Fluoxetine's Effect on Testosterone
Fluoxetine does not reduce testosterone levels in men. A prospective study of 44 men with major depressive disorder found no significant change in testosterone levels after one month of fluoxetine treatment (448.4 ± 139.6 to 439.5 ± 142.1 ng/dL, p > 0.05), and none of the men developed low testosterone during treatment 1.
Evidence on Fluoxetine and Testosterone
No testosterone reduction: In a controlled study of 14 depressed patients treated with fluoxetine (10 mg/day for 7 days, then 20 mg/day for one month), there was no relationship between fluoxetine treatment and testosterone levels in the study population as a whole (p = 0.4) 2.
Individual variation exists but no systematic effect: While some individuals showed increases or decreases in testosterone during fluoxetine treatment, these changes were random and not directionally consistent, indicating no causal relationship between the medication and testosterone levels 2.
Prolactin may increase in women but not men: Fluoxetine caused hyperprolactinemia in only 4.5% of men (compared to 22.2% of women), and this did not translate into testosterone suppression 1.
Sexual Side Effects Are Not Due to Low Testosterone
The sexual dysfunction caused by fluoxetine—including delayed ejaculation, anorgasmia, and erectile difficulties—occurs through serotonergic mechanisms, not through testosterone reduction.
Delayed ejaculation is the primary effect: Fluoxetine significantly delays ejaculation in healthy men through direct serotonergic effects on ejaculatory reflexes, not hormonal changes 3.
Sexual desire remains intact: Studies in healthy men show that fluoxetine does not affect sexual desire or libido, with IIEF-15 scores for sexual desire items remaining unchanged during treatment 3.
Erectile function is preserved: Objective measurements using RigiScan Plus during visual erotic stimulation showed no significant differences in erectile parameters between fluoxetine and placebo 3.
High incidence of sexual side effects: Retrospective chart review identified sexual dysfunction in 34 of 80 male patients (42.5%) receiving SSRIs, with loss of libido, erectile difficulty, anorgasmia, and delayed ejaculation reported across fluoxetine, paroxetine, and sertraline 4.
Management of Low Testosterone (If Present)
If a man on fluoxetine has confirmed low testosterone, the hypogonadism should be evaluated and managed independently of the antidepressant.
Diagnostic Confirmation
Obtain two morning testosterone measurements (8–10 AM) on separate days: Both values must be < 300 ng/dL to establish biochemical hypogonadism 5.
Measure LH and FSH: After confirming low testosterone, obtain gonadotropins to distinguish primary (elevated LH/FSH) from secondary (low or low-normal LH/FSH) hypogonadism 5.
Assess free testosterone and SHBG: In men with borderline total testosterone (231–346 ng/dL) or obesity, measure free testosterone by equilibrium dialysis and SHBG to identify true hypogonadism 5, 6.
Treatment Indications
Testosterone therapy is indicated only for specific sexual symptoms: The primary qualifying symptoms are diminished libido and erectile dysfunction, not fatigue, low energy, or mood disturbances 5.
Consider testosterone if total morning testosterone < 300 ng/dL with sexual symptoms: NCCN guidelines recommend testosterone therapy for erectile dysfunction, ejaculation problems, or orgasm disorders when morning testosterone is < 300 ng/dL and there are no contraindications 5.
Treatment Options
First-line: Transdermal testosterone gel 1.62% at 40.5 mg daily: This formulation provides stable day-to-day testosterone levels and carries lower erythrocytosis risk (15.4%) compared to injectable preparations (43.8%) 6.
Alternative: Intramuscular testosterone cypionate or enanthate 100–200 mg every 2 weeks: This is more economical but has higher erythrocytosis risk 6.
Target mid-normal testosterone levels (450–600 ng/dL): Measure testosterone levels 2–3 months after initiation, then every 6–12 months once stable 6.
Expected Outcomes
Small but significant improvement in sexual function: Testosterone therapy produces a standardized mean difference of 0.35 for sexual function and libido 5, 6.
Little to no benefit for energy, mood, or cognition: Testosterone replacement shows minimal or no improvement in physical functioning, energy, vitality, depressive symptoms, or cognition even in confirmed hypogonadism 5, 6.
Monitoring Requirements
Hematocrit at each visit: Withhold treatment if hematocrit > 54% and consider phlebotomy in high-risk cases 5, 6.
PSA in men > 40 years: Refer to urology if PSA increases > 1.0 ng/mL in the first 6 months or > 0.4 ng/mL per year thereafter 6.
Critical Pitfalls to Avoid
Do not attribute fluoxetine-induced sexual dysfunction to low testosterone: The sexual side effects of SSRIs occur through serotonergic mechanisms, not hormonal suppression 3.
Do not discontinue fluoxetine solely to "improve testosterone": There is no evidence that fluoxetine lowers testosterone, so stopping the medication will not raise testosterone levels 2, 1.
Do not start testosterone therapy without confirming biochemical hypogonadism: Require two morning testosterone measurements < 300 ng/dL plus specific sexual symptoms before initiating treatment 5.
Do not use testosterone to treat SSRI-induced sexual dysfunction in eugonadal men: Testosterone therapy is contraindicated in men with normal testosterone levels, even if they have sexual symptoms from antidepressants 6.