PT-141 for Women: How Bremelanotide Works, Results and Safety

What is PT-141 (bremelanotide)?

PT-141 is the research name for bremelanotide, a small synthetic peptide. It was originally developed from work on melanocortins, a family of signaling molecules the body uses for skin pigmentation, appetite and, it turned out, sexual motivation. In animal studies, drugs that switch on melanocortin receptors in the brain increased sexual solicitation, which is what led researchers to test bremelanotide for low desire in women (Pfaus 2022).

You will see the name used two ways. Vyleesi is the brand-name bremelanotide injection the FDA approved in 2019. "PT-141" is also used for compounded bremelanotide made by pharmacies, sometimes in other forms such as dissolving tablets or nasal sprays. Those products contain the same molecule, but they are not FDA-approved, and the clinical trial results below come from the injection.

How does PT-141 work in women?

Most older "female Viagra" ideas focused on blood flow to the genitals. Bremelanotide works upstream, in the brain. It activates melanocortin receptors, especially the MC4 receptor, in areas such as the hypothalamus that help regulate sexual motivation. Researchers think this shifts the balance of excitatory signals (including dopamine) in favor of desire, though the exact mechanism in humans is not fully mapped.

That is why PT-141 is aimed at desire, the wanting part of sex, rather than lubrication or physical arousal alone. For many women 40+, low desire comes from several things at once: hormones, sleep, stress, medications, relationship strain and pain with sex. A medicine that acts on brain signaling can help with one piece of that picture, which is why clinicians usually look at the whole picture first. Our guide to female sexual dysfunction explains how desire, arousal, orgasm and pain problems differ.

What did the PT-141 clinical trials show?

The approval of Vyleesi rested on two identical phase 3 trials, called RECONNECT. Together they randomized 1,267 premenopausal women (average age 39) with acquired, generalized HSDD to bremelanotide 1.75 mg or placebo, injected as needed for 24 weeks (Kingsberg 2019).

• Desire: women on bremelanotide had statistically significant gains on the desire score of the Female Sexual Function Index compared with placebo (an average difference of 0.30 and 0.42 points in the two trials, on a scale of 1.2 to 6.0).
• Distress: distress about low desire fell more with bremelanotide than placebo (an average difference of about a third of a point on a 0 to 4 scale).
• Satisfying sexual events: this was a secondary outcome, and the trials did not show a meaningful difference from placebo in the number of satisfying sexual events.

In plain terms: on average the benefit was real but modest, and some women noticed a clear change while others noticed little. Dropout was also notable. According to the prescribing information, about 40% of women on bremelanotide in one trial stopped before 24 weeks, compared with 13% on placebo (Vyleesi label).

By the numbers

The RECONNECT trials

1,267premenopausal women with HSDD randomized in the two phase 3 trialsSource: Kingsberg 2019

~40%stopped bremelanotide before 24 weeks in one trial, vs. 13% on placeboSource: Vyleesi label

Women who finished the core trials could continue in a 52-week open-label extension. Of 684 who enrolled, 272 completed it. Those who stayed on bremelanotide kept their improvements in desire and distress, and no new safety concerns appeared (Simon 2019). Because the extension had no placebo group and many women left, it says more about safety than about how many women benefit long term.

Is PT-141 a good fit if you are over 40?

The trials enrolled premenopausal women aged roughly 19 to 56, and Vyleesi's label says it is not indicated for postmenopausal women. Many women in their 40s are still premenopausal or in perimenopause, so they may fit the approved use. After menopause, any use of bremelanotide is off-label, and there is little trial evidence to say how well it works. That matters, because distressing low desire is most common in midlife: in a survey of 31,581 US women, distressing sexual problems peaked in women aged 45 to 64 (Shifren 2008).

How is PT-141 taken?

Vyleesi comes as a single-dose autoinjector. According to its label:

• The dose is 1.75 mg injected under the skin of the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity.
• No more than one dose in 24 hours, and no more than 8 doses a month.
• Stop after 8 weeks if there is no improvement.

Because it is used on demand, there is no daily pill and no build-up period, which is the biggest practical difference from flibanserin (Addyi). We compare the two in detail in PT-141 vs Addyi.

What are the side effects of PT-141?

In the pooled phase 3 trials, the most common side effects with bremelanotide were (Vyleesi label):

Nausea usually started within an hour of the dose and lasted about two hours. It was most common after the first dose (21%) and much less common after later doses. Still, 13% of women used anti-nausea medicine, and 8% left the trials because of nausea.

By the numbers

Nausea on bremelanotide

40%had nausea on bremelanotide, vs. 1% on placeboSource: Vyleesi label

8%left the trials because of nauseaSource: Vyleesi label

Blood pressure and heart rate

Bremelanotide raises blood pressure temporarily after every dose, by up to about 6 mmHg systolic and 3 mmHg diastolic, with a small drop in heart rate. These changes usually resolve within 12 hours. Taking doses closer together or more often than labeled can make the rise larger. Vyleesi is contraindicated in people with uncontrolled high blood pressure or known cardiovascular disease, and it is not recommended for anyone at high cardiovascular risk.

Skin darkening

About 1% of women in the trials developed focal hyperpigmentation, darker patches on the face, gums or breasts. It was more common with daily dosing in another study and in women with darker skin, and it did not always go away after stopping.

Medication interactions

Bremelanotide can slow stomach emptying, which may change how well some oral medicines are absorbed. The label specifically says to avoid it with oral naltrexone used for alcohol or opioid use disorder. It is not for use in pregnancy, and the label advises effective contraception while using it.

Who should not use PT-141?

• Anyone with uncontrolled high blood pressure or known heart or blood vessel disease
• Women who are pregnant, could be pregnant, or are trying to conceive
• Anyone taking oral naltrexone for alcohol or opioid use disorder
• Anyone whose low desire is better explained by another cause that should be treated first, such as depression, a medication side effect, pain with sex or a relationship problem

That last point is part of how HSDD is diagnosed. Expert guidance from the International Society for the Study of Women's Sexual Health recommends that clinicians first look for contributing factors, such as medications, mood, pain, hormones and relationship issues, and address those alongside any medicine (Clayton 2018).

How does PT-141 compare with other options?

For postmenopausal women, the evidence for testosterone is stronger than for bremelanotide; see testosterone and libido in women. For a broader look at pills and supplements, see female libido pills: what works, and for how PT-141 differs from blood-flow drugs, see PT-141 vs Viagra for women.

Where compounded PT-141 fits

Some telehealth services, including Amie, offer compounded prescriptions that contain bremelanotide. Amie's Blys™ is a rapid-dissolve tablet that combines PT-141 with oxytocin and tadalafil, taken 30 to 60 minutes before intimacy for low desire and arousal, and it was designed with women taking antidepressants in mind. Blys is compounded and is not FDA-approved; its combination and oral form have not been tested in trials like RECONNECT, and use is off-label.

Questions to ask before trying PT-141

• Do my symptoms fit HSDD, or is something else (pain, sleep, mood, a medication) the bigger driver?
• Am I premenopausal, perimenopausal or postmenopausal, and how does that change my options?
• Is my blood pressure well controlled, and do I have any heart or blood vessel conditions?
• Do I take any medicines that interact, including naltrexone, nitrates or blood pressure drugs?
• How will we judge whether it is working, and when should I stop if it isn't?