What are the treatment options for a premenopausal female with hypoactive sexual desire disorder (HSDD)?

Medications to Increase Female Sexual Desire in Premenopausal Women

For premenopausal women with hypoactive sexual desire disorder (HSDD), flibanserin 100 mg daily at bedtime is the first-line FDA-approved medication, with bremelanotide as an alternative FDA-approved option. 1, 2

First-Line FDA-Approved Options

Flibanserin (Addyi)

• Flibanserin 100 mg taken orally once daily at bedtime is the primary FDA-approved treatment for acquired, generalized HSDD in premenopausal women. 1, 3, 2
• The medication results in approximately 1 additional satisfying sexual event every 2 months compared to placebo—a modest but statistically significant benefit. 1, 3, 4
• Must be taken at bedtime specifically because daytime administration increases risks of hypotension, syncope, accidental injury, and CNS depression. 2
• Discontinue after 8 weeks if no symptom improvement is reported. 2

Critical Safety Warnings for Flibanserin

• Absolutely contraindicated with alcohol consumption—patients must wait at least 2 hours after consuming 1-2 standard drinks before taking flibanserin, or skip the dose entirely if they consumed 3+ drinks that evening. 2
• Contraindicated with all moderate or strong CYP3A4 inhibitors due to severe hypotension and syncope risk. 2
• Contraindicated in any hepatic impairment. 2
• Most common adverse effects include somnolence (11.8%), dizziness (10.5%), and fatigue (10.3%). 4

Bremelanotide (Vyleesi)

• Bremelanotide is the second FDA-approved option for premenopausal HSDD, administered as a self-injected subcutaneous dose as needed before anticipated sexual activity. 1, 5
• Functions as a melanocortin receptor agonist with a different mechanism than flibanserin. 1
• Significantly improves sexual desire and reduces distress related to low sexual desire compared to placebo in clinical trials. 5
• Offers the advantage of as-needed dosing rather than daily administration, which may appeal to patients who prefer episodic treatment. 1

Second-Line Off-Label Options

When first-line agents are contraindicated, not tolerated, or ineffective:

Bupropion

• Considered an off-label option by expert consensus panels despite limited safety and efficacy data. 1, 6, 7
• May work by increasing dopamine and norepinephrine in the brain, which are associated with sexual desire. 6

Buspirone

• Another off-label option supported by expert panels, though data remains limited. 1, 6, 7
• Mechanism may involve modulation of serotonergic pathways. 6

Treatment Algorithm

Step 1: Confirm diagnosis of acquired, generalized HSDD—low sexual desire causing marked distress that is NOT due to a co-existing medical/psychiatric condition, relationship problems, or medication effects. 2

Step 2: Initiate flibanserin 100 mg at bedtime as first-line therapy, ensuring patient understands alcohol restrictions and CYP3A4 inhibitor contraindications. 1, 2

Step 3: If flibanserin is contraindicated (hepatic impairment, concurrent CYP3A4 inhibitors, alcohol use concerns) or patient prefers as-needed dosing, offer bremelanotide. 1, 5

Step 4: If FDA-approved options fail or are not tolerated after 8 weeks, consider off-label bupropion or buspirone. 1, 6

Step 5: Integrate non-pharmacologic interventions including mindfulness-based cognitive behavioral therapy, pelvic physical therapy, and mechanical options like vibrators or clitoral stimulatory devices. 1, 6

What NOT to Use

• Phosphodiesterase type 5 inhibitors (PDE5i like sildenafil) are NOT recommended for female sexual dysfunction due to contradictory clinical trial results and lack of effectiveness data in women. 1
• Testosterone is not FDA-approved for HSDD in premenopausal women in the United States, though it may be discussed as an off-label option. 1, 6
• "Restorative or regenerative" therapies lack robust clinical trial data and FDA approval. 1

Critical Pitfalls to Avoid

• Setting unrealistic expectations—current pharmacological treatments show limited effectiveness, with the best option (flibanserin) producing only about one additional satisfying sexual event every two months. 1
• Failing to screen for psychological factors—anxiety, depression, and relationship issues significantly contribute to sexual dysfunction and require concurrent management. 1, 6
• Overlooking medication-induced sexual dysfunction—many common medications (SSRIs, antihypertensives) can cause or worsen HSDD. 6, 8
• Ignoring the 2-week washout period required when switching between flibanserin and CYP3A4 inhibitors. 2