Short answer: In men with truly low testosterone, TRT improved sexual desire and activity in a 1-year placebo trial. Bremelanotide, sold as Vyleesi and called PT-141 online, is FDA approved only for low sexual desire in premenopausal women, not men. Melanotan II has no approval anywhere we found, and case reports link it to mole changes and melanoma. Kisspeptin has only small, short human studies.
| Compound | Best evidence | What it shows |
|---|---|---|
| Testosterone (in men with low testosterone) | Approved for a different use | Approved for hypogonadism. In the Testosterone Trials it improved 10 of 12 measures of sexual activity vs placebo in men 65 and older with low libido. |
| Bremelanotide (Vyleesi, PT-141) | FDA-approved for this | Approved for acquired, generalized low sexual desire with distress in premenopausal women only. The label says it is not for men or postmenopausal women. |
| Melanotan II | Small or early human studies | In a 1998 crossover study, 8 of 10 men with psychogenic erectile dysfunction got erections. Not approved; unregulated use is tied to mole changes and melanoma case reports. |
| Kisspeptin | Small or early human studies | A 75-minute infusion into a vein changed brain responses to sexual videos in 32 men with low desire. No longer-term trial. FDA lists kisspeptin-10 in 503A Category 2. |
"Animal or lab studies only" means no published human trial for this goal that we could find. Results in rats or cells often do not carry over to people. Compounds that are not FDA-approved have no tested label for dose, purity or safety.
Only when testosterone is actually low, as far as trials show. The Testosterone Trials gave testosterone gel or placebo for 1 year to men 65 and older with total testosterone below 275 ng/dL. In the sexual function trial (470 men with low libido and a partner), testosterone improved 10 of 12 measures of sexual activity, along with sexual desire and erectile function. The gains grew with bigger rises in testosterone and estradiol, and no single threshold level was found.
The researchers described the benefit as moderate. A separate trial that blocked hormones in healthy men found sexual desire generally fell as testosterone doses were lowered, and that loss of estradiol contributed too. That is one reason lowering estradiol on TRT can backfire; see estrogen on TRT.
PT-141 is the research name for bremelanotide, the drug in Vyleesi. The label calls it a melanocortin receptor agonist and says how it improves low desire in women is unknown. The FDA label approves it for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD: low desire that causes marked distress and is not caused by another condition, a relationship problem or a medicine). The label states it is not for postmenopausal women or men, and not to enhance sexual performance.
| Measure | Vyleesi | Placebo |
|---|---|---|
| Desire score change (study 1 / study 2) | +0.5 / +0.6 | +0.2 / +0.2 |
| Distress about low desire, change | -0.7 / -0.7 | -0.4 / -0.4 |
| Satisfying sexual events | No significant difference | No significant difference |
| Nausea | 40% | 1.3% |
| Flushing | 20.3% | 0.3% |
| Stopped due to side effects | 18% | 2% |
The label also warns that blood pressure rises briefly after each dose (up to 6 mm Hg systolic) and heart rate drops, and it should not be used with uncontrolled high blood pressure or heart disease. Focal darkening of the skin occurred in 1% in trials and in 38% of people dosed daily for 8 days. It limits use to one dose in 24 hours and 8 doses a month. These label facts apply to the approved product; vials sold online as PT-141 are not that product.
Melanotan II is a lab-made analog of alpha-MSH (alpha-melanocyte-stimulating hormone), which drives skin pigmentation. In a small 1998 double-blind crossover study, 8 of 10 men with erectile dysfunction of no physical cause developed erections after injection. Nausea, stretching and yawning, and lower appetite were more common than on placebo.
It is not an approved drug. A 2017 dermatology review notes afamelanotide is the only alpha-MSH analog approved for any use, and says unregulated melanotan use is linked to changes in existing moles, new atypical moles, and four reported melanomas, though a direct cause was not proven. One case report describes melanoma in a 20-year-old woman after a 3 to 4 week course plus sunbeds. Because what is in an unregulated vial is unknown, the full range of side effects is also unknown.
Kisspeptin is a hormone that starts the reproductive hormone chain. In a 2023 randomized crossover trial, 32 men with HSDD got a 75-minute infusion of kisspeptin-54 into a vein or placebo. Kisspeptin changed activity in brain areas tied to sexual processing, increased penile response to sexual videos by up to 56% more than placebo, and raised one measure of happiness about sex. That was a single lab session with a form given by infusion. No trial has tested it as a treatment, and FDA lists kisspeptin-10 in Category 2 of its 503A list for significant safety risks.
The Vyleesi label itself rules out low desire caused by another medical or psychiatric condition, relationship problems or a medicine, which shows how many causes there can be besides hormones. Diagnosis and prescribing decisions belong with a licensed clinician who can examine you and order labs.
Terms on this page: Peptide · Research use only (RUO)