5-Alpha-reductase type 3 and PFS?

So for some time now I’ve been thinking how our symptoms vary between individuals so much. While some get mostly sexual sides, other get systematic impact on several tissues.

Looking into 5 alpha reductase type 2 (5AR2) this just doesn’t sit well with me.

So for some time I’ve been researching 5 alpha reductase type 3 (5AR3). I see that it’s been mentioned a few times on here before but it’s not been researched much at all.

Many people probably know that finasteride is a very potent inhibitor of 5AR2, but not very strong inhibitor of 5AR1. But what’s interesting is it’s effect on 5AR3. Finasteride (and dutasteride) are both potent inhibitors of 5AR3 as well.

When finasteride was developed, they looked into a population of people who has 5 alpha reductase deficiency, called “Guevedoce”. These people have a mutation in the SRD5A2 gene, the gene coding for 5AR2.

They are basically “normal”, except that their genitalia and prostate is not fully developed. The gene coding for 5AR3 (SRD5A3) is still functioning in these individuals. 5AR3 is expressed in a lot of tissues around the body, while 5AR2 is more tissue specific.

5AR3 is involved in a reaction called “N-glycosylation”.

  • Glycosylation is critical for physiological and pathological cellular functions

  • The pathogenesis of many autoimmune diseases, such as immunoglobulin A (IgA) nephropathy, systemic lupus erythematosus and inflammatory bowel disease, involves abnormal glycosylation of one or more glycoproteins; diabetes involves abnormal O -linked N -acetylglucosamine-mediated signalling and enhanced glycation of multiple proteins.

  • There are three types of glycosylation disorders sorted by the type of alterations that are made to the glycosylation process: congenital alterations, acquired alterations and non-enzymatic acquired alterations. All these diseases are difficult to diagnose because they do not only affect one organ, they affect many of them and in different ways. As a consequence, they are also hard to treat.

More info about glycosylation here and here.

I haven’t had time yet to understand this fully, and there’s very little (or none at all) research done on the effects of 5AR3 inhibition. But reading more about it, it does seem kind of likely it might be involved in the pathology of PFS.

“5AR3 expression at the mRNA level is higher than 5AR1 and 2 in frontal cortex, heart, colon, stomach, liver, pancreas, lung, BPH, prostate, testis, mammary gland, brain, cervix, ovary, dermis, epidermis, total skin, small intestine, spleen, and kidney
5AR2 mRNA was the most abundant in BPH and muscle”.


Been looking into this more and found this easy to read text about 5AR3 that I found really interesting.


  • SRD5A3 belongs to a group of enzymes called polyprenol reductases but its functions cannot be compensated for by the related polyprenol reductases. In the absence of SRD5A3, polyprenol is no longer converted (reduced) to dolichol. Dolichol is the lipid carrier that shuttles oligosaccharides to their site of transfer onto asparagine residues in freshly synthesized proteins.

  • SRD5A3 is expressed at high levels in human brain tissue, especially in the cerebellum, at moderate levels in the eye and heart, and at low levels in other organs.

  • The cerebellum is also involved in some cognitive functions such as attention and language as well as emotional control such as regulating fear and pleasure responses.

  • SRD5A3 defiency lead to eye diseases, something that has also been linked to finasteride use. But this could also be due to inhibited DHT, as DHT is needed for protecting the eye tissue.

I think this might be worth looking into in future research.

Obviously, we don’t have anything near as bad symptoms as people who are born with 5AR3 defiency. But I do believe there is some mild similarities.

Funnily enough 5AR3 doesn’t seem to contribute to much DHT, if any at all. So it being inhibited in a hair loss drug is just bad design.

5α-reductase SRD5A3 is not involved in steroid hormone formation or sexual development but instead plays a crucial role in the N-linked glycosylation of proteins.

N-linked glycosylations have an important role in both protein folding, but also trafficking of the protein.


I’m not sure how many people are reading this thread, but I’m wondering if anyone ever got their AMH tested?

It’s a test that can determine how healthy the sertoli cells are (sperm producing cells).

Apparently glycosylation of FSH is very important for it’s effect on the sertoli cells. And serum AMH can be used to check this.

Might be worth looking into, next time I do a blood panel I’ll include it.

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Glycosylation of hormones and sperm health.

  • Levels of free hCGα, by far the most abundant hCG variant in seminal plasma, were significantly reduced in men with abnormal semen analyses. Additionally, in men with reduced sperm counts, holo-hCG levels were accordingly lower, indicating a pathophysiological relevance of these hormone variants in spermatogenesis. hCGα in seminal plasma was identified as being a highly glycosylated large free subunit with a unique glycosylation pattern. Alternative glycosylation clearly might modify the function of the hormone subunit, thus free large hCGα purified from seminal plasma represents a promising molecular entity to further investigate the physiological role of free hCGα in spermatogenesis.

hCGa, a N-linked glycosylation product of hCG was reduced in men with abnormal sperm.

N-glycosylation is inhibited by finsteride and we know that finsteride is shown to reduce sperm health parameters.

In men with normal sperm it normalize after discontinuation but in people who already have bad sperm finsteride is shown to have persistent/permanent negative effect on their sperm.

Possible that people who have abundance 5AR3/N-glycosylation capacity doesn’t get PFS while other who doesn’t have that much capacity get it?

Also interesting how in the study they found that people with abnormal sperm had significantly higher serum prolactin. Something many of us had been left with post fin.

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I agree with you.

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