What supplements can be used to treat hypogonadism (low testosterone)?

Treatment Options for Hypogonadism (Low Testosterone)

For men with hypogonadism, testosterone replacement therapy is the recommended first-line treatment, while alternative approaches like selective estrogen receptor modulators (SERMs), aromatase inhibitors, and human chorionic gonadotropin (hCG) may be considered for those concerned about fertility preservation. 1, 2, 3

Testosterone Replacement Therapy (TRT)

Testosterone replacement therapy is indicated for men with symptomatic hypogonadism, defined as low testosterone levels with associated symptoms:

• FDA-approved for replacement therapy in males with conditions associated with deficiency or absence of endogenous testosterone 2
• Available in multiple formulations:
  • Intramuscular injections (testosterone cypionate, testosterone enanthate) 2, 4
  • Transdermal preparations (gels, patches) 3, 4
  • Buccal, subdermal, and nasal preparations 3

Important Considerations for TRT

• TRT should NOT be prescribed to men interested in current or future fertility as it suppresses the hypothalamic-pituitary-gonadal axis 1, 3
• Monitoring requirements include:
  • Baseline and annual testosterone levels 5, 4
  • Hematocrit and PSA levels at baseline and at least annually in men 40 years or older 4
  • Regular assessment of symptom improvement and side effects 4

Alternative Approaches for Hypogonadism

For men with hypogonadism who wish to preserve fertility, several alternatives to TRT exist:

1. Selective Estrogen Receptor Modulators (SERMs)

• May be used for men with low serum testosterone 1, 3
• Benefits are limited compared to results from assisted reproductive technologies 1
• Examples include clomiphene citrate 3

2. Aromatase Inhibitors (AIs)

• Can be used for infertile men with low serum testosterone 1, 3
• Work by reducing conversion of testosterone to estradiol 3

3. Human Chorionic Gonadotropin (hCG)

• May be used for infertile men with low serum testosterone 1, 3
• Mimics luteinizing hormone (LH) action to stimulate testosterone production 3

4. Combination Therapies

• Combinations of SERMs, AIs, or hCG may be considered based on individual patient factors 1, 3

Diagnostic Considerations

Before initiating treatment, proper diagnosis is essential:

• Free testosterone is a better index of gonadal status than total testosterone 1, 5
• Morning serum testosterone measurement is essential for diagnosis 5
• Measurements should be repeated to confirm low levels 5, 4
• Calculate free testosterone index (ratio of total testosterone to SHBG) when SHBG levels are abnormal 1, 5

Supplementary Approaches

In addition to hormone therapy, supportive measures include:

• Regular weight-bearing exercise 1, 5
• Smoking cessation 1, 5
• Adequate nutrition (low BMI is an independent risk factor for complications) 1, 5
• Calcium (1 g/day) and vitamin D3 (800 U/day) supplementation if there are bone health concerns 1, 5

Risks and Benefits of Treatment

Benefits of treating hypogonadism:

• Improved sexual function and libido 1, 6
• Increased muscle mass and decreased fat mass 6
• Improved bone mineral density 1, 6
• Enhanced mood and energy levels 4, 6

Potential risks:

• Suppression of spermatogenesis (with TRT) 3
• Erythrocytosis 4, 6
• Potential worsening of benign prostatic hyperplasia symptoms 6
• Controversial effects on cardiovascular health (recent large randomized trial showed no increased risk of myocardial infarction or stroke) 4

Special Considerations

• Testosterone therapy should not be used in men with prostate cancer on active surveillance or on androgen deprivation therapy 1
• Exogenous testosterone therapy should not be prescribed to those currently trying to conceive 1
• For men with non-obstructive azoospermia, limited data supports pharmacologic manipulation with SERMs, AIs, and gonadotropins prior to surgical intervention 1