Androgenetic alopecia (AGA) is a benign condition with variable psychosocial impact, with some individuals adapting well while others needing therapeutic support. Although 5α-reductase inhibitors ...like finasteride and dutasteride have proven effective in ameliorating AGA, their use/selection is currently a subject of debate.
Treatment of AGA with 5α-reductase inhibitors lead to variable adverse effects and relatively unstable results (therapeutic efficacy ending with treatment cessation), so the choice of optimal therapy is not straightforward. This paper presents a general perspective regarding AGA based on studies listed in PubMed, to better understand/appreciate the opportunity for long term use of medication for a biological condition having non-life threatening implications. Studies focussed on adverse effects suggest that finasteride should be used with caution in AGA, due to considerable and persistent side effects induced in some men. In contrast, efficacy data indicate that dutasteride (a stronger inhibitor) presents superior therapeutic results compared to finasteride.
This paper argues that finasteride should be preferred to dutasteride in the treatment of AGA. Thus, finasteride preserves important physiological roles of dihydrotestosterone (unrelated to AGA) and, in addition, its adverse effects seem to be (at least in part) predictable.
5α‐reductase inhibitors (5α‐RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. ...Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill‐defined.
The goal of this review is to discuss 5α‐RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects.
We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride.
Data reported in the literature were reviewed and discussed.
Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship.
We suggest discussion with patients on the potential sexual side effects of 5α‐RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia. Traish AM, Hassani J, Guay AT, Zitzmann M, and Hansen M. Adverse side effects of 5α‐reductase inhibitors therapy: Persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med 2011;8:872–844.
Summary
Concern regarding adverse effects of finasteride is increasing. We aimed to determine the type and frequency of symptoms in men having long‐term sexual and non‐sexual side effects after ...finasteride treatment (a condition recently called post‐finasteride syndrome, PFS) against androgenetic alopecia (AGA). Subjects were recruited at the Urology Unit of the Trieste University‐Hospital, and from a dedicated website. Out of 79 participants, 34% were white Italians, mean age was 33.4 ± 7.60 years, mean duration of finasteride use was 27.3 ± 33.21 months; mean time from finasteride discontinuation was 44.1 ± 34.20 months. Symptoms were investigated by an ad hoc 100 questions' questionnaire, and by validated Arizona Sexual Experience Scale (ASEX) and Aging Male Symptom Scale (AMS) questionnaires. By ASEX questionnaire, 40.5% of participants declared getting and keeping erection very difficult, and 3.8% never achieved; reaching orgasm was declared very difficult by 16.5%, and never achieved by 2.5%. By the ad hoc questionnaire, the most frequent sexual symptoms referred were loss of penis sensitivity (87.3%), decreased ejaculatory force (82.3%), and low penile temperature (78.5%). The most frequent non‐sexual symptoms were reduced feeling of life pleasure or emotions (anhedonia) (75.9%); lack of mental concentration (72.2%), and loss of muscle tone/mass (51.9%). We contributed to inform about symptoms of PFS patients; unexpectedly loss of penis sensitivity was more frequent than severe erectile dysfunction and loss of muscle tone/mass was affecting half of the subjects. Further studies are necessary to investigate the pathophysiological and biochemical pathways leading to the post‐finasteride syndrome.
Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent ...depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2–2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases.
•The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results.•We identified 93,197 men who initiated 5ARI therapy and ...matched them 1:1 to men who did not start a 5ARI.•After ≥2 years of 5ARI use the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79–0.94).
The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality.
We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non‐5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We measured 5 additional baseline variables which may have impacted the risk of future BC diagnosis: prior cystoscopy, urine cytology, urinalysis, gross hematuria episodes, and transurethral resection of a bladder lesion. Only the first period of continuous usage of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy and ended at the last date of 5ARI exposure + 1 year.
We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride) between 2003 and 2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (interquartile range 1.00, 4.27). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (hazard ratio HR 1.05, 95% confidence interval CI 0.82–1.32) during the period of 0 to <2 years of 5ARI use; however, after ≥2 years of 5ARI use, the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79–0.94). In a similarly adjusted model, BC mortality was lower among 5ARI users, but no longer statistically significant (HR 0.82, 95% CI 0.65, 1.02). When stratified by type of 5ARI, finasteride significantly reduced the risk of BC diagnosis after ≥2 years of continuous use (HR 0.86, 95% CI 0.76, 0.96); however, dutasteride did not (HR 0.92, 95% CI 0.83, 1.03).
In a large cohort of men, the use of a 5ARI was associated with a significantly decreased the risk of BC diagnosis after more than 2 years of continuous therapy.
The objective of this study was to evaluate the impact of finasteride on the progression of prostate intraepithelial neoplasia and levels of prostate-specific antigen (PSA) in patients. A total of ...120 patients with high-grade prostatic intraepithelial neoplasia were included in this study from January 2013 to January 2018. All patients underwent prostate biopsies. Among them, 60 patients were assigned to the observation group and received a daily dosage of 5 mg finasteride for 60 months, while the remaining 60 patients were assigned to the control group and did not receive finasteride. PSA levels were measured every six months, and imaging scans were conducted throughout the five-year study period. Additional biopsies were performed if PSA levels exceeded 10 ng/mL or imaging suggested the presence of prostate cancer. Statistical analysis was applied to the collected data. In total, 25 cases of prostate cancer were identified in this study. Of these cases, 7 patients belonged to the observation group, whereas the remaining 18 patients were from the control group. The observation group exhibited significantly lower levels of total serum PSA (p < 0.001) and Gleason scores (p < 0.001) compared to the control group. Our study, which involved 120 participants, demonstrated that finasteride effectively reduces serum PSA levels and mitigates the severity of prostate cancer. These findings suggest that finasteride holds potential as a treatment option for patients with -high-grade prostatic intraepithelial neoplasia.
Background To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. Objective We sought to ...describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. Methods This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. Results In all, 355 patients (343 women 49 premenopausal and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). Limitations The retrospective design is a limitation. Conclusions Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment.
A negative impact of finasteride on fertility has been reported, in which over production of reactive oxygen species and apoptosis were implicated. Hesperidin, a plant-derived bioflavonoid with ...antioxidant and anti-apoptotic effects, may mitigate these adverse effects. In order to investigate the possible protective role of hesperidin against finasteride-induced seminiferous tubules toxicity in adult male Wistar rats, 60 rats were randomized into five groups (I-V) receiving distilled water, 0.5% sodium carboxymethylcellulose solution, hesperidin, finasteride, and combined hesperidin and finasteride respectively. Testicular weight, sperm count and motility were determined. Testicular tissue homogenates were prepared to measure the level of malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH) and the gene expression of caspase-3 and B-cell lymphoma 2 (Bcl2). Testes were processed for light and electron microscopic evaluation. Johnsen score was calculated. Administration of finasteride resulted in significantly decreased testicular weights, sperm count and motility, Johnsen score, tissue levels of TAC and GSH together with significant increase in tissue MDA. Gene expression revealed significantly increased caspase-3 and decreased Bcl2. Furthermore, finasteride disrupted the seminiferous tubules, causing degenerative changes affecting Sertoli cells and spermatogenic cells. Co-administration of hesperidin with finasteride resulted in improvement in testicular weights, TAC, GSH, Bcl2, Johnsen score, sperm count and motility as well as preservation of the structure of the seminiferous tubules. To conclude, hesperidin was found to have a protective potential on finasteride-induced oxidative stress, apoptosis and testicular structural damage.
•Finasteride exhibited a negative influence on testicular weight and semen analysis.•Finasteride induced ultrastructural seminiferous tubules changes.•Finasteride increased apoptotic and oxidative stress markers.•Hesperidin ameliorated finasteride-induced deleterious effects.
Background
Analytical measures for the pharmacodynamics understanding of drug induced scalp hair responses are lacking.
Materials and methods
The present study measured in detail dynamics of hair ...productivity on two scalp test sites showing male pattern hair loss. The natural regression decay rate established after 2 years without treatment was followed by treatment with daily oral intake of 1 mg finasteride.
Results
While terminal hair (diameter ≥40 μm) were maintained “on‐drug,” within 30 months “off‐drug” MPHL significantly worsened as 94% terminal hair miniaturised and became unproductive. Accordingly, the viable drug responding follicles were qualified as “finasteride dependent” unravelling a hereto unreported “rebound effect” after interruption of the drug intake. Interestingly, the transformation of terminal hair into miniaturised hair occurred only after 12 months without treatment, that is the time necessary to complete a clinically significant full hair cycle initiated during the drug intake. This explains why exogen hair release and miniaturisation occurred only between 12 and 30 months “off‐drug” while resistant hair grew also slower.
Conclusion
Drug dependency and rebound phenomenon are new findings along with evidence against the hypothesis claiming that terminal hair growth arises from initial vellus hair follicles in drug‐treated MPHL.
Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare ...Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to include a statement that “persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.”
We sought to characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL.
We conducted standardized interviews with 71 otherwise healthy men aged 21–46 years who reported the new onset of sexual side effects associated with the temporal use of finasteride, in which the symptoms persisted for at least 3 months despite the discontinuation of finasteride.
The types and duration of sexual dysfunction and the changes in perceived sexual frequency and sexual dysfunction score between pre- and post-finasteride use.
Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale (P<0.0001 for both). The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date. Study limitations include a post hoc approach, selection bias, recall bias for before finasteride data, and no serum hormone levels.
Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride. Irwig MS and Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss.
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