Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

Sung, Hyun Hwan; Yu, Jiwoong; Kang, Su Jeong; Chae, Mee Ree; So, Insuk; Park, Jong Kwan; Lee, Sung Won

doi:10.5534/wjmh.180082

Cited by 13 publications

(9 citation statements)

References 32 publications

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“…Animal studies, case reports, human studies and AE data provide converging evidence for an association of 5ARI treatment with penile alterations. 20 Animal research has found 5ARI treatment is associated with: reduced size and weight of the penis 21,22 ; reduced erectile response; apoptosis 23 ; decreased smooth muscle density and increased collagen density in corpus cavernosum 21,23,24 ; fibrosis [25][26][27] ; reduced size of sinusoidal spaces in corpus cavernosum 21,26 ; reduced expression of endothelial nitric oxide synthase (eNOS) 24,28 ; reduced expression of erectile neurotransmitter calcitonin gene-related peptide (CGRP) 29 ; and, in a dutasteride study, reduced expression of androgen receptor. 27 A review noted that an animal study's findings "indicate that 5ARIs have a significant pathogenic impact on the penile histo-architecture and attenuate the NOS signaling pathway."…”

Section: Ari Treatment Has Been Associated With Penile Abnormalitiesmentioning

confidence: 99%

“…The ratio of smooth muscle to collagen in cavernosal tissue remained low after the washout period, while expression of fibrosisrelated factors such as TGF--. 25 Selected images of penile alterations emerging from 5ARI treatment have been reproduced in Figures 3-5. 21,23,26 Human research on penile abnormalities associated with 5ARI treatment is sparse, but bears consistency with the animal research.…”

Section: Ari Treatment Has Been Associated With Penile Abnormalitiesmentioning

confidence: 99%

“…23 Two recent animal studies found differing effects of dutasteride on expression of NOS isoforms in rat corpus cavernosum. 23,25 A review described the critical role of nitric oxide (NO) production and sensitivity in maintaining vascular homeostasis, and suggested that impairment of NO signaling has a "central link"…”

Section: Androgen Mediation Of Angiogenesismentioning

confidence: 99%

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From organ injury to disability: a proposed model for 5-alpha reductase inhibitor syndrome

Montaigne¹

2022

Preprint

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Persistent dysfunctions emerging from use and discontinuation of 5-alpha reductase inhibitors (PD-5ARI) may be explained as the aftermath of a pathological recovery from microvasculopathy or ischemia in multiple systems. Focusing on persistent sexual dysfunction, the most common class of symptoms: 5ARIs’ inhibition of angiogenesis leads to stress on penile microvasculature, depriving the tissue of blood supply and oxygen. These hypoxic conditions lead to tissue injury and atrophy, triggering a pathological recovery that further alters penile tissue, including smooth muscle loss, fibrosis, damage to vascular architecture and impairment of neural pathways supporting arousal and erectile function. This damaging cascade may result in severe and lasting sexual dysfunction. Persistent neuropsychiatric, cognitive, sensory and sleep dysfunctions emerging from 5ARI treatment may similarly be explained as pathological responses to microvasculopathy or ischemia in supporting structures, particularly those in the limbic system. Systemic spread is proposed to arise from a vicious cycle of tissue injury, oxidative stress and proinflammatory activity which spreads via the vascular network, leading to systemic endothelial dysfunction. The latter may in turn set off a damaging cascade in other organs and tissues. Risks of developing PD-5ARI may arise from 5ARI-mediated disruptions of vascular tone, angiogenesis and neoangiogenesis. Pharmacovigilance data, animal studies and human studies provide converging evidence for the proposed etiopathology. It is, moreover, consistent with variable presentation and severity of PD-5ARI symptoms; irreversibility of symptoms; typically normal results of clinical lab tests; and resistance to treatment.

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Section: Ari Treatment Has Been Associated With Penile Abnormalitiesmentioning

confidence: 99%

Section: Ari Treatment Has Been Associated With Penile Abnormalitiesmentioning

confidence: 99%

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From organ injury to disability: a proposed model for 5-alpha reductase inhibitor syndrome

Montaigne¹

2022

Preprint

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“…75 Interestingly, a recent pre-clinical study, in rats, also concluded that long-term 5-ARI medication can result in persistent ED. 76 Further prospective studies are warranted, since they may restrict the use of these drugs in the future. A critical aspect of the efficiency of 5ARIs is long-term adherence to the medication.…”

Section: α-Reductase Inhibitorsmentioning

confidence: 99%

Pharmacology of the lower urinary tract: update on LUTS treatment

Abreu-Mendes

Silva

Cruz

2020

Therapeutic Advances in Urology

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The number of compounds used in the pharmacological treatment of lower urinary tract symptoms (LUTS) of patients who do not respond to conservative measures has been relatively stable during the last decade, with the exception of the introduction of the new class of β3 adrenoceptor agonists. However, different combinations have been investigated, and the long-term use of these compounds has raised new concerns about adherence and safety. This review summarizes the current state of pharmacology for LUTS, and presents a thorough discussion of the possible challenges concerning their future use. In this narrative review, we analyze the most recent articles related to LUTS pharmacotherapy, after an initial review of mechanisms of bladder function relevant in present clinical practice. The main problems with pharmacotherapy in LUTS are associated with its moderate efficacy, low persistence on treatment, and the incidence of short- and long-term adverse events (AE) associated with some compounds. The long-term AE, such as cognitive impairment in the elderly vulnerable patients associated with antimuscarinic drugs or persistent erectile dysfunction in sexually active men after treatment with 5-α-reductase inhibitors (5-ARI), are some of the problems addressed in this review. Combination therapy taking advantage of the synergistic mechanisms of action between some classes of compounds may overcome AE associated with dose escalation. LUTS pharmacotherapy offers moderate results to most patients but not a full cure. The use of combination drugs to achieve better clinical results, reduce AE and improve both efficacy and adherence, will be used more frequently in the future. The recently raised concern on potential long-term irreversible AE associated with some of these drugs, like antimuscarinics and 5-ARI, are critically important and require further investigation.

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“…Finasteride is widely used in the treatment of benign prostatic hyperplasia (BPH) and androgenic alopecia (AGA). The effectiveness and safety of finasteride in the treatment of BPH have been extensively studied; however, there is insufficient research on the persistent severe side effects in young male patients with AGA who discontinue the drug (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). This study reports three cases of post-finasteride syndrome (PFS) occurring in young men after finasteride was used to treat hair loss.…”

Section: Introductionmentioning

confidence: 99%

Case report: a study of the clinical characteristics and genetic variants of post-finasteride syndrome patients

Li¹,

Ye²,

Lu³

et al. 2022

Transl Androl Urol

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Background: Finasteride is widely used in the treatment of benign prostatic hyperplasia (BPH) and androgenic alopecia (AGA). Post-finasteride syndrome (PFS) is a spectrum of persistent symptoms reported by some patients after treatment with finasteride for androgenetic alopecia. These patients show many abnormal clinical manifestations, including psychological disorders (depression and anxiety, among others) and sexual dysfunction. However, there is insufficient research on the persistent severe side effects in young male patients with PFS, and the underlying mechanism of PFS has not been fully elucidated. Growing evidence highlights the relevance of genetic variants and their associated responses to drugs. Therefore, we performed next-generation sequencing (NGS) in our study of PFS.Case Description: Here, we enrolled three young male patients aged 20-30 years with a PFS duration of 1-3 years and analyzed their clinical and genetic information. PFS patients suffered from erectile dysfunction (ED), anxiety, feelings of isolation, and insomnia. Variants in genes, including CA8, VSIG10L2, HLA-B, KRT38 and HLA-DRB1, were detected, and these genes represent potential risk genes.Conclusions: PFS, commonly observed in young men, has certain clinical manifestations, mainly psychological disorders and abnormal sexual functions. Young men who may take finasteride therapy for hair loss should receive consultation services and be informed of possible future harms. Psychological screening is an important method to reduce the occurrence of PFS. At present, the underlying mechanism of PFS is not very clear, and more research is needed to improve the understanding of the disease. Some genes are abnormal in PFS patients, suggesting that clinical and genetic evaluation might be needed before the prescription of 5α-reductase inhibitors. With research progress, genetic screening may be a promising way to avoid the harmful effects of finasteride in people with related genetic risk factors.

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Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

Cited by 13 publications

References 32 publications

From organ injury to disability: a proposed model for 5-alpha reductase inhibitor syndrome

From organ injury to disability: a proposed model for 5-alpha reductase inhibitor syndrome

Pharmacology of the lower urinary tract: update on LUTS treatment

Case report: a study of the clinical characteristics and genetic variants of post-finasteride syndrome patients

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