What medications are associated with low testosterone?

Medications Associated with Low Testosterone

Several medications can cause or contribute to low testosterone levels, with opioids, glucocorticoids, and certain antipsychotics having the strongest evidence for this effect. Understanding these associations is crucial for proper diagnosis and management of hypogonadism in patients taking these medications.

Common Medication Classes Associated with Low Testosterone

Strong Evidence

1. Opioids and Opiates

   • Cause secondary (hypogonadotropic) hypogonadism by suppressing the hypothalamic-pituitary axis 1
   • Associated with increased dosage of methadone and prolonged use 2
   • Can lead to decreased libido, erectile dysfunction, and other symptoms of testosterone deficiency

2. Glucocorticoids (Corticosteroids)

   • Chronic use suppresses the hypothalamic-pituitary-gonadal axis 1
   • Listed as medications that can cause weight gain, which indirectly affects testosterone levels 2

3. Antipsychotics

   • Particularly second-generation antipsychotics like olanzapine, quetiapine, and risperidone 2
   • Mechanism involves both direct hormonal effects and indirect effects through weight gain
   • Alternatives with less impact: ziprasidone, aripiprazole 2

Moderate Evidence

1. Spironolactone

   • Has anti-androgenic properties that can affect sex differentiation and hormone levels 3
   • Acts as an aldosterone antagonist but also has effects on androgen receptors

2. Certain Antidepressants

   • SSRIs have shown mixed effects on testosterone levels
   • Some studies show lower testosterone levels in patients with depression and anxiety disorders 4
   • Other research suggests SSRIs may actually increase salivary testosterone in both men and women 4
   • Tricyclic antidepressants like imipramine and amitriptyline may reduce 5-alpha-dihydrotestosterone levels 5

3. Hormonal Treatments

   • Androgen deprivation therapy (used in prostate cancer)
   • Estrogen therapy

Mechanisms of Testosterone Reduction

Medications can lower testosterone through several mechanisms:

1. Direct suppression of the hypothalamic-pituitary-gonadal axis

   • Opioids, glucocorticoids, and some psychiatric medications

2. Increased aromatization of testosterone to estradiol

   • Medications causing weight gain indirectly promote this mechanism
   • Obesity increases aromatization in adipose tissue, with subsequent estradiol-mediated negative feedback suppressing pituitary LH secretion 2

3. Alteration of sex hormone-binding globulin (SHBG) levels

   • Affects bioavailable testosterone without necessarily changing total testosterone

4. Direct anti-androgenic effects

   • Spironolactone and certain other medications directly block androgen receptors 3

Clinical Implications and Management

Diagnosis

• Morning total testosterone concentration should be drawn between 8-10 AM 2, 1
• Repeat low testosterone measurements to confirm the diagnosis 1
• Measure free testosterone by equilibrium dialysis and SHBG levels, especially in obese patients 2, 1
• Measure LH and FSH to distinguish primary from secondary hypogonadism 1

Management Approach

1. Consider medication adjustment when possible

   • Switch to medications with less impact on testosterone when clinically appropriate
   • For antipsychotics, consider ziprasidone or aripiprazole instead of olanzapine or risperidone 2
   • For antidepressants, bupropion may have less impact than some other options 2

2. Testosterone replacement therapy (TRT) considerations

   • Consider TRT when morning free testosterone is consistently low and symptoms are present 2
   • TRT should be considered when total testosterone level is below 300 ng/dL with symptoms 1
   • Contraindicated in patients with active prostate or breast cancer, hematocrit >50%, severe untreated sleep apnea, uncontrolled heart failure, and recent cardiovascular events 1

3. Lifestyle modifications

   • Weight loss for overweight/obese men
   • Regular physical activity and exercise
   • Adequate sleep and stress reduction
   • These can increase testosterone levels, particularly in men with metabolic disorders 1

Key Points to Remember

• Always consider medication effects when evaluating patients with symptoms of low testosterone
• The diagnosis of hypogonadism requires both clinical symptoms and biochemical evidence of testosterone deficiency 6
• Total testosterone levels <300 ng/dL are generally considered low 2
• In patients with obesity, free testosterone measurement is essential as obesity decreases SHBG, potentially masking hypogonadism 1
• Medication-induced hypogonadism is often reversible if the causative agent can be discontinued or reduced

By recognizing medications that can lower testosterone levels, clinicians can better diagnose and manage hypogonadism in affected patients, improving their quality of life and preventing long-term complications of testosterone deficiency.