Causes and Treatments of Hypogonadism (Low Testosterone)
Low testosterone (hypogonadism) is primarily classified as either primary (testicular dysfunction) or secondary (hypothalamic-pituitary-gonadal axis impairment), with various causes ranging from congenital conditions to lifestyle factors that require specific diagnostic evaluation and targeted treatment approaches. 1
Classification of Hypogonadism
Primary Hypogonadism (Testicular Failure)
- Klinefelter's syndrome, orchitis, testicular trauma, orchidectomy 2
- Cryptorchidism, bilateral torsion, vanishing testis syndrome 2
- Rare chromosomal abnormalities (XX male, 47 XYY syndrome, Down syndrome) 1
- Defects of testosterone biosynthesis 1
- Disorders of sex development (gonadal dysgenesis) 1
Secondary Hypogonadism (Hypothalamic-Pituitary Dysfunction)
- Congenital or acquired gonadotropin or LHRH deficiency 2
- Pituitary-hypothalamic injury from tumors, trauma, or radiation 2
- Idiopathic hypogonadotropic hypogonadism and its variants 1
- Combined hormone pituitary deficiency 1
Common Causes of Low Testosterone
Drug-Induced Causes
- Opiates, GnRH agonists/antagonists, glucocorticoids 1
- Estrogens, testosterone or anabolic steroids (via negative feedback) 1
- Progestogens (including cyproterone acetate) 1
- Drugs causing hyperprolactinemia 1
Metabolic and Systemic Conditions
- Obesity and metabolic syndrome 1
- Type 2 diabetes mellitus 3
- Insulin resistance 1
- Chronic systemic diseases and organ failure 1
- HIV infection 1
Endocrine Disorders
- Hyperthyroidism or hypothyroidism (affecting SHBG levels) 1
- Cushing's syndrome (glucocorticoid excess) 1
- Acromegaly 1
Lifestyle Factors
- Obesity (particularly visceral adiposity) 1, 3
- Excessive alcohol consumption 1
- Endurance exercise 1
- Eating disorders 1
Age-Related (Late-Onset Hypogonadism)
- Gradual decline beginning in mid-30s at approximately 1.6% per year 1
- Affects approximately 20% of men over 60,30% over 70, and 50% over 80 years 1
- Often presents with both organic and functional origins 1
Diagnostic Approach
Clinical Symptoms and Signs
- Sexual symptoms: reduced frequency of sexual intercourse, reduced libido, erectile dysfunction 1
- Physical symptoms: decreased energy, reduced physical strength/activity, hot flushes 1
- Psychological symptoms: concentration difficulties, sleep disturbances, depressive mood 1
Laboratory Assessment
- Morning total testosterone levels (decreased) on multiple occasions 1, 4
- Total testosterone <200 ng/dL indicates definite hypogonadism 4
- Levels between 200-400 ng/dL require repeat testing and free testosterone measurement 4
- Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to differentiate primary from secondary hypogonadism 5
Physical Examination
- Body mass index (BMI) and waist circumference 1
- Signs of testicular atrophy or muscle loss 1
- Secondary sexual characteristics assessment 5
Treatment Approaches
Lifestyle Modifications
- Weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism 1
- Physical activity shows benefits correlating with exercise duration and weight loss 1
- Addressing underlying metabolic disorders (diabetes, obesity) 3
Testosterone Replacement Therapy (TRT)
- Indicated for confirmed testosterone deficiency with symptoms 1
- Formulations include transdermal (gel), intramuscular injections, buccal, and oral preparations 3
- Intramuscular formulations may be preferred due to lower cost with similar effectiveness 1
- TRT improves sexual function and quality of life in men with low testosterone 1
Fertility Considerations
- TRT suppresses the hypothalamic-pituitary-gonadal axis and can decrease spermatogenesis 1
- For men desiring fertility with secondary hypogonadism, gonadotropin therapy is preferred 1, 6
- Combined hCG and FSH therapy promotes testicular growth and spermatogenesis in approximately 80% of patients 6
Contraindications to TRT
- Prostate cancer and male breast cancer 7, 5
- Uncontrolled congestive heart failure 5
- Severe lower urinary tract symptoms 5
- Erythrocytosis 5
Special Considerations
Young Men with Hypogonadism
- Always consider congenital causes in young men 8
- Acquired conditions like obesity, diabetes, anabolic steroid use are increasingly common 8
- Treatment must be tailored based on fertility goals 8
Monitoring During Treatment
- Prostate-specific antigen (PSA) 4
- Hemoglobin and hematocrit 4
- Testosterone levels 1
- Bone density in cases of osteoporosis 3