What is PT-141?

Indication (approved use): In 2019, the FDA approved it for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women when the condition causes marked distress and is not due to other medical/psychiatric conditions or drug side effects.

Mechanism of Action
PT-141 is a melanocortin receptor agonist (primarily MC4 receptor) that modulates sexual desire through central nervous system pathways.

Unlike PDE5 inhibitors (e.g., sildenafil), which mainly affect blood vessels, PT-141 works centrally to affect sexual motivation and arousal.

Pharmacology & Dosing
Administration: Subcutaneous injection, as needed (on-demand).
Approved dose: 1.75 mg s.c.

Pharmacokinetics:
Tmax ≈ ~60 minutes
t½ ≈ 2–3 hours
Effects can last several hours, in some reports up to ~16 hours.
Clinical Efficacy (Phase III Trials – RECONNECT, 24 weeks, RCTs)

Primary endpoints:
Female Sexual Function Index–Desire domain (FSFI-D)
Female Sexual Distress Scale (FSDS-DAO)
Key results (pooled studies 301 + 302):
FSFI-D improvement: +0.35 vs placebo (P<0.001)
FSDS-DAO score reduction: −0.33 vs placebo (P<0.001)
Other endpoints: Supportive outcomes (sexual function scores, patient-reported satisfaction) trended positive, but satisfactory sexual events (SSEs) did not always show consistent significant differences.

Adverse Events (most frequently reported in trials)
Common (≥10%):
Nausea (~30–40%; up to ~40% reported in trials)
Flushing (≥10%)
Headache (≥10%)

Cardiovascular effects:
Transient increases in blood pressure and changes in heart rate were observed, usually resolving within a few hours.
Contraindicated or used with caution in patients with uncontrolled hypertension or cardiovascular disease.
Liver: Rare reports of transient liver enzyme elevations; extremely rare case reports suggest possible acute liver injury, but not common.

Long-term Safety (Extension Study)
A 52-week open-label extension study found sustained improvements in desire with no new major safety signals.
Long-term safety profile considered generally well-tolerated, with the main tolerability issues still being short-term adverse effects like nausea.

Key Usage Notes
Approved population is limited: Only for premenopausal women with acquired, generalized HSDD.
Not broadly approved for men (ED or low desire in men remains investigational).
Safety screening is critical: Hypertension, cardiovascular disease, and liver history should be assessed prior to prescribing.

Quick Data Summary
FDA Approval: 2019 (Vyleesi).
Dose: 1.75 mg subcutaneous injection, on demand.
PK: Tmax ~60 min; t½ 2–3 h; effects up to ~16 h.
Efficacy (Phase III, pooled):
FSFI-D: +0.35 (P<.001)
FSDS-DAO: −0.33 (P<.001)

Adverse events:
Nausea: up to ~40%
Flushing: ≥10%
Headache: ≥10%
Transient BP increases noted.

Comparative Table & Graph (Summary)