PT-141, or bremelanotide, is the only molecule in the melanocortin peptide family approved as a drug for low sexual desire in women. The US Food and Drug Administration approved it in 2019 under the name Vyleesi. The approval rested on two phase 3 RECONNECT trials with 1267 women. Below you will find how PT-141 acts on desire, what each trial measured and how the peptide in a vial differs from the ready-made autoinjector.
How does PT-141 work on libido in women?
PT-141 acts in the brain, not in the genitals. It stimulates melanocortin receptors, mainly MC4R, which are found in many areas of the central nervous system. These receptors take part in regulating desire and arousal. The Vyleesi label states plainly that the exact mechanism by which it improves desire is unknown.
This sets PT-141 apart from the drugs women know from stories about treatment for men. Sildenafil widens blood vessels and does not create the wish for sex on its own. PT-141 targets the drive itself, that is whether the wish for intimacy appears at all. That is why the trials in women measured above all the level of desire and the distress linked to it.
What exactly is PT-141 approved for?
Vyleesi has a narrow indication: premenopausal women with acquired, generalised hypoactive sexual desire disorder. The short name for this disorder is HSDD. Acquired means that libido used to be normal. Generalised means that the drop applies to every situation and every partner. The low desire must also cause marked distress or difficulty in the relationship.
The indication excludes cases where low libido comes from another illness, from medicines or from problems in the relationship. The drug is not meant for postmenopausal women or for men. Studies in men do exist, and we cover them separately in the guide on PT-141 in men.
What did the RECONNECT trials show?
In the two RECONNECT trials, women taking PT-141 reported more desire and less distress than women on placebo. The results were published in Obstetrics and Gynecology in 2019. Both trials had the same design and lasted 24 weeks. Participants injected 1.75 mg of bremelanotide or placebo under the skin whenever they expected sexual activity.
1267 women were randomised, and 1202 entered the efficacy analysis. The average age was 39. Almost all participants came from sites in the United States. Desire was measured with the FSFI questionnaire, the Female Sexual Function Index. Distress was measured with the FSDS scale, which asks how upsetting low libido is.
| Result compared with placebo | Trial 301 | Trial 302 | Both combined |
|---|---|---|---|
| Increase in desire (FSFI) | +0.30 | +0.42 | +0.35 |
| Decrease in distress (FSDS) | -0.37 | -0.29 | -0.33 |
| Statistically significant | yes | yes | yes |
The differences were statistically significant in both trials and in their combined analysis. The numbers in the table are the advantage over placebo in scale points, not the share of women the drug helped. The authors concluded that bremelanotide improves desire and reduces the related distress in premenopausal women with HSDD.
Does PT-141 work regardless of age, weight and contraception?
Yes, a separate analysis from 2022 found improvement in almost all subgroups of women. The researchers divided the 1202 RECONNECT participants by age, body weight, BMI and testosterone level. Better desire and lower distress appeared in all of these groups, with few exceptions.
Women who did not use hormonal contraception reported a significant rise in desire. In women taking the pill, the advantage of PT-141 was visible in the numbers but smaller. The drop in distress was significant in both groups. The result also did not depend on how long a woman had had low libido.
What do the trial participants themselves say?
Women taking PT-141 described more desire, more physical arousal and better intimacy in the relationship. These findings come from an exit study from 2021, carried out after the placebo-controlled part had ended. 242 RECONNECT participants filled in a survey, and 80 of them also had a telephone interview.
At the time of the survey the women still did not know whether they had received the drug or placebo. Participants from the placebo group also described benefits, but of a different kind. These were about starting treatment at all and talking better with their partner. Physical responses such as arousal were not reported in this group.
What dose was studied and how was it given?
The phase 3 trials used a single dose: 1.75 mg of bremelanotide under the skin. An earlier trial from 2016 compared three doses, 0.75 mg, 1.25 mg and 1.75 mg, in 327 women over 12 weeks. The two higher doses combined gave more satisfying sexual events per month than placebo. They also improved the overall sexual function score and reduced distress.
The Vyleesi label describes injection into the abdomen or thigh at least 45 minutes before expected sexual activity. It advises no more than one dose in 24 hours and no more than eight a month. If a woman sees no improvement after eight weeks, the drug should be stopped. The table below collects the numbers from three trials in women.
| Trial | Number of women | Duration | Dose |
|---|---|---|---|
| Clayton et al., 2016 (phase 2b) | 327 in the analysis | 12 weeks | 0.75, 1.25 or 1.75 mg as needed |
| RECONNECT 301 | 1267 randomised across both trials | 24 weeks | 1.75 mg as needed |
| RECONNECT 302 | 1202 in the efficacy analysis | 24 weeks | 1.75 mg as needed |
What side effects were described in women?
The most common side effect was nausea, which occurred in 40.0 percent of women on PT-141 against 1.3 percent on placebo. The data come from a safety review of the whole clinical programme, published in 2022. The programme covered 3500 people in 43 studies. Flushing appeared in 20.3 percent of women, headache in 11.3 percent and injection site reactions in 5.4 percent.
Nausea was the most common reason for stopping treatment. The label states that in most women it eased with further doses. After each dose, blood pressure rises for a while and heart rate slows, and both usually return to normal within 12 hours. That is why the drug is contraindicated in people with uncontrolled high blood pressure or known cardiovascular disease.
A separate matter is darkening of the skin in some places, for example on the face, gums and breasts. With dosing as on the label it occurred in 1 percent of women. In a separate study in which participants took bremelanotide daily for 8 days, it appeared in 38 percent of people. More frequent dosing clearly raises this risk, which links PT-141 to its relative, melanotan 2.
How does PT-141 from a vial differ from Vyleesi?
PT-141 in the shop is the same molecule as in Vyleesi, but in a different form and with a different status. Vyleesi is a ready solution of 1.75 mg in a single-use autoinjector, made under drug quality control. A vial in the shop contains 10 mg of lyophilised powder that you dissolve and measure out yourself. Such a product is material for laboratory research and does not carry the drug approval.
One 10 mg vial is enough for many portions of the size used in the trials. How to convert the contents of a vial into insulin syringe units is explained in the guide on converting a peptide dose to syringe units. Dissolving the powder step by step is covered in the guide on how to reconstitute peptides.
Where to buy PT-141 and how much does it cost?
In the shop, PT-141 comes in 10 mg vials from two brands. PT-141 10 mg Genheal costs 25 EUR. PT-141 10 mg Bio-Peptide costs 30 EUR. Both versions, a description of the molecule and the price per milligram are on the PT-141 page.
Frequently asked questions
Does PT-141 work in women?
Yes. In two RECONNECT trials with 1267 premenopausal women, PT-141 significantly increased desire and reduced the related distress compared with placebo.
How fast does PT-141 work in women?
In the trials women injected 1.75 mg at least 45 minutes before expected sexual activity. The Vyleesi label describes it the same way.
Is PT-141 an approved drug?
Yes. The FDA approved bremelanotide in 2019 as Vyleesi for premenopausal women with acquired, generalised low sexual desire.
What are the most common side effects of PT-141?
In the phase 3 trials nausea occurred in 40.0 percent of women, flushing in 20.3 percent and headache in 11.3 percent.
Does PT-141 work in women using contraception?
A 2022 analysis found lower distress regardless of hormonal contraception. The rise in desire was significant in women without contraception and visible in the numbers in women using it.
This is information about published research, not medical advice. The choice of treatment belongs to a doctor.
Sources
- Kingsberg SA, Clayton AH, Portman D et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstetrics and Gynecology, 2019, 134(5): 899-908. https://doi.org/10.1097/AOG.0000000000003500
- Clayton AH, Althof SE, Kingsberg S et al. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Women's Health, 2016, 12(3): 325-337. https://doi.org/10.2217/whe-2016-0018
- Simon JA, Kingsberg SA, Portman D et al. Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide. Journal of Women's Health, 2022, 31(3): 391-400. https://doi.org/10.1089/jwh.2021.0225
- Koochaki P, Revicki D, Wilson H et al. The Patient Experience of Premenopausal Women Treated with Bremelanotide for Hypoactive Sexual Desire Disorder: RECONNECT Exit Study Results. Journal of Women's Health, 2021, 30(4): 587-595. https://doi.org/10.1089/jwh.2020.8460
- Clayton AH, Kingsberg SA, Portman D et al. Safety Profile of Bremelanotide Across the Clinical Development Program. Journal of Women's Health, 2022, 31(2): 171-182. https://doi.org/10.1089/jwh.2021.0191
- FDA. Vyleesi (bremelanotide injection), prescribing information, 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf