Fighting against baldness has been going on since men started to take care about their own appearance. Science has made a lot of progress, but sometimes it has been accidental, just like penicillin. An early story on men’s fight against baldness started with a treatment against hypertension called minoxidil. Researchers found out that this molecule had an unexpected side effect called hypertrichosis, which is excessive body hair. For many years, the way minoxidil acted on the hair follicles was unknown, but recent research shows it’s capable of stopping dihydrotestosterone from attacking hair follicles. But, how does that happen?
It is widely known that baldness in men usually has something to do with testosterone. There’s a condition called androgenic alopecia, which results from the interaction of testosterone in the hair follicles. Testosterone is the most widely known androgen, but there are many others with an increased level of activity. Dihydrotestosterone is one of the active forms of testosterone, capable of exerting many different effects on the human body, including androgenic alopecia.
Scientific studies confirm this because predisposed scalps have an increase in levels of dihydrotestosterone and androgen receptors. The enzyme that converts testosterone into its active version is also increased in this tissue. In a particular way, we can say that dihydrotestosterone attacks our hair follicles, and that’s why men with high testosterone levels may experience baldness faster than others. But testosterone is not a bad guy; it’s actually an excellent ally. So, there should be a way to avoid dihydrotestosterone from attacking hair follicles, and that is where antiandrogen products come in.
Finasteride, a typical antiandrogen
One of the methods to prevent androgenic alopecia is through 5 alpha-reductase inhibitors, such as finasteride. 5-alpha reductase is an enzyme that converts testosterone into its more active version, dihydrotestosterone. It has many other variants, such as dutasteride, which acts for a more extended period of time and it three times more potent because it inhibits not only one but two different versions of this enzyme. Type-1 5-alpha-reductase is localized on sweat glands and sebaceous glands, and type-2 is localized on hair follicles, so inhibiting both would result in less dihydrotestosterone in the scalp, and no more hair follicles being harmed in the process.
In a review of scientific data, the authors described a group of studies in which researchers compared how efficient finasteride and dutasteride are. According to their data, only 15% of patients improved their condition using 5-alpha reductase inhibitors alone. In contrast, the majority of patients had better results in combination with other topical drugs, such as topical steroid or topical minoxidil.
Minoxidil, a classical drug with newly discovered antiandrogen effect
In the introduction of this article, we described the early application of minoxidil to prevent, and even correct alopecia. Interestingly enough, scientists didn’t know for sure how this drug worked, but they knew it was useful. The research on minoxidil gave people a lot to talk about because its effects on the scalp seemed contradictory. For example, studies showed that minoxidil increased the blood flow in the scalp and smart people argued it made no sense to take it without antiandrogens because the increase in blood flow would expose the scalp to the attack of dihydrotestosterone on hair follicles. Interestingly enough, patients sometimes used minoxidil alone and reported a consistent improvement over time.
Recent research has detected a few in vitro effects of minoxidil that would likely explain why is it effective for androgenic alopecia. For example, it stimulates cell proliferation and the vascular endothelial growth factor, inhibits collagen synthesis, and slows down the aging of keratinocytes. All of this might explain why minoxidil is effective in treating alopecia, but there’s more: Recent studies have discovered an antiandrogen effect as well.
Some studies on the antiandrogen effect of minoxidil are still contradictory, but many authors support this drug may have an inhibitory effect on 5-alpha reductase on the scalp. Later studies proposed that minoxidil suppresses the functions triggered by androgen receptors. In other words, even having dihydrotestosterone around, the effect on the cells would be suppressed because the receptors are silenced.
How to stop testosterone from converting to DHT
It is clear that one of the primary therapeutic goals of androgenic alopecia is to prevent testosterone from converting to dihydrotestosterone. As we have discussed earlier, dihydrotestosterone is an active version with more androgenic activity. It is converted by the enzyme 5-alpha reductase, and couples with androgen receptors on the scalp. Stopping dihydrotestosterone from attacking hair follicles can be done by suppressing the activity of the receptors or inhibiting the action of the converting enzyme. According to evidence-based medicine, there’s a very high level of evidence to say that minoxidil 2% and 5% solutions prevent the progression of androgenic alopecia, but it should be used for 6 months and needs to be continued if patients don’t want to experience hair loss. On the other hand, finasteride and dutasteride also has a high level of evidence, and it’s even more effective when used in combination with minoxidil. There are other botanical options to stop testosterone from converting to dihydrotestosterone, such as Curcuma aeruginosa and Serenoa repens. While Serenoa repens shows inferior results, studies with Curcuma aeruginosa showed comparable results with topical minoxidil. However, these finding on botanical products should be confirmed in more extensive studies to be included in evidence-based practice.
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