Some people believe RU58841 (or RU-58841, or RU) is a safe alternative to finasteride. This blog will examine if it is true. A procedure for making your own solution is also provided.
RU58841, also known as PSK-3841 or HMR-3841, is a nonsteroidal anti-androgen (NSAA) which was investigated and developed by ProStrakan (a Scottish based speciality pharmaceutical company) for its potential therapeutic applications in conditions which were driven by androgens, such as acne, hirsutism (excessive hair growth) and androgenetic alopecia (male-pattern baldness). ProStrakan conducted phase I and II clinical studies and results of 5% RU58841, when applied twice daily, were reported to be similar to that of finasteride. However, it didn't perform any further clinical study. Thus this product was never officially approved for hair loss treatment.
How does it work?
As a non-steroidal anti-androgen, RU58841 binds to androgen receptors and directly inhibit the effects of endogenous (from our own body) androgens such as testosterone and dihydrotestosterone (DHT). As a first generation non-steroidal anti-androgen, RU-58841 selectively competes for the androgen receptors. This effectively attenuates the activity of testosterone and DHT, leading to an overall anti-androgen effect.
Performance & Evidence
There have been several studies on the performance, efficacy and safety of RU58841 since 1994 when it was developed by French researchers. In the original study by Battmann et al. (1994), it was found to display a high and extremely specific binding to androgen receptors in mice as well as in humans. Compared to other non-steroidal anti-androgens such as flutamide, RU had a staggering 30-fold higher affinity for the androgen receptors. Importantly, Battman and his fellow researchers found that the local activity of RU-58841 was significant at an extremely low dose (1µg/animal), but was limited to the site of application. This meant that the anti-androgenic effects of RU-58841 were limited to the target area where it was applied. Indeed, the researchers found that RU-58841 did not exert any anti-androgenic effects on deep accessory sex organs as well as the serum (blood) testosterone level.
Four years later, in 1998, American researchers tested RU-58841 in macaques . They found that the topical application of this substance resulted in a significant increase in the density, thickening as well as length of hair in macaques with androgenetic alopecia. Similar to the 1994 study, they did not observe any adverse systemic effects and concluded that RU was a promising therapeutic modality for patients with androgen driven conditions such as acne, hirsutism and androgenetic alopecia. These findings echoed observations made by Japanese researchers in a similar study – 20 bald scalps of macaques were subjected to Finasteride as well as RU. Finasteride is a potent 5α-reductase inhibitor which reduces the conversion of testosterone to DHT in the hair follicles, thereby acting as an androgen synthesis inhibitor. The researchers found that RU significantly outperformed Finasteride in regard to the increase in follicles at the 4-month interval; the strongest performance was seen at the 2-month interval. Significantly, the researchers also found that while Finasteride actively decreased the serum (blood) level of DHT with a concomitant increase in serum (blood) testosterone, RU had no impact on these levels. In conclusion, the researchers surmised that RU-58841 was not only more effective than Finasteride in suppressing androgenetic alopecia, it also did not exert any systemic side-effects in regard to serum (blood) androgen levels.
Another group of researchers looked at 20 scalp grafts from men with androgenetic alopecia; these were grafted onto mice and monitored every month for 6 months . 10 scalp grafts each were subjected to RU-58841 topical solution and ethanol (as a control) respectively. Although both groups had similar (28 vs 29) active follicles which appeared in total, the RU-58841 group demonstrated a second growth cycle more so than the ethanol group (8 vs 2). This led the researchers to conclude that RU-58841 led to a higher linear hair growth rate and had therapeutic potential for androgenetic alopecia .
How to make your own RU58841 solution?
Prior to preparing 5% RU, we need the following materials and devices:
The steps to preparing RU are as follows:
RU-58841 is able to be stored at room temperature for up to 2 weeks, and should be placed in airtight bags. It is recommended to store RU-58841 in a freezer so as to preserve and lengthen its shelf life and prevent degradation. Importantly, it should not be stored in areas where there is a direct light source. To maximise the stability of RU-58841, mixtures should be prepared freshly prior to topical application on the scalp.
Unfortunately, there have not been any Phase II or III clinical trials for this material. Hence, there is no publicly available longitudinal data concerning its side-effect and safety profile in humans. Indeed, the last known study to have verified its efficacy and performance was published in 2005 . No studies in the literature have been scoped to identify and risk-stratify the side-effects of this product. However, the side-effects can be extrapolated based on its classification as a non-steroidal anti-androgenic compound. Testosterone is typically converted to DHT by an enzyme known as 5α-reductase. An excess of DHT is implicated in androgenetic alopecia; RU directly competes for androgen receptors with testosterone and DHT, thereby limiting the effects of these androgens at the target site. Hence, the following side-effects are anticipated:
Although the old study with very limited number of subjects didn't report these side effects, all of these side effects were reported by users who used the product for 3 months or longer. Thus it is not true that RU-58841's effect is only limited to the area of application, and do not influence the serum (blood) androgen level.
There exist several alternatives to RU58841 which are more reliable, robust and safe as evidenced by more recent studies. Ketoconazole shampoo for example, is a universally recognized treatment for androgenetic alopecia. One landmark study in 1998 showed that 2% ketoconazole shampoo was equivalent to topical minoxidil treatment in promoting the density, size and proportion of hair follicles in patients with male pattern baldness . The ketoconazole shampoo which was only used two to four times weekly by participants over 21 months performed just as well as in participants who used once-daily minoxidil lotion for the same duration. Ketoconazole shampoos can be purchased in two forms – the Lipogaine Big 3 shampoo which synergistically combines ketoconazole with biotic, niacin and copper tripeptides, at https://www.lipogaine.com/lipogaine-big-3-shampoo/. Alternatively, the Hair Covet Hair Restoration Shampoo combines ketoconazole with biotin, saw palmetto, niacin, black castor oil, caffeine and argon oil and can be purchased at https://www.minoxidilmax.com/hair-covet-hair-restoration-shampoo.
Another alternative to RU is Finasteride. Finasteride is a competitive inhibitor of the 5α-reductase enzyme which is critical in converting testosterone to DHT. Finasteride has been shown to reduce serum (blood) DHT levels by up to 70% and has successfully been trialled in the management of androgenetic alopecia (1mg taken once daily)[7).
Yet another alternative is Minoxidil. Arguably the strongest alternative mentioned so far, minoxidil causes an influx of potassium ions into the smooth muscle cells of the arteries which supply the hair follicles. This causes them to dilate and increase the blood flow. Minoxidil also causes the hair follicles to stay in the anagen phase (the state during which hair grows) for a longer period of time. Unlike RU58841, minoxidil has been extensively studied. A randomized, placebo-controlled, double-blind study recently conducted in 2018 showed without doubt, that Minoxidil was safe and effective in promoting scalp hair growth in men with androgenetic alopecia .
Although RU58841 has been shown to effect hair growth in androgenetic alopecia, the evidence for this is outdated and extremely sparse. Indeed, most of the studies in the late 90s concerning RU were animal-studies. There has not been a single Phase II or III clinical study on its safety and long-term effects. Its long term safety was not established like finasteride. People who used the product have reported similar but even more lingering side effects than finasteride. Thus it is not recommend to use RU-58841 as a safe aternative to finasteride. If one hesitates to use finasteride, topical spironolactone or ketoconazole shampoo is probably a better option.
1. Battmann, T., et al., RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism. J Steroid Biochem Mol Biol, 1994. 48(1): p. 55-60.
2. Pan, H.J., et al., Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques. Endocrine, 1998. 9(1): p. 39-43.
3. Obana, N., C. Chang, and H. Uno, Inhibition of Hair Growth by Testosterone in the Presence of Dermal Papilla Cells from the Frontal Bald Scalp of the Postpubertal Stumptailed Macaque1. Endocrinology, 1997. 138(1): p. 356-361.
4. De Brouwer, B., et al., A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice. Br J Dermatol, 1997. 137(5): p. 699-702.
5. Munster, U., et al., RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia. Pharmazie, 2005. 60(1): p. 8-12.
6. Draelos, Z.D., et al., A pilot study evaluating the efficacy of topically applied niacin derivatives for treatment of female pattern alopecia. J Cosmet Dermatol, 2005. 4(4): p. 258-61.
7. Mysore, V. and B.M. Shashikumar, Guidelines on the use of finasteride in androgenetic alopecia. Indian J Dermatol Venereol Leprol, 2016. 82(2): p. 128-34.
8. Blume-Peytavi, U., et al., Efficacy and safety of a new 5% minoxidil formulation in male androgenetic alopecia: A randomized, placebo-controlled, double-blind, noninferiority study. J Cosmet Dermatol, 2019. 18(1): p. 215-220.
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