Can Vyleesi (bremelanotide) be given to postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD)?

Use of Vyleesi (Bremelanotide) in Postmenopausal Women with HSDD

Vyleesi (bremelanotide) is not recommended for use in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD) as it is only FDA-approved for premenopausal women with HSDD and lacks safety and efficacy data in the postmenopausal population. 1

Current Approval Status and Evidence

Bremelanotide (Vyleesi) is one of only two FDA-approved medications specifically for HSDD, but its approval is limited to premenopausal women with acquired, generalized HSDD. The approval was based on two phase III clinical trials that demonstrated:

• Statistically significant increase in sexual desire
• Statistically significant reduction in distress related to low sexual desire compared to placebo 1

However, these studies did not include postmenopausal women, creating a significant evidence gap for this population.

Treatment Options for Postmenopausal Women with Sexual Dysfunction

For postmenopausal women experiencing sexual dysfunction, the NCCN guidelines recommend several evidence-based approaches:

1. First-line treatments:

   • Water-, oil-, or silicone-based lubricants and moisturizers for vaginal dryness and sexual pain 1
   • Vaginal estrogen (pills, rings, or creams) for vaginal dryness, itching, discomfort, and painful intercourse 1

2. Additional options:

   • Pelvic floor muscle training to improve sexual pain, arousal, lubrication, orgasm, and satisfaction 1
   • Vaginal dilators for vaginismus, sexual aversion disorder, or vaginal scarring 1
   • Psychotherapy, particularly cognitive behavioral therapy 1

3. For dyspareunia in non-hormonally sensitive cancers:

   • Ospemifene may be considered 1

Why Not Bremelanotide for Postmenopausal Women?

1. Lack of safety and efficacy data: Bremelanotide has not been studied in postmenopausal cancer survivors 1

2. Regulatory limitations: FDA approval is specifically for premenopausal women with HSDD 1, 2

3. Potential safety concerns: The most common adverse reaction is nausea (40%), which may be problematic in certain populations 3

4. Modest clinical benefit: Despite statistical significance in clinical trials, the overall clinical benefit appears modest 3

Alternative Pharmacologic Options for HSDD in Postmenopausal Women

While not FDA-approved for postmenopausal women with HSDD, flibanserin has shown some promise in this population:

• The SNOWDROP and PLUMERIA trials demonstrated efficacy and safety in postmenopausal women 4
• Improvement in Female Sexual Function Index desire domain scores was significantly greater with flibanserin compared to placebo 4

However, the NCCN guidelines do not currently recommend flibanserin for postmenopausal women, as it is only FDA-approved for premenopausal women 1.

Clinical Decision-Making Algorithm

1. Confirm HSDD diagnosis in postmenopausal woman

   • Persistent or recurrent deficiency of sexual fantasies and desire causing marked distress
   • Not better explained by medical condition, medication, or relationship issues

2. First consider non-pharmacologic approaches:

   • Psychotherapy/sexual counseling
   • Pelvic floor physical therapy
   • Lubricants/moisturizers for concurrent vaginal dryness

3. For pharmacologic treatment:

   • If primarily experiencing vaginal dryness/dyspareunia: Consider vaginal estrogen preparations
   • If primarily experiencing HSDD: Do NOT use bremelanotide (Vyleesi) as it lacks approval and evidence in this population
   • Consider consultation with sexual medicine specialist for potential off-label options after discussing limitations of evidence

Important Caveats

• PDE5 inhibitors are not recommended for female sexual dysfunction due to contradictory results in clinical trials 1
• Vaginal laser therapy is not currently recommended by NCCN for treatment of vaginal dryness in postmenopausal individuals 1
• Any pharmacologic treatment should be preceded by addressing psychological, relationship, and contextual factors that may contribute to HSDD