What are the possible treatments for low libido in adult men?

Treatment of Low Libido in Adult Men

For men with confirmed low testosterone (two morning measurements <300 ng/dL) and diminished libido, testosterone replacement therapy provides small but meaningful improvements in sexual desire and function, with intramuscular formulations preferred over transdermal options due to equivalent efficacy at significantly lower cost. 1, 2, 3

Initial Diagnostic Approach

Before considering any pharmacologic treatment, confirm biochemical hypogonadism with two separate morning testosterone measurements below 300 ng/dL (10.4 nmol/L) 3, 4. This is critical because approximately 20-30% of men receiving testosterone in the United States lack documented low testosterone levels before treatment initiation 3.

Rule Out Secondary Causes

• Screen for hypogonadism causes: Check for primary hypogonadism (testicular failure from cryptorchidism, Klinefelter's syndrome, chemotherapy) versus secondary hypogonadism (pituitary/hypothalamic dysfunction) by measuring LH and FSH levels 4
• Evaluate for hyperprolactinemia: Prolactin elevation universally causes reduced libido and requires specific treatment 5
• Assess for depression and anxiety: These conditions independently reduce libido through central and peripheral pathways affecting sexual response 5, 6, 7
• Review medications: Psychoactive medications commonly impair sexual desire 5, 7
• Evaluate relationship factors: Domestic and dyadic relationship disturbances are strongly associated with primary reduced libido 5

Non-Pharmacologic Interventions

Optimize sleep quality and duration before initiating testosterone therapy, as poor sleep contributes to low testosterone levels 2. This represents a modifiable risk factor that should be addressed first.

Testosterone Replacement Therapy

Patient Selection Criteria

Testosterone therapy should only be considered when both conditions are met 3:

1. Confirmed biochemical hypogonadism (two measurements <300 ng/dL)
2. Primary symptoms of diminished libido or erectile dysfunction (not fatigue or low energy alone)

Expected Benefits

• Moderate-certainty evidence shows small improvement in global sexual function (standardized mean difference 0.35) 1, 3
• Low-certainty evidence demonstrates small improvement in erectile function (standardized mean difference 0.27) 1
• The improvements in libido and sexual activity are measurable but classified as "small" effects 1

Pre-Treatment Safety Screening

Mandatory baseline assessments 3:

• Hematocrit (contraindicated if >50-54%)
• Digital rectal examination and PSA in men over 40 (contraindicated if PSA >4.0 ng/mL without urologic evaluation)
• Cardiovascular risk assessment (low-certainty evidence suggests possible small increase in cardiovascular events) 1, 2

Formulation Selection

Intramuscular testosterone cypionate or enanthate 100-200 mg every 2 weeks is the preferred first-line option due to significantly lower annual cost ($156.24 vs $2,135.32 for transdermal) with similar clinical effectiveness 2, 3. Target mid-normal testosterone levels (500-600 ng/dL) during monitoring 3.

Topical testosterone gel 1.62% is an alternative starting at 40.5 mg daily (2 pump actuations), applied to shoulders and upper arms only 4. However, this carries risk of secondary exposure to children and women, requiring strict adherence to application instructions 4.

Alternative for Secondary Hypogonadism

For men with secondary hypogonadism (low LH with low testosterone) who desire fertility preservation, consider clomiphene citrate 25-50 mg daily as first-line therapy 3. This stimulates endogenous testosterone production without suppressing spermatogenesis and has lower risk of polycythemia 3.

Monitoring Protocol

Reevaluate symptoms within 12 months of starting testosterone treatment and periodically thereafter 2. The American College of Physicians recommends discontinuation if there is no improvement in symptoms 2.

Titrate dose based on pre-dose morning serum testosterone at approximately 14 days and 28 days after starting treatment 4:

• If testosterone >750 ng/dL: Decrease dose by 20.25 mg
• If testosterone 350-750 ng/dL: Continue current dose
• If testosterone <350 ng/dL: Increase dose by 20.25 mg

Monitor for adverse effects including cardiovascular events, polycythemia, and prostate changes 2, 3.

Treatment of Primary Reduced Libido (Normal Testosterone)

For men with normal testosterone levels and reduced libido (primary reduced libido), focus on psychosocial interventions 5:

• Address relationship conflicts and marital issues
• Treat comorbid depression or anxiety (noting that antidepressants may further impair libido) 7
• Manage chronic stress
• Evaluate for other sexual dysfunctions (erectile dysfunction, premature ejaculation) that may secondarily reduce desire 5

Testosterone therapy is not indicated for men with normal testosterone levels, as FDA labeling requires testosterone products be used only for low testosterone due to known medical causes 1, 4.

Critical Pitfalls to Avoid

• Never prescribe testosterone based on symptoms alone without confirmed biochemical hypogonadism (two measurements below 300 ng/dL) 3
• Do not use testosterone primarily for fatigue or low energy, as evidence shows only minimal benefit (standardized mean difference 0.17) that is not clinically meaningful 3
• Recognize that current guidelines primarily address age-related low testosterone in older men, with limited specific guidance for young adults 2
• Ensure proper application site for topical formulations (shoulders and upper arms only, never abdomen, genitals, chest, armpits, or knees) to prevent secondary exposure 4