endocrinologie

Finasteride as a treatment for acne vulgaris?

One of the fears of androgenic anabolic steroid (AAS) users is the development of acne vulgaris, or acne for short. Everyone knows what acne is, so I’m not gonna waste words on describing that. Anyways, it is widely accepted that androgens play an important role in the pathology of acne. And coincidentally, acne pops up around puberty. The time when hormones go a little whack. Acne is determined to make the lifes of people around the globe miserable. As if hitting puberty wasn’t bad enough as it is. Come on here is some extra shit on your face (and body) to make you feel even more gloomy and insecure. Finally, a lot of AAS users develop acne the moment they go on dat dere roids.

In a survey among Dutch AAS-(ab)using bodybuilders, 27.6% of the men, and 50% of the women reported to have experienced acne as a side-effect [1]. A recent publication from an outpatient AAS clinic in the Netherlands also shows that acne was the most-reported side-effect, with 38% of patients reporting it [2]. Do note that you should take Berkson’s bias into account with these numbers. But either way, it’s not really up to debate that a significant number of AAS users is plagued by acne.

Since I know a lot of AAS users who are under the impression that finasteride works against acne, let’s dive in.

Finasteride and dihydrotestosterone (DHT)

So before I continue, I need to cover a tiny bit of biochemistry. Testosterone is converted to the more potent androgen dihydrotestosterone (DHT) in various tissues. More specifically, it’s converted by the action of an enzyme named 5α-reductase. This enzyme lends it name to the chemical reaction it catalyzes. It reduces testosterone on its fifth carbon atom, by adding an α-oriented hydrogen atom. That’s it, nothing more, nothing less. DHT is testosterone with an extra hydrogen atom at a certain position. The result of this is that it binds and activates the androgen receptor more strongly. The effect of testosterone is thus amplified in tissues which express 5α-reductase.

You will find this enzyme in a lot of tissues, like the prostate, scalp, liver and skin. More specifically, the sebocytes also express the enzyme. Now, another thing about this, is that this enzyme comes in a few different ‘shapes’. There are 3 known 5α-reductase isozymes. That is, three different ‘types’ that catalyze the same reaction. This is important, because one tissue might express a different 5α-reductase isozyme than another, and certain drugs are isozyme-specific.

If we take a look at finasteride, it’s potent at inhibiting type II and type III 5α-reductase and is a lot less potent at inhibiting type I 5α-reductase [3]. So which ones are expressed in the sebaceous gland? Type I is richly expressed in it and type II is undetectable [4]. Type III also seems expressed in a human sebaceous gland cell line [5]. So finasteride appears a bad choice in this regard, as it’s relatively weak at inhibiting type I 5α-reductase. Indeed, a study demonstrated that 14 days of finasteride administration at 5 mg daily lowered sebum DHT concentration (a perfectly fine surrogate for its concentration in the sebaceous gland) by only 14.9% [6]. Yet it strongly decreased serum DHT concentration (-65.8%), highlighting it’s effectiveness at this dosage. Apparently the type III expression is of minor importance for sebaceous gland DHT production in light of these results.

So what about a type I inhibitor? The same trial with finasteride also experimented with the selective type I inhibitor MK-386 [6]. It demonstrated a decrease in sebum DHT concentration of 30.1% and 49.1% at 20 and 50 mg daily, respectively. That’s more like it.

But does this actually work against acne? Unfortunately, the answer is no [7]. A well-designed 3-month randomized placebo-controlled trial (n=182) compared the effect of the selective type I inhibitor (25 mg daily) to an antibiotic (minocycline, a standard treatment for acne) and a placebo. Additionally, they also evaluated whether the combination of minocycline with the type I inhibitor worked better. The type I inhibitor worked as well as the placebo (p=0.862) and the combination therapy did not work better than minocycline alone (p=0.23).

I would also like to note that there has been a large (n=106) randomized placebo-controlled trial with the usage of finasteride for the treatment of severe acne, but the results have never been published [8]. Given the small effect on sebum DHT concentration of an earlier study [6] and given that the study was sponsored by Elorac Pharmaceuticals, it is highly likely the study hasn’t been published because it simply had no effect. (What other reason would a pharmaceutical company have to not publish the results if their drug actually worked? Right.)

Concluding, there is no evidence to support the usage of 5α-reductase inhibitors for the treatment of acne.

References

  1. A. De Boer, S. Van Haren, F. Hartgens, D. De Boer, and A. Porsius. Onderzoek naar het gebruik van prestatieverhogende middelen bij bodybuilders in Nederland. Nederlands Centrum voor Dopingvraagstukken, 1996.
  2. Smit, D. L., and W. de Ronde. “Outpatient clinic for users of anabolic androgenic steroids: an overview.” The Netherlands Journal of Medicine (2018): 167-175.
  3. Yamana, Kazutoshi, and Fernand Labrie. “Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride.” Hormone molecular biology and clinical investigation 2.3 (2010): 293-299.
  4. Azzouni, Faris, et al. “The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases.” Advances in urology 2012 (2012).
  5. Samson, Melanie, Fernand Labrie, and Christos C. Zouboulis. “Biosynthesis of dihydrotestosterone by a pathway that does not require testosterone as an intermediate in the SZ95 sebaceous gland cell line.” The Journal of investigative dermatology 130.2 (2010): 602-604.
  6. Schwartz, Jules I., et al. “MK-386, an inhibitor of 5α-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen.” The Journal of Clinical Endocrinology & Metabolism 82.5 (1997): 1373-1377.
  7. Leyden, James, et al. “A systemic type I 5 α-reductase inhibitor is ineffective in the treatment of acne vulgaris.” Journal of the American Academy of Dermatology 50.3 (2004): 443-447.
  8. Finasteride Treatment of Severe Nodulocystic Acne, https://clinicaltrials.gov/ct2/show/NCT02502669

Geef een reactie

XHTML: U kunt deze tags gebruiken: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>