The dark side of 5α-reductase inhibitors' therapy

[xptriado]

The dark side of 5α-reductase inhibitors’ therapy: sexual dysfunction, high Gleason grade prostate cancer and depression.

Abstract

With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia (BPH) with concomitant lower urinary tract symptoms (LUTS). Because the prostate is an androgen target tissue, and transforms testosterone into 5α-dihydrotestosterone (5α-DHT), a potent androgen, via 5α-reductase (5α-R) activity, inhibiting this key metabolic reaction was identified as a target for drug development to treat symptoms of BPH. Two drugs, namely finasteride and dutasteride were developed as specific 5α-reductase inhibitors (5α-RIs) and were approved by the U.S. Food and Drug Administration for the treatment of BPH symptoms. These agents have proven useful in the reducing urinary retention and minimizing surgical intervention in patients with BPH symptoms and considerable literature exists describing the benefits of these agents. In this review we highlight the adverse side effects of 5α-RIs on sexual function, high grade prostate cancer incidence, central nervous system function and on depression. 5α-Rs isoforms (types 1-3) are widely distributed in many tissues including the central nervous system and inhibition of these enzymes results in blockade of synthesis of several key hormones and neuro-active steroids leading to a host of adverse effects, including loss of or reduced libido, erectile dysfunction, orgasmic dysfunction, increased high Gleason grade prostate cancer, observed heart failure and cardiovascular events in clinical trials, and depression. Considerable evidence exists from preclinical and clinical studies, which point to significant and serious adverse effects of 5α-RIs, finasteride and dutasteride, on sexual health, vascular health, psychological health and the overall quality of life. Physicians need to be aware of such potential adverse effects and communicate such information to their patients prior to commencing 5α-RIs therapy.

ncbi.nlm.nih.gov/pubmed/24955220

fuck man…

[nopecia]

How’s it still available?

[mcibofh]

Easy they blame cancer, age, and cancer treatment for all the fin. sides. Most of these people die within a few years and are older. No casual link to just fin.

[weaksides]

Who has read this study? Currently reading.

The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High...

It’s been posted several times, but I was curious what the current view on it is

[weaksides]

It has recently been shown that patients who had been treated with finasteride have reduced or undetectable levels of neuroactive steroids in their cerebro-spinal fluid and plasma, and exhibited higher levels of precursor steroids [75]. This observation strongly suggests that 5α-RIs have a deleterious effect on the biosynthesis and function of neurosteroids in the central nervous system. Finasteride treatment resulted in decreased levels of 5α-DHT and 3α, 5α-tetrahydroprogesterone (AP) and increased levels of testosterone supporting the hypothesis that deleterious effects of finasteride may be persistent or irreversible. This may explain some of the noted symptoms such as anxiety, depression and suicide in patients who have been treated with finasteride [76].

[weaksides]

Concomitant with these changes are the markedly reduced expression of neuronal nNOS and increased expression of the inducible NOS, suggesting that dutasteride induces altered gene expression in the corpus cavernosum. Oztekin et al. [38] investigated the effects of dutasteride on erectile function after 6 weeks of treatment followed by a washout period of 2 weeks. The ratio of ICP over mean arterial pressure [MAP] and total ICP in the dutasteride treated animals were significantly decreased when compared with control animals (Fig. 2). Even after two-week washout period the effects persisted and the ICP/MAP was significantly reduced in the dutasteride treated animal, suggesting a persistent effect of the drug on erectile physiology