PT-141 VS. FLIBANSERIN: EXPLORING OFF-LABEL TREATMENTS FOR LOW SEX DRIVE IN MEN

Introduction

Hypoactive Sexual Desire Disorder (HSDD) – commonly known as low libido or low sex drive – is a condition characterized by persistently low sexual desire that causes personal distress or relationship difficulties. While HSDD has been more widely recognized and studied in women, men can also experience this challenging condition. Men with HSDD often report a lack of interest in sexual activity, few sexual thoughts or fantasies, and frustration or distress about this loss of desire. Despite the impact on quality of life and relationships, there are currently no medications officially approved for low sexual desire in men. This leaves men and their doctors exploring off-label and experimental options to manage HSDD.

Two drugs that have gained attention for treating low sexual desire are Flibanserin (brand name Addyi) and Bremelanotide (PT-141, brand name Vyleesi). These medications are approved for use in certain women with HSDD, but neither is approved by the FDA for men. Flibanserin is a daily pill initially developed as an antidepressant, now used to boost libido in premenopausal women. Bremelanotide is an injectable therapy that activates sexual arousal pathways, approved as an as-needed treatment for women with low desire. Given their success in women, some researchers and clinicians are investigating whether these drugs might also help men with HSDD.

This article will discuss how each drug works, available studies in men, potential benefits, and side effects. We will emphasize that using these medications in men is experimental and off-label, highlight which patients might consider clinical trials or off-label use, and suggest questions to ask your doctor. The goal is to educate and empower men with HSDD (and their partners and providers) with up-to-date information in a balanced and professional manner.

Understanding Hypoactive Sexual Desire Disorder (HSDD) in Men

HSDD in men is defined by a persistent or recurrent lack of sexual interest or desire, accompanied by marked personal distress. It can be lifelong (primary) – present since a man became sexually active – or acquired (secondary), developing after a period of normal sexual interest. It may be generalized, affecting all sexual situations, or situational, only occurring with certain partners or circumstances. What distinguishes HSDD is not just low libido, but the distress and interpersonal difficulty it causes. A man with HSDD typically wants to have a normal sex drive and may feel frustration, loss of masculinity, guilt, or relationship strain due to his low interest.

How common is low desire in men? Studies suggest that it’s not uncommon, though exact prevalence varies. Libido naturally varies between individuals and can decline with age and life changes. In one survey, about 14% of men over 65 reported rarely having sexual interest, compared to only ~3-5% of men under 45. However, not all low desire is distressing – HSDD refers specifically to those troubled by their low drive. Some research indicates that a significant minority of couples (in one study, 26% of women said their male partner had lower desire than they did) experience a mismatch in desire. So, while we often stereotype men as always wanting sex, reality is that many men experience periods of reduced libido, and a subset find it distressingly low.

What causes HSDD in men? Libido is complex and influenced by biological, psychological, and social factors. A useful model is the “Dual Control Model” of sexual response: sexual desire is governed by a balance of excitation (things that turn libido “on”) and inhibition (things that turn it “off”). In men with HSDD, this balance is shifted – often too much inhibition and not enough excitation. For example:

• Biological factors: Low levels of testosterone can reduce sexual thoughts and interest. High levels of prolactinor certain medications (like antidepressants) can dampen desire. Neurotransmitters in the brain play a key role: dopamine and norepinephrine tend to increase sexual excitement, whereas serotonin and prolactin increase inhibition of sexual drive. Men with HSDD may have an imbalance in these systems (for instance, excessive serotonin or too little dopamine signaling). Chronic illnesses (diabetes, cardiovascular disease), fatigue, chronic pain, or surgeries (like prostate cancer treatment) can also lower desire.
• Psychological factors: Stress, anxiety (especially performance anxiety), and depression can significantly reduce libido. If a man has erectile dysfunction or other sexual problems, he may develop anxiety or aversion to sex, leading to low desire as a secondary effect. Past trauma or relationship conflicts can also diminish sexual interest.
• Relationship and social factors: Discord with a partner, lack of emotional intimacy, or simply the routine of a long-term relationship can affect desire. New parenthood, job stress, or financial worries are common life stressors that can transiently lower libido. Cultural or religious attitudes that induce guilt about sex might also contribute to inhibited desire.

Importantly, when evaluating a man for HSDD, doctors first look for treatable causes. This means checking hormone levels (and treating testosterone deficiency if present), reviewing medications (e.g., SSRIs for depression often blunt libido), and addressing any sexual dysfunction like erectile issues or premature ejaculation that might be underlying the loss of desire. Counseling or sex therapy can be very helpful if psychological or relationship factors are significant. Often, a combination of approaches is needed.

Why consider Flibanserin or Bremelanotide for men? These two drugs were designed to act on the central sexual pathways – essentially, to adjust that excitation/inhibition balance in favor of more sexual desire. In women, Flibanserin and Bremelanotide have shown the ability to modestly increase sexual desire and the frequency of satisfying sexual experiences. The rationale for trying them in men is that men’s and women’s sexual desire share similar neurochemical mechanisms (dopamine, serotonin, melanocortin pathways, etc.). If a man’s low desire is due to an imbalance in these pathways (after other causes are ruled out), a drug that tweaks brain chemistry might help restore a normal level of interest.

However, it must be stressed that evidence in men is very limited so far. Unlike in women, where large clinical trials were done, in men there have only been small pilot studies and some off-label real-world usage data. Neither Addyi nor Vyleesi is FDA-approved for men, and mainstream guidelines do not yet recommend them for male HSDD. The use in men is experimental, typically considered only by specialists after conventional treatments, and ideally in a research setting.

In the following sections, we’ll delve into each drug – how it works, what is known from female usage, and what research or experience exists in men – and then compare them side by side. This will help men with HSDD (and their doctors) understand the potential roles and limitations of Flibanserin and PT-141 in treating low male libido.

Flibanserin (Addyi): “Female Libido Pill” and Its Potential in Men

What is Flibanserin? Flibanserin, brand name Addyi, is often nicknamed the “female Viagra,” though its mechanism is very different from Viagra. It is a 100 mg tablet taken daily at bedtime and was approved in 2015 for treating acquired, generalized HSDD in premenopausal women. Unlike Viagra (which affects blood flow to treat erectile dysfunction), flibanserin works on the brain – it’s a non-hormonal, centrally acting drug that modulates certain neurotransmitters involved in sexual desire. Flibanserin was originally developed as an antidepressant; while it didn’t work well for depression, women in trials reported increased libido, leading to its repurposing for HSDD.

How Flibanserin Works (Mechanism of Action): Flibanserin is a multifunctional serotonin agonist antagonist (MSAA). In simpler terms, it affects several neurotransmitter receptors, lowering the influence of serotonin while increasing levels of dopamine and norepinephrine in specific brain circuits. Serotonin is generally inhibitory to sexual desire – high serotonin can suppress arousal and libido (this is why SSRIs, which boost serotonin, often cause sexual side effects). Flibanserin binds to serotonin receptors: it agonizes 5-HT1Areceptors(similar to how some anti-anxiety meds work) and antagonizes 5-HT2Areceptors, among others. The net effect is thought to reduce the brain’s inhibitory tone on sexual reward pathways. Meanwhile, by modulating these receptors, flibanserin leads to an increase in dopamine and norepinephrine releasein the brain’s sexual desire centers. Dopamine is a key excitatory neurotransmitter for sexual interest (it’s associated with motivation and reward), and norepinephrine can enhance arousal and attention. Thus, flibanserin essentially rebalances brain chemistry – dialing down the “brakes” (serotonin) and dialing up the “gas pedals” (dopamine/norepinephrine) of sexual desire.

It’s important to note that flibanserin is not an “aphrodisiac” that instantly increases lust. It must be taken every night, and its effect accumulates over weeks. In women, it often takes about 4–8 weeks of daily use to notice improvements in desire. If no improvement is seen after 8 weeks, women are advised to stop the medication. Flibanserin’s effect is more about restoring a balance so that a person’s natural sexual cues and thoughts return, rather than creating a sudden intense arousal.

Evidence of Flibanserin’s Effectiveness in Women: Because we have limited data in men, it’s useful to look at how flibanserin performed in female HSDD trials (to set expectations). In three major clinical trials with over 2,300 premenopausal women, flibanserin showed statistically significant but modest benefits. Women on flibanserin had an increase of about 1 to 2.5 additional satisfying sexual events (SSEs) per month from a baseline of ~2–3 per month, whereas placebo groups saw ~0.8 to 1.5 additional events. In other words, flibanserin’s net effect was roughly one extra sexually satisfying encounter per month compared to placebo. Women also reported slightly higher sexual desire scores on questionnaires, but notably many women did not subjectively feel a big change in desire. In fact, in two of the three trials, flibanserin did not significantly outperform placebo in improving self-reported sexual desire intensity or reducing distress about low desire. This highlights that the improvements, while real, were subtle on an individual level. Flibanserin did not magically turn low libido into high libido; it helped some women move from very low interest to somewhat higher interest.

Given these moderate results, flibanserin’s approval was somewhat controversial. There were debates about whether its benefits outweighed its risks and side effects, and whether the drug’s maker had influence in the approval process. Ultimately, it was approved with certain safety restrictions.

Flibanserin’s Side Effects and Safety (in Women): Flibanserin can cause a few common side effects due to its action on the central nervous system. The most frequent are dizziness (about 11% of users), sleepiness or sedation (11%), nausea (10%), and fatigue (9%). Some also report insomnia (5%) or dry mouth. Taking it at bedtime helps reduce noticing these effects (since one might sleep through the dizziness or sedation). About 1 in 8 patients stopped taking it due to side effects in trials.

A major safety concern is low blood pressure and fainting (syncope), especially when flibanserin is combined with alcohol. Because flibanserin can lower blood pressure and alcohol can enhance this effect, their combination led to some cases of severe hypotension. In fact, in studies, about 17% (1 in 6) of people who took flibanserin with alcohol experienced significant drops in blood pressure or fainting. This led to a boxed warning and a strict recommendation that patients abstain from alcohol while on flibanserin. (The irony is that the alcohol interaction study was done mostly in men – highlighting safety in men even though the drug wasn’t intended for them!). Flibanserin also cannot be used if one has liver impairment or with certain other medications (like some antifungals or HIV drugs) that affect its metabolism, because those situations can raise flibanserin levels and risk of side effects. Due to these risks, prescribers initially had to be certified in a special REMS program, and pharmacies had to be certified to dispense Addyi, to ensure women were counseled about no alcohol use. (In recent years, the FDA relaxed some of these restrictions, but the no-alcohol warning still stands for safety.)

In summary, for women flibanserin offers modest benefits in libido with some potential side effects and inconvenience (daily dosing, avoiding alcohol). It’s usually considered only after other causes of low desire are addressed and if the woman is truly distressed by HSDD.

What About Flibanserin in Men? Flibanserin is not FDA-approved for men, and routine use in men isn’t recommended due to lack of data. That said, the scientific rationale is there – men’s sexual desire also involves serotonin, dopamine, etc., so in theory a man with high inhibition/low excitation neurochemistry might benefit similarly from flibanserin. Over the past few years, some exploratory research and off-label prescribing have taken place:

• Clinical Trials: A pilot randomized controlled trial in men with HSDD is underway. Baylor College of Medicine (Dr. Mohit Khera as principal investigator) launched a Phase 2 study enrolling 60 men with HSDD, randomized to flibanserin 100 mg nightly vs placebo. The men must have normal testosterone, no erectile dysfunction, and be in a stable relationship, among other criteria. This trial (expected completion in 2026) will provide the first high-quality data on flibanserin’s efficacy in men. Until results are published, we won’t know if flibanserin can significantly increase male libido.
• Retrospective Case Series: In late 2022, Baylor researchers conducted a retrospective review of men who had already been prescribed flibanserin off-label for low desire. They presented results in 2024, describing 26 men (mean age ~58) who tried flibanserin. Most of these men had other sexual issues too – notably, 81% also had erectile dysfunction (likely being treated in parallel). They generally had normal testosterone levels (around 611 ng/dL on average). Over about 3 months of follow-up, 7 of the 26 men (27%) stopped flibanserin – primarily because they felt it wasn’t effective or due to high cost, and only one man (3.8%) stopped due to side effects. This suggests tolerability might be similar to women (few discontinuations purely from side effects). The study emphasized that interest in off-label flibanserin for men is rising, but it did not report detailed efficacy outcomes beyond stating the group had low baseline desire scores and that more research is needed. In essence, this was a safety and feasibility observation: it showed men can take flibanserin without any new or alarming safety issues beyond what’s known in women, but efficacy wasn’t clearly demonstrated in this short-term, uncontrolled review.
• Real-World Survey: A more informative glimpse comes from a 2024 survey study sponsored by the manufacturer (Sprout Pharmaceuticals) and conducted by sexual medicine specialists. They identified men across 5 clinics who had been prescribed flibanserin in the second half of 2022, and surveyed them about their experiences. Out of 75 eligible men, 34 responded (mean age 55). About 59% of the respondents were still actively taking flibanserin at the time of survey. Among those on flibanserin for over 2 months, 69% reported that they had noticed treatment-related benefits after starting the drug. These benefits included improvements in low desire and, interestingly, in the ability to reach orgasm. Some men had been prescribed flibanserin not just for low libido but for issues like delayed orgasm (8 of the 20 active users cited trouble reaching orgasm as their primary issue). This might be because flibanserin’s action on brain chemistry could potentially aid orgasmic function as well – though that’s speculative. Regarding side effects in this survey: about one-third of men noticed some impact on sleep (31% actually said their sleep improved, 16% said it worsened). Physicians reported that when men discontinued flibanserin, the top reasons were lack of effect and insomnia, followed by daytime sleepiness and fatigue. Importantly, physicians interviewed felt that flibanserin was generally well-tolerated in men, with a safety profile similar to that in women. No new safety concerns were noted. The bottom line from this survey: some men (about 2/3 after a couple months) felt flibanserin was helping their sexual function in some way, while others did not; side effects like insomnia led a few to quit, but serious adverse effects weren’t seen. The authors concluded more rigorous research is needed, but these early real-world experiences are encouraging enough to warrant further investigation.
• Other contexts: There is also interest in using flibanserin to help men whose libido has been suppressed by other treatments. For example, a trial has explored flibanserin in men undergoing androgen deprivation therapy for prostate cancer (a treatment that typically kills sex drive). That Phase II study (in men on hormone suppression for prostate cancer) aimed to see if flibanserin could boost sexual interest despite low testosterone. Such studies acknowledge that flibanserin might counteract some libido-crushing effects of low testosterone or high serotonin in these contexts, but results are not yet published.

What do we learn from these findings? First, flibanserin in men appears feasible from a safety standpoint, with similar side effects as in women (some drowsiness, occasional insomnia, dizziness). Men, just like women, would have to avoid alcohol strictly if using it, due to the hypotension risk – that precaution applies regardless of gender. Doctors also screen for the same contraindications (e.g. liver issues, medication interactions) in men as they do for women. Second, there is a signal that some men benefit – particularly in terms of feeling more desire or improved sexual function after a couple months – but it’s far from universal. Without placebo-controlled data yet, we must be cautious: the placebo effect in sexual dysfunction trials is known to be quite high. For instance, just the act of seeking treatment or being monitored can improve sexual outcomes in some people. So, while 69% reporting benefit sounds promising, we don’t know how much of that is a true drug effect. This is why the ongoing randomized trial is crucial.

For now, if a male patient with HSDD is considering flibanserin, he should do so only under close medical supervision, and ideally as part of a clinical trial or after other options. Off-label prescriptions are happening in specialist centers, but most general physicians won’t be familiar with it for men. The patient should ensure his doctor knows the flibanserin safety precautions (no alcohol, etc.). Dose for men would presumably be the same as for women (100 mg at bedtime), since that’s what’s been tried. It may take 8+ weeks to judge effect, and if no improvement by then, it’s reasonable to stop. Also, flibanserin is expensive (it can cost several hundred dollars a month), and insurance may not cover an off-label use, so cost is a practical consideration.

In summary, Flibanserin (Addyi) increases certain brain chemicals to potentially boost sexual desire. In women, it yields modest improvements. In men, early off-label experiences suggest it might help some men with low libido, but robust evidence is lacking. The drug must be taken daily and carries precautions like avoiding alcohol. Men intrigued by flibanserin should discuss enrolling in trials or carefully trying it with a specialist’s guidance, understanding that it’s an experimental off-label use for them.

PT-141 Bremelanotide (Vyleesi): “On-Demand” Arousal Drug and Its Use in Men

What is Bremelanotide? Bremelanotide (code name PT-141, brand name Vyleesi) is a novel medication originally derived from research on melanocortin peptides. It’s a synthetic peptide that is administered by subcutaneous injection (under the skin) via an autoinjector pen. Bremelanotide was approved by the FDA in 2019 for treating generalized HSDD in premenopausal women. Women use it “as needed,” meaning they inject themselves at least 45 minutes before anticipated sexual activity, but not more than once in 24 hours or 8 times per month. Unlike flibanserin’s daily regimen, bremelanotide is an on-demand therapy for low desire – somewhat analogous to how one might use an ED medication only when needed (though again, the mechanism is very different). Bremelanotide is noteworthy because it’s the first in its class; the FDA labeled it a “first-in-class” medication for sexual desire disorders.

How Bremelanotide Works (Mechanism of Action): Bremelanotide is a melanocortin receptor agonist. Specifically, it activates the melanocortin-4 (MC4) receptors (and to some extent MC3) in the brain. The melanocortin system is part of the excitatory side of sexual regulation – it’s involved in the brain pathways that promote sexual arousal. Interestingly, bremelanotide’s development was serendipitous: it’s related to a peptide hormone (α-MSH) that causes tanning. Researchers found that a similar peptide (Melanotan II) given for sunless tanning unexpectedly caused sexual arousal and spontaneous erections in male volunteers. This led to the idea that activating melanocortin receptors could treat sexual dysfunction. Bremelanotide was developed from that concept, refined to better target sexual centers without as much effect on blood pressure as its precursor (Melanotan II) had.

In the brain, MC4 receptors are located in regions like the hypothalamus that integrate sexual desire signals. Activation of MC4R is thought to increase dopamine release in the medial preoptic area and other key areas, thereby heightening sexual excitement. Essentially, bremelanotide hits a “go” switch in the brain’s arousal circuitry. This can have both psychological effects (increased desire, fantasizing, interest) and physiological effects (enhanced genital blood flow, easier arousal). Notably, in women’s studies, bremelanotide not only improved desire but also sometimes improved measures of arousal and orgasm. In men, melanocortin activation can facilitate erections – which is why it was initially tested as an erectile dysfunction drug. It doesn’t work the same way as Viagra (which is vascular); instead, it triggers central arousal pathways that secondarily lead to erection. Men have described it as creating a feeling of sexual urge or “mental arousal” that translates into physical readiness.

Bremelanotide in Women’s HSDD Trials: The approval of Vyleesi was based on two large Phase 3 trials (called the RECONNECT studies) in premenopausal women with HSDD. The women used bremelanotide injections over 24 weeks as needed. The outcomes showed significant, albeit modest, improvements in sexual desire and reductions in distress about sex. Specifically, compared to placebo, women on bremelanotide had higher scores on the female sexual desire index and lower scores (better) on the distress scale. The statistical significance was clear (p < 0.001), but the magnitude was small – an effect size of ~0.3 to 0.4 for increased desire, which is considered a small-to-moderate effect. Many researchers pointed out that the benefit is modestand questioned how meaningful it is in practice. Nevertheless, some women do feel it helps them engage in and enjoy sexual activity more. It’s likely that bremelanotide doesn’t create desire out of thin air, but if a woman has some baseline attraction or stimulus, the drug amplifies her body’s and brain’s responsiveness to it.

Bremelanotide’s Side Effects and Safety: Because it’s taken on-demand, side effects occur acutely around the time of use. The most common side effect – and the one that caused many participants to quit trials – is nausea. About 40% of women in trials experienced nausea after injections, and for about 13% it was severe enough to require medication or cause vomiting. Typically, the nausea can start within an hour of the shot and last a couple hours. Some women take an anti-nausea pill (like ondansetron) before injecting to help with this. Other common side effects include flushing (around 20% of users) – a feeling of warmth and redness, since melanocortin can affect blood vessels – as well as injection site reactions (reddening or pain, ~13%), headache (~11%), fatigue (~3%), and dizziness (~2%). There is a transient rise in blood pressureafter each dose: on average about a 6 mmHg systolic increase and 3 mmHg diastolic increase, accompanied by a slight drop in heart rate. For most healthy individuals this isn’t dangerous, but bremelanotide is contraindicated in people with uncontrolled high blood pressure or heart disease to be safe. Usually, blood pressure returns to normal within 12 hours. Unlike flibanserin, bremelanotide has no restriction with alcohol – studies found it does not interact with alcohol to cause hypotension (this is a relief to many, given the no-alcohol rule of flibanserin). However, one safety quirk is that frequent use of bremelanotide can cause hyperpigmentation (darkening of certain skin areas or gums). About 1% of patients in longer-term studies developed focal dark patches on the skin (like on the gums, face, breasts). This is due to its melanocyte-stimulating effects (like a tanning peptide). These spots may be permanent in some cases. This side effect was mostly seen in people who used >8 doses a month. Therefore, one should not exceed recommended dosing.

In summary, bremelanotide in women is an option to “jump-start” desire before sex, with the main downsides being an injection and frequent nausea/flushing.

Use of Bremelanotide in Men – Early Evidence and Experience: Bremelanotide’s story actually began in men. In the early 2000s, it was studied as a treatment for erectile dysfunction (ED), especially in men who didn’t respond well to Viagra or similar drugs. A notable trial in men who had failed sildenafil (Viagra) found that 33.5% of men receiving intranasal bremelanotide (an earlier formulation) had improved erections sufficient for intercourse, compared to 8.5% on placebo. That showed promise for ED, albeit not as high success as PDE5 inhibitors in general. Development for ED was halted at one point due to concerns about blood pressure side effects with the intranasal form. Later, the subcutaneous form was advanced for women’s HSDD. Now that Vyleesi is on the market, some male sexual medicine specialists have begun prescribing it off-label to men, particularly for those with difficult-to-treat sexual dysfunctions (like ED with psychological components, or mixed arousal and desire issues).

One of the leading experts, Dr. Irwin Goldstein (who was involved in Vyleesi’s development and runs a sexual medicine clinic), reported his clinic’s experience in using bremelanotide for men. In 2024, Goldstein and colleagues published an abstract of 21 men who were prescribed off-label bremelanotide for various sexual complaints. The results were quite striking (keeping in mind this is not a placebo-controlled trial, just an open-label report):

• The men had a range of issues: 69% had erectile dysfunction (the most common reason for prescribing PT-141), 45% had low sexual desire, 54% had anxiety about sexual performance, 36% weren’t enjoying sex, and some had orgasm or ejaculation difficulties. Many had multiple issues at once (which is often the case; for example, ED can lead to anxiety and low desire).
• After using bremelanotide (at least two doses were tried by each, and then they provided feedback), 91% of the men reported improvements in their sexual function overall. Importantly, all men with ED noted improved erectile function with bremelanotide use. This aligns with earlier research that PT-141 can help induce erections.
• Among those men who specifically had low desire or sexual anxiety, 100% reported improvement in those issues. In other words, every man in that subset felt bremelanotide helped increase their sexual desire and/or reduced their anxiety around sex. While that sounds almost too good to be true, it may reflect a strong effect in this highly motivated group – or some placebo effect, or the fact they were also getting comprehensive sex therapy in the clinic (we should interpret with caution, but it’s encouraging).
• Men’s subjective comments were intriguing: they described feeling more connected between brain and genitals, increased sensitivity, longer-lasting erections, ability to have additional erections for 18-24 hours after the dose, and greater confidence in initiating sex. Many said sex was more pleasurable and carefree, and they were more at ease starting intimacy. For example, 86% felt less anxious about initiating lovemaking and 79% anticipated sex would be more pleasurable, according to questionnaires. This hints that bremelanotide’s effect isn’t purely physical; it seems to alleviate some psychological barriers and enhance enjoyment, which is very relevant for HSDD.
• Side effects in men: In this same report, side effects were similar to what women experience: about 36% got flushing, 36% nausea, 27% headaches. Interestingly, 27% of men reported “bothersome spontaneous erections without sexual stimulation” lasting up to ~24 hours after the injection. Some men might not consider that a bad side effect (!), but it could be inconvenient or uncomfortable. It shows the potency of the drug’s effect on erectile tissues. A few men (9%) noted more unusual effects like mild incontinence, cramping, or an abdominal burning sensation. All side effects were transient; there were no reports of serious issues. No one in the report had to stop the drug due to side effects, as far as indicated.

Another abstract by a different team reported that in men for whom bremelanotide “worked,” they saw improvements not just in erections but also in desire and orgasmic function: specifically, 39% had improvement in HSDD symptoms, 52% in ED, 17% in orgasm issues, and 39% in performance anxiety. These numbers likely come from a subset analysis of men responding to therapy. It underscores that bremelanotide might have broad benefits across the sexual response cycle (desire, arousal/erection, orgasm) for some men by virtue of how it globally enhances sexual neurochemistry.

• Combination Therapy for ED: Beyond HSDD, bremelanotide is being studied as an adjunct to ED pills. There’s an ongoing interest in combining bremelanotide with PDE5 inhibitors (like a co-formulation injection) for men who don’t respond to PDE5 inhibitors alone. The logic is that bremelanotide adds a central kick (increasing arousal) and possibly some peripheral boost, which might help those “resistant” cases. A Phase 2 trial has been announced for such a combination in ED. For our topic – male HSDD – this is a bit tangential, but relevant in that a man with both ED and low desire could potentially benefit from a strategy that addresses both (for example, using bremelanotide to simultaneously help erections and desire).

Practical Considerations of PT-141 in Men: If a man were to use bremelanotide off-label for low desire, here’s how it might look: He would be prescribed the Vyleesi autoinjector (which comes as a kit of disposable injection pens). At a time when he plans to be sexually intimate (say, date night), he would self-inject 1.75 mg of bremelanotide into his thigh or abdomen about 45 minutes to an hour before sexual activity. The drug may start to have effect by 30-60 minutes, with peak plasma levels around 1 hour. If it works for him, he might feel more mentally aroused or “in the mood” and find any physical arousal is easier. His erection quality might improve if that was an issue. The effects can last a while – some men report they could have additional sexual episodes for up to 8-12 or even 24 hours after the dose (though with diminishing intensity).

He should not take more than one dose in 24 hours, and not exceed eight doses per month (to avoid overexposure and reduce risk of side effects like nausea or pigment changes). If he experiences bad nausea, his doctor might advise taking an antiemetic beforehand. He must also ensure he doesn’t have uncontrolled blood pressure or heart issues before using this medication.

It’s worth noting cost: Vyleesi can be expensive (several hundred dollars for a pack of 4 doses) and may not be covered for men. Also, the injection aspect is a barrier for some – you have to be comfortable self-injecting on a potentially routine basis.

Head-to-Head Comparison: Flibanserin vs. Bremelanotide for Men with HSDD

Both Addyi and PT-141 aim to address low sexual desire by altering brain chemistry, but they do so in very different ways and usage scenarios. Below is a breakdown of key points:

Mechanism of Action: Flibanserin is essentially a rebalancing agent for neurotransmitters – it lowers serotonin’s inhibition and boosts dopamine/norepinephrine to increase desire signals. Bremelanotide is a melanocortin receptor stimulator – it directly activates arousal pathways in the brain (and to some extent spinal cord), triggering the cascade that leads to sexual arousal, desire, and even erection. In simpler terms, flibanserin works more like a subtle “mood/libido enhancer” over time, whereas bremelanotide is more of an immediate “arousal igniter.”

Usage Pattern: Flibanserin is taken every night at bedtime (whether or not sexual activity is expected). It’s a chronic medication, meant to gradually improve baseline libido. This might suit men who have a persistent lack of sexual thoughts or interest throughout their days and want to generally feel a higher level of desire ongoing. Bremelanotide is taken on demand, only before sexual activity. A man who still has some sexual interest but maybe struggles to get “in the mood” or aroused at the right time might prefer this – for instance, if he wants to plan a romantic evening and ensure his libido and performance kick in. It’s less useful for spontaneous desire since by definition you plan the injection ahead of time. Some men with severe HSDD have so little spontaneous desire that they might not even think to use an on-demand drug; flibanserin might help them have more frequent natural sexual initiative. On the other hand, some men with low libido might say, “Once I get started I enjoy it, but I never initiate” – those men might benefit from a dose of PT-141 to help get started.

Onset and Time to Effect: With flibanserin, nothing happens acutely – you don’t feel a libido rush after taking a pill. It needs to be taken daily for weeks. Many men (and women) might not notice any change until at least 4 weeks, and maximal effect by 8 weeks. If a man is looking for a quick improvement by the weekend, flibanserin isn’t the solution. Bremelanotide, in contrast, works the day you use it. Men often feel a response within an hour or so of the shot, sometimes sooner. The effect can last several hours and even into the next day at a lower level. However, it’s not meant to be in your system continuously. It’s like comparing an antidepressant (flibanserin) to an as-needed anxiety pill (bremelanotide) in terms of usage style.

Efficacy (expected outcomes): We don’t have direct comparative efficacy since no head-to-head trials exist in men. From what we know:

• Flibanserin’s potential efficacy in men is still under study. The survey data suggests a fair portion of men feel it helps after a couple months, but we await RCT results. If it parallels women’s data, one might expect a mild improvement in desire frequency and sexual satisfaction. Men might report thinking about sex more often or being more receptive to sexual cues after using flibanserin, but it likely won’t transform one’s libido dramatically. Also, flibanserin will not directly cause erections or physical arousal – so if ED co-exists, flibanserin alone may not address that (in the Baylor trial they specifically require men to have good erectile function so that any improvement is truly desire-based).
• Bremelanotide’s efficacy in men, from observational reports, appears promising especially if there are combined arousal issues. Men who have used it off-label have reported improvements in desire, performance anxiety, and ability to achieve orgasm. It seems particularly useful for men who have a psychological inhibition (like anxiety or low confidence) secondary to past sexual difficulties – because PT-141 can break that cycle by simultaneously improving the physical arousal (erection) and giving a central boost of desire, which in turn increases confidence. For a man whose primary issue is low libido with no ED, bremelanotide might still help by providing that central spark of interest (some men describe a feeling of being horny which they hadn’t felt for a while). But since it’s tied to usage, it might mean they engage in sexual activity when they otherwise wouldn’t, thereby potentially improving their sexual frequency and satisfaction.

To put it succinctly: Flibanserin might modestly raise the “baseline” level of sexual desire over time, whereas Bremelanotide acutely raises desire and arousal “in the moment.” They’re not mutually exclusive – conceivably, a man could use both (flibanserin daily and PT-141 on occasion) if appropriate and safe, although that’d be entirely experimental and one would need to watch out for combined side effects like hypotension or headache.

Safety Profile Differences: This is a big consideration:

• Flibanserin – main risks are sedation and low blood pressure. Men (like women) would need to avoid alcohol strictly. A man who enjoys regular drinks might find this onerous. Flibanserin also can interact with many medications due to liver enzyme (CYP3A4) interactions – so if a man is on certain blood pressure meds, antifungals, etc., he might be disqualified. It’s taken at night largely to reduce daytime side effects, but men have reported insomnia as well (possibly due to an effect on sleep neurotransmitters). If a man already has issues with dizziness or blood pressure, flibanserin could exacerbate those slightly. However, flibanserin is not associated with immediate changes in blood pressure or heart rate in the way bremelanotide is – its hypotension risk is mostly when combined with alcohol or certain drugs.
• Bremelanotide – main risks are nausea and blood pressure increases. A man who has a strong stomach might handle it fine; others might vomit and then sex is off the table. If a man has hypertension that’s not well-controlled, using PT-141 could be risky (even though average BP rise is small, if his baseline is high it could spike). It also causes flushing and sometimes headache, which though transient, can spoil the mood for some. On the bright side, bremelanotide does not have an alcohol interaction issue (so having a glass of wine on a date night when also using PT-141 is okay). Another consideration: since it’s used in the moment, if side effects hit, they hit when you’re about to or are engaging in intimacy – a bad headache or nausea at that time might be quite disruptive. With flibanserin, side effects like dizziness might be more separate from sexual activity (since you take it at bedtime).

Administration and Convenience: Taking a nightly pill is easy for most (though remembering to take it daily is the challenge). Using an injection is more involved – some people are needle-averse. The Vyleesi autoinjector is designed to be simple, but it still requires a pinch of skin and a little poke; there’s a learning curve to feel comfortable. Also, there’s the planning aspect (carrying an injector if traveling, etc.). However, some might prefer not having to take a drug every day when they might have sex only occasionally.

Effect on Erectile Function: While HSDD is about desire, many men with low desire also have some degree of erection difficulty or lessened physical arousal. Bremelanotide clearly can help erectile function (it was almost an ED drug). So in a man who has mixed ED and low desire, PT-141 might tackle both – an important advantage. Flibanserin does not directly improve erections, and in the male trial they exclude those with ED, so it’s not intended to address that. If an HSDD man also has ED, he might need a separate ED therapy (like a PDE5 inhibitor) alongside flibanserin, whereas bremelanotide alone might suffice for both issues.

Partner considerations: For partnered sex, one might ask: does it bother a partner that the man has to use a drug? This is personal, but with flibanserin the partner may not even notice (since it’s taken daily, not explicitly tied to sex). With bremelanotide, the partner will likely know (“I need to take my shot 45 minutes before”) – which could either be a positive (“we’re planning and addressing this together”) or a negative if it feels too clinical. Some couples integrate it as part of foreplay (the anticipation can even be sexy in a way, knowing help is on the way), while others may find it cumbersome.

Below is a summary table highlighting key differences:

As the table shows, each drug has distinct advantages and drawbacks. Flibanserin is subtle and slow-acting but easy to take and may better suit men seeking a general lift in libido without tying it to sexual encounters. Bremelanotide is fast-acting and likely more noticeable in effect, which can be very useful for situational low desire or when desiring a guaranteed boost, but it requires injections and can cause considerable side effects in the moment (like nausea).

One way to think of it: if a man’s low desire is intrinsically tied to psychological hurdles or a lack of arousal (for example, he fears failure in sex due to past ED, so he’s lost desire – a common scenario), bremelanotide might break the ice effectively by directly creating arousal and positive experiences, thereby restoring confidence and interest. If a man’s low desire is more persistent and not linked to any specific sexual attempt (for example, he just never feels “in the mood” even if everything physically works), and he wants to feel more daily interest in sex or intimacy, flibanserin might provide that gradual neurochemical nudge to increase libido generally.

It’s also possible that these could be sequential or combined in practice: a doctor might first try flibanserin for a few months to raise baseline desire. If partial improvement or if the man still has trouble in specific situations, they might add on bremelanotide for those occasions. This is speculative but not out of the question in real-world off-label practice. Of course, cost and cumulative side effects (like combining two drugs’ side effects) would need careful attention.

Which Patients Might Consider These Treatments?

Given that neither flibanserin nor bremelanotide is officially indicated for men, the average man with a bit of low libido would not be a candidate for these drugs as a first-line solution. So who might benefit, and under what circumstances would a doctor and patient even contemplate using these?

Men with Diagnosed HSDD and No Other Explanations: The ideal candidate is a man who clearly meets criteria for HSDD – meaning he has had low sexual desire for at least 6 months, which is causing him significant distress, and importantly, there is no major medical, psychological, or relationship issue solely responsible for it. Essentially, if a man has done all the right evaluations and treatments (normal testosterone or is on testosterone replacement if needed, treated any depression or anxiety, addressed relationship issues, optimized other health problems, and perhaps tried therapy), and he still experiences persistent low libido and distress, then exploring off-label pharmacological help could be reasonable. These medications are typically managed by urologists or endocrinologists with a sexual medicine focus, or by specialized sexual health psychiatrists.

Men with Concurrent Sexual Dysfunction (like ED or Delayed Orgasm) + Low Desire: A subset of men lose desire secondary to other sexual problems. For instance, a man with erectile dysfunction might start avoiding sexual situations and over time his brain lowers his libido to protect him from repeated failure – this can present as HSDD. In such cases, treating the primary issue (ED) often improves desire (success breeds libido). But if standard ED treatments alone aren’t sufficient to restore sexual confidence, bremelanotide might be an attractive option since it can address both issues at once. The data from Goldstein et al. showed men with ED and low desire did very well on PT-141. Similarly, some men on antidepressants or post-prostate surgery have orgasmic difficulties and low desire – flibanserin, due to its serotonergic mechanism, might help counter SSRI-induced libido loss or arousal deficits, as hinted by the survey where some men used it for difficulty reaching orgasm. So, men in these complex scenarios might consider these drugs, typically in consultation with a specialist.

Men Interested in Clinical Trials: If you are a man suffering from HSDD, one of the best ways to access these treatments in a safe, supervised manner is through clinical trials. As mentioned, there is a Phase 2 trial of flibanserin in men ongoing (recruiting as of 2025). Participants in such trials not only get a chance at the active treatment (or placebo) for free, but also get close monitoring, frequent check-ins, and contribute to advancing knowledge. You can ask your doctor or search ClinicalTrials.gov for “HSDD in males” to find any recruiting studies. Additionally, keep an eye on research networks; for example, if bremelanotide trials in men commence (none public yet for HSDD, but possibly in ED contexts), those could be opportunities.

Men Who Have Exhausted Conservative Options: Before turning to medications like these, doctors will usually try more established strategies:

• Testosterone optimization: Even if a man’s testosterone is “low-normal,” some men with low desire might benefit from a trial of testosterone therapy under medical guidance (provided there are no contraindications). Testosterone is the main hormone driving male sexual thoughts and frequency of fantasies. If a man is hypogonadal (low T), that must be addressed first (and would likely resolve the libido issue in many cases). The Baylor trial for flibanserin only enrolls men with normal T or men already on stable T therapy if needed.
• Psychosexual therapy: Working with a sex therapist can help uncover psychological inhibitors of desire – performance anxiety, relationship resentments, body image issues, etc., and teach techniques to revive intimacy and interest. Often couples-based therapy can rekindle desire on both sides.
• Lifestyle changes: Stress reduction, better sleep, exercise, moderating porn use (since excessive pornography can sometimes reduce desire for partnered sex), and spicing up routine can all help naturally improve libido.
• Other off-label meds with some evidence: Before flibanserin or PT-141, doctors sometimes try bupropion (an antidepressant that boosts dopamine) which in some cases can increase sex drive. Or buspirone (an antianxiety med that is a 5-HT1A agonist) which is somewhat similar to flibanserin’s serotonin action. These have mixed evidence but are oral and inexpensive. Dopamine agonists like cabergoline (especially if prolactin is high) have also been used to enhance libido. None are officially approved either, but some studies in women showed benefit and they are options a doctor might consider before moving to newer, costlier drugs.
• PDE5 inhibitors (Viagra/Cialis): Interestingly, some studies reported that men put on Viagra for mild ED noted an increase in libido as well, possibly because successful erections improved their sexual confidence and interest. If low desire is intertwined with subtle arousal issues, a trial of such medication could be enlightening – if it helps desire, the issue may have been secondary to erection problems.

If all the above have been tried or are not sufficient, and the man is still very distressed by low sexual desire, at that point a specialist might consider an off-label trial of flibanserin or bremelanotide, fully informing the patient of the off-label status and potential risks.

Conclusion

Flibanserin and Bremelanotide represent two novel approaches to low sexual desire that have made strides in women’s sexual health. Translating their use to men is an exciting frontier but one that is still in its infancy. For a man dealing with HSDD, these drugs offer a ray of hope that biology can be tweaked to rekindle libido. Flibanserin (Addyi) may be thought of as a “slow burner” – gradually lifting the weight of low desire over weeks by recalibrating brain chemistry. PT-141 Bremelanotide (Vyleesi) is more of a “spark” – igniting sexual interest and arousal in the moment through a different brain pathway.

Current evidence suggests that some men do respond positively to these treatments: flibanserin’s early off-label data show a subset of men feeling improved desire and sexual satisfaction, and bremelanotide’s case series demonstrate enhanced arousal, confidence, and libido in men with complex sexual dysfunction. However, it is equally clear that these are not magic solutions nor one-size-fits-all remedies. Many men might find little benefit, or side effects may limit use. The psychological components of HSDD often still need to be addressed alongside any medication.

Men and clinicians considering these therapies must do so in an informed, cautious manner. It is highly recommended to involve a healthcare provider with expertise in sexual medicine. As research continues – including the ongoing placebo-controlled trial for flibanserin in men – we will gain clearer insight into how effective these drugs truly are for male HSDD, and which men are the best candidates.

In the meantime, for the man who has tried standard approaches without success, an individualized off-label trial of Addyi or Vyleesi (or both sequentially) might be considered, with the understanding that this is an experiment undertaken with careful monitoring. It’s heartening to see that sexual health research is expanding to include men’s desire issues, not just performance issues. Low libido in men has historically been under-discussed, possibly due to stigma or the cultural expectation that men are always ready for sex. Acknowledging HSDD in men as a genuine condition deserving of treatment is an important step.

Finally, remember that improving sexual desire often requires a holistic approach: emotional intimacy, communication with one’s partner, physical health, and mental wellbeing all play roles. Medications can assist, but they work best when integrated into a comprehensive plan for sexual wellness.

Disclaimer: Flibanserin (Addyi) and Bremelanotide (Vyleesi) are not FDA-approved for use in men. Any use of these medications in men is considered off-label. The information above is for educational purposes and any man considering these treatments should do so only under the guidance of a qualified healthcare professional, after a thorough discussion of potential risks and benefits.

References (AMA Style)

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