What medication is used to treat hypoactive sexual desire disorder (HSDD) in premenopausal women to increase female libido?

Medications for Female Hypoactive Sexual Desire Disorder (HSDD)

For premenopausal women with HSDD, flibanserin is the first-line FDA-approved medication, with bremelanotide as an alternative FDA-approved option. 1

First-Line Treatment Options

Flibanserin (Addyi)

• FDA-approved specifically for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women 2
• Recommended dosage is 100 mg taken once daily at bedtime 2
• Mechanism: 5-HT1A agonist/5-HT2A antagonist that modulates neurotransmitters involved in sexual desire 3
• Clinical efficacy:
  • Results in approximately 1 additional satisfying sexual event every 2 months compared to placebo 1
  • Significantly improves sexual desire as measured by the Female Sexual Function Index (FSFI) desire domain score 3, 4
  • Reduces distress related to low sexual desire 3, 4
• Common adverse effects include dizziness, somnolence, nausea, and fatigue 2, 5
• Important safety considerations:
  • Contraindicated with moderate or strong CYP3A4 inhibitors 2
  • Contraindicated in patients with hepatic impairment 2
  • Boxed warning regarding hypotension and syncope risk when used with alcohol 2

Bremelanotide (Vyleesi)

• FDA-approved for premenopausal women with HSDD 1
• Self-administered subcutaneous injection used as needed 1
• Mechanism: Melanocortin receptor agonist 1
• Clinical efficacy:
  • Significantly increases sexual desire compared to placebo 1
  • Significantly reduces distress related to low sexual desire 1
• Has not been extensively studied in cancer survivors, but considered an appropriate option for HSDD 1

Second-Line/Off-Label Options

For Premenopausal Women

• Bupropion (off-label) 1
  • Antidepressant that may improve sexual desire
  • Limited safety and efficacy data, but considered an option by expert panels
• Buspirone (off-label) 1
  • Anxiolytic that may improve sexual desire
  • Limited data but considered an option by expert panels

For Postmenopausal Women

• Flibanserin may be effective in postmenopausal women despite not being FDA-approved for this population 1, 6
• The PLUMERIA study showed improvement in FSFI desire scores in postmenopausal women taking flibanserin 6

Special Considerations

• Ospemifene is FDA-approved for dyspareunia (painful intercourse) in postmenopausal women but is not specifically indicated for HSDD 1
• Phosphodiesterase type 5 inhibitors (PDE5i) are not recommended for female sexual dysfunction due to limited and contradictory evidence 1
• For cancer survivors with HSDD, treatment options should be carefully selected based on cancer type, particularly for hormone-sensitive cancers 1

Treatment Algorithm

1. Confirm diagnosis of HSDD: Ensure low sexual desire causes marked distress or interpersonal difficulty and is not due to a medical/psychiatric condition, relationship problems, or medication effects 2

2. For premenopausal women:

   • First-line: Flibanserin 100 mg daily at bedtime 1, 2
   • Alternative: Bremelanotide as needed 1
   • Consider discontinuing flibanserin after 8 weeks if no improvement 2

3. For postmenopausal women:

   • Consider off-label use of flibanserin (evidence suggests efficacy) 1, 6
   • For those with concurrent dyspareunia, consider ospemifene (if no history of estrogen-dependent cancers) 1

4. For patients with contraindications or intolerance to first-line options:

   • Consider off-label use of bupropion or buspirone 1

Common Pitfalls and Caveats

• Flibanserin must be taken daily at bedtime to minimize adverse effects; administration during waking hours increases risks 2
• Alcohol must be avoided until the following day after taking flibanserin due to risk of severe hypotension and syncope 2
• Patients should avoid activities requiring full alertness for at least six hours after taking flibanserin 2
• The modest efficacy of these medications (approximately one additional satisfying sexual event every two months for flibanserin) should be discussed with patients to set realistic expectations 1, 5
• Careful consideration of medication interactions is essential, particularly with CYP3A4 inhibitors and flibanserin 2