Table of contents 

Personal Note

Compound description and mechanism of action

• How it treats androgenic alopecia
• How it differs from finasteride
• Should it be used with finasteride?
• How effective is it used as a monotherapy

Important History 

Safety Profile Discussion 

PERSONAL NOTE

I’m not affiliated with any research chemicals manufacturers/suppliers, and do not encourage its use. All information used is based on research, of which is cited. If information is missing a citation email x and the citation will be provided to further your own personal research.

Compound description and Mechanism of Action

Brief explanation of Androgenic Alopecia (AGA): 

The cause of androgenic alopecia (which leads to hair loss in almost all bald men) in men is a process where a hormone called DHT (DiHydroTestosterone) binds to the androgen receptors in the scalp, and this DHT-AR complex signals for the miniaturization of the hair follicle until it eventually stops growing. DHT is created when an enzyme called ‘5 Alpha Reductase’ converts testosterone into DHT. This is where a drug called Finasteride comes into play, as the conventional treatment for AGA, and it inhibits this 5AR enzyme, leading to a lowering of DHT levels.

RU58841 is a non-steroidal anti-androgen compound which was primarily researched for its potential use in treating conditions like androgenetic alopecia and acne. Its mechanism of action to treat AGA is different to that of Finasteride as it acts as an androgen receptor antagonist. In layman’s terms it binds to androgen receptors in the scalp and occupies them, preventing DHT from binding to them and causing miniaturization (hair loss). It is applied topically to the scalp in order for this anti-androgenic effect to only happen in significant amounts in the scalp.

Ru58841 has a molar mass of 369.34 g/mol (369.34 daltons), which is under the 500 dalton maximum for compounds to be absorbed by the skin, and thus is able to be applied topically to the skin and pass the corneal layer to enter locally into the body. 

Ru58841s exact binding affinity isn’t known, however in a study published in 1998 called 

“Evaluation of RU58841 as an Anti-Androgen in Prostate PC3 Cells and a Topical Anti-Alopecia Agent in the Bald Scalp of Stumptailed Macaques” 

Researchers found that it exhibited a binding affinity higher or equivalent to testosterone which has a binding affinity of, ka = 1.1 nM, thus the binding affinity of Ru58841 is ~ 1.1nM. (DHT has a binding affinity of 0.25-0.5 nM for the human AR, 2-3 x higher than Test/Ru)

The way Ru58841 treats androgenic alopecia is essentially by “competitive inhibition”. It is an androgen receptor antagonist, so it competes with Testosterone and Dihydrotestosterone (DHT) to bind with the human Androgen receptor, so despite having a lower binding affinity than DHT if one can introduce a large enough amount of Ru58841 to the scalp it can outcompete the smaller number of DHT molecules and thus prevent DHT-induced miniaturization. However, having too many anti-androgenic molecules in your body could have negative side effects, so the goal of using Ru58841 is not to completely inhibit Test and DHT via competitive inhibition but to induce a efficacious amount of androgen receptor binding without large amounts going systemic. The accepted dose that does this is 5%, see bottom section for more information about its safety profile.

This competitive inhibitory method is what makes it such a compelling adjacent treatment with a 5AR inhibitor like Finasteride or Dutasteride for those with aggressive androgenic alopecia. Finasteride 1mg (the typical dose) can reduce scalp DHT levels by as much as 64%, however there is still the residual 36% of DHT remaining that can still affect the hair, plus the subsequent spike in testosterone due to the inhibition of the 5a reductase enzyme by Finasteride. It is feasible that with much less DHT and more Testosterone Ru58841 could more effectively bind to more Androgen Receptors as now it just has to compete with more testosterone which has an equal binding affinity too, rather than DHT which is 2-3x higher. 

Finasteride by itself is an effective treatment of androgenic alopecia, however a minority of men on Finasteride (and men in general) may be sensitive to testosterone-induced miniaturization, and just partially treating DHT-induced miniaturization (~70%), and that’s where a adjacent Ru58841 treatment shows promise as it effectively deals with the remaining potential DHT-induced miniaturization and serves as an equal competitive inhibitor to the spike in scalp Testosterone. 

HISTORY

Initial Discovery: RU58841 was first synthesized in the 1980s by French pharmaceutical company Roussel Uclaf. The compound was developed as a topical treatment to target androgen receptors in the skin and hair follicles without systemic side effects. 

In its earliest study in 1994, it was shown to be applied topically on hamsters, “while being devoid of antiandrogenic activity on deep accessory sex organs and of any affect on testosterone level”

Key outcomes from this study, although limited, were that RU58841 could be useful as a topical treatment for skin conditions related to androgens, such as acne, and androgenic alopecia.

It wasn’t long before the Researchers explored its potential for treating androgenetic alopecia. 

After this speculation about Ru58841 began to build amongst researchers and those looking for hair loss treatments as options were limited at the time, especially as Ru58841 showed to have a mechanism of action that doesn’t cause changes in sex hormones and the undesirable side effects (which for the most part are rare) that come with such changes. 

The results of this 1994 study were replicated in another study later that year on mice. This study was able to conclude the reason this compound displays anti-androgenic activity without causing systemic effects is likely because it doesn’t easily break down into another form (called the N-desalkyl metabolite) that could cause broader effects in the body. 

So essentially at this point it had shown itself as a potential treatment of hair loss without any apparent side effects in the animal models, which amongst enthusiasts suggested that it could be used on men to ‘feminize’ their scalp, without causing other feminizing effects throughout the rest of the body.

Next a 1995 study compared Ru58841 to other non-steroidal anti-androgens, RU 56187 and RU 38882, on syrian mice, and concluded that Ru58841 was the most efficacious out of the three, and had good potential to treat androgen related conditions

The three studies had essentially all concluded the same thing about Ru58841, that it was a promising topical treatment for androgenic alopecia with no systemic side effects. But it wasn’t until after Finasteride was FDA approved for the treatment of androgenic alopecia, that very compelling studies about Ru58841 came out. 

A study published in 1995 compared head to head the effects of Finasteride and Ru58841 stump-tailed macaques. What is very compelling and interesting about this study is that the chosen animal model, the stump-tailed macaque, is one of the 3 other species known to suffer from androgenic alopecia, with the others being two dog species, the dachshund and the greyhound. Thus it is a suitable biological model for studies on human androgenetic alopecia.

This study deserves a deep dive because it provides lots of important information.

Firstly important part to know is the exact treatments the monkeys received.

Finasteride (FS):

• Administered orally at a dose of 1 mg/kg/day.
• Given to 10 animals for a duration of 6 months

Topical RU58841 (RU):

• Administered topically in two concentrations: 5% and 0.5%.
• The total amount applied was 0.5 ml/kg/day.
• Given to a total of 10 animals, divided into three groups: 4 animals received the 5% concentration, 3 animals received the 0.5% concentration, and 3 animals received the vehicle (placebo).
• The treatment duration for RU58841 was 4 months.

What is interesting is finasteride was given at a dosing 10mg per day (Male stump-tailed macaques typically weigh ~10kg, 1 mg/kg/day = 10mg each day), which far exceeds the typically prescribed dose of 1mg per day, whereas Ru58841 was given at the typical dose of 5%, so the study basically compares the effects of a maxed out dose of finasteride to a regular dose of Ru58841. Additionally Ru58841 was 2 less months too yield results, which makes the results even more interesting.

Results: Anagen follicles increased an average of 88% with Finasteride. Anagen follicles increased an average of 103% with a 5% strength RU58841 solution. Their side effect profiles were also compared. The finasteride group decreased systemic DHT serum by 70%, while the group treated by RU58841 did not see any decrease in systemic DHT or Testosterone levels. 

The growth of Vellus follicles into terminal hairs (thick, strong, and fully pigmented) was 12% with Finasteride, and the Finasteride placebo showed no effect. With the 5% strength RU58841, the growth was 26%. The 0.5% strength RU58841 solution had little to no effect.

Thus the 5% strength RU58841 solution produced the most overall hair growth and outperformed finasteride, despite having less time to work, and being dosed lower to the dosing of finasteride. It also showed no systemic side effects, which is quite promising as Finasteride and other traditional hair loss treatments are notorious for side effects (despite them being quite rare). 

Key takeaway about Ru58841’s potential to cause side effects: Many people believe that Ru58841 is destined to have catastrophic side effects if its able to surpass local topical effects and go systemic, and although this study confirmed that it does have a chance to go systemic it does not cause a systemic reaction which many theorize it could have (this is explained below). 

In the study, at the 3-month mark, 2 of the stump-tailed macaques had detectable levels of RU58841 and its metabolites in their plasma. By the 6-month mark, only 1 macaque had detectable levels of RU58841 and its metabolites. If there had been a cumulative drug effect, we would have expected more animals to show detectable metabolites after an additional 3 months of dosing, rather than fewer. The reason for this is because it has a very short half life, meaning that even if a small amount goes systemic when u apply it topically at night, by the time you apply it the next night, the amount that had gone systemic the night before has already been metabolized by your system, and as a result it is unable to accumulate systematically to the point where it can cause side effects.

*See the bottom of the article for a more in depth explanation for Ru58841 being likely devoid of side effects based on findings of this study

The next study, published in 1997 again tested the effects of Ru58841 on stump-tailed macaques, but instead with a focus on Testosterone’s role in Androgenic Alopecia. It concluded that Testosterone had an age-dependent effect on hair growth, with testosterone showing no effects on dermal papilla cells when cultivated from pre-pubescent macaques and its negative effects in post-pubescent macaques. The study concluded that Ru58841 had a unique method of stopping hair loss and helping regrowth, as unlike Finasteride which purely targets DHT suppression, Ru58841 can effectively block Testosterone from binding to the androgen receptor.

Another study in 1997 on mice, tested Ru58841 and two 5a-reductase inhibitor’s (MK-386 and Finasteride) effects on sebaceous glands. 

The only real takeaway from this study is it added to the growing body of evidence that when Ru58841 is applied topically it has no systemic effect on hormonal production.

Another study in 1997 tested its method of penetration when applied locally, and found it was best when applied in an alcohol solution. (Relatively unimportant)

The next important study, also happened in 1997, but used a unique method of experimentation. It had been found, that human hair growth was still progressive after transplantation of scalp samples from men with androgen-dependent alopecia onto female nude mice. This study testing Ru58841’s effects on these transplanted hairs.

Once again concluding it had significant effects on hair growth and treatment of androgenic alopecia. 

The controversy around Ru58841 began around 1997, after the company Hoechst AG, who owned the rights to Ru58841 didn’t not pursue its marketing or approval, and suddenly stopped its research on it. This raised immediate red flags about the compound, suggesting it had a large risk profile, however this is just speculation. 

The real reason research on Ru58841 had to stop was due to the combination of financial problems, and factors regarding brand image. In 1997, American anti-abortion groups forced the French pharmaceutical company Roussel-Uclaf, a subsidiary of the German company Hoechst AG (the owners of Ru58841), to abandon production of Ru-486. Although this is a product unrelated to Ru-58841, we can theorize that research discontinuation had nothing to do with the substance itself, but was to avoid controversy surrounding continued endocrinologic research. As mentioned earlier, some financial problems came into play, and a french article in 1996 explained as a result all research projects that didn’t consider the Central Nervous System, anti-infectives, and cardiovascular system were forced to stop. 

External research progressed steadily from 1998 – 2004, although with much less traction about its ability to treat androgenic-alopecia likely due to its sudden abandonment by Roussel-Uclaf however as discussed above the reasons had nothing to do with the compound itself.

Aside from these there were some not so easily accessible studies I found on Ru58841, that were notable.

Key findings from these studies:

• Study 1: Ru58841 was an effective treatment of the root cause of androgenic alopecia by blocking DHT activation of the AR, as well as stimulating an increase in density and thickness of hair, without causing any systemic effects – however study 2 contradicts this and concludes Ru58841 itself does not stimulate any new hair growth, this is a bit of a debatable topic but it likely just causes existing thinner areas of hair thicker which may appear to be causing regrowth, but it doesn’t actually cause the regrowth/stimulation of dormant follicles
• Ru58841 combined with minoxidil is a significant treatment combination in causing follicular growth

During this time period of 1998-2004, the rights to Ru58841 was passed around to a few pharmaceutical companies via a series of mergers and acquisitions. Ru58841 research began again in 2005, after company ‘ProStrakan’ and its subsidiary ‘Proskelia’ acquired the full rights to RU58841, now referred to as PSK-3841. They conducted two human clinical trials (a phase 1 and a phase 2 trial). The first trial lasted 4 weeks, and the second lasted 6 months. However the results were never published.

This appeared as a red flag to people optimistic about Ru58841, and led to speculation online that there were serious side effects with the human test subjects. Even stranger is on ProStrakan’s old website page, in a section detailing Ru58841, the company claimed,  without posting results, that it caused an ‘increase in net hair count’ and ‘no systemic anti-androgenic effect was observed’. 

People in reddit forums have speculated that the reason research never progressed to phase 3 trials is because hair loss treatments aren’t as lucrative as you would think. There is a Prostrakan strategy paper which lists PSK3841 as a non-priority and estimates that it will only bring in 100-200 Million Dollar which isn’t a lot for many pharmaceutical products. Around the early 2000s, there was no fear mongering about the side effects of finasteride, so at the time there wasn’t a large market of people looking for finasteride alternatives, hence RU didn’t look very profitable. Additionally there are a few news articles that show ProStrakan faced financial problems, which led to them being acquired by company Kyowa Kurin in 2011.

And also considering the fact that Ru58841 has a very short shelf life because it is an unstable compound, it would be very hard to sell, so there is a reasonable probability it was just abandoned because at the end of the day these pharmaceutical companies are just looking to make a profit. This is backed up by the following statement made by Prostrakan, who commented on its efficacy which was comparable to that of FINASTERIDE:

RU58841 SAFETY PROFILE DISCUSSION

To be clear, no research chemical is going to be safe to use recreationally. RU58841 is no exception then this and the human data is needed to make an informed decision. However im going to present all the information known about RU58841 side effects…

Out of all the published studies

• There were 18 that were publicly accessible
• 9 considered their systemic effects when looking at treatment of androgenic alopecia, and all 9 reported no systemic effects

There were 2 unpublished human clinical trials, but the company released a statement on their website citing that it had no systemic side effects, and this statement remained on the company website for 4 years.

Anti-androgens taken orally, can counteract the effect of androgens such as Testosterone and DHT in the body, as a result many people are scared to even take topical anti-androgens, because they believe if they were to get systemic it would cause the same result, and while its true anti-androgens applied topically will eventually be absorbed in the bloodstream hence go systemic, it is a little more complicated than that.

Firstly, RU58841 is a silent antagonist of the androgen receptor. It binds to the androgen receptor but it doesn’t actually transcribe any effect and just serves to block the androgen receptor.

The ability for a compound to cause systemic effects is also predicated on things such as its molecular size, binding affinity, half life, and its ic50 (Half-maximal inhibitory concentration), as well as those factors for its resultant metabolites. 

Lets loom at the study on ru58841s effects on stump-tailed macaques (which is a monkey – and one of the three mammals to suffer from androgenic alopecia – making it such a compelling study), 

In the study, at the 3-month mark, 2 of the stump-tailed macaques had detectable levels of RU58841 and its metabolites in their plasma. By the 6-month mark, only 1 macaque had detectable levels of RU58841 and its metabolites. If there had been a cumulative drug effect, we would have expected more animals to show detectable metabolites after an additional 3 months of dosing, rather than fewer. The reason for this is because it has a very short half life, meaning that even if a small amount goes systemic when u apply it topically at night, by the time you apply it the next night, the amount that had gone systemic the night before has already been metabolized by your system, and as a result it is unable to accumulate systematically to the point where it can cause side effects. This is the reason why topical finasteride treatments don’t negate side effects, because since finasteride and dutasteride have such long half lifes, when inevitably that small amount of fin/dut goes systemic when you apply it once daily, it is still present in your blood so when you take it the next day the amount increases and eventually it accumulates systemically (this is why when taken over the same period of time as oral fin, topical fin shows to have similar effects on serum DHT). 

Another reason is because scalp hair follicles are not nearly as dense with androgen receptors compared to other systems such as organs, the prostate, and brain. So after the large majority of the ru58841 molecules bind to the hair follicles, even if by the unlikely chance they were absorbed systemically before they could be metabolized (and thus removed from your body), the amount would be too small to affect the totality of androgen receptors in these systems.  

What many fail to consider is that RU58841 is a non-steroidal compound that functions as a competitive silent antagonist of the androgen receptor. This means that even if RU58841 enters the systemic circulation, it blocks the androgen receptor, preventing the negative feedback typically caused by androgens via the hypothalamic-pituitary-gonadal (HPG) axis in men.

This explanation suggests that even if you were irresponsible with your application of ru58841 (such as overdosing the concentration you were taking, or taking it multiple times a day leading to its accumulation to a significant extent systemically) the effects it has on your body would be entirely reversible following discontinuation of the formulation

Another compelling piece of evidence it has no side effects in humans, is the previously mentioned statement Prostakan made on its website about Ru, before it was bought and the clinical trials were lost.

“No systemic anti-androgenic effect was observed (n=90)

To test whether systemic effects are present in human trials a company must assess for changes in serum test and DHT levels, luteinizing hormone (LH), Prostate-specific antigen (PSA), and body weight and organs. If even one of these factors were affected by RU,I strongly doubt they would publicly lie about it, especially if they eventually wanted FDA approval for human use. I doubt the company would have put out this statement so absent mindedly and allow it to be susceptible for litigation if the clinical trial results didn’t actually show this. 

The other part worth noting is the statement 

“This product is available for licensing” 

This shows that the company was confident it would eventually be approved for human use open to entering into a legal agreement with another party (such as another pharma company, or investor) to allow that party to develop, manufacture, market, or sell the compound under specific conditions. 

They also released a statement about the effiacy of Ru58841 (PSK 3841) after it completed its 6 month phase IIa human clinical trial.

Another thing to factor in is that many non-steroidal antiandrogens produced by Roussel Uclaf were discontinued, such as RU-22930, which interestingly enough was shown to INCREASE Testosterone levels.

The company’s statement that RU58841 had no systemic side effects—remember, they would’ve been assessing all the important factors, like serum testosterone, DHT levels, and PSA. If even one of these showed an effect, they wouldn’t have made that claim so openly, especially if they wanted to be FDA-approved.

And they didn’t just make the claim—they also put it out there for licensing, which suggests they were confident in its potential for human use. You don’t offer something for licensing if you think it’s going to get shot down later or land you in legal trouble.

All in all, Ru58841 is a research chemical and probably will never get developed and I strongly discourage its use however there is lots of misinformation about it that needs to be cleared up.