What are the treatment options for a patient with low libido, considering their underlying medical conditions, hormone levels, and mental health status?

Treatment of Low Libido

The treatment approach for low libido must be guided by identifying whether the cause is primary (relationship/psychological factors) versus secondary (hormonal, medication-induced, or medical comorbidities), with testosterone replacement therapy indicated only when morning testosterone is <300 ng/dL on two separate occasions in men, while women with hypoactive sexual desire disorder should be offered flibanserin or bremelanotide as first-line pharmacological options. 1, 2, 3

Initial Diagnostic Workup

For Male Patients

• Measure total morning testosterone (8-10 AM) on two separate occasions to confirm biochemical hypogonadism, with levels <300 ng/dL indicating potential testosterone deficiency 1, 3, 4
• If total testosterone is low or borderline, measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG), as this prevents unnecessary investigation in up to 50% of men with low total testosterone but normal free testosterone 1, 3
• Measure LH and FSH if testosterone is confirmed low to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism, which has critical treatment implications for fertility preservation 3, 4
• Measure serum prolactin if testosterone is low OR if loss of libido is the primary complaint, as elevated prolactin universally causes reduced libido 3
• Screen for reversible medication causes: SSRIs, beta-blockers, opioids, 5-alpha reductase inhibitors (finasteride/dutasteride), antipsychotics, and antiandrogens all commonly reduce libido 1, 3
• Evaluate for psychological factors: depression, anxiety, relationship distress, and body image concerns are major contributors and nearly double the prevalence of reduced libido 3, 5

For Female Patients

• Screen for medications impairing libido, particularly SSRIs, narcotics, and hormonal therapies 2
• Assess for vaginal symptoms including dryness, dyspareunia, or atrophy, as these contribute to sexual avoidance and decreased libido 2, 6
• Evaluate for psychological factors including anxiety, depression, relationship distress, body image concerns, and partner sexual dysfunction 2
• Review traditional risk factors including cardiovascular disease, diabetes, obesity, smoking, and alcohol abuse 2

Treatment Algorithm for Men

Step 1: Address Reversible Causes First

• Lifestyle modifications: Weight loss through low-calorie diets, increased physical activity, smoking cessation, and limiting alcohol consumption can improve testosterone levels and sexual function without medication 1, 4
• Medication adjustments: Consider switching from SSRIs to bupropion, from beta-blockers to ACE inhibitors or calcium channel blockers, and discontinuing 5-alpha reductase inhibitors if medically appropriate 3
• Treat underlying depression and anxiety with appropriate psychiatric treatment, as these conditions are major contributors even when testosterone is normal 3

Step 2: Testosterone Replacement Therapy (If Indicated)

Testosterone therapy is indicated when:

• Morning testosterone <300 ng/dL on two separate occasions AND
• Patient has specific symptoms (diminished libido, erectile dysfunction) AND
• No contraindications are present 1, 4

Absolute contraindications to testosterone therapy:

• Active desire for fertility preservation (use gonadotropin therapy instead: hCG plus FSH) 1, 4
• Active or treated male breast cancer 1, 4
• Hematocrit >54% 1, 4
• Untreated severe obstructive sleep apnea 4

Testosterone formulation selection:

• First-line: Transdermal testosterone gel 1.62% at 40.5 mg daily provides more stable day-to-day levels and lower erythrocytosis risk, though annual cost is approximately $2,135 4
• Alternative: Intramuscular testosterone cypionate or enanthate 50-400 mg every 2-4 weeks (typically 100-200 mg every 2 weeks), with annual cost of approximately $156, though higher erythrocytosis risk 4, 7
• Target testosterone levels: Mid-normal range of 500-600 ng/dL 4

Monitoring requirements:

• Check testosterone levels at 2-3 months after initiation or dose change, then every 6-12 months once stable 4
• For injectable testosterone, measure levels midway between injections (days 5-7) 4
• Monitor hematocrit at each visit—withhold treatment if >54% and consider phlebotomy 1, 4
• Monitor PSA in men over 40 years—refer for urologic evaluation if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 4

Expected outcomes with testosterone therapy:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 1, 4
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition, even with confirmed hypogonadism 1, 4
• Reevaluate at 12 months and discontinue if no improvement in sexual function 4

Step 3: Adjunctive Therapy for Erectile Dysfunction

• PDE5 inhibitors (sildenafil, tadalafil, vardenafil) are first-line treatment for erectile dysfunction and can be used with testosterone therapy for optimal results 1, 8
• The American College of Physicians recommends initiating therapy with a PDE5 inhibitor as first-line treatment, with choice based on individual preferences including ease of use, cost, and adverse effects profile 1
• Tadalafil dosing: 10 mg as needed (can adjust to 5-20 mg) taken prior to anticipated sexual activity, or 2.5-5 mg daily for once-daily use 8
• A minimal level of testosterone is required for complete effect of PDE5 inhibitor therapy, explaining why some men fail these medications when testosterone is low 4

Step 4: Referral to Sexual Health Specialist

• Refer for primary reduced libido (low libido without hormonal abnormalities) or when multiple issues are identified 1
• Psychosexual therapy shows 50-80% success rates and should be considered, especially for relationship-based causes 3
• Cognitive behavioral therapy has demonstrated effectiveness for improving sexual functioning 2

Treatment Algorithm for Women

Step 1: Non-Pharmacological First-Line Approaches

• Cognitive behavioral therapy (CBT) has demonstrated effectiveness for improving sexual functioning in women with low libido 2
• Psychoeducational support, sexual counseling, and couples therapy can address relationship issues and psychological factors 2
• Lifestyle modifications: Increased physical activity, smoking cessation, weight loss if overweight, and limiting alcohol consumption 2

Step 2: Treatment of Concurrent Vaginal Symptoms

These symptoms often contribute to sexual avoidance and must be addressed:

• First-line: Vaginal moisturizers and lubricants (water-, oil-, or silicone-based), with silicone-based products lasting longer than water-based or glycerin-based products 2
• Pelvic floor physical therapy can improve sexual pain, arousal, lubrication, orgasm, and satisfaction 2
• For postmenopausal women: Vaginal estrogen (pills, rings, or creams) is the most effective treatment for vaginal dryness leading to sexual dysfunction 2
• Vaginal DHEA (prasterone) has shown significant improvements in sexual desire, arousal, pain, and overall sexual function in survivors of breast or gynecologic cancer 2

Step 3: Pharmacological Treatment Options

For premenopausal women with hypoactive sexual desire disorder:

• First-line: Bremelanotide (subcutaneous injection) administered as needed before anticipated sexual activity 2
• Alternative: Flibanserin (FDA-approved for premenopausal women) taken daily, can result in approximately one additional satisfying sexual event every two months, though side effects include substantial dizziness, somnolence, nausea, and fatigue 1, 2
• Second-line off-label options: Bupropion or buspirone may be considered despite limited safety and efficacy data 2

What NOT to use:

• PDE5 inhibitors (sildenafil) are NOT recommended for female sexual dysfunction due to lack of effectiveness data in women 2
• Vaginal laser therapy is NOT recommended due to limited safety and effectiveness data and lack of FDA approval 2

Step 4: Special Considerations for Cancer Survivors

• For survivors of estrogen-sensitive cancers, avoid hormonal therapies 2
• Ospemifene may be considered for dyspareunia in survivors of cancers that are not hormonally sensitive 2
• Hormonal therapies are not recommended for women on aromatase inhibitors 2

Critical Pitfalls to Avoid

For All Patients

• Never diagnose hypogonadism based on symptoms alone without confirmed biochemical testing on two separate occasions 3, 4
• Never automatically attribute low libido to "normal aging" without proper evaluation of reversible causes 2, 6
• Never ignore medication side effects as a primary cause—SSRIs, beta-blockers, opioids, and hormonal therapies are common culprits 2, 3
• Never skip screening for psychological factors—depression, anxiety, and relationship distress are major contributors that require treatment 2, 3

For Male Patients

• Never start testosterone without confirming the patient does not desire fertility, as testosterone causes azoospermia and permanently compromises fertility 1, 4
• Never prescribe testosterone to eugonadal men (normal testosterone levels) even for weight loss, energy, or vitality complaints, as there is no benefit and potential harm 3, 4
• Never expect testosterone to improve energy, physical function, or cognition—the primary indication is sexual dysfunction only 1, 4
• Never fail to monitor hematocrit—injectable testosterone carries significant risk of erythrocytosis 4

For Female Patients

• Never prescribe hormonal therapies without considering cancer history, especially estrogen-sensitive cancers 2
• Never ignore vaginal symptoms such as dyspareunia and vaginal dryness, as these contribute to sexual avoidance and decreased libido 2
• Never assume low libido is purely hormonal—partner erectile dysfunction, fatigue, body image concerns, and life stressors are common contributors that require addressing 6