What is the differential diagnosis and treatment approach for low libido?

Differential Diagnosis of Low Libido

Low libido has distinct primary (psychosocial/relational) and secondary (hormonal/medical) causes that require systematic evaluation, with hypogonadism, hyperprolactinemia, medications, and relationship distress being the most critical factors to identify.

Hormonal and Endocrine Causes

Hypogonadism (Low Testosterone)

• Total morning testosterone <300 ng/dL is the threshold for considering testosterone deficiency as a cause of reduced libido 1.
• Free testosterone or androgen index measurement is preferred over total testosterone alone, as this prevents unnecessary endocrine investigation in up to 50% of men with low total testosterone 1.
• Hypogonadism is strongly associated with diminished libido and is universally present when testosterone levels are significantly suppressed 2, 3.
• Both primary (testicular) and secondary (pituitary/hypothalamic) hypogonadism can cause low libido 1.

Hyperprolactinemia

• Elevated prolactin universally causes reduced libido and should be measured when testosterone is low or when loss of libido is the primary complaint 1, 3.
• Prolactin elevation inhibits libido through central nervous system pathways 4.

Other Endocrine Disorders

• Thyroid dysfunction (both hyperthyroidism and hypothyroidism) affects sex hormone binding globulin (SHBG) and can indirectly impact libido 1.
• Cushing's disease, acromegaly, and adrenal insufficiency are associated with sexual dysfunction 1.
• In women, both insufficient and excessive estrogen levels negatively impact libido 2.

Medication-Induced Causes

Cardiovascular Medications

• Beta-blockers are strongly associated with sexual dysfunction and reduced libido 1, 2.
• Alternative agents with lower risk include ACE inhibitors, calcium channel blockers, and loop diuretics (furosemide, bumetanide) 1.

Psychiatric Medications

• SSRIs (paroxetine, sertraline, citalopram, fluoxetine) commonly cause reduced libido 1.
• Antipsychotics can elevate prolactin and suppress libido 1.

Hormonal Medications

• Antiandrogens (cyproterone acetate, spironolactone, flutamide, bicalutamide) directly block androgen receptors 1.
• 5-alpha reductase inhibitors (finasteride, dutasteride) reduce DHT and can cause persistent sexual dysfunction 1.
• Excessive anti-androgen use in feminizing HRT can suppress testosterone below optimal levels 2.

Other Medications

• Opioids, corticosteroids, and H2-receptor antagonists are associated with reduced libido 1.

Psychological and Psychiatric Causes

Mood Disorders

• Depression and anxiety are major contributors to low libido and are more prevalent in individuals with hormonal imbalances 1, 2.
• Generalized anxiety states, depressive illness, and psychosis should be addressed before treating sexual dysfunction 1.
• Psychopathology nearly doubles the prevalence of reduced libido 3.

Relationship Factors

• Dissatisfaction with the relationship or marriage is the most common factor in patients with depressed desire 5.
• Disturbances in domestic and dyadic relationships characterize primary reduced libido 3.
• Partner-specific problems, including partner erectile dysfunction, contribute to loss of libido 4.

Medical Comorbidities

Chronic Diseases

• Diabetes mellitus is associated with sexual dysfunction through vascular and neurological mechanisms 1.
• Cardiovascular disease, including hypertension and atherosclerosis, impairs sexual function 1.
• Chronic kidney disease, liver failure, and metabolic syndrome (obesity, insulin resistance) reduce libido 1.
• Multiple sclerosis, Parkinson's disease, and other neurological conditions affect sexual desire 1.

Cancer and Cancer Treatment

• Prostate cancer treatment, pelvic radiation, and colorectal cancer surgery cause sexual dysfunction 1.
• Chemotherapy and hormonal cancer treatments suppress libido 1.

Primary (Idiopathic) Reduced Libido

• Primary reduced libido occurs without hypogonadism, hyperprolactinemia, psychopathology, or medication causes 3.
• Characterized by higher educational attainment, more relationship disturbances, and paradoxically better metabolic health (lower glycemia, triglycerides, cardiovascular risk) 3.
• Represents a distinct entity requiring psychosexual intervention rather than hormonal treatment 3.

Diagnostic Approach

Essential Laboratory Testing

• Measure total morning testosterone in all patients with low libido 1.
• If testosterone is low, measure LH to distinguish primary from secondary hypogonadism 1.
• Measure prolactin if testosterone is low OR if loss of libido is the primary complaint 1, 3.
• Free testosterone or androgen index is preferred over total testosterone alone 1, 2.

Conditional Testing

• Fasting glucose or HbA1c to exclude diabetes 1.
• TSH and free T4 if thyroid dysfunction is suspected 1.
• Consider FSH, estrogen (in premenopausal women), and DHEA levels in specific contexts 1, 2.

Clinical Evaluation

• Assess for sudden versus gradual onset (psychogenic versus organic) 1.
• Evaluate quality of spontaneous/morning erections in men 1.
• Review all current medications for sexual side effects 1.
• Screen for depression, anxiety, and relationship distress 1, 5.
• Examine for signs of hypogonadism (testicular size, body habitus) 1.

Treatment Implications

Hormonal Treatment

• Testosterone therapy is indicated when morning testosterone is <300 ng/dL and there are no contraindications 1.
• DHEA replacement is controversial but can be considered in women with low libido who are otherwise well-replaced on hormone therapy 1.
• Adjust HRT regimens to maintain optimal testosterone levels while avoiding excessive suppression 2.

Non-Hormonal Treatment

• Refer to sexual health specialist for primary reduced libido or when multiple issues are identified 1.
• Psychosexual therapy shows 50-80% success rates and should be considered, especially for relationship-based causes 1.
• Address underlying depression and anxiety with appropriate psychiatric treatment 1, 2.
• Consider medication changes when drug-induced causes are identified 1, 2.

Critical Pitfalls to Avoid

• Do not assume low libido is purely psychological without measuring testosterone and prolactin 1, 3.
• Do not measure only total testosterone; use free testosterone or androgen index to avoid false positives 1.
• Do not overlook medication causes, particularly antihypertensives, SSRIs, and antiandrogens 1, 2.
• Do not treat with testosterone without first confirming deficiency (<300 ng/dL) 1.
• Do not ignore relationship factors even when hormonal abnormalities are present 4, 5, 3.