Flibanserin (Addyi) vs. Topical Testosterone – How They Differ

Mechanism of Action:

Flibanserin works primarily by altering brain neurotransmitters. It decreases serotonin (which can suppress libido) and increases dopamine and norepinephrine (which enhance sexual desire and motivation). It achieves this through serotonin receptor modulation—agonizing 5-HT1A and antagonizing 5-HT2A and 5-HT2C. It has no effect on hormone levels.

Topical testosterone, on the other hand, works as a steroid hormone by binding directly to androgen receptors. It boosts dopamine synthesis, increases sensitivity to pleasure, and improves mood, energy, and libido. It also modulates neurotransmitters like GABA, norepinephrine, endorphins, and oxytocin. Testosterone has systemic benefits, affecting metabolism, bone density, and muscle mass.

Onset and Effects:

Flibanserin must be taken nightly and takes 4 to 8 weeks for full effect. It is only approved for premenopausal women and works best for those with acquired low libido not caused by relationship issues or medications. Side effects can include fatigue, dizziness, nausea, and low blood pressure, especially when combined with alcohol.

Topical testosterone starts working faster—sometimes within days to weeks. It is often used off-label in both pre- and postmenopausal women with low libido, fatigue, or mood issues related to hormone deficiency. It can improve mood, motivation, skin, and overall quality of life when used in physiologic doses. Risks include acne, hair growth, voice deepening, and potential hormonal imbalance if overdosed.

Brain Activity:

Flibanserin targets the prefrontal cortex and hypothalamus by adjusting neurotransmitter tone. Testosterone affects broader brain areas, including the amygdala, hippocampus, and reward circuits—supporting motivation, memory, and emotional stability.

Hormonal vs Non-Hormonal:

Flibanserin is not a hormone. It does not change testosterone or estrogen levels. It’s ideal for women who want a non-hormonal approach.

Testosterone is a bioidentical hormone and directly raises free testosterone levels. It can also mildly raise estradiol (via aromatization), which may help postmenopausal women with vaginal atrophy or mood issues.

💬 Which One Should You Choose?

My honest clinical perspective:

Choose flibanserin (Addyi) if:

• The woman is premenopausal and prefers a non-hormonal treatment
• The issue is purely low sexual desire without other systemic symptoms
• She has tried counseling and lifestyle changes without improvement
• She does not drink alcohol regularly (due to serious hypotension risk)

Choose topical testosterone if:

• The woman is perimenopausal or postmenopausal
• Libido is low along with fatigue, mood changes, brain fog, poor muscle tone, or vaginal dryness
• She is open to hormone therapy and wants more comprehensive benefits
• She prefers individualized dosing and faster onset of benefits

For many women, especially those in perimenopause or menopause, topical testosterone offers broader mood, cognitive, and sexual benefits. It also allows for more flexible, dose-adjustable therapy.

💰 Cost Comparison (2025 estimates):

• Flibanserin (Addyi): ~$400–$600/month without insurance. Some coupon programs or savings cards may reduce it to $99–$150/month.
• Topical Testosterone (compounded cream): ~$40–$80/month from most compounding pharmacies (depending on dose and base used).

In most functional or hormone clinics, testosterone is more affordable and often offers better value, especially if you’re treating more than just libido.