PT-141 FOR MEN: A NEW DRUG TO TREAT ERECTILE DYSFUNCTION AND LOW LIBIDO

Introduction

Erectile dysfunction (ED) and other male sexual dysfunctions can significantly impact quality of life and relationships. While phosphodiesterase-5 inhibitors (PDE5is) like sildenafil (Viagra®) are effective for many men, a substantial minority (estimated 30–40%) see little or no improvement with these standard therapies. Moreover, PDE5is act peripherally on blood vessels and require sexual stimulation to be effective, which may not address issues of low sexual desire or psychological barriers to arousal. PT-141, known generically as bremelanotide, is an emerging therapy that works through a completely different mechanism. Originally approved as an on-demand treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, bremelanotide is now being explored off-label for men with ED and related conditions. This comprehensive post presents clinical evidence to explain how PT-141 works in men, its safety, dosing, effectiveness, and how it compares with existing treatments.

What is PT-141 (Bremelanotide)?

Bremelanotide is a synthetic peptide drug and the first of a new class: melanocortin receptor agonists. It was derived from research on melanotan II – a peptide initially developed for sunless tanning that unexpectedly induced sexual arousal and erections in early tests. Bremelanotide is essentially a refined metabolite of melanotan II, designed to maximize sexual effects while minimizing side effects. In 2019, the U.S. FDA approved bremelanotide (brand name Vyleesi®) as an as-needed injectable treatment for women with HSDD. Though not officially approved for men yet, growing clinical data suggest PT-141 may help men with ED or low libido, especially those who do not respond to or cannot take existing therapies. In the sections below, we delve into how PT-141 works in males, its clinical evidence, safety profile, dosing strategies, ways to gauge its effectiveness, combination uses, ideal candidates, and current availability.

Mechanism of Action in Males

Central Pathway Activation: Unlike Viagra and other ED pills that act on blood vessels, PT-141 works on the brain. Bremelanotide is a melanocortin receptor agonist, primarily targeting the MC4 receptor in the hypothalamus – a key brain region for sexual function. By activating melanocortin receptors, bremelanotide triggers a cascade of neural signals that ultimately stimulate sexual arousal and the erectile response. In simple terms, bremelanotide initiates arousal and erections via the central nervous system, rather than directly relaxing penile blood vessels. This central mechanism sets it apart from PDE5 inhibitors, which facilitate an erection only when a man is already sexually stimulated.

Dopamine Release and Sexual Arousal: Activation of MC4 receptors by PT-141 is thought to increase the release of dopamine in the medial preoptic area of the hypothalamus, a region that governs sexual desire and arousal. Dopamine is a neurotransmitter strongly associated with sexual excitement. By raising dopamine levels in key brain pathways, PT-141 can heighten libido (sexual desire) and initiate the physiological processes leading to an erection. This central dopaminergic effect means PT-141 has the potential to help men who have low sexual desire or psychological ED, in addition to those with purely vascular erectile problems.

Initiating vs. Facilitating Erections: Because PT-141 acts on the brain’s sexual centers, it can “initiate” an erection even in the absence of direct sexual stimulation. This is different from PDE5is (like sildenafil or tadalafil), which only enhance the quality of an erection in response to arousal signals that must already be present. In fact, early studies noted that bremelanotide could produce erections in men without visual sexual stimuli by purely central activation. Clinicians sometimes describe this as a more “natural” arousal pathway – PT-141 essentially works upstream, prompting the body’s own arousal signals, whereas PDE5is work downstream by improving blood flow to an already aroused penis.

Melanocortin Receptors and Effects: Bremelanotide is non-selective among melanocortin receptors 1 through 5 (except MC2), but its pro-sexual effects are primarily linked to MC4 receptor stimulation. The MC4 receptor plays a role in sexual function for both men and women, as evidenced by increased sexual desire observed when it’s activated. Notably, melanocortin receptors also affect other processes like pigmentation and appetite. MC1 receptors control skin pigmentation, which explains one rare side effect of PT-141: transient skin darkening or freckling in some individuals. MC4 activation in the brain, meanwhile, leads to neuronal signals down the spinal cord to the pelvic organs, resulting in penile erection via increased parasympathetic activity and possibly some direct pro-erectile effects on penile tissue.I mportantly, bremelanotide’s mechanism does not rely on nitric oxide, so it can work even when nitric oxide pathways (targeted by Viagra and others) are insufficient.

In summary, PT-141’s mechanism in males can be thought of as “flipping the switch” in the brain that turns on sexual desire and erection signals. It leverages the body’s central pathways (melanocortin and dopamine systems) to produce an erection and heighten libido, rather than directly affecting the penis’ blood vessels. This novel approach positions bremelanotide as a complementary therapy to existing ED drugs and a promising option for men whose sexual dysfunction has a significant central or psychological component.

Clinical Evidence for PT-141 in Men

Research on bremelanotide for male sexual dysfunction spans over 15 years, including clinical trials in men with ED and more recent real-world clinical experience. Below we review the key evidence:

Early Clinical Trials (Intranasal Bremelanotide)

Initial studies of PT-141 in men utilized an intranasal spray formulation. In the mid-2000s, several Phase II trials were conducted in men with erectile dysfunction, including those with psychogenic ED and those who had not responded to Viagra or similar drugs. One large placebo-controlled trial (presented at the AUA meeting in 2007) tested intranasal bremelanotide in 726 men with ED (average age 55) over 12 weeks. Doses ranged from 5 mg up to 15 mg given as a nasal spray on-demand ~45 minutes before sexual activity. The findings were promising:

Improved Erectile Function: Men receiving bremelanotide (at doses 7.5 mg and above) showed statistically significant improvements in erectile function scores (IIEF) compared to placebo.In particular, doses of 7.5, 10, 12.5, and 15 mg were all associated with better International Index of Erectile Function outcomes than placebo.This indicated a dose-dependent efficacy, with higher intranasal doses yielding better erections. Notably, some men achieved sufficient rigidity for intercourse with PT-141 even if they had failed prior PDE5 therapy.
Enhanced Sexual Confidence and Satisfaction: This trial also assessed men’s Self-Esteem and Relationship (SEAR) scores – a psychological metric of sexual confidence and satisfaction. Bremelanotide users reported significant improvements in sexual self-confidence and relationship satisfaction versus baseline.According to lead investigator Dr. Stanley Althof, these results suggested PT-141 meaningfully improved the psychosocial aspects of sexual function, not just the physical ability to get an erection.In other words, men felt more assured and satisfied in their sexual encounters when using PT-141.

One randomized controlled trial published in the Journal of Urology (Safarinejad et al., 2008) specifically looked at men with ED who did not respond to sildenafil (Viagra). In this trial, 342 men with sildenafil-failure ED were given either intranasal PT-141 (10 mg dose) or placebo on demand over ~4–8 weeks.The outcomes demonstrated a clear benefit of bremelanotide:

About 33.5% of men on bremelanotide achieved a “positive clinical response” (improved erections sufficient for intercourse) compared to only 8.5% on placebo. This was a statistically significant difference (p = 0.03). These responders had previously failed to achieve satisfactory erections with Viagra, highlighting PT-141’s potential as a “salvage” therapy for PDE5i non-responders.
Men on PT-141 reported greater intercourse satisfaction and an increased number of successful coitus episodes, as measured by diary and the Intercourse Satisfaction domain of the IIEF. This indicates not only were erections improved, but the overall sexual experience was better.
The authors concluded that bremelanotide can be an effective alternative treatment for ED, with a “potentially broad patient base,” though they called for further studies. (It’s worth noting that this particular study’s data were later subject to an expression of concern, so results should be interpreted with some caution. Nonetheless, the weight of evidence from multiple studies supports similar positive outcomes.)

Synergy with PDE5 Inhibitors (Combination Therapy): The unique mechanisms of PT-141 and PDE5 inhibitors raised the question: what if you combine them for men who need extra help achieving an erection? A small exploratory study in 2005 did just that. Researchers gave 32 men with ED a combination of intranasal PT-141 (either 7.5 or 10 mg) plus oral sildenafil (50 or 100 mg), then used a RigiScan device to objectively measure erectile rigidity over 6 hours.Impressively, adding PT-141 to sildenafil increased the duration of erectile activity by over five-fold compared to sildenafil alone. On average, men had erections lasting 5.3 times longer when using the combo versus Viagra by itself. The enhancement was statistically significant in most dose comparisons, and no serious adverse events occurred. This early data signaled a powerful synergy: PDE5is improve the vascular response while PT-141 boosts central arousal signals, together yielding a stronger and longer-lasting erection.

Clinical Note: Because bremelanotide initiates erections via central pathways and sildenafil maintains them via local blood flow, their combination addresses two aspects of ED. Co-therapy could be especially useful in difficult cases – for example, a man with significant performance anxiety (who struggles to get an erection started) and some vascular ED (who struggles to maintain it). The combination approach is currently under more rigorous study in Phase II trials (discussed below).

Shift to Subcutaneous Injection and Recent Studies

Intranasal bremelanotide was eventually discontinued in development because some men experienced dose-related increases in blood pressure (more on safety later). By 2008, the manufacturer (Palatin Technologies) halted nasal formulation trials and pivoted to a subcutaneous injection route, which showed fewer cardiovascular side effects. The injection form was tested and refined in women (leading to the 2019 FDA approval for HSDD), but what about men? Clinicians did not wait for formal approval – off-label use of the injectable PT-141 in men began in specialized centers, contributing to a growing body of real-world evidence.

One recently reported study comes from a sexual medicine clinic that routinely prescribes bremelanotide off-label to men. In 2024, Goldstein and Goldstein published results from an observational study of 21 men with various sexual dysfunctions (low libido, ED, trouble with orgasm, etc.) who were given subcutaneous bremelanotide to use as needed. Key findings from this real-world survey include:

High Patient Satisfaction: After using PT-141 on at least two occasions, 80% of men reported being more satisfied with their lovemaking experience and its duration. Over 70% said that sex was more pleasurable for both themselves and their partner, and 86% felt more at ease initiating intimacy. This highlights significant improvements in confidence and reduction in performance anxiety.
Improved Desire and Orgasm: Among those who responded well to therapy, 39% noted improvement in low sexual desire (male HSDD) and 52% noted improvement in their erectile dysfunction symptoms. About 17% even reported improvements in difficulty achieving orgasm. These numbers suggest bremelanotide’s benefits in men may extend beyond erections to broader sexual functioning (desire and climax).
Global Improvement Scores: Using the Patient Global Impression of Improvement (PGI-I) scale, over half of the men (53%) initially, and up to 70% in an updated analysis, rated their sexual function as “a little better” to “very much better” after starting PT-141.In other words, a majority felt a noticeable overall improvement.
Consistent Use (Refills): The clinic tracked prescription refill rates as a surrogate for efficacy/satisfaction. Men were refilling their bremelanotide prescriptions at much higher rates than women were (65% of dispensed prescriptions to men were refills, versus ~29–52% for women). Over an 18-month period, men had a 73% refill rate, indicating they found the treatment beneficial enough to continue long-term. This real-world adherence speaks to men perceiving value from PT-141 therapy.

It’s important to mention that the above was an uncontrolled study (no placebo group), but it provides a snapshot of outcomes in actual clinical use. The improvements in male patients’ desire, erectile function, and sexual satisfaction corroborate the mechanism we expect from PT-141’s central action.

Ongoing and Future Studies

Building on past data, formal clinical trials of bremelanotide in men are active once again. Palatin Technologies (the developer) has launched a Phase II study in men with ED who are PDE5 inhibitor non-responders, using a new co-formulation of bremelanotide plus a PDE5i in a single injection. This open-label trial (50 patients) aims to optimize dosing and evaluate safety/efficacy of the combo approach, with topline results expected by end of 2024. The interest is high because, as Palatin’s CEO noted, PDE5i non-response represents a substantial unmet need – these drugs account for ~$4 billion in sales, yet up to 40% of ED patients don’t respond adequately. Early clinical data from Palatin indicated that bremelanotide on its own, and even more so combined with a PDE5i, produced statistically significant improvements in erectile function in men.

If the Phase II results are positive, Palatin plans to advance to a larger Phase III trial in 2025. The goal is to obtain an FDA approval for a bremelanotide-based therapy for male ED, potentially offering the first new class of ED medication in over two decades. Investigators like Dr. Jed Kaminetsky, a urologist involved in the trial, have voiced optimism: “I have used bremelanotide in my practice for men with ED... The combination of bremelanotide with a PDE5i could potentially be an effective treatment option for PDE5i non-responders”. In parallel, smaller studies and case series continue to report on off-label use, adding to our knowledge. For example, there is exploration of PT-141 in men with psychogenic ED, men with low testosterone (in conjunction with hormone therapy), and even use of intranasal PT-141 via compounding pharmaciesfor needle-averse patients – though robust data on the latter are lacking.

Bottom Line: The clinical evidence to date supports that PT-141 is effective in a subset of men with ED or sexual dysfunction, particularly in enhancing sexual desire, confidence, and the initiation of erections. It has shown efficacy on its own in men who failed standard ED meds, and even greater potential when used alongside those meds.. While more large-scale trials are forthcoming, real-world usage and prior studies indicate that bremelanotide can safely improve male sexual function in at least a significant minority of patients.

Dosage and Administration in Men

One of the unique aspects of PT-141 is the route of administration and on-demand dosing strategy. Here’s what men and healthcare providers should know:

Subcutaneous Injection (Preferred Route): The FDA-approved formulation of bremelanotide is a subcutaneous (SC) injection of 1.75 mg, supplied in an autoinjector pen. Patients self-inject this medication under the skin of the abdomen or thigh, similar to how one might administer an insulin pen. For men using PT-141 off-label, the same dose and method are typically employed. The injection is relatively quick (delivered in seconds) and is done on an as-needed basis.
Timing of Dose: It is recommended to administer PT-141 at least 30 to 45 minutes prior to anticipated sexual activity.In female trials, onset of effect was noted around 30-60 minutes after injection, and similarly men report that it takes about half an hour (sometimes up to an hour) to start feeling the effects. Peak effects (in terms of erection rigidity or heightened arousal) often occur around 1 to 2 hours post-injection, though this can vary.
Duration of Action: The pro-arousal and erection-facilitating effects of bremelanotide can last for several hours. Most men will experience the main benefit within the first 8 hours after a dose. However, some reports (and anecdotal clinic feedback) suggest that an enhanced level of sexual arousal may persist into the next day for certain individuals. In the Goldstein clinic study, a few men even noted “bothersome spontaneous erections” intermittently for ~24 hours after a dose. Generally, you can expect 6-12 hours of increased sexual responsiveness, with diminishing effects after that. It’s advisable not to plan important activities immediately after dosing, in case an erection occurs unexpectedly.
Intranasal Spray (Experimental): As discussed, an intranasal form of PT-141 was used in research trials with higher doses (e.g. 7.5–20 mg nasally). However, no commercially available nasal spray of bremelanotide currently exists for patients. Some compounding pharmacies might prepare PT-141 nasal sprays, but the consistency and absorption can be variable. If such a route is used, the timing is similarly ~30-60 minutes pre-intercourse. Due to historically higher rates of side effects (especially blood pressure elevation) with intranasal delivery, the injection is generally preferred for both efficacy and safety.
Dosing Frequency: Bremelanotide is intended as an as-needed (PRN) therapy, not a daily medication. The FDA guidelines (for women, which clinicians also follow for men) say no more than one dose in 24 hours, and no more than 8 doses per month. This maximum frequency helps minimize side effects and is because the trials did not evaluate very frequent use. In practice, most users take PT-141 once a week or a few times per month depending on their sexual activity schedule. If a patient finds themselves needing it more often than 2 doses per week, a re-evaluation of underlying issues or alternative therapies may be warranted.
Administration Technique: For the subcutaneous injection, proper technique is important. Men should be taught to clean the injection site (abdomen or thigh) with alcohol, pinch the skin, and inject at a 90-degree angle (if using the autoinjector, it’s as simple as pressing it against the skin and hitting the button). The injection is relatively painless since the needle is small. Rotating injection sites is recommended to avoid irritation. Do not inject into veins or muscle; this is a subcutaneous (under the skin) shot.
Dose Adjustment: Currently, 1.75 mg is the standard dose. There isn’t extensive data on lower or higher dosing in men with the SC route, although some physicians might experiment off-label with slightly lower doses (e.g. 1.25 mg) to mitigate side effects for sensitive patients. It’s crucial not to exceed the recommended dose on your own – higher doses could increase adverse effects without clear evidence of greater efficacy in men.
Storage: Bremelanotide injection pens should be stored per instructions (usually refrigerated until use, then can be at room temperature for a short time). Patients should check expiration dates and solution appearance (do not use if the liquid is cloudy or discolored).

Overall, men using PT-141 will self-administer a subcutaneous shot on demand, ~45 minutes before sex, and should not redose for at least 24 hours. The convenience of an autoinjector makes this relatively straightforward, but it does mean ED treatment with PT-141 is more invasive than simply taking a pill. For those comfortable with injections (or who haven’t had success with pills), this trade-off can be worthwhile.

Measuring Treatment Effectiveness

When starting PT-141 therapy, both patients and healthcare providers will want to know: Is it working? Because sexual function has subjective elements, effectiveness is assessed through a combination of patient-reported outcomes and objective measures:

Patient Self-Reports: Men can track improvements using validated questionnaires. The most common is the International Index of Erectile Function (IIEF), particularly the IIEF-EF domain which focuses on erectile firmness and frequency. An increase in IIEF-EF score (e.g., from moderate ED range into mild or normal range) indicates improvement. In trials, clinically meaningful improvement is often defined as a change of several points or achieving an erection sufficient for intercourse. Patients might also use simpler diaries or logs of sexual activity – noting each attempt at intercourse, whether penetration was successful, and whether the erection was maintained to climax (these correspond to the Sexual Encounter Profile (SEP) questions often used in ED studies). For example, a man could note that with PT-141, he was “able to penetrate” and “able to satisfactorily complete intercourse” X out of Y attempts, whereas before treatment those outcomes were inconsistent.
Libido and Satisfaction Scales: Since PT-141 affects sexual desire, men might fill out scales like the Sexual Desire Inventory (SDI) or simply be asked to rate their level of sexual interest before and after treatment. The Patient Global Impression of Improvement (PGI-I) is another useful single-question measure; it asks the patient to rate their sexual function now compared to before (ranging from “very much improved” to “very much worse”). In the off-label study, 70% of men rated themselves as at least “a little better” on the PGI-I after starting PT-141.Similarly, the Global Assessment Question (GAQ) used in some ED trials simply asks, “Has the treatment improved your erections?” – a yes/no that provides a quick snapshot of perceived efficacy.
Partner Feedback: Because sexual activity involves a partner, their feedback can also be valuable. Improved ease of penetration, increased frequency of satisfying sex, and the partner’s satisfaction are all part of a successful outcome. In surveys, men on PT-141 reported that their partner’s overall experience was more pleasurable in ~79% of cases after starting the therapy.A simple conversation or a partner questionnaire can capture this aspect.
Objective Measures: In research settings, devices like the RigiScan can objectively measure penile rigidity and tumescence over time. A RigiScan is a wearable device that detects the firmness of erections (often used during sleep or for drug trials). For instance, the combination study mentioned earlier used RigiScan to show men had erections above a certain rigidity threshold for a significantly longer total duration with PT-141+sildenafil than with sildenafil alone.While not used in routine practice, such objective measures can confirm the physiological effect of PT-141. In some cases of severe ED, a physician might conduct an in-office stimulation test (visual sexual stimulation after dosing, to see if an erection occurs and how rigid it gets). However, this is rarely necessary outside of research.
Hormonal or Physiological Markers: There is no specific lab test to gauge PT-141 efficacy, but if a man’s ED is partly due to low testosterone, then checking testosterone levels is pertinent. Successful treatment of underlying hypogonadism (if present) in conjunction with PT-141 might yield better outcomes, though that’s more about identifying other factors rather than measuring PT-141’s effect.

In practice, a combination of these approaches is used. Clinicians typically ask patients for subjective feedback: “Were you able to achieve an erection adequate for intercourse? How did you feel about the experience? Did your desire improve? Any issues?” They may also repeat an IIEF questionnaire after a month or two on therapy to quantify any change. If the man and his partner report clearly better sexual encounters (with perhaps a return to normal erectile function on a questionnaire), that signals success. On the other hand, if there’s minimal improvement after a fair trial (e.g., 4–8 doses over 2 months), guidelines would suggest discontinuing PT-141fda.gov and exploring other options.

Expectation setting: It’s helpful to set realistic goals at the outset. PT-141 might not work for everyone, and “effectiveness” can vary – some men might see stronger erections, others mainly notice increased libido or reduction in anxiety. Any positive change in the ease of initiating sex, quality of erections, or satisfaction can count as a win. Keeping a brief treatment diary can help both patient and provider review progress objectively.

Safety Profile and Side Effects

Every medication has potential side effects, and bremelanotide is no exception. However, its safety profile is well-understood from clinical trials (in both women and men) and years of research. Here we outline common side effects, rare but notable risks, and safety precautions for PT-141 use in men:

Nausea and Gastrointestinal Effects: The most frequent side effect of bremelanotide is nausea. In fact, about 40% of people (based on female trials) experienced nausea after a 1.75 mg dose, compared to only ~1% on placebo. This nausea can sometimes be significant; around 13% needed to take an anti-emetic (anti-nausea medication) to cope with it. Nausea tends to be worst with the first injection and often lessens on subsequent uses as some individuals acclimate. It usually starts shortly after the injection and, in most cases, resolves within 2–4 hours. Along with nausea, some people experience vomiting (about 5% incidence) or mild stomach discomfort. To minimize this, doctors often advise taking PT-141 on an empty stomach (food can sometimes exacerbate nausea) and perhaps taking an over-the-counter anti-nausea drug if needed. Staying well-hydrated and lying down for a bit after the shot can help if you feel queasy. If severe nausea persists with each dose, discontinuation is advisable.
Flushing and Facial Reddening: Because melanocortin receptors can affect blood vessels and skin pigment cells, flushing (a feeling of warmth and redness, especially in the face) is common. About 20% of users report flushing. This is usually transient and harmless. Some men liken it to the warm sensation one gets after a niacin supplement or a hot drink. Unless accompanied by other symptoms, flushing is not concerning and typically passes within an hour or so.
Headache: Approximately 11–12% of people get a headache after PT-141. These are usually mild to moderate. Staying hydrated and using a mild analgesic (like acetaminophen) can alleviate headache if it occurs. The mechanism might be related to blood pressure changes or the flushing effect. If a severe headache occurs (e.g., migraine-level), one should report it to their doctor.
Injection Site Reactions: Because it’s an injection, some local reactions can occur – about 5% of users had injection site reactions such as slight pain, redness, or itching at the shot site. Rotating sites and using proper technique helps. These local reactions are generally minor and resolve quickly.
Blood Pressure and Cardiovascular Effects: Transient blood pressure elevation is an important safety consideration. In earlier intranasal studies, higher doses of PT-141 caused increases in blood pressure and were the reason trials were paused. With the 1.75 mg SC dose, the effect on blood pressure is smaller but still present. On average, bremelanotide can raise systolic BP by ~2–3 mmHg and diastolic BP by ~1–2 mmHg shortly after dosing, accompanied by a slight decrease in heart rate by ~2 beats per minute. These changes typically peak within the first hour and return to baseline within 12 hours. While these average changes seem minimal, caution is warranted: if a patient has underlying high blood pressure or heart disease, even transient increases could be risky. For that reason, Vyleesi’s label carries a warning not to use it in individuals with uncontrolled hypertension or known cardiovascular disease. Men with high-risk cardiac conditions (recent stroke, unstable angina, severe heart failure, etc.) are generally advised to avoid PT-141. In someone with well-controlled blood pressure, these small bumps are usually benign, but it’s wise to monitor. Measuring one’s blood pressure a few times after the first dose can be useful to see how you respond. If significant hypertension (e.g., BP > 160/100) is noted after dosing, the medication should be discontinued. Fortunately, clinical studies in men have not reported serious cardiac events attributable to bremelanotide, and the injection formulation’s BP effect is much less pronounced than the old intranasal version.
Darkening of Skin and Gums: A peculiar side effect seen in about 1% of female trial participants was hyperpigmentation – darkening of the gums or skin (particularly on the face and breasts). This is due to bremelanotide’s action on MC1 receptors (which stimulate melanocytes, the pigment-producing cells). Interestingly, this side effect was more common in individuals with darker baseline skin and in those who took many doses. In roughly half of the affected patients, the pigmentation changes did not completely disappear after stopping the drug. For men, this side effect has not been widely reported yet, but it’s something to be aware of, especially if using the medication frequently. If you notice new freckling, moles darkening, or patches of skin getting darker, mention it to your provider. It’s mostly a cosmetic issue, but permanent changes can occur, so it factors into the risk-benefit consideration for long-term frequent use.
Spontaneous Erections/Priapism: Given the nature of PT-141, one might wonder about priapism (erections lasting too long). There have been no significant reports of priapism in clinical trials; however, some men do experience spontaneous erections that occur without intentional stimulation and potentially at inconvenient times (due to the central arousal effect). In the observational study, ~13% reported “bothersome spontaneous erections” lasting up to a day after the shot. These were not continuous erections, but intermittent ones without sexual activity. True priapism (a single erection >4 hours requiring medical intervention) is very rare with PT-141, especially at recommended doses, but men should be informed of the possibility. Combining PT-141 with other ED treatments (like PDE5is or penile injections) could theoretically increase priapism risk, so caution and medical supervision are advised in such combinations.
Other Side Effects: Some less common effects (around 2-5%) include dizziness, fatigue, mild nasal congestion or cough, and injection site itching. Rarely, some have reported cramping or abdominal discomfort.These tend to be transient. Allergic reactions are extremely rare but could manifest as rash, swelling, or difficulty breathing – if any such signs occur, seek immediate medical help.

In terms of safety monitoring, it’s wise to periodically check blood pressure, especially in the early phase of use. Because PT-141 can slow gastric emptying, it might affect the absorption of oral medications – for example, it significantly reduced the absorption of oral naltrexone in studies. Therefore, men on important oral meds (like certain diabetes drugs, blood thinners, etc.) should separate their dosing from PT-141 by a couple of hours and monitor those medications’ effectiveness. Alcohol interaction: Unlike flibanserin (a women’s HSDD drug that has a major alcohol contraindication), bremelanotide does not have a meaningful interaction with alcohol. Still, drinking alcohol can independently affect erections and might worsen flushing, so moderation is key.

Finally, long-term safety data (beyond 1 year of use) in men are not yet robust. In women, up to 12 months of use showed no evidence of tissue changes or serious issues emerging.There was no accumulation of effects on blood pressure or heart rate with ongoing use – the cardiovascular effects remained transient. This is somewhat reassuring for men as well. However, given that PT-141 is an “as-needed” medication, men typically use it infrequently, further limiting long-term exposure risks.

In summary, PT-141 is generally well tolerated. The main side effects men should anticipate are nausea (especially initially), possible flushing, and maybe a headache or mild dizziness. Most side effects are short-lived. Serious risks can be mitigated by careful patient selection (avoiding those with unstable cardiovascular conditions) and adhering to recommended dosing frequency. Always communicate with your healthcare provider about any adverse effects – sometimes adjusting the dose or pre-medicating (e.g., with an antiemetic) can make therapy more comfortable.

Ideal Candidates for PT-141 Therapy

Considering its unique mechanism and safety profile, which men are the best candidates for PT-141? Here are some scenarios where bremelanotide may be particularly beneficial:

PDE5 Inhibitor “Non-Responders”: Men who have tried standard ED pills (sildenafil, tadalafil, etc.) without adequate success are prime candidates. As noted, a significant subset of ED patients (~30% or more) do not respond fully to PDE5is. This may include men with diabetes, after prostate surgery, or those with more severe vascular ED. PT-141 offers a different pathway to erection, and clinical studies have shown it can produce erections in some men refractory to Viagra/Levitra/Cialis. In practice, these men might use PT-141 alone or in combination with a PDE5i to achieve a satisfactory result. For example, a man who gets partial erections on Cialis but not enough for intercourse might add bremelanotide to successfully initiate and complete intercourse. Ongoing trials targeting this population reflect how suitable it is.
Men with Mixed Sexual Dysfunction (ED + Low Desire): Some men suffer not only from erection problems but also low libido (diminished sex drive) or arousal difficulties. In such cases, PT-141 is especially appealing because it can address the psychological/central side (desire and interest) as well as the erection. Male hypoactive sexual desire disorder (male HSDD) is not officially labeled like the female version, but men do experience chronic low sexual desire that causes distress. A man who “just isn’t in the mood” and also struggles with firmness could benefit from PT-141 giving him that central spark. The Goldstein study clearly indicated improvements in desire for a good portion of men using PT-141.These patients often report more spontaneous sexual thoughts and a greater willingness to initiate sex when on bremelanotide. This makes PT-141 a unique option in the male sexual medicine toolbox, as standard ED drugs do not increase libido.
Psychogenic Erectile Dysfunction and Performance Anxiety: Men whose ED is largely psychological – for instance, tied to performance anxiety, fear of failure, or situational stress – may find PT-141 very helpful. Because it works on the brain, it can reduce the anxiety related to sexual performance. In surveys, about 39% of men said bremelanotide reduced their anxiety about sexual performance. Patients often describe feeling “more relaxed and confident” after using PT-141, likely due to its pro-arousal effect that can overshadow anxious thoughts. By biologically kickstarting the erection process, it leaves less room for anxiety to sabotage the encounter. Thus, a young man with ED rooted in performance anxiety might use PT-141 on a few occasions to break the cycle of worry and failure, restoring confidence.
Men Who Cannot Take PDE5 Inhibitors: There are individuals who are unable to use PDE5is due to contraindications – most notably, those who take nitrate medications (for angina or heart disease) or certain alpha-blockers. For these men, PDE5is are off the table because of dangerous blood pressure interactions. Bremelanotide, on the other hand, does not have the same contraindication with nitrates since it doesn’t cause vasodilation-induced hypotension. (However, caution: if someone needs nitrates, they have heart disease, and PT-141 might be risky due to raising BP. So this scenario must be evaluated carefully by a doctor.) Additionally, men who experienced severe side effects from ED pills (migraines, vision changes, etc.) might seek an alternative like PT-141. In essence, bremelanotide can fill a gap for those who cannot use or tolerate the first-line oral medications.
Patients Seeking Combination Therapy for Maximal Effect: Some men with tough-to-treat ED (e.g., post-prostatectomy, severe vasculogenic ED) might benefit from a multimodal approach. PT-141 can be an adjunct for those already on other treatments. For example, a man on testosterone replacement therapy (for hypogonadism) might add PT-141 to boost libido and erection quality if testosterone alone isn’t fully resolving the issue. Or a man using a vacuum erection device or penile injection could use PT-141 to improve the spontaneity and subjective arousal. These are individualized cases, but ideal candidates are those open to trying a novel therapy in addition to conventional ones to achieve the best outcome.
Men Who Prioritize Improved Sexual Experience: Because PT-141 has shown benefits in domains like orgasm intensity, partner satisfaction, and overall pleasure., a man who is getting “okay” results from a PDE5i but wants to enhance the qualitative aspects of sex might be a candidate. For instance, some men report that while Viagra gives them a physical erection, PT-141 adds to the mental sexual excitement, making the experience more fulfilling. That said, this is a less common reason to start a medication, but in sexual medicine, patient goals vary – some seek not just function but enhanced function.

On the flip side, who should not use PT-141? Key contraindications and poor candidate scenarios include:

Men with significant cardiovascular disease or uncontrolled hypertension – as mentioned, the transient BP increase is not suitable for those with serious heart conditions. If a man has had a recent heart attack or stroke, or has blood pressure that isn’t well managed, PT-141 is contraindicated.Patient safety comes first; other ED treatments (like local therapies) that don’t affect the cardiovascular system might be safer here.
Men prone to nausea or who have GI disorders that could be worsened by delayed gastric emptying. For example, someone with severe gastroparesis or a history of vomiting with any medication might find PT-141 intolerable. If after a trial the nausea is debilitating and doesn’t lessen, that patient might not continue therapy.
If a man’s ED can be corrected by other means (for instance, severe hypogonadism causing ED – treatable with testosterone, or an anatomical issue like Peyronie’s requiring different interventions), those underlying issues should be addressed first. PT-141 is ideally for functional improvement, not as a Band-Aid over an untreated primary problem. That said, it can still play a role in combination.
Recreational use: PT-141 is not intended for men without dysfunction who are simply seeking to “enhance” normal sexual performance. Given side effects like nausea, a man with normal erectile function is unlikely to find the trade-off worthwhile. The ideal user is someone who genuinely has difficulty with arousal or erection that needs pharmacological help.

In conclusion, ideal candidates are men with ED (especially tough cases) or low libido who are in good enough cardiovascular health and are willing to use an injection for improved sexual outcomes. They should have realistic expectations and be counselled on side effects. When prescribed appropriately, these men often report life-changing improvements in their sexual function and confidence.

Comparison to Existing Therapies

Placing PT-141 in context requires comparing it with the existing standard therapies for male sexual dysfunction. Each therapy has its pros and cons, and in some cases, they can be used together with PT-141 for a synergistic effect. Here’s how bremelanotide stacks up:

Versus PDE5 Inhibitors (Viagra, Cialis, etc.): PDE5 inhibitors are the well-established first-line oral treatments for ED. They work by increasing blood flow to the erectile tissue by inhibiting the enzyme that breaks down cGMP (a vasodilator). These medications are highly effective for many men with organic ED and have the convenience of a pill. However, PDE5is require sexual arousal to work – they facilitate an erection in response to arousal but do not create desire or arousal. PT-141, as discussed, can trigger arousal and erection centrally.This means PT-141 may succeed where a PDE5i fails, especially in men who don’t get aroused easily or have performance anxiety. Another difference: PDE5is (especially sildenafil) have interactions (e.g., with high-fat meals delaying absorption, with nitrates causing hypotension). Bremelanotide has no food interaction on efficacy (though we avoid heavy food to reduce nausea) and a different side effect profile (no visual disturbances or risk of low blood pressure; instead risk of nausea and slight BP rise). Some men who get stuffy nose or blue-tinged vision from PDE5is might find PT-141 doesn’t cause that. Onset-wise, sildenafil and PT-141 are similar (~30-60 min), whereas daily tadalafil is always on-board but not on-demand. One notable distinction: PT-141 does not directly improve penile hemodynamics as potently as a PDE5i, so if a man has severe vascular issues, a PDE5i or injection is needed to get sufficient rigidity. That’s why combining PT-141 with a PDE5i can yield the best of both – central initiation plus maximal blood flow. In a head-to-head sense, PDE5 inhibitors still remain the first step for pure ED, whereas PT-141 is carving out a role for cases beyond PDE5i’s reach or adding to their effect..
Versus Alprostadil (Injectable or Urethral ED therapy): Alprostadil is a prostaglandin E1 that can be injected into the penis (Caverject®) or inserted as a urethral pellet (MUSE®) to cause an erection by locally dilating blood vessels. It’s often used in men who don’t respond to pills. Compared to bremelanotide: alprostadil has a very direct effect on the penis, often guaranteeing an erection suitable for intercourse in many cases of severe ED. However, it requires a penile injection (which some men find intimidating, even more so than a tiny SC shot in the abdomen) or urethral insertion (which can cause urethral pain). Alprostadil erections can occur without sexual arousal too (since it’s a local drug), and there is a risk of priapism or significant penile pain/burning. Bremelanotide’s injection is less invasive (abdomen vs. penis) and causes a more “natural” feeling erectionbecause it involves arousal. But bremelanotide might be insufficient alone for a man with complete neurogenic ED (e.g., after spinal injury) where no amount of brain signal can overcome nerve damage – in such cases, alprostadil injection directly into the penile tissue is more effective. Alprostadil doesn’t cause nausea or systemic effects but can cause dizziness and low blood pressure rarely. So each has different side effect profiles. One could envision a future combination where a man might use a low dose of PT-141 to get in the mood and an intra-penile injection for guaranteed rigidity – but that’s a fairly involved regimen and would be reserved for extreme cases.
Versus Testosterone Therapy: Testosterone replacement (TRT) is not an acute ED treatment, but it’s relevant for men with hypogonadism (low T) who have low libido and ED. TRT can improve sexual desire, energy, and erectile function if low testosterone is the cause. It’s more of a foundational, long-term therapy. Bremelanotide, in contrast, works regardless of testosterone level because it acts on neural pathways. For a man with low T, the ideal approach is to correct the deficiency (with TRT or other means) and then, if needed, add PT-141 to further boost libido/erections. There’s theoretical synergy here: TRT provides the hormonal substrate for libido, while PT-141 provides the neural pushregenxhealth.comregenxhealth.com. Clinics that specialize in men’s health sometimes combine these – for instance, a man on testosterone who still has suboptimal sexual function might use PT-141 for an extra lift. However, PT-141 is not a hormone and does not increase testosterone levels (despite some internet myths). It’s purely acting on brain receptors. So it’s not a replacement for TRT; rather, it’s an adjunct if symptoms persist. In terms of safety, TRT has its own considerations (polycythemia, prostate effects, etc.) which are unrelated to PT-141’s profile.
Versus Apomorphine (Uprima): Apomorphine is a dopamine agonist that was used in some countries for ED (sublingual tablet) due to its central action to initiate erections via the brain’s dopamine pathways. In a way, apomorphine was a predecessor concept to PT-141: a centrally-acting ED drug. However, apomorphine’s efficacy was modest, and it tended to cause a lot of nausea (because it stimulates dopamine receptors indiscriminately, including in the chemoreceptor trigger zone). It never gained FDA approval in the U.S. for ED. Bremelanotide can be thought of as a more targeted and potent central acting agent – it works on melanocortin receptors upstream of dopamine, which might provide a more specific sexual arousal effect. While PT-141 also causes nausea in many, its overall benefit-risk seems better than what apomorphine offered. Apomorphine is rarely used nowadays; if a clinician wants a central agent, PT-141 is likely the go-to.
Versus Psychotherapy and Other Approaches: For men with psychological ED or low desire, sex therapy, counseling, and behavioral techniques are important treatments. PT-141 doesn’t replace those, but it can complement them. For example, a man undergoing therapy for performance anxiety might use PT-141 to help accomplish successful sexual encounters, which reinforces therapeutic progress by restoring confidence. Unlike a pill that just fixes the mechanics, PT-141 engages the emotional and arousal aspects, which might actually aid psychological healing (the man sees himself becoming aroused and successful, breaking the negative cycle). So, rather than versus these approaches, PT-141 can be integrated with them.
Overall Efficacy: It’s worth noting that PT-141’s efficacy rate (as monotherapy) for ED is probably lower than that of PDE5 inhibitors. PDE5is help about 70% of men with ED, whereas bremelanotide in trials helped around 30–50% (particularly among difficult cases). This is not a direct comparison since populations differ, but it underscores that PT-141 might not replace PDE5is as the first choice for everyone. Instead, it fills a niche. Patient satisfaction with PT-141 can be high among responders – some men prefer the “feeling” of a PT-141-induced arousal versus the sometimes more mechanical effect of PDE5i. For instance, PDE5is do not directly influence orgasm or pleasure, whereas some men on PT-141 reported easier or more pleasurable orgasms. Thus, qualitatively, PT-141 might offer advantages in the sexual experience that traditional ED meds do not.

In sum, bremelanotide is not a replacement for existing ED therapies but rather a novel addition. For many men, it will be used after or alongside PDE5 inhibitors. It addresses gaps – notably desire and central arousal – that other treatments leave open. Each therapy (oral ED meds, injections, hormones, devices, counseling) has its role, and part of personalized sexual medicine is choosing the right tool or combination for the patient. PT-141 expands our toolkit, giving hope to men who previously had limited options.

Regulatory Status and Availability

The regulatory approval and availability of bremelanotide differ by country and by indicated use. Understanding this landscape is important for both patients and providers considering PT-141 for men:

United States: Bremelanotide (Vyleesi) was approved by the U.S. FDA in June 2019, but only for women with acquired, generalized HSDD (Hypoactive Sexual Desire Disorder). There is currently no FDA-approved indication for use in men. This means prescribing bremelanotide for a male patient is an off-label use. Off-label prescribing is legal and not uncommon in sexual medicine (physicians sometimes repurpose FDA-approved drugs for other populations based on emerging evidence). Men can obtain PT-141 in the U.S. via a doctor’s prescription, typically through specialty pharmacies. The medication is the same autoinjector used for women, as no separate “male” version exists at this time. Insurance coverage for off-label use may be challenging – many insurance plans do not cover Vyleesi even for women, and they certainly may not for an unapproved use in men. However, some men have accessed it via compounding pharmacies (which create the peptide in injection or nasal form). Patients should be cautious to use legitimate pharmacies, as the peptide market has many grey-market products. As of the time of writing, bremelanotide remains a prescription-only medication in the U.S.
Europe: Bremelanotide is not yet approved by the European Medicines Agency (EMA) for any indication. After the FDA approval, Palatin’s European partner (Gedeon Richter) was evaluating the Phase 3 data for a possible EU application, but as of the latest updates, it appears no EMA approval has been granted for female HSDD or any use. The process may have been delayed or the application withdrawn. Thus, in European countries, Vyleesi is generally not commercially available. That said, clinicians could theoretically import it on a named-patient basis or use compounded versions, but this would be uncommon and subject to local regulations. Men in Europe interested in PT-141 might have to wait for future approvals or research trials, or obtain it through special channels that allow importation of non-approved medicines (if permitted).
Canada: As of now, Health Canada has not approved bremelanotide either. Similar to Europe, it would not be found in pharmacies. Canadian patients might access it via online peptide suppliers (with all the caveats that entails) or cross-border if they have a U.S. prescription, but officially it’s not authorized in Canada for women or men.
Asia and Other Regions: Palatin has licensing agreements with companies in certain regions. For example, Fosun Pharma in China and Kwangdong Pharmaceutical in South Korea have rights to bremelanotide. In China, as of late 2022, a Phase 3 trial for premenopausal women was underway, and there was a report of the first prescription being dispensed in Hainan province under a special pilot program. This suggests that in parts of China (like Hainan’s special medical zone), bremelanotide may be accessible to patients on a trial or early-access basis. Full national approval in China is likely pending completion of trials. In South Korea, the status is similar – no public approval yet, but licensing is in place. Other territories included in deals were countries in Asia Pacific. Men’s use in those regions would also be off-label unless a country specifically approves it for ED in the future.
Global Clinical Trials: Men interested in PT-141 might also seek out clinical trials. With Palatin’s renewed development for ED, trials in the U.S. (and potentially elsewhere) may recruit men with erectile dysfunction who have not responded to other treatments. Participation in a trial could provide access to the therapy under research conditions.
Commercial Availability: In the U.S., after FDA approval for women, Vyleesi was marketed by AMAG Pharmaceuticals initially, then rights were transferred. As of 2023, it appears a company called Covisit (a division of Palatin) or Cosette Pharmaceuticals took on commercializationfiercepharma.com. The drug is typically obtained via specialty mail-order pharmacies. There have also been direct-to-consumer telemedicine platforms partnering with Palatin to prescribe Vyleesi to womenreuters.com. Conceivably, men might use some of these telehealth services off-label, but that would depend on the platform’s policies. In any case, one cannot buy PT-141 over the counter; a prescription is required in jurisdictions where it’s legal.
Cost: While prices can vary, bremelanotide is relatively expensive. In the U.S., a single-use Vyleesi autoinjector pen can cost on the order of several hundred dollars (list price), although discounts or insurance might reduce that. Compounded versions might be cheaper per dose, but quality and reliability are considerations. Men should discuss costs with their provider and pharmacist. As it stands, PT-141 is a premium therapy, which is another reason it’s often tried after more affordable options.
Future Regulatory Outlook: If ongoing Phase 2–3 trials in men demonstrate clear safety and efficacy, we could see an FDA submission for a male indication (for ED or another male sexual disorder) in a couple of years. Approval would greatly expand access and possibly lower cost through insurance coverage. It’s also possible that a combination product (bremelanotide + a PDE5i in one injection) could be what comes to market for men..That would be a novel approach and would require its own approval process. Globally, as the female HSDD indication gets approved in more places, off-label use in men might organically increase, followed by formal studies. It’s an evolving area.

Accessibility note: Patients should always obtain medications like PT-141 through legitimate healthcare channels. There is a known underground market for peptides, and while PT-141 is not a controlled substance, buying it without a prescription carries risks of adulterated or subpotent product. Given that this drug affects blood pressure and other systems, medical supervision is important for safe use.

Conclusion

PT-141 (bremelanotide) represents an exciting development in the field of male sexual medicine. By leveraging a unique mechanism of action in the brain – activating melanocortin receptors to spark sexual desire and erections – it offers hope to men who struggle with conventional ED treatments or whose sexual dysfunction includes a loss of libido and confidence. Clinical evidence to date, from early trials to recent real-world studies, shows that bremelanotide can improve erectile function, enhance sexual satisfaction, and reduce performance anxiety in a significant subset of menresearchgate.net.. Its ability to pair with PDE5 inhibitors for a one-two punch to ED is particularly promising, potentially defining a new standard for treating difficult cases.

That said, PT-141 is not a magic bullet for everyone. It has a distinct side effect profile – most notably nausea and flushing – and practical considerations like injection administration. Proper patient selection and counseling are crucial to success. Men with underlying cardiovascular issues must approach this therapy cautiously, and all users should be aware of the do’s and don’ts (no more than one dose per 24 hours, etc.) to use it safely.When used correctly, the safety data is reassuring: side effects are generally transient and manageable, with transient blood pressure increasesbeing the main concern to monitorfda.gov.

From an availability standpoint, we are in a phase where the drug is approved for women and used off-label for men, so access may require finding a knowledgeable physician and potentially paying out of pocket. However, as research progresses, we anticipate broader approvals and perhaps more convenient formulations or combinations for men. Each patient’s situation is unique – some may use PT-141 as a standalone solution to rekindle their sex life, others might use it alongside their Viagra or testosterone therapy as part of a comprehensive approach.

For healthcare professionals, the advent of bremelanotide for men expands the toolkit for treating sexual dysfunction. Its blend of conversational ease (“libido boost”) and technical nuance (melanocortin agonism) means discussions about it can engage patients who have felt hopeless about their sexual function. For patients, it’s empowering to know that science is finding new ways to address intimate issues that were once thought unfixable.

In summary, PT-141 in men is a bridge between the mind and the body – it reignites the mind’s desire and in turn helps the body perform. Used judiciously, it can restore a sense of vitality and intimacy for men and their partners. As always, patients should work closely with their healthcare providers to determine if this therapy is right for them, weigh the benefits against side effects, and ensure it’s integrated safely with their overall care. The field of sexual medicine continues to evolve, and bremelanotide is at the forefront of that evolution, bringing us closer to truly holistic treatment of sexual dysfunction.

References:

Safarinejad, M. R., & Hosseini, S. Y. (2008). Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo-controlled study. Journal of Urology, 179(3), 1066-1071.
Goldstein, I., & Goldstein, S. (2024). Use of Bremelanotide (Vyleesi) in Men with Sexual Dysfunctions: Results from a Sexual Medicine Clinic. Journal of Sexual Medicine, 21(Supplement_1). (Abstract).
Palatin Technologies, Inc. (2024). Press Release: Palatin Announces the Initiation of a Phase 2 Clinical Study of Bremelanotide Co-Administered with a PDE5i for the Treatment of Erectile Dysfunction (ED). Cranbury, NJ.
Urologic Times – Clarke, H. (June 20, 2024). Phase 2 study launches of bremelanotide plus a PDE5 inhibitor for erectile dysfunction. Urology Times...
Palatin Technologies & King Pharmaceuticals (April 8, 2005). Two-drug combination shows positive results in men with ED. Urology Times..
Schieszer, J. (Sept 15, 2007). Intranasal Drug Holds Promise for ED. Renal & Urology News.
Wikipedia. Bremelanotide. (Accessed 2025) – for general background and side effect incidence from Phase 3 trials.
FDA News Release (June 21, 2019). FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women. U.S. Food & Drug Administration.
Clayton, A. H., et al. (2018). Bremelanotide for female sexual dysfunction: mechanism of action and clinical evidence. Journal of Sexual Medicine, 15(12), 1816-1824. (For neurobiological mechanism details)
Ückert, S., et al. (2014). Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies. Expert Opinion on Investigational Drugs, 23(11), 1477-1483. (Review article summarizing melanocortin agonist trials)

Disclaimer:
The use of PT-141 (bremelanotide) for the treatment of sexual dysfunction in men is not approved by the U.S. Food and Drug Administration (FDA). While this blog discusses clinical research and off-label applications of bremelanotide in men, any such use should be undertaken only under the supervision of a licensed healthcare provider. This information is provided for educational purposes only and is not intended to substitute for professional medical advice, diagnosis, or treatment. Always consult your physician or other qualified health provider regarding any medical condition or treatment decisions. The authors and publishers of this content do not endorse or promote unapproved uses of pharmaceutical products.