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Sexual Health

PT-141 (Bremelanotide)

Melanocortin Receptor Agonist - Sexual Dysfunction Guide

Clinical Disclaimer: This guide is for educational purposes only and does not constitute medical advice. Prescribers should exercise independent clinical judgment and verify all information before making treatment decisions.

What is PT-141?

PT-141, also known as bremelanotide, is a synthetic peptide analog of alpha-melanocyte-stimulating hormone (α-MSH). Unlike PDE5 inhibitors that work peripherally, PT-141 acts centrally on melanocortin receptors in the brain to enhance sexual desire and arousal.

Structure: Cyclic heptapeptide derived from Melanotan II

FDA Status: Approved as Vyleesi for HSDD in premenopausal women (2019)

Mechanism: Central nervous system action via melanocortin 4 receptors (MC4R)

Mechanism of Action

Melanocortin System Activation

MC4 Receptor Agonism:

  • Binds to melanocortin 4 receptors (MC4R) in the hypothalamus
  • Activates neural pathways involved in sexual arousal
  • Enhances dopaminergic signaling in sexual response circuits
  • Works centrally, not peripherally like PDE5 inhibitors

Sexual Response Pathway

  • Increases sexual desire (libido) rather than just physical response
  • Enhances arousal and genital engorgement
  • Acts on motivational/desire component of sexual function
  • Independent of hormonal status

Distinct from Erectile Dysfunction Medications

  • Does not require physical stimulation to work
  • Acts on desire/motivation, not just blood flow
  • Effective even when PDE5 inhibitors fail
  • Works for both psychological and physiological dysfunction

Clinical Applications

FDA-Approved Indication

Hypoactive Sexual Desire Disorder (HSDD) in Premenopausal Women:

  • Acquired, generalized HSDD
  • Causes marked distress or interpersonal difficulty
  • Not due to other conditions or medications

Off-Label Uses

Male Sexual Dysfunction:

  • Erectile dysfunction (especially psychogenic)
  • Low libido
  • ED non-responsive to PDE5 inhibitors
  • Performance anxiety

Other Considerations:

  • Post-menopausal sexual dysfunction
  • Medication-induced sexual dysfunction (SSRIs, etc.)
  • Anorgasmia (limited data)

Dosing Protocols

FDA-Approved Dosing (Vyleesi)

Premenopausal Women with HSDD:

  • 1.75 mg subcutaneously
  • Administer at least 45 minutes before anticipated sexual activity
  • Maximum: 1 dose per 24 hours
  • Maximum: 8 doses per month

Off-Label Male Dosing

Erectile Dysfunction/Low Libido:

  • 0.5-2.0 mg subcutaneously
  • Administer 30-60 minutes before anticipated activity
  • Start with lower dose (0.5-1.0 mg) and titrate
  • Maximum: 1 dose per 24 hours

Administration

  • Subcutaneous injection (abdomen or thigh)
  • Auto-injector available (Vyleesi)
  • Effects begin within 45-60 minutes
  • Duration of effect: 4-6 hours for most patients

Patient Selection Criteria

Good Candidates

Women:

  • Premenopausal with acquired HSDD
  • Significant distress related to low desire
  • No untreated underlying psychiatric conditions
  • Not explained by relationship or other issues
  • Failed or intolerant of other HSDD treatments

Men (Off-Label):

  • Psychogenic erectile dysfunction
  • Low libido despite normal testosterone
  • ED non-responsive to PDE5 inhibitors
  • Performance anxiety contributing to dysfunction

Contraindications

Absolute:

  • Uncontrolled hypertension
  • Known cardiovascular disease
  • Hypersensitivity to bremelanotide

Relative:

  • Controlled hypertension (monitor BP)
  • History of hypertensive crisis
  • Concurrent use of naltrexone (may reduce efficacy)
  • Significant psychiatric disorders
  • Hepatic impairment

Safety Profile

Common Adverse Effects

Most Frequent:

  • Nausea (40% - most common, usually transient)
  • Flushing (21%)
  • Injection site reactions (13%)
  • Headache (11%)
  • Hot flush

Other Reported Effects:

  • Transient hypertension
  • Hyperpigmentation (rare, usually reversible)
  • Fatigue
  • Dizziness

Blood Pressure Considerations

  • Transient BP increase of ~3-5 mmHg typical
  • Peak effect 2-4 hours post-injection
  • Contraindicated in uncontrolled hypertension
  • Monitor patients with cardiovascular risk factors

Nausea Management

  • Nausea is typically most severe with first doses
  • Often diminishes with repeated use
  • Take on relatively empty stomach
  • Anti-emetics may be used prophylactically

Hyperpigmentation Warning

  • Focal hyperpigmentation reported (face, gingiva, breasts)
  • Usually reversible with discontinuation
  • More common with frequent use
  • Counsel patients on this possibility

Monitoring Parameters

Baseline Assessment

  • Blood pressure measurement
  • Cardiovascular risk assessment
  • Mental health screening
  • Sexual function assessment (validated questionnaires)
  • Relationship and psychosocial factors
  • Rule out reversible causes of low desire

Ongoing Monitoring

  • Blood pressure before each dose (home monitoring)
  • Treatment efficacy (desire, satisfaction scores)
  • Adverse effect assessment
  • Skin examination for hyperpigmentation
  • Mental health status

Cardiovascular Monitoring

  • Check BP before initial doses
  • Patients should have access to BP monitoring
  • Avoid use if pre-dose BP is elevated
  • Discontinue if significant hypertension develops

Drug Interactions

Clinically Significant

Naltrexone:

  • May reduce efficacy of PT-141
  • Naltrexone blocks opioid receptors involved in sexual response
  • Avoid concurrent use if possible

Antihypertensives:

  • Monitor for additive effects on blood pressure
  • May need dose adjustment of antihypertensives

PDE5 Inhibitors (Viagra, Cialis):

  • Can be used in combination
  • Monitor for cumulative cardiovascular effects
  • May provide complementary mechanisms

Other Considerations

  • SSRIs: May still be effective for SSRI-induced sexual dysfunction
  • Alcohol: May increase nausea; moderate intake
  • Hormonal therapies: Can be used alongside HRT

Compounding Considerations

Quality Requirements

  • Certificate of Analysis (identity, purity, potency)
  • Sterility and endotoxin testing
  • Lyophilized formulation preferred
  • Proper reconstitution protocols

Reconstitution

  • Use bacteriostatic water
  • Reconstitute to appropriate concentration
  • Gently swirl, do not shake
  • Clear solution required; discard if cloudy

Storage

  • Lyophilized: Refrigerate or room temperature (short-term)
  • Reconstituted: Refrigerate at 2-8°C
  • Use within 21 days of reconstitution
  • Protect from light

Regulatory Status

  • FDA-approved as Vyleesi (bremelanotide) for HSDD in premenopausal women
  • Available through compounding pharmacies
  • Off-label use for male sexual dysfunction
  • Not FDA-approved for men or postmenopausal women

Clinical Pearls

  1. Manage nausea expectations: Warn patients about first-dose nausea; it often improves with continued use
  2. Central mechanism: Explain that PT-141 works on desire, not just physical response
  3. Timing matters: Effects begin at 45-60 minutes; plan accordingly
  4. Not for daily use: Maximum 8 doses monthly per FDA labeling
  5. Complementary to PDE5 inhibitors: Can be combined for multi-mechanism approach
  6. Address underlying factors: PT-141 works best as part of comprehensive sexual health approach

References

  1. Clayton AH, et al. Bremelanotide for Hypoactive Sexual Desire Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Womens Health. 2019;28(10):1310-1318.
  2. Kingsberg SA, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908.
  3. Diamond LE, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141. Int J Impot Res. 2004;16(1):51-59.
  4. FDA Prescribing Information for Vyleesi (bremelanotide injection).