What are the best medications for an adult patient with tiredness and low libido, without a known cause or gender?

Treatment of Tiredness and Low Libido

Initial Diagnostic Approach

The first step is to identify whether this is primary (no underlying cause) or secondary (due to medications, hormonal deficiency, or psychological factors) reduced libido and fatigue, as this fundamentally changes management.

Essential Assessment Components

• Screen for medication-induced causes, particularly SSRIs, narcotics, and hormonal therapies, which commonly impair libido 1
• Evaluate for hypogonadism with morning testosterone testing (free testosterone or androgen index preferred over total testosterone) in both men and women, as low testosterone is strongly associated with both fatigue and reduced libido 2, 3
• Check prolactin levels if low libido is present with low testosterone, as hyperprolactinemia universally causes reduced libido 4
• Assess thyroid function (TSH, free T4) as thyroid disorders commonly cause both fatigue and sexual dysfunction 2
• Screen for psychological factors including depression, anxiety, relationship distress, and body image concerns, which are major contributors to low libido 2, 1
• Evaluate for chronic medical conditions including diabetes, cardiovascular disease, obesity, and liver disease that affect sexual function 2

Treatment Algorithm by Gender

For Women with Low Libido and Fatigue

First-line pharmacological treatment for premenopausal women with hypoactive sexual desire disorder is flibanserin (FDA-approved), which results in approximately one additional satisfying sexual event every two months 5, 1.

Pharmacological Options for Women:

• Flibanserin: FDA-approved for acquired, generalized hypoactive sexual desire disorder in premenopausal women 5, 1
• Bremelanotide: FDA-approved alternative for premenopausal women, administered as subcutaneous injection as needed before anticipated sexual activity 5, 1
• Bupropion: Off-label option that may help both fatigue and libido, though evidence is limited 1, 6
• Buspirone: Off-label option for hypoactive sexual desire disorder with limited data 1
• DHEA supplementation (10-50 mg daily): Consider for postmenopausal women with persistent lack of libido and/or low energy levels 2

Non-Pharmacological Approaches:

• Cognitive behavioral therapy has demonstrated effectiveness for improving sexual functioning 1
• Psychosexual therapy shows successful outcomes in 50-80% of patients 2
• Address vaginal symptoms with water-, oil-, or silicone-based lubricants and vaginal moisturizers as first-line treatment (silicone-based products last longer) 1
• Pelvic floor physical therapy for dyspareunia that may contribute to sexual avoidance 1

For Men with Low Libido and Fatigue

Testosterone replacement therapy is the primary treatment for men with documented hypogonadism (low testosterone levels) who present with lack of energy and decreased sex drive, which are the most bothersome symptoms reported by 90% and 55-66% of hypogonadal men respectively 5.

Testosterone Formulations:

• Intramuscular testosterone: Most cost-effective option at $156.24 annually, preferred by 53% of patients 5
• Transdermal gel: Preferred by 71% of long-term users for convenience and ease of use, though more expensive at $2,135.32 annually 5

Alternative Pharmacological Options:

• Bupropion: Off-label use for both depression-related fatigue and sexual dysfunction, as it is devoid of sexual side effects unlike SSRIs 6
  • Important caveat: Use extreme caution with drugs that lower seizure threshold 7
  • Avoid concomitant use with MAOIs (requires 14-day washout period) 7
  • Can increase libido as a side effect 7

Critical Pitfalls to Avoid

• Do not prescribe hormonal therapies without considering cancer history, especially estrogen-sensitive cancers in women 1
• Do not ignore SSRI-induced sexual dysfunction - these medications commonly cause reduced libido and switching to bupropion, mirtazapine, or nefazodone may resolve the issue 6
• Do not automatically attribute symptoms to "normal aging" - many causes are treatable 8
• Do not use PDE5 inhibitors (sildenafil) for female sexual dysfunction due to lack of effectiveness data 1
• Avoid vaginal laser therapy for women as it lacks FDA approval and sufficient safety data 5, 1

Special Considerations

When Testosterone is Indicated:

• Men with documented hypogonadism presenting with lack of energy (most bothersome symptom in 90%), decreased strength/endurance (86%), and decreased sex drive (55-66%) benefit most from testosterone therapy 5
• Discontinuation rates are high (30-62%), so patient education about realistic expectations is essential 5
• Long-term safety data is limited, and evidence on mortality is inconclusive 5

When Psychological Factors Predominate:

• Primary reduced libido (without hypogonadism, hyperprolactinemia, or psychopathology) is characterized by disturbances in domestic and dyadic relationships and requires relationship-focused interventions 4
• Open communication between partners is essential but often difficult - consider couples therapy 8

Addressing Contributing Factors:

• Fatigue and bodily pain commonly contribute to low libido in older adults and should be addressed directly 8
• Partner erectile dysfunction significantly impacts female libido and requires concurrent treatment 8
• Lifestyle modifications including increased physical activity, smoking cessation, weight loss if overweight, and limiting alcohol can improve both fatigue and sexual function 1