What medications, such as Addyi (flibanserin), are available to treat low libido in women with hypoactive sexual desire disorder (HSDD)?

Medications for Female Low Libido (HSDD)

For premenopausal women with hypoactive sexual desire disorder (HSDD), flibanserin (Addyi) 100 mg taken once daily at bedtime is the FDA-approved first-line medication, though its efficacy is modest—resulting in approximately one additional satisfying sexual event every two months compared to placebo. 1, 2, 3

FDA-Approved Options for Premenopausal Women

Flibanserin (Addyi)

• Dosing: 100 mg once daily at bedtime only 3
• Mechanism: 5-HT1A agonist and 5-HT2A antagonist that modulates neurotransmitters involved in sexual desire 4, 5
• Efficacy: Increases satisfying sexual events by approximately 0.5-1.0 additional events per month, improves sexual desire scores, and reduces distress related to low desire 4, 6
• Critical safety warnings:
  • Absolute contraindication with alcohol: Do not drink alcohol from the time of dosing until the following day due to severe risk of hypotension and syncope 3
  • Contraindicated with moderate/strong CYP3A4 inhibitors (including fluconazole, erythromycin, ciprofloxacin, HIV protease inhibitors, diltiazem, verapamil) due to increased drug levels causing hypotension and fainting 3
  • Contraindicated with liver disease 3
  • Must be taken at bedtime only—daytime dosing increases risk of hypotension, syncope, and accidents 3
• Common adverse effects: Somnolence (11.8%), dizziness (10.5%), fatigue (10.3%) 4, 6

Bremelanotide

• Alternative FDA-approved option for premenopausal women with HSDD 2
• Dosing: Self-administered subcutaneous injection as needed 2
• Mechanism: Melanocortin receptor agonist 2

Off-Label Medication Options

For Premenopausal Women

• Bupropion: Off-label option with limited but supportive data, particularly useful if concurrent depression exists 1, 2, 7
• Buspirone: Off-label option with limited data but considered reasonable by expert consensus 1, 2, 7

For Postmenopausal Women

• Flibanserin: While FDA-approved only for premenopausal women, data from the PLUMERIA trial suggests efficacy in postmenopausal women with significant improvement in desire scores 8
• Vaginal DHEA (prasterone): FDA-approved for dyspareunia but also improves sexual desire, arousal, pain, and overall function in postmenopausal women, including cancer survivors 1, 7
• Ospemifene: FDA-approved SERM for dyspareunia in postmenopausal women, but contraindicated in women with history of breast cancer or estrogen-dependent cancers 1

What NOT to Use

• Phosphodiesterase-5 inhibitors (sildenafil, etc.): NOT recommended for female sexual dysfunction due to contradictory trial results and lack of evidence for effectiveness despite increasing genital blood flow 1, 2, 7
• Testosterone therapy: Not FDA-approved for HSDD and safety/efficacy not well established, particularly concerning after breast cancer 1

Clinical Algorithm for Treatment Selection

Step 1: Assess menopausal status and exclude contraindications

• Review all current medications, particularly SSRIs/SNRIs (which worsen libido), CYP3A4 inhibitors, and alcohol use 1, 3
• Screen for liver disease, cardiovascular disease, depression, and relationship factors 7, 3
• For cancer survivors, determine if cancer was hormone-sensitive 1, 7

Step 2: For premenopausal women

• First-line: Flibanserin 100 mg at bedtime IF patient can abstain from alcohol and is not on contraindicated medications 2, 3
• Alternative first-line: Bremelanotide subcutaneous injection 2
• Second-line: Bupropion or buspirone off-label 1, 2

Step 3: For postmenopausal women

• If concurrent dyspareunia: Vaginal DHEA (prasterone) addresses both desire and pain 1, 7
• If dyspareunia without hormone-sensitive cancer history: Ospemifene 1
• If isolated low desire: Consider off-label flibanserin based on PLUMERIA data 8

Step 4: Address contributing factors

• Discontinue or switch SSRIs/SNRIs if contributing to dysfunction 1
• Refer for pelvic physical therapy for orgasm difficulties 1, 7
• Consider cognitive behavioral therapy or sex therapy 7
• Recommend lifestyle modifications: exercise, stress reduction, adequate sleep 7

Critical Pitfalls to Avoid

• Never prescribe flibanserin without explicit alcohol counseling—the combination causes dangerous hypotension and syncope 3
• Do not use ospemifene or vaginal estrogens in breast cancer survivors or women with estrogen-dependent cancers 1
• Avoid setting unrealistic expectations—even the most effective medication (flibanserin) only adds about 0.5-1 satisfying sexual event per month 1, 4, 6
• Do not prescribe testosterone for HSDD—it lacks FDA approval and safety data, especially in cancer survivors 1
• Screen for depression and relationship issues—these often require concurrent treatment for sexual dysfunction therapy to be effective 1, 7

Special Considerations for Cancer Survivors

• Sexual dysfunction is highly prevalent after breast cancer treatment but lacks robust treatment options 1
• Avoid estrogen and tibolone in breast cancer survivors due to recurrence risk 1
• Vaginal DHEA showed significant improvements in a trial of 441 breast/gynecologic cancer survivors without clinically important systemic estrogenic activity 1
• For severe symptoms impacting quality of life in advanced cancer, hormone therapy may be considered after multidisciplinary discussion 1