PEAK TESTOSTERONE

Propecia: An Irreversible 5-Alpha-Reductase Inhibitor

Several studies have now documented the fact that Propecia (finasteride) seems to have persistent hormonal, psychological and sexual side effects. This has also been verified in the practices of many physicians and in a large body of FDA complaints that eventually inspired the FDA to require a label change in 2012. [6] In fact, one could say that the symptoms in some men are "irreversible."  I use that term deliberatley, because it turns out that Propecia was initially thought to be a reversible enzyme inhibitor but later was found to be an irreversible one.  Below I will explain just exactly what that means and why:

But first let me give a little history and explain that are two general classes of enzyme inhibitor:  reversible and irreversible.  In the case of a reversible inhibitor, the medication weakly binds to the enzyme and can be fairly easily backed out, leaving the original enzyme functional and usable.  The irreversible inhibitor acts in the opposite fashion and  binds powerfully and chemically to the enzyme via covalent bonding - remember your high school chemistry - and thus completely takes the enzyme out of commission.  Another term for an irreverisble inhibitor is - and I have a page on this:  Suicide Inhibitors. The term suicide inhibitors sounds a little scary, but perhaps they should be if you stop and think about what they are doing.  Essentially, these type of inhibitors go in and annihilate an enzyme from your system or at least a large percentage and your body is then left with the ominous and all-critical task of rebuilding those enzymes.  More on this below.

1.Originally Thought to Be a Reversible 5-Alpha-Reductase Inhibitor.  According to some reports, it was originally thought to be a more tame reversible enzyme inhibitor as this 1995 book states:  

"Finasteride was originally reported to be a competitive, reversible inhibitor of SR [Steroid 5-Alpha Reductase]...Recent work suggests that finasteride is an irreversible inhibitor for the human Type 2 isoform, while it appears to be reversible with the rat Type I isoform." [2]

I find it a little hard to believe no one knew, but that is the official version anyway.  For those who don't know, 5-alpha-reductase is the enzyme that converts testosterone into the even more potent androgen dihydrotestosterone (DHT). 

2. Reversible versus Irreversible 5-Alpha-Reductase Inhibitor.  . Some men may be familiar with Aromasin (exemestane), which is an irreversible aromatase inhibitor that is used quite often in men on HRT (testosterone therapy).  If a man accidently crashed his estradiol with Aromasin, then it can take the body 2-3 weeks to rebuild its stores of aromatase enzymes.

3. Enzymes Are Rebuilt Within Two Weeks (The Great Majority of Times). Research shows that it takes your body two weeks to rebuild the missing enzymes generally.  This is based on the observation that "multiple daily doses for 1 2 weeks led to a similar 65 80% suppression of serum DHT, suggesting that tolerance did not develop to a chronic finasteride regimen in men. It has been reported that DHT concentrations recover within 2-weeks following the cessation of finasteride treatment in men , a finding that would be consistent with the slow turnover for the human Type I and Type II enzyme complexes." [3] Again, this is similar to the recovery time from Aromasin mentioned above.

4. What If Your 5-Alpha-Reductase is Crashed?  There is little evidence of permanent crashes from Aromasin (exemestane), which works on aromatase.  From what I can tell, the steroid community is pro-Aromasin and is not concerned about permanent crashes and they, of course, often take too much Aromasin and leave their estradiol in very low states. However, we did have one man who believed Aromasin permanently crashed his estradiol, and I documented on this page called  Permanent Low Estradiol from Aromatase Inhibitors?

Is this the root cause of Propecia's issues?  Probably not, but I mention it here, because if you test very low for DHT post-finasteride with solid levels of tesetosterone, it might make one wonder.

REFERENCES:

1) J Clin Psychiatry, 2012 Sep, 73(9):1220-3, "Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects"

2) Current Medicinal Chemistry, June 1995, p. 594

3) CNS Drug Reviews, 12(1):53 76, "A New Look at the 5 -Reductase Inhibitor Finasteride"

4) http://www.peaktestosterone.com/forum/index.php?topic=7760.0

5) J Clin Endocrinol Metab, 2003 Dec, 88(12):5951-6, "Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin (exemestane), in young males"

6) http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm