ORIGINAL ARTICLE
Ahead of print publication  

Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: a systematic review and meta-analysis


1 Department of Urology, The Third Xiangya Hospital, Central South University, Changsha 410008, China
2 Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
3 Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
4 Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, China

Date of Submission18-Dec-2020
Date of Acceptance02-Sep-2021
Date of Web Publication29-Oct-2021

Correspondence Address:
Long Wang,
,
China

Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aja202171

PMID: 34747724

  Abstract 


Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64–2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74–2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80–2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

Keywords: 5α-reductase inhibitors; adverse effects; androgenetic alopecia; benign prostatic hyperplasia; postfinasteride syndrome


Article in PDF

How to cite this URL:
Zhang JJ, Shi X, Wu T, Zhang MD, Tang J, Yin GM, Long Z, He LY, Qi L, Wang L. Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: a systematic review and meta-analysis. Asian J Androl [Epub ahead of print] [cited 2021 Dec 9]. Available from: https://www.ajandrology.com/preprintarticle.asp?id=329730


  Introduction Top


Postfinasteride syndrome (PFS) is an ill-defined and controversial syndrome associated with a constellation of sexual, physical, and neuropsychiatric symptoms that develop during or after 5α-reductase inhibitor (5ARI) exposure and persist after discontinuation.[1] Sexual symptoms include loss of libido, erectile dysfunction (ED), ejaculatory disorders, sexual anhedonia, decreased semen volume and force, reduction in penis size and scrotal shrinkage, and numbness. Physical symptoms include skin rash, gynecomastia, fatigue, muscle weakness and elevated creatine kinase levels, lipoatrophy, hearing defects and tinnitus, and metabolic anomalies. Neuropsychiatric symptoms associated with PFS include memory impairment, slow cognition, depression, suicidal ideation, anxiety, emotional flatness and anhedonia, insomnia, and obstructive sleep apnea.[1],[2],[3],[4]

The hallmark of PFS is persistent adverse events after discontinuing 5ARIs. However, researchers rarely focus on this special point in clinical trials. By searching the PubMed, Embase, and Cochrane Library databases, information regarding PFS mostly originate from case reports, observational studies, and uncontrolled surveys, making a systematic review and meta-analysis difficult.[1]

Given the abovementioned reasons, we conducted a systematic review and meta-analysis to focus on the PFS-like (sexual, physical, and neuropsychiatric) adverse effects during treatment. To our knowledge, this is the first attempt to pool current evidence from placebo-controlled randomized clinical trials (RCTs) to evaluate PFS-like adverse effects. This study may provide new insights and inspiration for future research on PFS and help us better define the adverse effects of 5ARIs.


  Materials and Methods Top


This systematic review and meta-analysis was conducted on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.[5] This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42020191731).

Study aim

The purpose of this systemic review and meta-analysis was defined using Patient–Intervention–Comparison–Outcome (PICO) statements. The aim was to examine male patients with androgenetic alopecia (AGA) or benign prostatic hyperplasia (BPH; P) to determine whether treatment with oral 5ARIs (I) compared with placebo (C) increases the risk of PFS-like adverse effects (O).

Search strategy

A comprehensive search of studies published before May 10, 2020, was performed in the following electronic databases: PubMed, EMBASE, and Cochrane Library. The combined search terms (“finasteride” OR “dutasteride”) AND “placebo” AND “adverse effects” were used. The reference list of retrieved publications was manually screened to identify any additional sources.

Study selection

Studies were selected using the inclusion and exclusion criteria defined prior to initiation of the literature search. Two main reviewers (JJZ and XS) independently evaluated the titles and abstracts of the retrieved studies, and discrepancies were discussed with the research group. The included trials were RCTs that investigated the use of oral 5ARIs in male patients with BPH or AGA and that reported the incidence of any sexual, physical, and neuropsychiatric adverse effects during the trial. The exclusion criteria were as follows: (1) trials that investigated the use of topical 5ARIs; (2) studies that included subjects with diseases other than BPH or AGA, such as prostate cancer; (3) studies including female studies; (4) studies that did not report the incidence of adverse effects; or (5) open-label extension studies. If the abstract did not provide sufficient information for study inclusion or exclusion, a full-text review was performed to determine eligibility. When at least 2 studies were reported by the same institution and/or investigators in an overlapping or continuing period, only the study that was reported first was included. Moreover, for crossover trials, only data from the first period were included to avoid potential confounding events that may have occurred during the crossover of the study with the same subjects.

Data extraction and quality assessment

Two main reviewers (JJZ and TW) compiled the data in a predefined spreadsheet and performed data extraction and quality assessment of the included studies. In the event of disagreement, a final decision was reached through consensus discussion. The data extracted from each study included year, setting, design, trial duration, study population, specific 5ARI and dose, and data on the number, mean age, and age range of subjects. If data measurements among different studies were not the same, data were converted (e.g., from month to week). The main outcome for ascertainment was the incidence of PFS-like adverse effects of 5ARIs or placebo during the trial. If available, data on individual risk of sexual, physical, and neuropsychiatric adverse effects were also collected. The Cochrane Collaboration risk of bias tool was utilized for quality assessment to evaluate the potential risk of bias of the included RCTs.[6]

Data synthesis and outcome

Meta-analyses were performed to calculate the overall relative risk (RR) of PFS-like adverse effects of 5ARIs. The individual RRs of sexual, physical, and neuropsychiatric adverse effects were also calculated using the eligible studies. The meta-analyzed RRs were calculated by combining the datasets using an inverse variance method. Heterogeneity among the included studies was calculated using the χ2 test for heterogeneity (with P < 0.1 indicating significant heterogeneity) and the I2 statistic for inconsistency. A random-effects model was used for data synthesis given the heterogeneous study population, study setting, and trial duration of the included studies. The results were expressed using a forest plot. If an adequate number of related studies were available to assess the same outcome, publication bias was assessed using Egger's test.[7] Sensitivity analysis was undertaken to demonstrate the overall influence of an individual study where I2 >50%. Statistical analysis was performed using RevMan 5.2 (the Cochrane Collaboration) and STATA 16.0 (StataCorp., College Station, TX, USA). All P values reported were two-sided with P < 0.05 considered statistically significant.


  Results Top


Study selection, characteristics, and quality assessment

The PRISMA flow diagram of study selection is shown in [Figure 1]. Of 621 retrieved articles, 28 were included in the study. The characteristics of the 34 studies from 28 articles are summarized in [Table 1]. All studies involved RCTs reporting the incidence of any sexual, physical, and neuropsychiatric adverse effects during the trial in both the 5ARIs and placebo groups. Of these articles, 9 investigated 5 mg day−1 finasteride;[8],[9],[10],[11],[12],[13],[14],[15],[16] 7 investigated 1 mg day−1 finasteride;[17],[18],[19],[20],[21],[22],[23] 6 investigated 0.5 mg day−1 dutasteride;[24],[25],[26],[27],[28],[29] 4 investigated both 5 mg day−1 finasteride and 1 mg day−1 finasteride;[30],[31],[32],[33] 1 investigated both 5 mg day−1 finasteride and 0.5 mg day−1 dutasteride;34 and 1 investigated both 1 mg day−1 finasteride and 0.5 mg day−1 dutasteride.[35] The mean age of the 5ARI and placebo groups was comparable in each study. These studies had a moderate risk of bias assessment [Supplementary Figure 1 [Additional file 1]] and were included in the data synthesis. A total of 25 696 subjects treated with 5ARIs or placebo were included in the analysis.
Figure 1: Flow diagram of literature search. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. RCT: randomized clinical trial.

Click here to view
Table 1: Characteristics of the included studies

Click here to view


Data extraction and synthesis

The number of PFS-like adverse effects in groups treated with 5ARIs or placebo is summarized in [Table 2]. All studies provided the individual number of sexual adverse effects. Ten studies from 8 articles provided the exact number (not zero) of physical adverse effects.[10],[11],[14],[15],[25],[26],[31],[35] Only 1 study provided the exact number (not zero) of neuropsychiatric adverse effects.[31] Thirty studies were included in our pooled data, and 4 were excluded due to the lack of exact total data.[10],[12],[14],[17] Of these subjects, 1804 of 11 886 treated with 5ARIs and 800 of 9524 treated with placebo experienced at least one PFS-like adverse effect. Regarding the dose/5ARI subgroup, 1275 of 7473 subjects treated with 5 mg day−1 finasteride and 545 of 5127 subjects treated with placebo experienced at least one PFS-like adverse effect. In total, 134 of 1650 subjects treated with 1 mg day−1 finasteride and 60 of 1650 subjects treated with placebo experienced at least one PFS-like adverse effect. In total, 395 of 2763 subjects treated with 0.5 mg day−1 dutasteride and 195 of 2747 subjects treated with placebo experienced at least one PFS-like adverse effect [Figure 2]. For the disease subgroup, 1677 of 10 164 subjects treated with 5ARIs and 718 of 7786 subjects treated with placebo in the BPH subgroup had at least one PFS-like adverse effect; 127 of 1722 subjects treated with 5ARIs and 82 of 1738 subjects treated with placebo in the AGA subgroup had at least one PFS-like adverse effect [Figure 3].
Figure 2: Increased risk of PFS-like adverse effects with the use of 5α-reductase inhibitors (dose subgroup). a/bOne article includes 2 studies. PFS: postfinasteride syndrome; df: degree of freedom; CI: confidence interval; M–H: Metropolis-Hastings.

Click here to view
Figure 3: Increased risk of PFS-like adverse effects with the use of 5α-reductase inhibitors (disease subgroup). a/bOne article includes 2 studies. BPH: benign prostatic hyperplasia; AGA: androgenetic alopecia; PFS: postfinasteride syndrome; df: degree of freedom; CI: confidence interval; M–H: Metropolis-Hastings.

Click here to view
Table 2: Outcomes of the included studies

Click here to view


Overall use of 5ARIs

In the random-effects model, the overall use of 5ARIs had a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64–2.14). Heterogeneity among the included studies was acceptable (I2 = 26%), and heterogeneity among studies in the dose/5ARI subgroup was minimal (I2 = 0), as shown in [Figure 2]. However, the heterogeneity among studies in the disease subgroups was significant (I2 = 72%; [Figure 3]. Regarding specific types of adverse effects, the use of 5ARIs exhibited a 1.89-fold risk of sexual adverse effects (95% CI: 1.74–2.05) and was associated with an increased risk of physical adverse effects (RR: 1.31, 95% CI: 0.80–2.15), albeit without statistical significance [Supplementary Figure 2 [Additional file 2]] and [Supplementary Figure 3 [Additional file 3]]. Only 1 study reported the exact number of neuropsychiatric adverse effects.[31] Thus, we did not calculate the RR.

Different 5ARI subgroups

5 mg day−1 finasteride

In the subgroup analysis of 11 studies, 5 mg day−1 finasteride had a 1.85-fold risk of PFS-like adverse effects (95% CI: 1.49–2.29) compared with placebo.[8],[9],[11],[13],[15],[16],[30],[31],[32],[33],[34] Heterogeneity among the included studies was moderate (I2 = 53%; [Figure 2]. The risk of publication bias was low based on Egger's test results (P = 0.518). To explore the sources of heterogeneity, sensitivity analysis was performed by excluding studies sequentially. The results showed that after omitting the study by Marberger,[11] the I2 value decreased from 53% to 20%, and the RR increased to 2.01 (95% CI: 1.67–2.42). These findings suggested the main source of the heterogeneity. Regarding specific types of adverse effects, there was a 1.93-fold risk of sexual adverse effects (95% CI: 1.70–2.18), and the incidence of physical adverse effects (RR: 1.06, 95% CI: 0.62–1.82) also tended to be greater than that for placebo, albeit without statistical significance [Supplementary Figure 2] and [Supplementary Figure 3].

1 mg day−1 finasteride

In the subgroup analysis of 11 studies, 1 mg day−1 finasteride had a 2.08-fold risk of PFS-like adverse effects (95% CI: 1.54–2.82) compared with placebo.[18],[19],[20],[21],[22],[23],[30],[31],[32],[33],[35] Heterogeneity among the included studies was minimal (I2 = 0; [Figure 2]). The risk of publication bias was low based on the Egger's test results (P = 0.568). Regarding specific types of adverse effects, a 1.85-fold risk of sexual adverse effects (95% CI: 1.50–2.28) was observed. However, the incidence of physical adverse effects (RR: 0.97, 95% CI: 0.25–3.73) tended to be lower than that for placebo, albeit without statistical significance [Supplementary Figure 2] and [Supplementary Figure 3].

0.5 mg day−1 dutasteride

In the subgroup analysis of 8 studies, 0.5 mg day−1 dutasteride was significantly associated with an increased risk of PFS-like adverse effects (RR: 2.01, 95% CI: 1.71–2.37; [Figure 2].[24],[25],[26],[27],[28],[29],[34],[35] Heterogeneity among the included studies was minimal (I2 = 0). The risk of publication bias was low based on the Egger's test results (P = 0.506). Regarding specific types of adverse effects, 0.5 mg day−1 dutasteride tended to increase the sexual adverse effects (RR: 1.85, 95% CI: 1.50–2.28). The incidence of physical adverse effects (RR: 3.10, 95% CI: 1.80–5.35) also tended to be significantly higher than that for placebo (P < 0.001), as shown in [Supplementary Figure 2] and [Supplementary Figure 3].

Different disease subgroups

BPH group

In the subgroup analysis of 16 studies from 14 articles, patients treated with 5ARIs had a 2.05-fold risk of PFS-like adverse effects (95% CI: 1.71–2.46) compared with placebo.[8],[9],[10],[11],[12],[13],[14],[15],[16],[25],[26],[28],[31],[33] Heterogeneity among the included studies was moderate (I2 = 58%; [Figure 3]). The risk of publication bias was significant based on Egger's test results (P = 0.034). To explore the sources of heterogeneity, sensitivity analysis was performed by excluding studies sequentially. The results showed that after omitting the study by Marberger,11 the I2 value decreased from 58% to 20%, and the RR increased to 2.12 (95% CI: 1.85–2.43). These findings suggested the main source of the heterogeneity. Regarding specific types of adverse effects, a 2.02-fold risk of sexual adverse effects (95% CI: 1.80–2.26) was observed, and the incidence of physical adverse effects (RR: 1.26, 95% CI: 0.75–2.13) also tended to be greater than that for placebo, albeit without statistical significance [Supplementary Figure 4 [Additional file 4]] and [Supplementary Figure 5 [Additional file 5]].

AGA group

In the subgroup analysis of 17 studies from 14 articles, patients treated with 5ARIs had a 1.49-fold risk of PFS-like adverse effects (95% CI: 1.13–1.97) compared with placebo.[17],[18],[19],[20],[21],[22],[23],[24],[27],[29],[30],[32],[34],[35] Heterogeneity among the included studies was minimal (I2 = 0; [Figure 3]). The risk of publication bias was low based on the Egger's test results (P = 0.210). Regarding specific types of adverse effects, a 1.50-fold risk of sexual adverse effects (95% CI: 1.17–1.91) was observed. The incidence of physical adverse effects (RR: 2.99, 95% CI: 0.31–28.63) tended to be greater than that for placebo, albeit without statistical significance [Supplementary Figure 4] and [Supplementary Figure 5].


  Discussion Top


In this meta-analysis, available data regarding the neuropsychiatric adverse effects were limited. The low prevalence and incidence of neuropsychiatric adverse effects are inconsistent with the literature data. In a cohort study, 19 of 23 patients developed a mood disturbance (moderate to severe depression) during treatment; depression significantly impaired social relations and increased anxiety.[33] Several other studies also reported that neuropsychiatric adverse effects were significantly more prevalent in finasteride users compared with nonusers.[36],[37] Potential biases, including sample size, targeted population, cultural and psychological differences between genders, and lack of rigorous prospective investigations, may account for this difference. Additionally, compared with the other two adverse effects, the neuropsychiatric adverse effects may be more complicated and hidden, and the investigators typically conducting such RCTs may not necessarily be well trained to spot mental symptoms. Thus, further studies are needed to confirm the risk of neuropsychiatric adverse effects with the use of 5ARIs.

Regarding sexual adverse effects, surprisingly, we found a higher RR in patients treated with 1 mg day−1 finasteride compared with patients treated with 5 mg day−1 finasteride, albeit without statistical significance. This finding may be partly due to the nondose-dependent effect of finasteride on dihydrotestosterone (DHT) pharmacokinetics.[38] All daily finasteride doses between 0.4 mg and 100 mg lead to steady-state DHT plasma levels between 0.1 ng ml−1 and 0.15 ng ml−1.[38] Additionally, the discontinuation of finasteride treatment results in a normalization of DHT levels within 2 weeks, irrespective of the finasteride dose. In this regard, more underlying mechanisms are worth of further exploration.

In our study, patients treated with 5ARIs in the BPH subgroup were associated with a 2.02-fold risk of sexual adverse effects. However, the risk of sexual adverse effects was only 1.5-fold for men with AGA. This finding is consistent with previously reported results.[39] BPH is a common medical condition in men over 50 years old, and sexual dysfunction in men increases with age. The different risks of sexual dysfunction between these two groups may be partly due to advancing age.

Many systematic reviews and meta-analyses concerning the adverse effects of 5ARIs have been conducted and are reported in the literature.[39],[40],[41] Lee et al.[41] investigated the risk of adverse sexual effects caused by 5ARIs in male patients with AGA. The use of 5ARIs carried a 1.57-fold risk of sexual dysfunction (95% CI: 1.19–2.08). In the subgroup analysis, the RR was 1.66 (95% CI: 1.20–2.30) for 1 mg day−1 finasteride and 1.37 (95% CI: 0.81–2.32) for 0.5 mg day−1 dutasteride, respectively.[41] In our study, there was a 1.89-fold risk of sexual adverse effects (95% CI: 1.74–2.05) in patients treated with 5ARIs. In the subgroup analysis, the RR was 2.01 (95% CI: 1.53–2.63) for 1 mg day−1 finasteride and 1.85 (95% CI: 1.50–2.28) for 0.5 mg day−1 dutasteride, respectively. This difference may be attributed to different inclusion criteria between the two studies. In addition to patients with AGA, we also included BPH patients. Patients with BPH more easily develop sexual dysfunction.

In the case of PFS, there are strong selection biases and the nocebo factors. A significant placebo/nocebo effect has been documented among patients informed about possible side effects, which may explain the high prevalence of reported sexual dysfunction and psychiatric side effects in subjects participating in internet groups and blogs.[42] Mondaini et al.[43] also reported that the nocebo effect was relatively significant when patients were informed about possible sexual dysfunction caused by the therapy. Sexual side effects increased from 29.3% to 43.6% when information was given at the beginning of the treatment. Thus, this finding may inspire us to balance the information bias in the design of future studies and inform the participants about the potential adverse effects in both groups before the start of the experiment.

Several potential solutions have been proposed to protect patients from the immediate and persistent adverse effects of finasteride.[44] For BPH patients, administration of finasteride concomitantly with a phosphodiesterase type 5 inhibitor may provide an improvement in sexual function with no reduction of effectiveness in prostate treatment. In addition, tamsulosin and surgery may be an alternative treatment options for BPH patients. For AGA patients, the use of topical finasteride (0.25% solution) seems to be less harmful than an oral formulation with a similar effectiveness. Other auxiliary treatments, such as topical minoxidil, platelet-rich plasma, low-level laser therapy, and surgery, may also represent good treatment choices.

To date, there are no predictive factors for the risk of developing PFS. Nevertheless, it would seem appropriate to evaluate the history of preexisting mental health issues and the possibility of potential sexual dysfunction.[45] Additionally, a stricter selection of patients is needed before the initiation of 5ARI treatment, such as patients with repeated inquiries on safety issues of the drug or holding on to their belief system tenaciously despite any rational argumentation against it.[45] Administration of 5ARIs may more easily put these patients at an increased risk of developing sexual or emotional disorders.

The greatest limitation of our study is that we focused on sexual, physical, and overall adverse effects rather than real PFS. The persistent effect is the hallmark of PFS, and this phenomenon is particularly prominent in the subset of young AGA patients. Both AGA (<40 years old) and BPH (> 40 years old) patients were included in the present study. Data obtained in different situations might cause some confusion and bias. Although we employed subgroup analysis to reduce this deviation, it is not sufficient. In the future, we may solve this problem by improving the acquisition, analysis, and interpretation of data on PFS. Additionally, to examine the persistence of symptoms, placebo-controlled RCTs using validated questionnaires and long-term follow-up after the discontinuation of 5ARIs are needed.


  Conclusion Top


Our study demonstrated that 5ARIs were associated with a significantly increased risk of sexual, physical, and overall adverse effects than placebo for men with AGA or BPH during treatment. Clinicians should assess the risk of preexisting mental health issues and the possibility of potential sexual dysfunction before 5ARI treatment. Alternative treatments may be used to protect patients from the immediate and persistent adverse effects of 5ARIs.


  Author Contributions Top


JJZ and LW contribute to conception and design. JJZ and XS contribute to acquisition of data. JJZ and TW contribute to analysis of data. JJZ contributes to drafting the article. MDZ, JT, GMY, ZL, LYH, and LQ contribute to revising it critically for important intellectual content. All authors read and approved the final manuscript.


  Competing Interests Top


All authors declared no competing interests.


  Acknowledgments Top


The authors would like to thank the National Natural Science Foundation of China for their support in generating this manuscript (No. 81770758 to LW).

Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.



 
  References Top

1.
Gray SL, Semla TP. Post-finasteride syndrome. BMJ 2019; 366: l5047.  Back to cited text no. 1
    
2.
Mervis JS, Borda LJ, Miteva M. 'Post-finasteride syndrome': what to tell our female patients? Br J Dermatol 2018; 179: 785–6.  Back to cited text no. 2
    
3.
Pereira A, Coelho TO. Post-finasteride syndrome. An Bras Dermatol 2020; 95: 271–7.  Back to cited text no. 3
    
4.
Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertil Steril 2020; 113: 21–50.  Back to cited text no. 4
    
5.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1.  Back to cited text no. 5
    
6.
Cumpston M, Li T, Page MJ, Chandler J, Welch VA, et al. Updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions. Cochrane Database Syst Rev 2019; 10: Ed000142.  Back to cited text no. 6
    
7.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–34.  Back to cited text no. 7
    
8.
Kirby RS, Vale J, Bryan J, Holmes K, Webb JA. Long-term urodynamic effects of finasteride in benign prostatic hyperplasia: a pilot study. Eur Urol 1993; 24: 20–6.  Back to cited text no. 8
    
9.
Byrnes CA, Morton AS, Liss CL, Lippert MC, Gillenwater JY. Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. Clinl Ther 1995; 17: 956–69.  Back to cited text no. 9
    
10.
Lepor H, Williford WO, Barry MJ, Brawer MK, Dixon CM, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. New Engl J Med 1996; 335: 533–9.  Back to cited text no. 10
    
11.
Marberger MJ. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group. Urology 1998; 51: 677–86.  Back to cited text no. 11
    
12.
Nickel JC, Fradet Y, Boake RC, Pommerville PJ, Perreault JP, et al. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). Proscar Safety Plus Efficacy Canadian Two year Study. CMAJ 1996; 155: 1251–9.  Back to cited text no. 12
    
13.
Tenover JL, Pagano GA, Morton AS, Liss CL, Byrnes CA. Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group. Clinl Ther 1997; 19: 243–58.  Back to cited text no. 13
    
14.
Kaplan SA, Lee JY, Meehan AG, Kusek JW. Time course of incident adverse experiences associated with doxazosin, finasteride and combination therapy in men with benign prostatic hyperplasia: the MTOPS trial. J Urol 2016; 195: 1825–9.  Back to cited text no. 14
    
15.
McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. New Engl J Med 1998; 338: 557–63.  Back to cited text no. 15
    
16.
Yu HJ, Chiu TY, Lai MK. Therapeutic effects of finasteride in benign prostatic hyperplasia: a randomized double-blind controlled trial. J Formos Med Assoc 1995; 94: 37–41.  Back to cited text no. 16
    
17.
Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 1998; 39: 578–89.  Back to cited text no. 17
    
18.
Leyden J, Dunlap F, Miller B, Winters P, Lebwohl M, et al. Finasteride in the treatment of men with frontal male pattern hair loss. J Am Acad Dermatol 1999; 40: 930–7.  Back to cited text no. 18
    
19.
Van Neste D, Fuh V, Sanchez-Pedreno P, Lopez-Bran E, Wolff H, et al. Finasteride increases anagen hair in men with androgenetic alopecia. Br J Dermatol 2000; 143: 804–10.  Back to cited text no. 19
    
20.
Leavitt M, Perez-Meza D, Rao NA, Barusco M, Kaufman KD, et al. Effects of finasteride (1 mg) on hair transplant. Dermatol Surg 2005; 31: 1268–76.  Back to cited text no. 20
    
21.
Price VH, Menefee E, Sanchez M, Ruane P, Kaufman KD. Changes in hair weight and hair count in men with androgenetic alopecia after treatment with finasteride, 1 mg, daily. J Am Acad Dermatol 2002; 46: 517–23.  Back to cited text no. 21
    
22.
Kawashima M, Hayashi N, Igarashi A, Kitahara H, Maeguchi M, et al. Finasteride in the treatment of Japanese men with male pattern hair loss. Eur J Dermatol 2004; 14: 247–54.  Back to cited text no. 22
    
23.
Whiting D, Olsen E, Savin R, Halper L, Rodgers A, et al. Efficacy and tolerability of finasteride 1 mg in men aged 41 to 60 years with male pattern hair loss. Eur J Dermatol 2003; 13: 150–60.  Back to cited text no. 23
    
24.
Eun HC, Kwon OS, Yeon JH, Shin HS, Kim BY, et al. Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study. Clin Drug Invest 2010; 63: 252–8.  Back to cited text no. 24
    
25.
Na Y, Ye Z, Zhang S. Efficacy and safety of dutasteride in Chinese adults with symptomatic benign prostatic hyperplasia: a randomized, double-blind, parallel-group, placebo-controlled study with an open-label extension. Clin Drug Invest 2012; 32: 29–39.  Back to cited text no. 25
    
26.
Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434–41.  Back to cited text no. 26
    
27.
Stough D. Dutasteride improves male pattern hair loss in a randomized study in identical twins. J Cosmet Dermatol 2007; 6: 9–13.  Back to cited text no. 27
    
28.
Tsukamoto T, Endo Y, Narita M. Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. Int J Urol 2009; 16: 745–50.  Back to cited text no. 28
    
29.
Tsai TF, Choi GS, Kim BJ, Kim MB, Ng CF, et al. Prospective randomized study of sexual function in men taking dutasteride for the treatment of androgenetic alopecia. J Dermatol 2018; 45: 799–804.  Back to cited text no. 29
    
30.
Drake L, Hordinsky M, Fiedler V, Swinehart J, Unger WP, et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol 1999; 41: 550–4.  Back to cited text no. 30
    
31.
Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, et al. The effect of finasteride in men with benign prostatic hyperplasia. New Engl J Med 1992; 327: 1185–91.  Back to cited text no. 31
    
32.
Roberts JL, Fiedler V, Imperato-McGinley J, Whiting D, Olsen E, et al. Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss. J Am Acad Dermatol 1999; 41: 555–63.  Back to cited text no. 32
    
33.
The Finasteride Study Group. Finasteride (MK-906) in the treatment of benign prostatic hyperplasia. Prostate 1993; 22: 291–9.  Back to cited text no. 33
    
34.
Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, et al. The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol 2006; 55: 1014–23.  Back to cited text no. 34
    
35.
Gubelin Harcha W, Barboza Martínez J, Tsai TF, Katsuoka K, Kawashima M, et al. A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia. J Am Acad Dermatol 2014; 70: 489–98.  Back to cited text no. 35
    
36.
Irwig MS. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry 2012; 73: 1220–3.  Back to cited text no. 36
    
37.
Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A. Finasteride induced depression: a prospective study. BMC Clin Pharmacol 2006; 6: 7.  Back to cited text no. 37
    
38.
Gormley GJ, Stoner E, Rittmaster RS, Gregg H, Thompson DL, et al. Effects of finasteride (MK-906), a 5 alpha-reductase inhibitor, on circulating androgens in male volunteers. J Clin Endocrinol Metab 1990; 70: 1136–41.  Back to cited text no. 38
    
39.
Liu L, Zhao S, Li F, Li E, Kang R, et al. Effect of 5α-reductase inhibitors on sexual function: a meta-analysis and systematic review of randomized controlled trials. J Sex Med 2016; 13: 1297–310.  Back to cited text no. 39
    
40.
Coskuner E, Ozkan B, Culha M. Sexual problems of men with androgenic alopecia treated with 5-alpha reductase inhibitors. Sex Med Rev 2019; 7: 277–82.  Back to cited text no. 40
    
41.
Lee S, Lee Y, Choe S, Lee W. Adverse sexual effects of treatment with finasteride or dutasteride for male androgenetic alopecia: a systematic review and meta-analysis. Acta Derm Venereol 2019; 99: 12–7.  Back to cited text no. 41
    
42.
Fertig R, Shapiro J, Bergfeld W, Tosti A. Investigation of the plausibility of 5-alpha-reductase inhibitor syndrome. Skin Appendage Disord 2017; 2: 120–9.  Back to cited text no. 42
    
43.
Mondaini N, Gontero P, Giubilei G, Lombardi G, Cai T, et al. Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon? J Sex Med 2007; 4: 1708–12.  Back to cited text no. 43
    
44.
Casabé A, Roehrborn C, Da Pozzo L, Zepeda S, Henderson R, et al. Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. J Urol 2014; 191: 727–33.  Back to cited text no. 44
    
45.
Trueb RM, Regnier A, Dutra Rezende H, Gavazzoni Dias MF. Post-finasteride syndrome: an induced delusional disorder with the potential of a mass psychogenic illness? Skin Appendage Disord 2019; 5: 320–6.  Back to cited text no. 45
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

 
Top
 
 
  Search
 
 Search Pubmed for
 
    -  Zhang JJ
    -  Shi X
    -  Wu T
    -  Zhang MD
    -  Tang J
    -  Yin GM
    -  Long Z
    -  He LY
    -  Qi L
    -  Wang L
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
Author Contributions
Competing Interests
Acknowledgments
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed512    
    PDF Downloaded31    

Recommend this journal