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5-Alpha-Reductase Inhibitors (5ARIs)

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As an example, a popular trending topic among our members is 5α-Reductase Inhibitors (5ARIs).

5α-Reductase Inhibitors (5ARIs) are a class of drugs that are best known for their use in treating benign prostatic hyperplasia (BPH) and androgenic alopecia (male pattern hair loss). 5ARIs inhibit the activity of the 5α-Reductase enzymes that convert testosterone into dihydrotestosterone (DHT). While DHT is important for male fetal development, an excess of DHT in older males can cause a variety diseases, like BPH.

There are three types of 5α-Reductase enzymes, simply named types I, II, and III. The type II enzyme is primarily found in the prostate, where it actively converts testosterone into DHT. Therefore, DHT levels are often higher in the prostate than in the serum. As DHT accumulates in the prostate it acts as a strong cell signaling agent because it binds to the androgen receptor more strongly than testosterone and stimulates a variety of growth factors that encourage prostate growth. This is the primary pathway of BPH development, and 5ARIs that target the type II enzyme have seen success in shrinking the prostate size in patients with BPH [1,2].

The Type I 5α-Reductase enzyme is found in the hair follicle, among other tissues, where the conversion of testosterone into DHT is believed to contribute to androgenic alopecia. The mechanism of the progression of androgenic alopecia and the precise role of DHT is still unclear, although there are several theories [3]. However, taking a 5ARI that targets type I enzymes has been found to effectively increase hair growth and slow the progression of androgenic alopecia [4].

However, there are risks and side-effects associated with taking 5ARIs. The most commonly researched and reported side-effects are erectile dysfunction and decreased libido [5]. In addition, the FDA issued a warning in 2011 that taking 5ARIs could increase the risk of developing a high grade prostate cancer [6].


References:

No. Citation
1 T.M. Nicholson and W.A. Ricke. “Androgens and estrogens in benign prostatic hyperplasia: past, present and future.” Differentiation 2011, 82: 184-199. Read Article
2 S.A. Kaplan. “5α-Reductase Inhibitors: What Role Should They Play?” Urology 2001, 58: 65-70. Read Article
3 E.T. Ustener. “Cause of Androgenic Alopecia: Crux of the Matter.” Plast. Reconstr. Surg. Glob. Open 2013, 1: e64. Read Article
4 D.A. Whiting. “Male Pattern Hair Loss: Current Understanding.” Int. J. Dermatol. 1998, 37: 561-566. Read Article
5 A.M. Traish et al. “Adverse Effects of 5α-Reductase Inhibitors: What do we know, don’t know, and need to know?” Rev. Endocr. Metab. Disord. 2015, 16: 177-198. Read Article
6 Food and Drug Administration. “FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer.” 06-09-11, Accessed March 16, 2017.

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