Setipiprant for Hair Loss: 2024 Update

Did you know that a new pathway for hair loss was discovered in 2012? This new pathway could mean there’s more to hair loss than we currently understand, and that new drugs can be useful in regrowth.

In this post, I’ll introduce you to a possible future hair loss treatment: setipiprant. You’ll learn how the drug works, as well as:

• How clinical trials work, and where the drug currently is in the process.
• The possible side effects associated with use.
• The difference between oral and topical setipiprant, and the pros/cons of each.
• How setipiprant compares to finasteride, and whether the drugs can be used together.

Of course, I’ll also share with you the natural alternatives to setipiprant that I recommend. These alternatives have been used by myself and many others with positive results.

And leave us a comment at the bottom of this article if you have any questions on this topic.

2024 Update: The results of the Phase 2A trial showed there was little risk, but also little benefit to using setipiprant for hair growth.

What is Setipiprant?

Setipipran is an oral drug that’s currently being tested for use as a hair loss treatment. It was initially developed as a treatment for allergic rhinitis, but recent hair loss-related discoveries have made it a better candidate for hair loss reversal.

How Does It Work?

In short, setipiprant is an antagonist of the prostaglandin D2 receptor 2 (DP2). This receptor is responsible for bonding with and responding to certain prostaglandins, particularly PGD2. This prostaglandin has been linked to various pathological responses, including those linked to allergies, asthma, and inflammation.

For Allergies/Asthma

As setipiprant is believed to interfere with the receptors known to contribute to allergies/allergic responses, the drug was first tested on allergies and asthma.

In clinical trials, the drug performed quite well in the treatment of allergen-induced airway responses in asthmatic patients. It was also well tolerated by participants. However, its results were similar to those of drugs already on the market, so further trials were discontinued.

For Hair Loss

In 2012, researchers discovered a link between the PGD2 receptor and hair loss. More specifically, this receptor is seen at high levels in the scalps of men diagnosed with Androgenetic Alopecia (AGA).

AGA (Male-Pattern Baldness) is the most common cause of hair loss in men, though it’s also seen in women (Female Pattern Hair Loss). It’s believed to be caused by a sensitivity to DHT, which is an androgen hormone that attaches to the follicles and leads to inflammation and irritation.

If left untreated, this inflammation causes hair follicle miniaturization. This can then lead to balding. But, where exactly does DHT fit in?

It’s known that PGD2 is produced from PGD2 synthase, an enzyme. And PGD2 synthase levels are increased by — you guessed it! — DHT. With an increase in PGD2, the PGD2 receptor on the scalp is then triggered, which causes inflammation.

According to researchers, setipiprant steps in before PGD2 attaches to the receptors, and therefore prevents receptor activation and, as a result, hair loss.

With the discovery of the possible link to PGD2 receptors, the drug was acquired by Kythera, and trials began to test the effects of setipiprant on hair loss.

Development and Clinical Trials

As of yet, trials are still underway. The drug is currently in Phase II.

How Clinical Trials Work

To better understand where setipiprant is in its clinical phases, it’s important to understand how clinical trials work.

Four main phases take place during clinical trials. They are:

Phase I – These trials assess the safety of a drug on a small number of healthy individuals (typically less than 100). This can take a few months, and the results will determine whether further testing can be implemented.

Phase II – These test the efficacy of a drug, and are commonly carried out on a larger number of participants than Phase I. These studies are commonly ‘blinded’, and they can take a few months to a few years to complete.

Phase III – Involving several hundred to several thousand participants, these studies can take a few years to complete. Their goal is to further gauge the efficacy of a drug, as well as provide insight into possible side effects. Once completed, it is then that the pharmaceutical company will apply for FDA approval.

Phase IV – These take place after a drug has entered the market, and they’re used to test the long-term efficacy of said drug, and/or compare it to similar drugs on the market. The results of these studies can lead to the drug being removed from the market, or dosage changes being made.

With a greater understanding of the process, let’s take a closer look at the clinical trials performed on setipiprant.

Phase 2 and Phase 3 Studies on Setipiprant for Allergic Rhinitis

While you and I are more interested in how setipiprant works for hair loss, it’s important to consider the results of non-hair loss related studies. Why? Because studies are so scarce, it’s good to look at all the available information.

Phase 2

This study was conducted at seven centers in Texas during the Mountain Cedar pollen season. It consisted of both adult and elderly participants (ranging in age from 18 – 70 years). The participants were randomized to receive either: placebo, setipiprant at doses of 100 mg b.i.d., 500 mg b.i.d., 1000 mg b.i.d. or 1000 mg o.d., or cetirizine 10 mg o.d. (active reference).

Once the trial began, a total of 579 participants were included. There were 96 – 98 participants per treatment group, and 577 completed the trial.

As shown above, the Daytime Nasal Symptom Score (DNSS) decreased steadily when treated with setipiprant.

Phase 3

This study was similarly conducted at seven centers throughout Texas during the Mountain Cedar pollen season. It consisted of adolescent, adult, and elderly participants (ranging in age from 12 – 76 years). The participants were randomized to either: placebo, setipiprant 1000 mg o.d., or cetirizine 10 mg o.d.

A total of 630 participants were included in the study. There were 210 participants per treatment group, and 604 completed the trial.

As with the previous study, cetirizine performed better in reducing DNSS. Interestingly, the setipiprant results were similar to those of placebo.

This is likely due to the decreased dosage, as the previous study included participants who took setipiprant twice per day (as opposed to this study’s once per day).

What Do These Results Tell Us?

Overall, it appears that setipiprant is useful in treating symptoms associated with seasonal allergic rhinitis. Such symptoms include nasal congestion, runny nose, nasal itching and sneezing.

These symptoms are consistent with an allergic reaction, which causes inflammation within the sinuses. As such, setipiprant is shown to reduce inflammation, which can be useful in the treatment of hair loss.

Phase 2A Study on Setipiprant for Hair Loss

The study aims to “evaluate the safety, tolerability, and efficacy of the oral administration of setipiprant tablets 1000 mg twice daily”.

The Participants

This particular study consists of 169 active participants, all of whom have been diagnosed with AGA. The participants are all male, and range in age from 18 – 49 years of age.

To further ensure participants are up to par, these are the inclusion and exclusion criteria as laid out by researchers.

Inclusion Criteria:

• A diagnosis of AGA
• The participants must agree to maintain their current hair care routine and refrain from weaving, colorants/dyes, and any non-study hair loss treatments.

Exclusion Criteria:

• History of non-AGA hair loss.
• Scarring of the scalp.
• Conditions or diseases of the scalp, hair, or hair shaft.
• Use of products within 6 months of study that were used continuously for 1 month may impact hair growth.
• Hair weaving within 6 months.
• Use of hair colorants/dyes within 6 months.

While the above may seem restrictive, these criteria ensure that results are as accurate as possible.

Locations

This study is being carried out in numerous locations across the United States. These include:

• Arkansas (Hot Springs and Little Rock)
• California (San Diego and Santa Rosa)
• Illinois (Chicago)
• Kansas (Wichita)
• Michigan (Clinton Township)
• Minnesota (Fridley and Minneapolis)
• North Carolina (Winston-Salem)
• Ohio (Cleveland)
• Oregon (Portland)
• Pennsylvania (Hershey)
• South Carolina (Greer)
• Texas (Austin and Katy)
• Virginia (Lynchburg)

This enables a large number of participants to join the study, which helps to improve results.

Methods

This interventional study consists of two arms: experimental (setipiprant) and placebo.

The experimental group will take 1000 mg setipiprant (two 500 mg tablets) twice daily at 12-hour intervals for a duration of 24 weeks.

The placebo group will take two placebo pills twice daily at 12-hour intervals for a duration of 24 weeks.

The study is quadruple masked, meaning the participants, care providers, investigators, and outcome assessors are blinded to which patients are within which group. This helps to keep results unbiased.

Results

At week 24, there were hair growth improvements seen via target area hair count or blinded Subject Self-Assessment with setipiprant versus placebo.

While the drug was well tolerated, it did not demonstrate efficacy versus placebo.

When Will Setipiprant Be Available?

Due to lack of results in the 2A trial, it does not appear setipiprant will ever be available as a medication for the treatment of hair growth.

Are There Side Effects?

While the full effects of setipiprant on hair loss are still unknown, previous studies have shed some light on possible adverse effects.

The studies which were focused on setipiprant as a treatment for allergic rhinitis and asthma saw side effects, such as:

• Dry mouth
• Nausea
• Drowsiness
• Elevation of liver enzymes
• Anxiety

In one patient, cholelithiasis (gallstones) developed during the time of the trial. This could very well be directly related to setipiprant (as it’s been shown to effect liver enzymes).

Further Considerations

As PGD2 is inhibited by setipiprant, there can be some side effects associated with its use.

One such effect may be sexual in nature, as PGD2 plays a major role in male sexual development. This prostaglandin is also known to be associated with vasodilation (which is crucial for hair loss sufferers) and the attraction of neutrophils (white blood cells that play a critical role in the immune system).

It’ll be interesting to see what the long-term effects of setipiprant are (especially on men), and whether these are similar in nature to finasteride or not.

A topical form of setipiprant may reduce said effects, but further research needs to be done.

Is Setipiprant Safe?

As far as the earliest studies have shown, setipiprant is relatively safe. There has been no mention of severe side effects. However, only with larger-scale studies can we truly understand the drug’s effects on humans.

Setipiprant Oral vs Topical

While setipiprant has still not been approved by the FDA, it’s possible to obtain powdered setipiprant online. This is not advised, however I thought I’d still discuss the pros and cons of oral versus topical use of setipiprant and similar drugs.

Topical treatments aren’t uncommon when it comes to treating hair loss, and in some cases, a topical treatment can reduce the side effects associated with oral dosages. This is believed to be the case with topical finasteride, in which testing is still underway.

However, not all oral drugs can be used topically. This is for a variety of reasons, one of which is shelf life.

In the studies above, setipiprant was shown to be most effective when taken twice daily at 12-hour intervals. The reason for this is setipiprant needs to be present within the body continuously, or else the drug will not be as effective.

This tells us one very important thing about the drug, and that’s it has a 12-hour shelf life. This means the drug is metabolized by the body within 12 hours of dosing, and only by taking it at 12-hour intervals will it remain effective.

This doesn’t take topical uses of setipiprant off the table, but it does make them less likely to be effective. After all, applying something topically twice per day is a lot more work than simply taking an oral dose.

Setipiprant vs. Finasteride

There’s no doubt that setipiprant and finasteride have a similar end game, and that’s to prevent hair loss. But how different are their mechanisms, and which is better?

If you think of the hair loss process as a timeline, then finasteride interferes much sooner in the process. That is, it inhibits the expression of 5-alpha-reductase (5AR), which is responsible for the production of DHT. In this way, fewer androgen receptors are activated on the scalp and PGD2 production is slowed or even ceased.

Setipiprant, though, enables 5AR to create DHT, and the process continues until PGD2 comes into play. It is then that the drug interferes, preventing PGD2 receptors from being activating (which is, essentially, the final step).

Setipiprant + Finasteride: A More Effective Treatment Method?

As previously mentioned, finasteride is a drug commonly used in the treatment of hair loss. It works similarly to setipiprant, though with a few differences. So, does this mean both drugs can be used together to provide better results?

In theory, this is possible. Since they work along separate pathways, it’d be like taking a dual approach to hair loss prevention. However, this could lead to some unpleasant side effects.

As finasteride inhibits 5AR and reduces DHT levels, it has numerous side effects. These include:

• Loss of libido
• Difficulting achieving/maintaining an erection
• Decreased ejaculatory volume
• Depression
• Anxiety
• Fatigue

This means that while using it alongside setipiprant may help to increase results, it can also lead to unwanted adverse effects. And unfortunately, some of these can even be long-lasting.

Setipiprant + Minoxidil: A Possibility?

If setipiprant and finasteride can likely be used alongside each other, what about setipiprant and minoxidil? After all, they too work along different pathways to fight hair loss.

While the exact mechanism isn’t known, minoxidil is believed to work by increasing blood circulation to the scalp. It may also increase the length of anagen phase, though there’s nothing to back up this claim.

Essentially, minoxidil makes it possible for your hair follicles to thrive despite the presence of DHT.

On the other hand, setipiprant works by inhibiting the follicles’ PGD2 receptors which have recently been shown to be increased in men with AGA.

In theory, both drugs could be used together for increased results. Though, there may be some complications.

Foremost, both setipiprant and minoxidil are known vasodilators. Using both could lead to dangerously low blood pressure levels, as the more dilated your blood vessels the lower your pressure.

There very well could be trials in the future that study the effects of both setipiprant and minoxidil (as I expect there to be with setipiprant and finasteride), though it’s best to wait until the results are released.

Is Setipiprant Right for You?

While setipiprant has not been approved for use as a hair growth treatment, and studies on the drug have shown mixed results, you may consider using setipiprant for off-label use.

Ultimately, there are a few things you’ll need to consider before undergoing any baldness treatment. In particular, you should ask yourself:

• Do you know the actual cause of your hair loss, and whether it’s even reversible?
• Do you want to treat your hair loss, or just temporarily cover up the issue?
• Are you aware of any possible side effects, and willing to experience them?
• Do you understand that most treatments will need to be taken for a lifetime, as stopping treatment will end the positive results?

As you answer the above questions, you’ll get a clearer picture of whether setipiprant (or any other drug) is right for you. If not, there are other options available.

Natural Alternatives to Setipiprant

Setipiprant still has quite a ways to go in clinical trials, and there’s much unknown regarding its exact side effects and health implications. However, current on-market options (including finasteride and minoxidil) also have their own downsides. So, where does this leave you?

As I’ve said time and again, natural is the best way to go. Not only can you see positive results, but you can also do so without many (if any) side effects.

5-Alpha-Reductase Inhibitors

If you’re looking to replace finasteride, you’ll be happy to know there are natural ways to inhibit 5AR.

By introducing 5AR inhibitors, you reduce the levels of DHT. With less DHT attaching to the follicles, you’ll theoretically experience less hair loss.

There are plenty of 5AR inhibitors, though some of the most powerful include:

• Saw palmetto
• Reishi mushroom
• Green tea

With just a few simple tweaks to your current diet, you can add these natural 5AR inhibitors and begin to see positive hair changes.

DHT Blockers

5AR inhibitors are one way to block DHT, but you can also take a more direct route. This can be done with DHT blockers.

This is sometimes seen as a superior option, as the DHT is still created within the body (so DHT serum levels aren’t affected). However, their use can prevent DHT from causing hair loss.

You can block DHT both internally and topically. However, topical blockers have fewer side effects and can be more effective.

Some DHT blockers to consider adding to your hair care routine include:

• Saw Palmetto
• Stinging Nettle
• Reishi Mushroom
• Rosemary Oil and Extract
• Ecklonia Cava

How to Prepare Your Scalp for DHT Blockers

Whichever blocker(s) you choose, it’s important to prepare your scalp beforehand. This ensures there is no buildup which is blocking the pores, so the topical ingredients can best be absorbed.

Ingredients:

• Himalayan or Celtic sea salt (1/2 tablespoon)
• Powdered activated charcoal (1 teaspoon)
• Ginger and Cucumber Juice (100 mL)
• Lemon juice (1 whole)
• A juicing machine (or a blender and muslin cloth)

Directions:

Using your juicer, juice the ginger and cucumber (in that order). If you’re instead using a blender or nutribullet, blend both the ginger and cucumber and pass the mixture through a cheesecloth or strainer.

Add the juice of one whole lemon to 100mL of your ginger and cucumber juice, and then combine the mixture with ½ tablespoon of Himalayan or Celtic salt and 1 teaspoon of activated charcoal. Mix well.

Before each use, shake thoroughly.

To use, apply the mixture to the areas of your scalp affected by hair loss. Use your fingertips to massage, and then let it sit for 5 – 10 minutes. This gives the salt and lemon time to break down the plaque, which is essential for truly cleansing the scalp.

Rinse thoroughly.

You can now use your fingertips to remove any excess scrub and even use a brush to gently dislodge any remaining pieces of the peel. You may need to repeat this process one or two times, but we recommend waiting a week between sessions.

Scalp Circulation

As DHT attaches to the hair follicles and causes miniaturization, the blood flow to the follicles can be severely restricted. If left untreated, this will eventually lead to loss of blood flow entirely.

This can have serious consequences, as blood is responsible for delivering nutrients and oxygen. It also removes buildup (including DHT).

This is why scalp circulation is crucial to hair health, and why it shouldn’t be forgotten if you truly want to regrow your hair. In fact, you can use the techniques below on their own, or combine them with the ones previously mentioned.

Scalp Massage

Perhaps the quickest and easiest to improve blood circulation to the scalp is through massage. You can do so yourself (using your fingertips or scalp massager), or even have it professionally done.

To perform an effective massage, begin by forming both hands into a claw and placing on either side of your head (just above the ears). Press down firmly (though, not too firmly as this can dislodge the hairs). Using your fingertips (and avoiding using your nails), gently massage in a circular motion. Continue for 1 to 2 minutes, and then slowly work your way towards the crown.

At the crown, begin at the middle (with both hands working near each other) and slowly fan out.

Now work your way towards the front of the scalp, and slowly move towards the temples. Finally, make your way towards the back of the scalp, and continue your circular motions.

Keep in mind that you can backtrack to previous areas of the scalp at any time, and also be sure to focus particularly on areas with pronounced thinning/hair loss.

The entire massage should take 10 minutes, and it can be performed daily.

Scalp Exercises

To further increase circulation, you can use your fingers and scalp muscles to perform scalp exercises. These can be performed just about anywhere, and they’re an easy way to incorporate hair care into your daily routine.

With your index and middle fingers, apply pressure to areas of the scalp where thinning/hair loss is present. Use the pressure to gently pull the skin from side to side. To improve effectiveness, you can also vary the levels of pressure you’re applying as you ‘pull’.

You can also give your muscles a workout with these three simple steps:

1. Raise your eyebrows as high as possible, and hold for 1 – 2 minutes. Slowly return to resting position.
2. Furrow your eyebrows as deep as possible, and hold for 1 – 2 minutes. Slowly return to resting position.
3. Lift your eyebrows as high as possible, and hold for 1 – 2 minutes. Then immediately furrow your eyebrows as deep as possible, and hold for 1 – 2 minutes. Finally, return to resting position.

This is a very quick ‘workout’, but one that can be used to further increase blood circulation (and perhaps even reduce stress!).

Dermarolling/Dermastamping

If you’re really looking to get serious about scalp circulation, I recommend you check out microneedling. This technique involves the use of tiny needles to puncture the scalp. When these ‘wounds’ heal, they help to regenerate healthy skin and hair follicles. Of course, they also increase blood flow.

I know that wounding the scalp can seem counterproductive, but there’s actual proof that it works. One study shows that individuals who received both microneedling therapy and minoxidil performed better than the minoxidil-only group:

The two tools most commonly used in microneedling are the dermaroller and the dermastamp. I’ve previously recommended the dermaroller, as it’s often easier to find in stores. However, the dermastamp can be more effective (as it targets areas more specifically) and cause less damage to the scalp.

Which Treatment Option Do I Recommend?

If you’re looking for a ‘quick’ solution to hair loss, you aren’t going to find one. This is because you must target the cause of your hair loss, and only then can you begin to see real improvement in your hairline.

This is why I strongly recommend that hair loss sufferers focus extensively on scalp circulation. While the 5AR inhibitors and DHT blockers can help temporarily, they usually won’t solve the real problem.

By increasing blood flow to the scalp, you increase oxygen and nutrient levels. This can also help to unclog the follicles, and make it more likely for any topical treatments you do use work.

With proper scalp circulation, you also make it possible for your hair follicles to thrive despite the presence of DHT. This is the true goal for anyone looking to permanently treat their hair loss.

Conclusion

There are many medications already available to help treat hair loss.

However, a lot of said medications have unwanted side effects. While there’s still much to learn about setipiprant, it’s results do show it may be a good alternative to the various medications currently available (including finasteride and minoxidil).

Talk to a qualified medical professional if you are looking to treat your hair loss.