For a male patient with SSRI‑induced sexual side effects and no documented hypogonadism, is dihydrotestosterone (DHT) a better treatment option than testosterone?

DHT is Not Recommended Over Testosterone for SSRI-Induced Sexual Dysfunction in Eugonadal Men

Neither DHT nor testosterone should be used to treat SSRI-induced sexual dysfunction in men without documented hypogonadism. The European Association of Urology explicitly recommends against testosterone therapy in eugonadal men, even for sexual dysfunction, vitality, or other quality-of-life complaints 1. This prohibition extends to DHT, which is simply a non-aromatizable androgen with no proven superiority for this indication.

Why Androgen Therapy is Contraindicated in This Scenario

Lack of Biochemical Hypogonadism

• Testosterone therapy requires both biochemical confirmation (two morning total testosterone measurements <300 ng/dL) and specific symptoms (diminished libido, erectile dysfunction) before initiation 1.
• In a eugonadal man with SSRI-induced sexual dysfunction, the sexual symptoms are medication-induced, not androgen-deficiency related 2.
• Approximately 25-30% of men currently receiving testosterone therapy do not meet diagnostic criteria for hypogonadism—a practice pattern that violates evidence-based guidelines 1.

Minimal Expected Benefit Even in True Hypogonadism

• Even when hypogonadism is confirmed, testosterone produces only small improvements in sexual function (standardized mean difference 0.35) 1.
• The primary mechanism of SSRI-induced sexual dysfunction is serotonergic, not androgenic 3.
• Adding testosterone to a eugonadal man will not reverse SSRI-mediated delayed ejaculation, anorgasmia, or decreased libido 2, 3.

Significant Harms Without Benefit

• Erythrocytosis risk: Injectable testosterone causes hematocrit >52% in approximately 44% of users; transdermal preparations in 15% 1.
• Fertility suppression: Exogenous testosterone (and DHT) suppress the hypothalamic-pituitary-gonadal axis, causing prolonged and potentially irreversible azoospermia 1.
• Cardiovascular concerns: Although the TRAVERSE trial showed no increased major adverse cardiac events with transdermal testosterone in hypogonadal men with cardiovascular risk factors 1, prescribing androgens to eugonadal men for off-label indications introduces unnecessary risk.

Why DHT Offers No Advantage Over Testosterone

Theoretical Rationale is Unproven

• DHT is a non-aromatizable androgen that cannot convert to estradiol 4.
• The hypothesis that DHT might have "muted effects on prostate growth" compared to testosterone remains unsubstantiated in clinical practice 4.
• Any theoretical advantage on prostate tissue must be balanced against potential negative effects on bone, lipids, and sexuality when a pure androgen replaces an aromatizable one 4.

No Evidence for SSRI-Induced Sexual Dysfunction

• There are no clinical trials evaluating DHT for SSRI-induced sexual dysfunction in eugonadal men.
• The single study combining testosterone with PDE5 inhibitors or buspirone for SSRI-induced sexual dysfunction was conducted in women, not men, and used sublingual testosterone, not DHT 5.
• Another trial showing benefit of transdermal testosterone for SSRI-emergent loss of libido was also in women 6.

DHT is Not FDA-Approved for Male Hypogonadism

• DHT formulations are not standard therapy for male hypogonadism in the United States 7.
• Testosterone remains the first-line androgen replacement when hypogonadism is confirmed 1.

Evidence-Based Management of SSRI-Induced Sexual Dysfunction

First-Line: Antidepressant Optimization

• Switch to bupropion if depression control allows, as it has significantly lower sexual dysfunction rates (8-10%) compared to all SSRIs 2.
• Dose reduction of the current SSRI to the minimum effective level, as sexual side effects are strongly dose-related 2.
• Among SSRIs, escitalopram and fluvoxamine cause the lowest rates of sexual dysfunction, while paroxetine has the highest (70.7%) 2.

Adjunctive Pharmacotherapy

• PDE5 inhibitors (sildenafil, tadalafil) can address erectile dysfunction if present, though they do not restore libido 2.
• Combination therapy with testosterone plus PDE5 inhibitors showed benefit in women with SSRI-induced sexual dysfunction 5, but this does not translate to eugonadal men.

Non-Pharmacologic Interventions

• Vibratory therapy can enhance orgasm intensity in patients with SSRI-related loss of genital sensation 2.
• Pelvic floor physical therapy addresses co-existing pelvic floor dysfunction 2.
• Sex therapy or couples counseling helps patients adapt to sensory changes 2.

Monitoring and Reassessment

• Evaluate testosterone levels to exclude true hypogonadism (two morning measurements <300 ng/dL) 1.
• If hypogonadism is confirmed, treat the hypogonadism with standard testosterone therapy—not DHT 1.
• Reassess at 6-8 weeks; if no improvement, modify the antidepressant regimen 2.

Critical Pitfalls to Avoid

• Never prescribe testosterone or DHT to eugonadal men for sexual dysfunction, even when SSRI-induced 1.
• Never diagnose hypogonadism based on symptoms alone without biochemical confirmation 1.
• Never assume that adding an androgen will reverse SSRI-mediated serotonergic sexual dysfunction 2, 3.
• Always confirm fertility intentions before considering any androgen therapy, as exogenous testosterone and DHT cause azoospermia 1.

Clinical Decision Algorithm

1. Confirm eugonadal status: Obtain two morning total testosterone measurements (8-10 AM). If both are ≥300 ng/dL, the patient is eugonadal 1.
2. Optimize antidepressant therapy: Switch to bupropion or reduce SSRI dose 2.
3. Add PDE5 inhibitor if erectile dysfunction is present 2.
4. Consider non-pharmacologic interventions (vibratory therapy, pelvic PT, sex therapy) 2.
5. Reassess at 6-8 weeks: If no improvement, refer to psychiatry for further antidepressant adjustment 2.
6. Do not prescribe testosterone or DHT unless true biochemical hypogonadism is confirmed 1.