assessment in men with osteoporosis risk factors 2
- Lipid profile monitoring given potential effects on cholesterol 6
Critical Pitfalls to Avoid
Do not diagnose androgen deficiency based on:
- Single testosterone measurement 2, 5, 3
- Non-fasting or afternoon testosterone levels 1, 3
- Symptoms alone without biochemical confirmation 2, 3
- Age-related decline in otherwise asymptomatic men ("andropause") 6
Do not use testosterone therapy in: