Why is flibanserin (Addyi) not indicated for men with orgasmic dysfunction despite a study reporting restoration of orgasm?

Why Flibanserin Is Not Indicated for Men

Flibanserin is FDA-approved exclusively for premenopausal women with hypoactive sexual desire disorder (HSDD) and is explicitly contraindicated for use in men because it was never studied or approved for male sexual dysfunction, and established treatments for male orgasmic dysfunction already exist. 1

FDA Approval and Indication Specificity

• The FDA approved flibanserin in August 2015 specifically and exclusively for acquired, generalized HSDD in premenopausal women. 2, 1
• The FDA drug label explicitly states: "ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men." 1
• This sex-specific limitation exists because flibanserin's entire clinical development program, safety profile, and efficacy data were generated exclusively in female populations with HSDD. 3, 4

Mechanism of Action and Sex-Specific Pathophysiology

• Flibanserin acts as a postsynaptic 5-HT1A agonist and 5-HT2A antagonist, designed to correct neurotransmitter imbalances specifically implicated in female HSDD by increasing dopamine and norepinephrine while decreasing serotonin. 3, 5
• This mechanism targets the neurobiological substrate of desire disorders, not orgasmic dysfunction, which has different underlying pathophysiology. 5, 6
• The drug was developed based on theories about neurotransmitter imbalances in female sexual desire, not male orgasmic function. 6

Established Treatment Paradigm for Male Orgasmic Dysfunction

For men with orgasmic dysfunction, NCCN guidelines recommend phosphodiesterase type 5 inhibitors (PDE5i) as the established first-line pharmacological treatment, which can specifically address problems with male orgasms including less intensity and difficulty achieving orgasm. 2

Male Sexual Dysfunction Treatment Algorithm:

• First-line: Lifestyle modifications (smoking cessation, weight loss, increased physical activity, avoiding excess alcohol). 2
• Second-line pharmacological: PDE5i therapy (sildenafil, tadalafil, vardenafil) for erectile dysfunction and orgasmic difficulties, with proven efficacy and tolerability in men. 2
• Adjunctive therapy: Testosterone replacement if total morning testosterone is <300 ng/dL, which may relieve symptoms of ED, ejaculation problems, or orgasm difficulties. 2
• Concurrent psychological intervention: Referral to sex and couples therapy, as psychological overlay frequently exists in male sexual dysfunction. 2

Why the Study You Reference Is Irrelevant

• Any isolated study reporting orgasm restoration in men would represent off-label, unapproved use without the requisite safety and efficacy data required for FDA approval in male populations. 1
• Flibanserin's modest efficacy (approximately 1 additional satisfying sexual event every 2 months) was demonstrated specifically for desire disorders in women, not orgasmic dysfunction in men. 2, 7
• The drug carries significant safety concerns including hypotension, syncope, CNS depression, and dangerous interactions with alcohol and CYP3A4 inhibitors—risks that have only been characterized in female populations. 1, 4

Critical Safety Considerations

• Flibanserin carries a boxed warning for hypotension and syncope, particularly when combined with alcohol or moderate/strong CYP3A4 inhibitors. 1
• The safety profile includes dizziness, somnolence, nausea, fatigue, insomnia, and sedation—adverse events typical of centrally acting drugs that have only been studied in women. 1, 5
• Use is contraindicated with hepatic impairment and requires bedtime dosing specifically to mitigate risks of hypotension, syncope, accidental injury, and CNS depression during waking hours. 1

Common Pitfall to Avoid

• Do not extrapolate efficacy or safety data from female HSDD studies to male orgasmic dysfunction—these represent fundamentally different conditions with different underlying pathophysiology, and flibanserin's mechanism of action targets desire, not orgasm. 3, 5
• For male patients with orgasmic dysfunction, prescribe evidence-based treatments: PDE5i as first-line pharmacotherapy, testosterone replacement if hypogonadal, and psychological/couples therapy as indicated. 2