Finasteride [5ARI] Induced/Associated Effects

[Michael Scally MD]

Tsunemi Y, Irisawa R, Yoshiie H, et al. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. J Dermatol. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia - Tsunemi - 2016 - The Journal of Dermatology - Wiley Online Library

Androgenetic alopecia is an androgen-induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long-term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5-alpha-reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open-label, prospective outpatient study (clinicaltrials.gov NCT01831791, GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end-points included adverse event assessment, incidence of drug-related adverse event and premature discontinuations. Secondary end-points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug-related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long-term safety, tolerability and efficacy within this study population.

 

[Michael Scally MD]

Enatsu N, Miyake H, Haraguchi T, Chiba K, Fujisawa M. Effects of dutasteride on serum free-testosterone and clinical significance of testosterone changes. Andrologia. Effects of dutasteride on serum free-testosterone and clinical significance of testosterone changes - Enatsu - 2016 - Andrologia - Wiley Online Library

Sixty-two patients with benign prostate hyperplasia (BPH) who were being treated with dutasteride participated in this study.

Prostate volume, uroflowmetry, blood tests, the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) were determined before and 1, 3 and 12 months after the treatment with dutasteride.

Patients were divided into two groups based on changes in serum testosterone after 1 month:
Group A (>20% increase; n = 33) or
Group B (<20% increase; n = 29).

Serum free-testosterone levels were 20.4% higher after 1 month and remained constant thereafter.

When Groups A and B were compared, baseline free-testosterone levels were significantly lower in Group A, IPSS QOL was significantly better in Group A at 3 and 12 months, and no significant differences were observed in uroflowmetry, prostate volume, IPSS or IIEF-5.

A univariate analysis identified serum free-testosterone levels and the IPSS storage symptom subscore as significant factors influencing IPSS QOL at 12 months, and only the IPSS storage symptom subscore appeared to be independently related to IPSS QOL.

These results indicate that dutasteride increases serum free-testosterone levels in BPH patients, particularly with low baseline free-testosterone levels, and the increase in free-testosterone may have further add-on impacts on their urinary tract symptoms.

 

[Michael Scally MD]

Motofei IG, Rowland DL, Georgescu SR, Mircea T, Baleanu BC, Paunica S. Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia? Exp Dermatol. Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia? - Motofei - Experimental Dermatology - Wiley Online Library

Sexual side effects of Finasteride seem to be redoubtable, being encountered not only during therapy but also after treatment cessation. Consequently, any possible clinical/ paraclinical elements that might predict these adverse effects would be useful in the selection of a therapeutic strategy for male androgenic alopecia. Previous published studies show that some compounds that interfere with sexual hormones can decrease sexual activation and response, according to hand preference (as reported for finasteride and tamoxifen) and according to sexual orientation (as noted for bicalutamide). Our preliminary published data and the arguments presented here suggest that these two individual parameters might be used by dermatologists in the therapeutic approach of male androgenic alopecia, so as to alert specific subsets of men, prior to treatment, of the potential increased risk for developing adverse effects to finasteride. This article is protected by copyright. All rights reserved.

 

[sexypizza]

Hello guys, I think I have the same problem. I used dutasteride for 2 years and stopped taking it about 4 and a half months ago. but I still have sexual side effects. diminished labido, erectile disfunction, and lowered semen.

my doctor gave me a hormone test and everything according to him was in the normal range. all the doctors im seeing are brushing me off telling me its in my head. they gave me cialis and told me to use it for one month to rule out psychological bias.

I started using it today, even on 5mg of cialis I still have trouble maintaining an erection all though it is easier. labido and semen are still the same.

Ive read about other people with my condition, it seems most never recover and the ones that do take literally decades to get better. I simply cant live with that. Ive decided im going to end my life next year if I don't get better. not even joking about it.

I would like some help as I really don't know what to do right now.

 

[Dr JIM]

Hello guys, I think I have the same problem. I used dutasteride for 2 years and stopped taking it about 4 and a half months ago. but I still have sexual side effects. diminished labido, erectile disfunction, and lowered semen.

my doctor gave me a hormone test and everything according to him was in the normal range. all the doctors im seeing are brushing me off telling me its in my head. they gave me cialis and told me to use it for one month to rule out psychological bias.

I started using it today, even on 5mg of cialis I still have trouble maintaining an erection all though it is easier. labido and semen are still the same.

Ive read about other people with my condition, it seems most never recover and the ones that do take literally decades to get better. I simply cant live with that. Ive decided im going to end my life next year if I don't get better. not even joking about it.

I would like some help as I really don't know what to do right now.

Ganzer CA, Jacobs AR. Emotional Consequences of Finasteride: Fool's Gold. Am J Mens Health. Emotional Consequences of Finasteride

Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization.

Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions.

The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory.

An important finding in this study was that almost 57% (n = 97) of men reported a psychiatric diagnosis and 28% (n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported.

Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients.

50% grossly underestimates the number of patients who have had psychological issues BEFORE the onset of 5ARI treatment. Read further and one notes an 84% incidence of either "anxiety or depression" in "Finesteride sufferers" that PREDATED said therapy!

Yea most don't "recover" bc the underlying causation is a FUNCTIONAL DISORDER!

One can only hope you have a psychiatrist if not locate one!

 

[sexypizza]

50% grossly underestimates the number of patients who have had psychological issues BEFORE the onset of 5ARI treatment. Read further and one notes an 84% incidence of either "anxiety or depression" in "Finesteride sufferers" that PREDATED said therapy!

Yea most don't "recover" bc the underlying causation is a FUNCTIONAL DISORDER!

One can only hope you have a psychiatrist if not locate one!

What?

 

[Dr JIM]

Ive decided im going to end my life next year if I don't get better. not even joking about it.

I would like some help as I really don't know what to do.

SEE A PSYCHIATRIST and I'm not "joking" either

 

[sexypizza]

SEE A PSYCHIATRIST and I'm not "joking" either

oh sorry, I didn't understand what you meant by functional disorder. Yeah I agree with you. I will try to see a psychiatrist but I don't think I can afford it. thanks for the advice though.

 

[Dr JIM]

oh sorry, I didn't understand what you meant by functional disorder. Yeah I agree with you. I will try to see a psychiatrist but I don't think I can afford it. thanks for the advice though.

Then you should go to the ED where Mental Health Workers are available to provide you with the emotional assistance you NEED, bc premeditated suicidal thoughts have NOTHING to do with 5ARI therapy!

 

[ViaSwiss]

Hello guys, I think I have the same problem. I used dutasteride for 2 years and stopped taking it about 4 and a half months ago. but I still have sexual side effects. diminished labido, erectile disfunction, and lowered semen.

my doctor gave me a hormone test and everything according to him was in the normal range. all the doctors im seeing are brushing me off telling me its in my head. they gave me cialis and told me to use it for one month to rule out psychological bias.

I started using it today, even on 5mg of cialis I still have trouble maintaining an erection all though it is easier. labido and semen are still the same.

Ive read about other people with my condition, it seems most never recover and the ones that do take literally decades to get better. I simply cant live with that. Ive decided im going to end my life next year if I don't get better. not even joking about it.

I would like some help as I really don't know what to do right now.

PropeciaHelp.com and SolvePFS.com are communities that you should sign up at.

PFSfoundation.com has been funding studies into PFS. 2 very important ones will be released by the end of this year. Hang in there.

 

[JackTorrance]

I started taking Propecia. I already had difficulties getting hard before it, and never got morning wood before taking it since I was a teenager... So all in all I can't say I've seen any difference lmao.

I take 1 mg EoD though, and might even go to 0.5 mg EoD if I can get away with it. 1 mg per day is probably not necessary, not sure though, might be for guys who are shedding very rapidly.

 

[Michael Scally MD]

Kaplan SA. Re: 5alpha-Reductase Type 1 Modulates Insulin Sensitivity in Men. J Urol 2015;194(3):736-7. http://www.jurology.com/article/S0022-5347(15)04164-6/fulltext

When the dual 5α-reductase (5αR) inhibitor dutasteride became commercially available, there was a pervasive sense that it must be more effective than the 5αR2 inhibitor finasteride. This assumption was partly due to the finding that dihydrotestosterone suppression was greater with dutasteride than with finasteride. Subsequent studies clearly demonstrated that from virtually every clinical efficacy parameter there were no differences between the 2 agents. However, are there differences regarding biochemical effect?

These authors report that glucose disposal, as measured by a stepwise hyperinsulinemic-euglycemic clamp, is reduced by dutasteride only, presumably by inhibition of the 5αR1 enzyme. These findings highlight a phenomenon that urologists were unaware of, namely that 5αR1 modulates metabolic signaling in humans. Moreover, in the group of men in this study who were on dutasteride there was an increase in body fat and a decrease in insulin sensitivity. These effects were not seen with finasteride. Could some of the breast issues seen with dutasteride, which may be greater than those reported with finasteride, be influenced by this pathway? Moreover, there is a striking difference in effects in insulin sensitivity between dutasteride and finasteride in peripheral tissues, including adipose and skeletal tissue. In fact, insulin sensitivity was improved by finasteride. Based on my own experience of prescribing these agents for more than 20 years, and for this reason and others, including fewer sexual adverse effects, the preferred 5αR agent has been finasteride. The ultimate role of modulating metabolic dysfunction remains to be determined. Just when we thought we had it all figured out, things continue to evolve!

 

[Michael Scally MD]

Pirozzi Farina F, Pischedda A. Comments concerning the real risk of sexual adverse events secondary to the use of 5-ARIs. Arch Ital Urol Androl 2016;87(4):312-6. Comments concerning the real risk of sexual adverse events secondary to the use of 5-ARIs | Pirozzi Farina | Archivio Italiano di Urologia e Andrologia
Comments concerning the real risk of sexual adverse events secondary to the use of 5-ARIs | Pirozzi Farina | Archivio Italiano di Urologia e Andrologia

Treatment-induced sexual dysfunctions (SD) are a recurrent and controversial topic in recent literature on the adverse events related to the use of 5-alpha-reductase inhibitors (5ARIs) (1, 2). In order to deal adequately with the various aspects of this topic, it is necessary to first cover some of the steps that allow a better definition and understanding of the subject.

 

[Michael Scally MD]

Re: 5alpha-Reductase Type 1 Modulates Insulin Sensitivity in Men

When the dual 5α-reductase (5αR) inhibitor dutasteride became commercially available, there was a pervasive sense that it must be more effective than the 5αR2 inhibitor finasteride. This assumption was partly due to the finding that dihydrotestosterone suppression was greater with dutasteride than with finasteride. Subsequent studies clearly demonstrated that from virtually every clinical efficacy parameter there were no differences between the 2 agents.

However, are there differences regarding biochemical effect?

These authors report that glucose disposal, as measured by a stepwise hyperinsulinemic-euglycemic clamp, is reduced by dutasteride only, presumably by inhibition of the 5αR1 enzyme. These findings highlight a phenomenon that urologists were unaware of, namely that 5αR1 modulates metabolic signaling in humans.

Moreover, in the group of men in this study who were on dutasteride there was an increase in body fat and a decrease in insulin sensitivity. These effects were not seen with finasteride. Could some of the breast issues seen with dutasteride, which may be greater than those reported with finasteride, be influenced by this pathway?

Moreover, there is a striking difference in effects in insulin sensitivity between dutasteride and finasteride in peripheral tissues, including adipose and skeletal tissue. In fact, insulin sensitivity was improved by finasteride.

Based on my own experience of prescribing these agents for more than 20 years, and for this reason and others, including fewer sexual adverse effects, the preferred 5αR agent has been finasteride. The ultimate role of modulating metabolic dysfunction remains to be determined.

Just when we thought we had it all figured out, things continue to evolve!

Kaplan SA. Re: 5alpha-Reductase Type 1 Modulates Insulin Sensitivity in Men. J Urol 2015;194(3):736-7. http://www.jurology.com/article/S0022-5347(15)04164-6/fulltext

 

[Raven101]

Interesting. Finasteride increases insulin sensitivity.. Thats a good thing.

 

[Michael Scally MD]

Post-Finasteride Syndrome: Real or Imagined?
http://www.aua2016.org/abstracts/abstractprint.cfm?id=MP89-08

Introduction and Objectives - Post-finasteride syndrome (PFS) has recently been recognized as a medical disorder comprising a cluster of sexual, physical, and psychological/neurologic symptoms associated with 5-alpha reductase inhibitor (5ARI) use with purported persistent symptoms despite cessation of drug usage. The aim of this study was to help quantify reports, create a demographic of patient reports, and assess the cluster of symptoms to correlate consistency of the PFS complaints.

Methods - We collected the entire dataset of 3,295 Food and Drug Administration Adverse Event Reporting System (FAERS) cases that were submitted from April 2011 to October 2014 on all 5ARIs. We then evaluated the single-dose 5ARI monotherapies and analyzed these cases for symptoms and side effects associated with different doses.

Results - 2,048 monotherapy cases using 5ARIs were identified with 1581 being finasteride 1mg, 240 5mg, and 226 of unreported doses.

Overall there was an increase event reporting as time progressed with the majority of these involving the 1mg dose. Finasteride was associated with many sexual side effects: decreased libido, ejaculatory disorder, erectile dysfunction, testicular atrophy, orgasmic disorders, hypogonadism, and overall increased sexual complaints.

Other common complaints were dermatologic in nature (dry skin or thinning of skin) as well as changes in metabolism (weight gain, elevated glucose, and elevated lipids).

Psychological/neurologic conditions of self-harm (suicide), slow cognition, psychological pathologies, emotional anhedonia, insomnia and overall psychological symptoms were prevalent with finasteride use.

One mg of finasteride demonstrated more adverse events than the 5mg in the following areas: sexual dysfunction, libido decrease, ejaculation disorders, erectile dysfunction, testicular atrophy, hypogonadism, skin abnormalities, metabolic abnormalities, self-harm, slow cognition, depression, anxiety, emotional anhedonia, and insomnia. Dutasteride was never reported to cause a PFS-like symptom.

Conclusions - FAERS data suggests that finasteride is associated with a diverse collection of symptoms, particularly in the 1 mg dosage. Dutasteride was not implicated for PFS, resulting in only one AE report. Whether or not PFS is real or imagined is not discernable within this context and database.

 

[Michael Scally MD]

Atypical Post-Finasteride Syndrome: A Pharmacological Riddle

Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II.

The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH) as well as androgenic alopecia (AGA) while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well.

Although the postfinasteride syndrome (PFS) is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting.

Gupta AK, Sharma N, Shukla P. Atypical post-finasteride syndrome: A pharmacological riddle. Indian J Pharmacol 2016;48(3):316-7. Atypical post-finasteride syndrome: A pharmacological riddle Gupta AK, Sharma N, Shukla P - Indian J Pharmacol

 

[Michael Scally MD]

Effect of 5alpha-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials

INTRODUCTION: 5alpha-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA).

AIM: To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction.

METHODS: A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests.

MAIN OUTCOME MEASURES: Sexual dysfunction, erectile dysfunction, and decreased libido.

RESULTS: After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA.

The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48-4.42) in men with BPH and 1.21 (95% CI = 0.85-1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14-2.12) in men with BPH and 0.66 (95% CI = 0.20-2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03-2.79) in men with BPH and 1.16 (95% CI = 0.50-2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed.

CONCLUSION: Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.

Liu L, Zhao S, Li F, et al. Effect of 5alpha-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials. J Sex Med. http://www.jsm.jsexmed.org/article/S1743-6095(16)30314-9/abstract

 

[Dr JIM]

CONCLUSION: However, the association was not statistically significant in men with AGA.

I'm not surprised bc I've also noted this trend, and suspect one of the major (and objective) differences is the dose being used for BPH is roughly FIVE TIMES that which is approved for AGA therapy (5mg vs 1mg respectively).

THX Doc S
Jim

 

[Michael Scally MD]

Choi GS, Kim JH, Oh SY, et al. Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia. Ann Dermatol 2016;28(4):444-50. http://synapse.koreamed.org/DOIx.php?id=10.5021/ad.2016.28.4.444 (Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia)

BACKGROUND: After the approval of dutastride for androgenic alopecia (AGA) in 2009, Korean authority required a post-marketing surveillance to obtain further data on its safety profile. OBJECTIVE: The objective was to monitor adverse events (AEs) of dutasteride 0.5 mg in Korean AGA male patients in a clinical practice environment.

METHODS: Open label, multi-center, non-interventional observational study was done from July 2009 to July 2013. AGA subjects (18~41 years of age) with no experience of dutasteride were enrolled. Dosage regimen was recommended according to the prescribing information. The incidences of any AEs, serious adverse events (SAEs), and adverse drug reactions (ADRs) were evaluated. Multiple logistic regression method was used to identify risk factors related to ADRs. Effectiveness was generally evaluated by physicians.

RESULTS: During study period, 712 subjects were enrolled. The subjects of 29.3+/-6.0 years old exposed to dutasteride for 204.7+/-161.5 days. One hundred and ten (15.4%) of subjects reported 138 AEs.

Four subjects (0.6%) reported 5 SAEs (right radius fracture, 2 events of chronic follicular tonsillitis, influenza infection, and acute appendicitis).

Sixty-six subjects (9.3%) reported 80 ADRs. Most frequent ADRs were libido decreased (9 subjects, 1.3%), dyspepsia (8 subjects, 1.1%), impotence (7 subjects, 1.0%), and fatigue (5 subjects, 0.7%). Other interested ADRs were sexual function abnormality (4 subjects, 0.6%), gynecomastia (2 subjects, 0.3%), and ejaculation disorder (1 subject, 0.1%).

Most subjects (78.6%) showed overall improvement after treatment of dutasteride in the effectiveness.

CONCLUSION: Dutasteride 0.5 mg is to be well-tolerated in 18 to 41 years old AGA patients in a clinical practice environment.