Does Lithium Cause a Decrease in Testosterone?
Yes, lithium causes a decrease in testosterone levels in males, based on both FDA drug labeling information and multiple research studies demonstrating this effect through various mechanisms including impairment of Leydig cells and disruption of the hypothalamic-pituitary-gonadal axis.
Evidence from FDA Drug Labeling
The FDA-approved lithium prescribing information does not explicitly list testosterone reduction as a labeled adverse effect 1. However, the label does document thyroid abnormalities (hypothyroidism, euthyroid goiter) and various endocrine disturbances, suggesting lithium's broader impact on hormonal systems 1.
Research Evidence Supporting Testosterone Reduction
Human Studies
Environmental and therapeutic lithium exposure consistently demonstrates testosterone suppression. A 2025 cohort study of 582 college students in China found that each interquartile range increase in urinary lithium levels was associated with a 2.47% decrease in serum testosterone (95% CI: -4.52%, -0.38%), with similar findings for seminal plasma lithium levels showing a 2.67% decrease (95% CI: -4.79%, -0.50%) 2. This study also demonstrated impaired Leydig cell function with mitochondrial damage as the underlying mechanism.
A 2015 systematic review specifically examining lithium and sexual dysfunction concluded that preclinical studies show lithium reduces testosterone levels and impairs nitric oxide-mediated relaxation of cavernosal tissue 3. Clinical reports indicate lithium reduces sexual thoughts, desire, erectile function, and overall sexual satisfaction, with sexual dysfunction significantly associated with lower overall functioning and reduced medication compliance 3.
Animal Studies
Multiple animal studies confirm dose-dependent testosterone suppression:
A 2024 rat study demonstrated that lithium carbonate at 40 mg/kg/day significantly decreased serum testosterone and LH levels, with concurrent reduction in sperm motility and concentration 4. Importantly, this study showed that magnesium sulfate and moderate-intensity training could partially reverse these effects.
A 2006 study in rats showed testosterone decreased and spermatogenesis stopped in males treated with lithium carbonate at doses of 2-4 g/kg of food daily, with serum lithium concentrations reaching 1.34-1.45 mM 5.
A 2005 French study confirmed that lithium serum concentrations as low as 0.62-0.75 mM induced testosterone reduction and arrested spermatogenesis in male rats 6. These concentrations fall within the therapeutic range used for bipolar disorder treatment in humans (0.6-1.2 mEq/L).
Mechanisms of Action
The testosterone reduction occurs through multiple pathways:
- Direct Leydig cell damage with mitochondrial vacuolation and swelling 2
- Disruption of the hypothalamic-pituitary-gonadal axis, evidenced by concurrent LH reduction 4, 5
- Impairment of testosterone synthesis pathways at the cellular level 2
Clinical Implications
Monitoring Recommendations
While the AUA guideline recommends measuring testosterone in patients with chronic medication use that may affect levels 7, and the ACP guideline addresses testosterone replacement 8, neither specifically addresses lithium-induced testosterone deficiency. However, based on the evidence:
- Measure baseline testosterone levels (two early morning measurements) before initiating lithium therapy
- Monitor testosterone levels periodically during lithium treatment, particularly if symptoms of hypogonadism develop (reduced libido, erectile dysfunction, fatigue, decreased muscle mass)
- Assess for sexual dysfunction at regular intervals, as this is significantly underreported and affects medication compliance 3
Management Considerations
If testosterone deficiency develops during lithium therapy:
- Verify the diagnosis with two early morning total testosterone measurements showing levels consistently <300 ng/dL, combined with symptoms 7
- Measure LH and prolactin levels to determine if the deficiency is primary (testicular) or secondary (hypothalamic-pituitary) 7
- Consider testosterone replacement therapy following ACP guidelines if sexual dysfunction is present and the patient desires improvement 8
- Evaluate lithium necessity and explore alternative mood stabilizers if appropriate
- Consider adjunctive interventions such as magnesium supplementation or exercise, which showed benefit in animal models 4
Important Caveats
- The severity of testosterone reduction appears dose-dependent, with higher lithium levels causing more pronounced effects 5, 6
- Sexual dysfunction may occur even at therapeutic lithium levels (0.6-1.2 mEq/L) 6
- Concomitant benzodiazepine use increases the risk of sexual dysfunction in lithium-treated patients 3
- This remains an under-researched area with limited high-quality human studies, though animal data are consistent and compelling 3