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Background Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration. Objective To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin. Design Retrospective, population-based cohort study using new-user and active-comparator design. Setting General population. Subjects Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018. Methods Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs. Results We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98–1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02–1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87–1.12], in the subgroup analyses. Conclusions We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence. [ABSTRACT FROM AUTHOR]

We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator. One year later, bilateral mammoplasty was performed to remove the remaining breast tissue. Finasteride, a 5-alpha-reductase inhibitor, is widely used for the treatment of androgenetic alopecia. Gynecomastia is an expected side effect of this therapy given its mechanism of action. However, only 8 cases of gynecomastia have been reported with low-dose (1 mg daily) finasteride treatment since its approval for androgenetic alopecia in 1997. This raises the concern that gynecomastia resulting from low-dose finasteride is significantly underreported, causing inadequately informed patients. Further, because of the risk of gynecomastia, it is important for prescribing physicians to counsel patients regarding this complication and to consider early intervention when finasteride-induced gynecomastia first arises to prevent fibrosis and thus irreversible gynecomastia. [ABSTRACT FROM AUTHOR]

Introduction: It has been suggested that 5AR (5-alpha reductase) inhibitors may have negative effects on psychosexual activity, but there is still debate. Objective: We aimed to observe the effect of 5AR type 2 inhibition on brain tissue by using finasteride. Methods: 14 weeks old, eight male rats were assigned to each group (group 1 as the control group, group 2 as the finasteride group, and group 3 as the finasteride withdrawal group). Each rat was isolated and acclimatized in a single cage, then mated for 2 days. Rats in group 2 and 3 were administrated with finasteride for 4 weeks, then rats in group 2 were sacrificed whereas rats in group 3 were sacrificed 4 weeks thereafter. Before sacrifice, they were exposed to female bedding at least for 2 days. RT-PCR, western blot, and immunohistochemistry were performed for brain tissue evaluation where the target genes/proteins were 5AR (type 2) and c-Fos. Results: Dihydrotestosterone (ng/dl) and dihydrotestosterone to testosterone ratio (%) plunged after 1 month administration of finasteride (group 2), and they were ameliorated after discontinuation of the drug (group 3) (Figure 1). These results were parallel to those from the western blot and immunohistochemistry (Figure 2 and 3). On the contraty, RT-PCR showed elevation of each gene (5AR and c-Fos) expression (Figure 2). Conclusions: Finasteride exerted an influence on brain tissue including hippocampus and ventromedial preoptic area via 5AR-2 inhibition, resulting in decrease of c-Fos protein activation. However, the negative impact of finasteride on rat brain in regard with c-Fos activation may fall away in a month cessation of the drug. Disclosure: No. [ABSTRACT FROM AUTHOR]

Summary: Background: Given its widely accepted efficacy, androgen blockade therapy for hidradenitis suppurativa (HS) has become a standard of care. Although much less frequently used than spironolactone, a small number of HS studies have reported finasteride as an alternative treatment for women. In this study, we describe the response to and perception of finasteride therapy in a diverse cohort of women with HS. Aim: To describe finasteride therapy in a diverse cohort of female patients with HS. Methods: We conducted an institutional review board‐approved retrospective chart review and telephone survey of 20 female patients aged ≥ 18 years with a diagnosis of HS. Finasteride was prescribed by a single provider at a specialized HS centre. Results: The mean age of the patients was 34.3 ± 13.5 years. Finasteride was initiated predominantly because of one or more contraindications or poor responsiveness to spironolactone. Most patients interviewed (90%; n = 18) were willing to take finasteride again or continue with therapy if indicated. Of the 20 patients, 10 (50%) reported overall satisfaction with finasteride, while 7 (35%) were neutral and 3 (15%) were dissatisfied. No patient reported worsening disease activity while on finasteride and only one (5%) reported decreased quality of life. When asked about adverse effects of finasteride, 80% (n = 16) reported none, while 20% (n = 4) experienced ≥ 1 of the following: headache, nausea, menstrual irregularities, breast tenderness or reduced libido/sexual function. Conclusions: Our study suggests that androgen blockade therapy with finasteride is a safe and effective alternative for female patients with HS who have contraindication(s) or intolerance to spironolactone. [ABSTRACT FROM AUTHOR]

An organic etiology underpinning post-finasteride syndrome, a constellation of persistent sexual, neuropsychiatric, and somatic symptoms reported by men exposed to 5-alpha-reductase inhibitors (5ARIs), is debated. Persistent changes in neurosteroid levels or androgen receptor expression have been implicated. To determine whether differences in gene expression, especially in relevant biologic pathways, exist between patients reporting post-finasteride syndrome symptoms and healthy controls. This was a single center, prospective case-control study taking place between March 2013 and September 2018. Men 18 years and older being evaluated for sexual dysfunction (study) or circumcision (control) were eligible for inclusion. Twenty-six men with a history of 5ARI use reporting symptoms consistent with post-finasteride syndrome were included in the patient group. Twenty-six men consented to inclusion in the control group. The primary outcome measure is gene expression data for genes affecting neurosteroid levels and androgen receptor activity from penile skin cells. Gene expression of cells from penile skin samples from twenty-six men of median age 38 years (IQR, 33-42) in the study group was compared with that from twenty-six men of median age 41 years (IQR, 35-62) in the control group (P =.13), with 1,446 genes significantly over-expressed and 2,318 genes significantly under-expressed in study patients. Androgen receptor expression was significantly higher in study patients compared to controls (9.961 vs 9.494, adjusted P value =.01). Serum levels of androgen receptor activity markers 5α-androstanediol (0.950 ng/mL [0.749-1.587] vs 0.949 [0.817-1.337], P =.34) or 3α-androstanedione (3.1 ng/mL [1.925-5.475] vs 6.7 [3.375-11.4], P =.31) revealed no significant differences. No significant differences were found between the number of trinucleotide repeats (21.5 [20-23.75], 22 [19-25], P =.94). In this study we present evidence of gene expression correlating with observed biologic differences in patients with post-finasteride syndrome; providers who prescribe 5ARIs should be aware and advise their patients accordingly. Strengths of this study include the evaluation of multiple proposed etiologies for post-finasteride syndrome. The study is also strengthened by the fact that not all data matched the initial hypotheses, qualifying the argument for the existence of PFS. Limitations include potential selection bias arising from more severe phenotypes seeking care; lack of gene expression data prior to 5ARI exposure; lack of non-penile tissue samples supposedly involved; and a lack of mechanistic data to imply causality. This study is the first to consider and demonstrate gene expression differences in patients with PFS as a potential etiology of sexual dysfunction. Howell S, Song W, Pastuszak A, et al. Differential Gene Expression in Post-Finasteride Syndrome Patients. J Sex Med 2021;18:1479–1490. [ABSTRACT FROM AUTHOR]

Context: Glucocorticoids (GCs) are commonly prescribed, but their use is associated with adverse metabolic effects. 5α-reductase inhibitors (5α-RI) are also frequently prescribed, mainly to inhibit testosterone conversion to dihydrotestosterone. However, they also prevent the inactivation of GCs.Objective: We hypothesized that 5α-RI may worsen the adverse effects of GCs.Design: Prospective, randomized study.Patients: A total of 19 healthy male volunteers (age 45 ± 2 years; body mass index 27.1 ± 0.7kg/m2).Interventions: Participants underwent metabolic assessments; 2-step hyperinsulinemic, euglycemic clamp incorporating stable isotopes, adipose tissue microdialysis, and biopsy. Participants were then randomized to either prednisolone (10 mg daily) or prednisolone (10 mg daily) plus a 5α-RI (finasteride 5 mg daily or dutasteride 0.5 mg daily) for 7 days; metabolic assessments were then repeated.Main Outcome Measures: Ra glucose, glucose utilization (M-value), glucose oxidation, and nonesterified fatty acids (NEFA) levels.Results: Co-administration of prednisolone with a 5α-RI increased circulating prednisolone levels (482 ± 96 vs 761 ± 57 nmol/L, P = 0.029). Prednisolone alone did not alter Ra glucose (2.55 ± 0.34 vs 2.62 ± 0.19 mg/kg/minute, P = 0.86), M-value (3.2 ± 0.5 vs 2.7 ± 0.7 mg/kg/minute, P = 0.37), or glucose oxidation (0.042 ± 0.007 vs 0.040 ± 0.004 mmol/hr/kg/minute, P = 0.79). However, co-administration with a 5α-RI increased Ra glucose (2.67 ± 0.16 vs 3.05 ± 0.18 mg/kg/minute, P < 0.05) and decreased M-value (4.0 ± 0.5 vs 2.6 ± 0.4 mg/kg/minute, P < 0.05), and oxidation (0.043 ± 0.003 vs 0.036 ± 0.002 mmol/hr/kg, P < 0.01). Similarly, prednisolone did not impair insulin-mediated suppression of circulating NEFA (43.1 ± 28.9 vs 36.8 ± 14.3 μmol/L, P = 0.81), unless co-administered with a 5α-RI (49.8 ± 8.6 vs 88.5 ± 13.5 μmol/L, P < 0.01).Conclusions: We have demonstrated that 5α-RIs exacerbate the adverse effects of prednisolone. This study has significant translational implications, including the need to consider GC dose adjustments, but also the necessity for increased vigilance for the development of adverse effects. [ABSTRACT FROM AUTHOR]

Abstract Background Men often experience deterioration of sexual function after the use of α-blockers and 5-α reductase inhibitors for the treatment of lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia. Thus, an alternative treatment with water vapor thermal therapy (Rezūm System, Boston Scientific, Marlborough, MA, USA) which is an efficacious minimally invasive surgical treatment that preserves sexual function was examined. Aim To compare sexual function over 3 years after continuous daily treatment with pharmaceutical agents in the Medical Therapy of Prostatic Symptoms (MTOPS) study vs a single thermal therapy procedure (Rezūm study) in subjects with matched criteria for LUTS severity and prostate size. Methods We used sexual function data from sexually active cohorts in the MTOPS study (1,209) randomized to doxazosin, finasteride, combination drugs and placebo, and sexually active men who received thermal therapy (86). MTOPS study participants completed the Brief Male Sexual Function Inventory; men in the Rezūm trial completed the International Index of Erectile Function and Male Sexual Health Questionnaire. Main Outcome Measure Estimated mean changes from baseline for sexual function variables were compared using a linear mixed repeated measures model with fixed effects for treatment and follow-up visits. Results With continued daily drug use, men experienced significant worsening of sexual desire, erectile and ejaculatory function with finasteride and combination drug therapy, and reduced desire and erectile function with doxazosin. Thermal therapy was not associated with significant negative changes in sexual function throughout 3 years after treatment. Clinical Implications Water vapor thermal therapy can result in greater LUTS improvements than either doxazosin or finasteride alone, whereas combination drug therapy may equal that of this Rezūm procedure, but all drug therapies did have a significant negative impact on sexual function in contrast to the preservation of libido, erectile, and ejaculatory function after thermal therapy. Strength & Limitations The report includes high-quality data from 2 large randomized controlled trials in subjects with similar baseline inclusion criteria for LUTS severity and prostate size. It is the first longitudinal assessment of sexual function domains restricted to sexually active men treated with drugs or a single minimally invasive surgical treatment with the Rezūm procedure. A limitation of the study is the use of 2 different, although validated sexual function inventories (Brief Male Sexual Function Inventory and International Index of Erectile Function). Conclusion A single water vapor thermal therapy procedure for targeted prostate tissue ablation for LUTS/ benign prostatic hyperplasia had no deleterious effect on 4 sexual function domains compared with appreciable worsening of sexual function after long-term single or combination drug use. McVary KT, Rogers T, Mahon J, et al. Is Sexual Function Better Preserved After Water Vapor Thermal Therapy or Medical Therapy for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia? J Sex Med 2018;15:1728–1738. [ABSTRACT FROM AUTHOR]

Background: Investigators have used administrative claims to better understand cancer outcomes when a research question cannot feasibly be examined within a study. The Prostate Cancer Prevention Trial (PCPT) showed that seven years of finasteride reduced prostate cancer (PC) risk by 25% in men age 55 years or older. However, it was unclear whether the observed reduction in PC for finasteride participants would be maintained after finasteride discontinuation.Methods: We examined PC diagnoses identified by PCPT study records and Medicare claims (finasteride = 9423, placebo = 9457). A Medicare-defined PC diagnosis algorithm was defined using diagnosis and procedure codes. Multivariable Cox regression was used to examine time to PC within prespecified follow-up windows (<6.5, 6.5-7.5, and >7.5 years) using time-dependent covariates interacting with intervention assignment to account for the PCPT protocol-specified end-of-study biopsy at seven years. All statistical tests were two-sided.Results: Median follow-up using the linked database was 16 years. Overall, finasteride arm participants had a 21.1% decrease in the hazard ratio of PC (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.74 to 0.84, P < .001). The beneficial effect of finasteride in reducing the hazard ratio of PC was most pronounced in the first 7.5 years (HR = 0.71, 95% CI = 0.66 to 0.77, P < .001), consistent with the original study findings; after 7.5 years, there was no increased risk of PC for finasteride arm participants (HR = 1.10, 95% CI = 0.96 to 1.26, P = .18).Conclusions: Finasteride provides a substantial reduction in PC through 16 years of follow-up. There was no strong evidence that the benefit of finasteride diminished after the end-of-study follow-up. Utilizing Medicare claims to augment PCPT follow-up illustrates how the novel use of secondary data sources can enhance the ability to detect long-term outcomes from prospective studies. [ABSTRACT FROM AUTHOR]

Stability studies of the pharmaceutically important compound finasteride were conducted in order to evaluate decomposition of the drug under forced degradation conditions. A simple stability-indicating liquid chromatography method was developed and validated for the evaluation of finasteride and degradation products formed in pharmaceutical preparations and the raw material. Isocratic LC separation was achieved on a C18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 2.8 with triethylamine (10% v/v) and acetonitrile (52:48 v/v), with a flow rate of 1.0 mLmin-1. The alkaline degradation kinetics of the drug were also evaluated and could be best described as second-order kinetics under the experimental conditions applied for the tablets and raw material. Based on in silico studies and molecular weight confirmation, a comprehensive degradation pathway for the drug and the identity of its major product could be suggested without complicated isolation or purification processes. Furthermore, a biological safety study was performed to evaluate the effect of the degraded sample in relation to the intact molecule. The results showed that the degraded sample affected the cell proliferation. Therefore, these studies show that special care must be taken during the manipulation, manufacture and storage of this pharmaceutical drug. [ABSTRACT FROM AUTHOR]

Substantial preclinical data suggest estrogen's carcinogenic role in prostate cancer development; however, epidemiological evidence based on circulating estrogen levels is largely null. Compared with circulating estrogen, the intraprostatic estrogen milieu may play a more important role in prostate carcinogenesis. Using a nested case-control design in the Prostate Cancer Prevention Trial (PCPT), we examined associations of genetic variants of genes that are involved in estrogen synthesis, metabolism and function with prostate cancer risk. A total of 25 potentially functional single nucleotide polymorphisms (SNPs) in 13 genes (PGR, ESR1, ESR2, CYP17A1, HSD17B1, CYP19A1, CYP1A1, CYP1B1, COMT, UGT1A6, UGT1A10, UGT2B7, UGT2B15) were examined in whites only. Controls (n = 1380) were frequency matched to cases on age, PCPT treatment arm, and family history (n = 1506). Logistic regression models adjusted for age and family history were used to estimate odds ratios (OR) and 95% confidence intervals (CI) separately in the placebo and finasteride arms. SNPs associated with prostate cancer risk differed by treatment arm. The associations appeared to be modified by circulating estrogen and androgen levels. CYP19A1 was the only gene harboring SNPs that were significantly associated with risk in both the placebo and finasteride arms. Haplotype analysis with all three CYP19A1 SNPs genotyped (rs700518, rs2445765, rs700519) showed that risk-allele haplotypes are associated with the increased prostate cancer risk in both arms when comparing with the non-risk allele haplotype. In conclusion, associations between SNPs in estrogen-related genes and prostate cancer risk are complex and may be modified by circulating hormone levels and finasteride treatment. [ABSTRACT FROM AUTHOR]

Background Androgenic treatment of female-to-male transgender patients may result in androgenetic alopecia (AGA). Use of 5-alpha-reductase inhibitors are useful as oral treatment of AA in men. There are no previous studies of the use of finasteride in transgender men as treatment of AGA. Aim To evaluate the effectiveness and safety of an oral 5α-reductase inhibitor (finasteride) for AA developed in transgender men. Methods This single-centre retrospective study enrolled female-to-male transgender patients with a clinical diagnosis of AGA to receive 1 mg of an oral type II 5α-reductase inhibitor for at least 12 months. Results In all, 10 patients were included in the study. All the patients received a clinical diagnosis of male-pattern AGA, with 90% classified as stage IV on the Norwood-Hamilton scale. Mean onset of AGA was 3.25 years after the introduction of androgenic treatment, and 70% of the patients had a family history of AGA. All the patients improved one grade on the Norwood-Hamilton scale after a mean of 5.5 months (range 4-6 months) since the start of finasteride treatment. Two patients stopped treatment for economic reasons and one stopped due to dyspepsia. No sexual or other adverse effects were observed. Patients were given periodic physical and analytical examinations by endocrinologists without any significant finding. Mean follow-up of patients was 16.2 months. Conclusion AA in transgender men has a delayed onset, and is clinically and therapeutically similar to the common male-pattern-AGA in cis-gender men. [ABSTRACT FROM AUTHOR]

Background: Finasteride has been found to reduce the risk of low-grade prostate cancer but to have no impact on overall survival. The long-term adverse and beneficial consequences of finasteride have not been examined.Methods: We used a linkage between data from the Prostate Cancer Prevention Trial (PCPT) and Medicare claims. Patients were examined by randomized study arm (finasteride vs placebo for 7 years) for long-term consequences of the intervention, including cardiac, endocrine, and sexual dysfunction, depression, diabetes, and benign prostatic hyperplasia (BPH)-related events. To examine time to events, we used cumulative incidence and Cox regression, adjusting for covariates. All statistical tests were two-sided.Results: A total of 13 935 of 18 880 participants (73.8%) in the PCPT were linked to Medicare claims, with median Medicare follow-up assessment time of 16 years from trial registration. There were no differences between finasteride and placebo participants with respect to important baseline factors or amount of Medicare follow-up assessment time. Finasteride patients had a 10% higher risk of new claims for depression (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.01 to 1.19, P = .04) and a 6% lower risk of procedures for BPH-related events (primarily lower urinary tract symptoms; HR = 0.94, 95% CI = 0.89 to 1.00, P = .03). No other differences were found in rates of long-term consequences of intervention in the two study arms.Conclusions: Finasteride use is associated with reduced need for procedures for relief of BPH-related events and a modest increase in depression. Overall, there is little need to worry about long-term noncancer consequences of finasteride use in those who use it for treatment of symptomatic BPH, hair growth, or prevention of cancer. [ABSTRACT FROM AUTHOR]

Finasteride, a 5α-reductase inhibitor, is used in the management of androgenetic alopecia and benign prostatic hyperplasia (BPH). There is growing attention to the post-finasteride syndrome, a constellation of adverse events associated with finasteride use which include sexual dysfunction. To investigate reports of sexual dysfunction associated with finasteride. We conducted a pharmacovigilance study using VigiBase, the World Health Organization's international database of individual case safety reports. We used the reporting odds ratio (ROR). Sensitivity analyses stratified by indication (BPH and alopecia) and age (<45 and ≥45); compared finasteride signals to those of drugs with different mechanisms but similar indications (minoxidil for alopecia and tamsulosin for BPH); compared finasteride to a drug with a similar mechanism of action (dutasteride); and compared reports of sexual dysfunction before and after 2012. We identified 7700 sexual dysfunction reports associated with finasteride. There was a disproportionality signal for sexual dysfunction associated with finasteride (ROR 50.3, 95% confidence interval (CI) 49.0-51.6). Patients under 45 (ROR 56.4, 95% CI 53.1-59.9) and alopecia patients (ROR 64.9, 95% CI 62.7-67.2) drove the signal. All sensitivity analyses met the threshold of signal significance. Results of primary analyses are presented in Tables 1. We detected disproportional signals of sexual dysfunction linked with finasteride use. Despite sexual dysfunction being more prevalent in older BPH patients, we detected larger signals of sexual dysfunction in young alopecia patients. Sensitivity analyses suggest that reports of sexual dysfunction linked with finasteride use may be confounded by indication and by stimulated reporting. However, confounding alone is unlikely to account for the totality of the signal observed in young patients with alopecia. Work supported by industry: no. A consultant, employee (part time or full time) or shareholder is among the authors (QDT reports personal fees from Astellas, Bayer, Janssen, Insightec, and Intuitive Surgical, outside the submitted work. NB, DSE, and KCZ reports consulting fees from Procept Robotics, Olympus, and BSC. BC reports consulting fees from BSC, Olympus, Meditate, Ferring, and Urovant.). [ABSTRACT FROM AUTHOR]

Introduction Tadalafil ( TAD) 5 mg coadministered with finasteride ( FIN) 5 mg significantly improves lower urinary tract symptoms ( LUTS) in men with benign prostatic hyperplasia ( BPH) and prostatic enlargement. However, its effects on erectile/sexual function have yet to be fully described. Aim Assess the effects of TAD/ FIN coadministration (compared with placebo [ PBO]/ FIN) on erectile and sexual function in sexually active men with LUTS and prostatic enlargement secondary to BPH with or without baseline comorbid erectile dysfunction ( ED). Methods A randomized, double-blind, PBO-controlled study of 695 men (610 sexually active; 450 with baseline ED; 404 sexually active with baseline ED) conducted at 70 sites in 13 countries. TAD 5 mg or PBO once daily coadministered with FIN 5 mg once daily for 26 weeks. Main Outcome Measures International Index of Erectile Function ( IIEF) domain and single-item scores; proportions of patients who demonstrated minimal clinically important differences ( MCIDs) in IIEF- Erectile Function domain scores ( IIEF- EF; MCID defined as ≥4-point improvement); and sexual dysfunction adverse events ( AEs). Results Compared with PBO/ FIN, TAD/ FIN resulted in improvements for all IIEF domain and single-item scores assessed among patients with baseline ED ( P ≤ 0.002 for all measures) and among patients without baseline ED ( P ≤ 0.041 for all measures). Compared with PBO/ FIN, significantly larger percentages of sexually active men with baseline ED treated with TAD/ FIN achieved an IIEF- EF MCID after 4, 12, and 26 weeks of therapy ( P < 0.001 for odds ratio comparisons between TAD/ FIN and PBO/ FIN at all 3three postbaseline timepoints). The incidence of sexual AEs was low: five TAD/ FIN patients and seven PBO/ FIN patients reported sexual AEs, including ED, decreased/lost libido, and ejaculation disorders. Conclusions TAD/ FIN coadministration for the treatment of men with LUTS and prostatic enlargement secondary to BPH concurrently leads to statistically significant improvements in erectile/sexual function and is well-tolerated, regardless of the presence/absence of ED at treatment initiation. Glina S, Roehrborn CG, Esen A, Plekhanov A, Sorsaburu S, Henneges C, Büttner H, and Viktrup L. Sexual function in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: Results of a 6-month, randomized, double-blind, placebo-controlled study of tadalafil coadministered with finasteride. J Sex Med 2015;12:129-138. [ABSTRACT FROM AUTHOR]

The therapeutic regimen of the first group ( I n i = 17) was hydroxychloroquine and tacrolimus (hydroxychloroquine 200 mg daily and topical tacrolimus 0-1% twice daily). Patient-measured global assessment and patient satisfaction in the hydroxychloroquine + tacrolimus group was better than the finasteride + tacrolimus group at 8 and 12 weeks, but were not statistically significant ( I P i > 0-05). Physician satisfaction in the hydroxychloroquine + tacrolimus group was better than the finasteride + tacrolimus group at 12 weeks, but this was not statistically significant ( I P i > 0-05). [Extracted from the article]

Allopregnanolone is a neurosteroid that has been reported to fluctuate during early developmental stages. Previous experiments reported the importance of neonatal endogenous allopregnanolone levels for the maturation of the central nervous system and particularly for the hippocampus. Changes in neonatal allopregnanolone levels have been related to altered adult behaviour and with psychopathological susceptibility, including anxiety disorders, schizophrenia and drug abuse. However, the mechanism underlying these changes remains to be elucidated. In the present study we assessed changes in hippocampal expression of α4 and δ GABAA receptor (GABAAR) subunits as a consequence of neonatal finasteride (a 5-α reductase inhibitor) administration during early development (PD6 to PD15) in male rats. We observed that the treatment altered the temporal window of the natural peak in the expression of these subunits during development. Additionally, the level of these subunits were higher than in non-handled and control animals in the adult hippocampus. We observed that in adulthood, neonatal finasteride-treated animals presented an anxiogenic-like profile in response to progesterone administration which was absent in the rest of the groups. In conclusion, these results corroborate the relevance of neonatal maintenance of neurosteroid levels for behavioural anxiety responses in the adult, and point to some of the mechanisms involved in this alterations. [ABSTRACT FROM AUTHOR]

Aims: We tested whether an exposure to alcohol in late adolescence, an age of rapid increase in neuroactive steroid precursors, would increase voluntary alcohol consumption in adult rats and whether this effect would be modulated by finasteride, an inhibitor of neuroactive steroid synthesis. Methods: In Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for 1 week during late adolescence [postnatal days (PNDs) 51–58], and then measured voluntary alcohol consumption 1 month later in adulthood (PNDs 91–104). In Experiment 2, finasteride was administered during the forced alcohol exposure in late adolescence and, in Experiment 3, during voluntary alcohol consumption in adulthood. Plasma was collected at the end of each finasteride treatment to confirm the reduction of plasma neuroactive steroid levels. Results: We found that a daily 12-h exposure to alcohol for 7 days in late adolescence significantly increased voluntary alcohol consumption (4-fold) a month later during adulthood. Finasteride administration in late adolescence increased group alcohol intake in late adolescence but did not block the effect of adolescent alcohol exposure on increasing alcohol preference in adulthood. There was no effect of finasteride treatment in adulthood on alcohol preference. Conclusions: A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to induce chronically increased alcohol preference in adulthood, indicating that this age may be sensitive to the effects of alcohol. [ABSTRACT FROM PUBLISHER]

ABSTRACT Introduction. Finasteride has been associated with sexual side effects that may persist despite discontinuation of the medication. In a clinical series, 20% of subjects with male pattern hair loss reported persistent sexual dysfunction for ≥6 years, suggesting the possibility that the dysfunction may be permanent. These subjects also reported a wide range of symptoms including changes in cognition, ejaculate quality, and genital sensation. Other medications have been associated with irreversible neurological effects, such as phenothiazines with tardive dyskinesias. Aim. To prospectively study whether the persistent sexual side effects associated with finasteride resolve or endure over time. Methods. Subjects (N = 54) with persistent sexual side effects associated with finasteride were reassessed after 9-16 months (mean 14 months). All subjects were otherwise healthy young men without any baseline sexual dysfunction, medical conditions, psychiatric conditions, or use of oral prescription medications prior to taking finasteride for male pattern hair loss. Main Outcome Measure. Scores from the Arizona Sexual Experience Scale (ASEX). Results. The participation rate was 81%. At reassessment persistent sexual side effects continued to be present in 96% of subjects. According to the ASEX scores, 89% of subjects met the definition of sexual dysfunction. Neither the length of finasteride use nor the duration of the sexual side effects correlated to changes in scores of sexual dysfunction. Conclusion. In most men who developed persistent sexual side effects (≥3 months) despite the discontinuation of finasteride, the sexual dysfunction continued for many months or years. Although several rat studies have shown detrimental changes to erectile function caused by 5 alpha reductase inhibitors, the persistent nature of these changes is an area of active research. Prescribers of finasteride and men contemplating its use should be made aware of the potential adverse medication effects. Irwig MS. Persistent sexual side effects of finasteride: Could they be permanent? J Sex Med 2012;9:2927-2932. [ABSTRACT FROM AUTHOR]

Background. 5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. Methods. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Results. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00- 3.59; overall cancer: OR = 1.51; 95% CI: 1.00 -2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17- 80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. Conclusions. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. Many clinical studies reported finasteride-related erectile dysfunction, but to date, few animal experiments have focused on it. Aim. To investigate the effects of oral finasteride on erectile function in a rat model. Main Outcome Measures. Erectile responses and morphological changes. Methods. Adult, male Sprague-Dawley rats were divided into four groups (25/group): (i) control; (ii) castration; (iii) castration with testosterone (T) replacement; and (iv) oral finasteride treatment. Four weeks later, erectile function was measured by the ratio of intracavernosal pressure and mean arterial blood pressure upon electrical stimulation of the cavernous nerve. Serum T and dihydrotestosterone (DHT) and intraprostatic DHT were measured. The weights and histopathological features of the penile corpus cavernosum and prostate were examined. Results. Serum T and DHT and intraprostatic DHT concentrations, erectile function, and mean weights of the corpus cavernosum and prostate were lowest in group 2. There was no significant difference in the serum T concentration and erectile function between groups 4 and 1. However, the serum and intraprostatic DHT concentrations were significantly lower in group 4 than in group 1 (both P < 0.001). The tissue weights of the corpus cavernosum and prostate were reduced by 25.9% and 92.3% in group 4 compared with group 1 (both P < 0.001). Histopathology revealed a significant atrophy of the prostate in groups 2 and 4. There was a significant decrease in the smooth muscle content in group 2, but not in groups 3 and 4. Conclusions. In a rat model, finasteride treatment for 4 weeks reduces the weight of the corpus cavernosum but appears not to affect the erectile responses to electrical stimulation of the cavernous nerve. As erection is a complex process involving important signaling in the brain, further studies are necessary to demonstrate the long-term effects of finasteride on both central and peripheral neural pathways of erection. Zhang M-G, Wu W, Zhang C-M, Wang X-J, Gao P-J, Lu Y-L, and Shen Z-J. Effects of oral finasteride on erectile function in a rat model. J Sex Med 2012;9:1328-1336. [ABSTRACT FROM AUTHOR]

Summary Androgenetic alopecia affects both men and women. In men it produces male pattern hair loss with bitemporal recession and vertex baldness. In women it produces female pattern hair loss (FPHL) with diffuse alopecia over the mid-frontal scalp. FPHL occurs as a result of nonuniform hair follicle miniaturization within follicular units. Diffuse alopecia is produced by a reduction in the number of terminal fibres per follicular unit. Baldness occurs only when all hairs within the follicular units are miniaturized and is a relatively late event in women. The concepts of follicular units and primary and secondary hair follicles within follicular units are well established in comparative mammalian studies, particularly in sheep. However, discovery of these structures in the human scalp hair and investigation of the changes in follicular unit anatomy during the development of androgenetic alopecia have provided a clearer understanding of the early stages of androgenetic alopecia and how the male and female patterns of hair loss are related. FPHL is the most common cause of alopecia in women and approximately one-third of adult caucasian women experience hair loss. The impact of FPHL is predominantly psychological. While men anticipate age-related hair loss, hair loss in women is usually unexpected and unwelcome at any age. Treatment options to arrest hair loss progression and stimulate partial hair regrowth for FPHL include the androgen receptor antagonists spironolactone and cyproterone acetate, the 5α-reductase inhibitor finasteride and the androgen-independent hair growth stimulator minoxidil. These treatments appear to work best when initiated early. Hair transplantation should be considered in advanced FPHL that is resistant to medical treatments. Hair transplantation requires well-preserved hair growth over the occipital donor area. The psychological impact of FPHL may also be reduced by cosmetic products that improve the appearance of the hair. These agents work to minimize hair fibre breakage, improve hair volume or conceal visible bald scalp. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose. A case of severe bradycardia and hypotension associated with concomitant tizanidine and lisinopril therapy is reported. Summary. An 85-year-old man with a chief complaint of profound weakness was admitted to the hospital with a blood pressure reading of 60/32 mm Hg and a heart rate of 37 beats/min. His medical history included type 2 diabetes mellitus, congestive heart failure, gastroesophageal reflux disease, chronic obstructive pulmonary disease, osteoarthritis, restless leg syndrome, benign prostatic hyperplasia, generalized anxiety disorder with depression, and severe chronic back pain for which he was receiving treatment at a pain clinic. Two days before hospital admission, he had been seen at the pain clinic and started on tizanidine. Additional medications included acetaminophen, chlorpromazine, citalopram, finasteride, lidocaine patch, lisinopril, metformin, pramipexole, omeprazole, simvastatin, theophylline, diclofenac topical gel, hydrocodone-acetaminophen, and ondansetron. After taking three doses of the newly prescribed tizanidine, he developed severe hypotension and bradycardia. Notable laboratory test values included a serum creatinine concentration of 1.90 mg/dL, a blood urea nitrogen concentration of 21 mg/dL, a serum potassium concentration of 5.5 meq/L, and a serum sodium concentration of 128 meq/L. Upon admission, tizanidine, lisinopril, theophylline, omeprazole, and simvastatin were withheld, and i.v. fluids were administered. The patient's vital signs began to gradually improve. Within 24 hours, the patient's blood pressure and heart rate had improved, as had the previously abnormal laboratory test values. Tizanidine was discontinued, and all of his other preadmission medications were restarted at discharge. Conclusion. The addition of tizanidine in a patient receiving long-term treatment with lisinopril was associated with severe hypotension and bradycardia. [ABSTRACT FROM AUTHOR]

Background Hair loss is an unwelcome event at any age, but it can be particularly distressing for adolescents and their families. While androgenetic alopecia (AGA) is the most common form of hair loss in adults, little is known about its prevalence, clinical features and response to treatments in the paediatric population. Objectives To better characterize the causes of alopecia in a paediatric population. Methods We performed a retrospective chart review to identify all patients with hair loss seen in an academic paediatric dermatology practice at New York University over a 12-year period to better characterize the causes of alopecia in this population. We review the clinical and histological features, natural progression and associated laboratory abnormalities of AGA in 57 paediatric patients. Results AGA was identified as the most frequent cause of hair loss in adolescents and the second most common diagnosis overall. The male to female ratio was 2 : 1 and the average age at initial presentation with AGA was 14·8 years. Adolescent girls had diffuse thinning or thinning at the crown, and boys frequently presented with female pattern hair loss. When biopsies were performed, perifollicular inflammation was a common finding. A family history of AGA was reported in 83% of patients. Laboratory evaluation for androgens revealed polycystic ovarian syndrome in three girls and late-onset congenital adrenal hyperplasia in one boy. Conclusions AGA is the most common form of hair loss in adolescents, and can be the presenting sign of an underlying endocrine disorder. An accurate and timely diagnosis is essential for appropriate medical and psychosocial intervention when warranted. [ABSTRACT FROM AUTHOR]

With the analysis of complex, messy data sets, the statistics community has recently focused attention on “reproducible research,” namely research that can be readily replicated by others. One standard that has been proposed is the availability of data sets and computer code. However, in some situations, raw data cannot be disseminated for reasons of confidentiality or because the data are so messy as to make dissemination impractical. For one such situation, we propose 2 steps for reproducible research: (i) presentation of a table of data and (ii) presentation of a formula to estimate key quantities from the table of data. We illustrate this strategy in the analysis of data from the Prostate Cancer Prevention Trial, which investigated the effect of the drug finasteride versus placebo on the period prevalence of prostate cancer. With such an important result at stake, a transparent analysis was important. [ABSTRACT FROM PUBLISHER]

Introduction. Benign prostatic hyperplasia (BPH) is a common problem affecting middle-aged and elderly men. First-line medical therapy includes α 1blockers and 5α-reductase inhibitors (5ARIs), such as finasteride and dutasteride. 5ARI use has been associated with adverse sexual outcomes, including erectile dysfunction (ED), ejaculatory dysfunction (EjD), and decreased libido. Aim. To clarify the association between sexual adverse effects (AEs) and 5ARIs through review of literature concerning 5ARIs and to review the proposed mechanisms of these effects. Methods. A comprehensive literature review, using MEDLINE and PUBMED search engines, was conducted for all publications concerning 5ARIs and sexual AEs. Main Outcome Measure. Sexual adverse effects, such as ED, EjD, and decreased libido, were the measured outcomes of this literature review. Results. Sexual AEs are reported in clinical trials at rates of 2.1% to 38%. The most common sexual AE is ED, followed by EjD and decreased libido. These effects occur early in therapy and attenuate over time. A proposed mechanism for sexual dysfunction involves decreased nitric oxide synthase activity due to decreased dihydrotestosterone. Conclusions. The connection between 5ARIs and sexual dysfunction is apparent upon review of the literature. Though theories have been proposed, little is known about the exact mechanisms behind 5ARI-related sexual dysfunction. Since the connection between 5ARIs and sexual AEs is established in the literature, future research should be directed toward deciphering the pathophysiologic mechanisms. When more basic science knowledge is attained in this area, the focus can shift toward prevention and treatment. Erdemir F, Harbin A, and Hellstrom WJG. 5-alpha reductase inhibitors and erectile dysfunction: The connection. J Sex Med **;**:**–**. [ABSTRACT FROM AUTHOR]

Background Finasteride is a 5α -reductase inhibitor that has proved to be an effective treatment for men with androgenetic alopecia. Objectives To investigate the hormonal influence of finasteride 1 mg daily on hormonal levels and hair growth in men of different ages and with different degrees of alopecia according to the Hamilton–Norwood scale. Methods Two hundred and seventy men aged 14–58 years with male androgenetic alopecia III–VI Hamilton–Norwood score (II–III Ebling score) were treated with finasteride 1 mg daily. Steroid hormone (free testosterone, 5α-dihydrotestosterone, dehydroepiandrosterone-sulphate, δ4-androstenedione, 17-hydroxyprogesterone), prostate-specific antigen (PSA) and sebum levels, and trichogram changes were determined at baseline, and at 6 and 12 months of treatment. Results According to significant hormonal statistical analysis, the patients were divided by age (up to or over 26 years). In the group of patients ≤ 26 years, higher levels of 5α-dihydrotestosterone were found at the beginning of the treatment, but there was a 50% decrease between the onset of treatment and month 12, particularly noticeable at 6 months ( P < 0·05) of treatment, running parallel to an improvement of the alopecia and an increase of anagen hairs in the trichogram. At 1 year, PSA levels decreased 20%, particularly in patients > 26 years. No variations in sebum levels were observed. Conclusions High levels of 5α-dihydrotestosterone in patients ≤ 26 years at the beginning of treatment are a predictive factor of good response to treatment with finasteride 1 mg daily. [ABSTRACT FROM AUTHOR]

An analytical method is developed and validated for the quantitative determination of finasteride, a potent 5 α–reductase inhibitor, in human plasma. Calibration curves are linear in the concentration range of 1 to 100 ng/mL. Sample pretreatment involves a liquid–liquid extraction with ethyl acetate using 0.2 mL aliquots of plasma. Finasteride and the internal standard (beclomethasone) are separated on a Waters Symmetry Shield RP18 column (50 × 2.1 mm, 3.5 µm) and eluted using a gradient mobile phase composed of acetonitrile and 10mM ammonium acetate with 0.1% formic acid. The column eluant is monitored by mass spectrometry with electrospray ionization. A complete validation of the method is performed. For quality control samples at three different concentrations that were analyzed in quintuplicate, on six separate occasions, the accuracy and precision range from 95.2% to 101% and 3.4% to 7.3%, respectively. The developed method is subsequently applied to measure the steady state finasteride concentration of patients who participated in the Prostate Cancer Prevention Trial. [ABSTRACT FROM AUTHOR]

Introduction. Sexual adverse experiences such as erectile dysfunction (ED), loss of libido, and ejaculation disorders have been consistent side effects of finasteride in a maximum percentage of 15% after 1 year of therapy. Such data could be seen as far from reality, if compared to a higher percentage that may be found in any common clinical practice. Aim. This study aims to explain the dichotomy between literature's data and clinical practice data. Methods. One hundred twenty patients with a clinical diagnosis of benign prostatic hyperplasia (BPH), sexually active and with an International Index of Erectile Function-erectile function (IIEF-EF) domain ≥25 were randomized to receive finasteride 5 mg concealed as an “X compound of proven efficacy for the treatment of BPH” for 1 year with (group 2) or without (group 1) counseling on the drug sexual side effect. The phrase used to inform group 2 patients was “. . . it may cause erectile dysfunction, decreased libido, problems of ejaculation but these are uncommon”. Main Outcome Measures. The estimation of side effect was conducted at 6 and 12 months using the male sexual function-4 (MSF-4 item) questionnaire and a self-administered questionnaire. Results. One hundred seven patients completed the study. Group 2 patients (N = 55) reported a significant higher proportion of one or more sexual side effects as compared to group 1 (N = 52) (43.6% vs. 15.3%) ( P = 0.03). The incidence of ED, decreased libido, and ejaculation disorders were 9.6, 7.7, and 5.7% for group 1, and 30.9, 23.6, and 16.3% for group 2, respectively ( P = 0.02, P = 0.04, and P = 0.06). Conclusion. In the current study, blinded administration of finasteride was associated with a significantly higher proportion of sexual dysfunction in patients informed on sexual side effects (group 2) as compared to those in which the same information was omitted (group 1) ( P = 0.03). A scenario similar to group 2 of the current study is likely to occur in clinical practice, where the patient is counseled by the physician and has access to the drug information sheet. The burden of this nocebo effect (an adverse side effect that is not a direct result of the specific pharmacological action of the drug) has to be taken into account when managing finasteride sexual side effects. Mondaini N, Gontero P, Giubilei G, Lombardi G, Cai T, Gavazzi A, and Bartoletti R. Finasteride 5 mg and sexual side effects: How many of these are related to a nocebo phenomenon? J Sex Med 2007;4:1708–1712. [ABSTRACT FROM AUTHOR]

Background The Prostate Cancer Prevention Trial (PCPT) reported a decreased incidence of prostate cancer overall but an increase in the incidence of high-grade prostate cancer with finasteride compared with placebo. We assessed whether the increased high-grade prostate cancer associated with finasteride in the PCPT was due to finasteride's potential effects on tumor morphology or prostate size. Methods Prostate biopsies with Gleason score 8-10 (n = 90, finasteride; n = 52, placebo) were examined histologically for hormonal effects, and those with Gleason score 7-10 (n = 282, finasteride; n = 244, placebo) were examined for pathologic surrogates of disease extent. Prostate volumes were measured at biopsy. Samples from radical prostatectomies (n = 222, finasteride; n = 306, placebo) were examined for tumor grade and extent, and, where possible, grades at biopsy and prostatectomy were compared between the groups. Logistic regression was used to analyze differences between treatment groups with respect to pathologic criteria. All statistical tests were two-sided. Results Degenerative hormonal changes in high-grade biopsies were equivalent between the finasteride and placebo groups, but prostate volumes were lower in the finasteride group (median = 25.1 versus 34.4 cm³, P<.001). Pathologic surrogates for tumor extent were lower with finasteride than with placebo, including mean percentage of positive cores (34% versus 38%, P = .016), mean tumor linear extent (greatest [4.4 versus 4.8 mm, P = .191 and aggregate [7.6 versus 9.2 mm, P = .13]), bilaterality (22.8% versus 30.6%, P= .046), and perineural invasion (14.2% versus 20.3%, P= .07). Among patients who had prostatectomy, the finasteride-associated increase in high-grade disease (Gleason score 2 7) at biopsy (42.7% finasteride versus 25.4% placebo, P<.001) was diminished at prostatectomy (46.4% finasteride versus 38.6% placebo, P = .10). Biopsy identified a greater proportion of patients with high-grade disease present at prostatectomy in the finasteride group than in the placebo group (69.7% versus 50.5%, P= .01). The rate of upgrading (from low-grade cancer at biopsy to high-grade cancer at prostatectomy) and pathologic stage at prostatectomy were similar in both groups. Conclusions Effects of finasteride on prostate volume and selective inhibition of low-grade cancer, rather than effects on tumor morphology, may have contributed to the increase in high-grade cancers with finasteride in the PCPT. Although induction of high-grade cancer cannot be excluded, the results suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group. [ABSTRACT FROM AUTHOR]

Background The Prostate Cancer Prevention Trial (PCPT) demonstrated a 24.8% reduction in the 7-year prevalence of prostate cancer among patients treated with finasteride (5 mg daily) compared with that among patients treated with placebo; however, a 25.5% increase in the prevalence of high-Gleason grade tumors was observed, the clinical significance of which is unknown. One hypothesized explanation for this increase is that finasteride reduced prostate volume, leading to detection of more high-grade tumors due to increased sampling density. This possibility was investigated in an observational reanalysis of the PCPT data, with adjustment for sampling density. Methods A logistic model for the association of high-grade (Gleason score 7-10) prostate cancer with baseline covariates and/or baseline covariates plus prostate volume and number of cores obtained at biopsy was developed using the placebo group (n = 4775) of the PCPT. This model was then applied to the finasteride group (n = 5123) to compare the predicted and observed numbers of high-grade tumors in that group. In a second approach, odds ratios (ORs) for prostate cancer in the finasteride versus placebo groups calculated from binary and polytomous logistic regression models that contained or excluded covariates for gland volume and number of needle cores were compared. Results Median prostate volume was 25% lower in the finasteride group (median = 25.1 cm³) than in the placebo group (median = 33.5 cm³). The logistic model developed in the placebo group showed that the likelihood of detection of high-grade prostate cancer decreased as volume increased (for each 10 cm³ increase in prostate volume, OR = 0.81, 95% confidence interval [CI = 0.74 to 0.90). Based on this model, 239 high-grade prostate cancers were predicted in the finasteride group, whereas 243 were observed, a non-statistically significant difference. Among all participants, the odds ratios for high-grade cancer in the finasteride versus placebo groups decreased from 1.27 (95% CI = 1.05 to 1.54) with adjustment for baseline covariates to 1.03 (95% CI = 0.84 to 1.26) following additional adjustment for gland volume and number of biopsy cores in binary outcome models and from 1.14 (95% CI = 0.94 to 1.38) to 0.88 (95% CI = 0.72 to 1.09) following these adjustments in the polytomous models. Conclusions Although analyses using postrandomization data require cautious interpretation, these results suggest that sampling density bias alone could explain the excess of high-grade cancers among the finasteride-assigned participants in the PCPT. [ABSTRACT FROM AUTHOR]

Background: In the Prostate Cancer Prevention Trial (PCPT), men receiving finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo but a higher risk of high-grade cancer. We examined the impact of finasteride on the sensitivity and area under the receiver operating characteristic curve (AUC) of prostate-specific antigen (PSA) for detecting prostate cancer. Methods: We studied men in the placebo and finasteride groups of the PCPT who had a prostate biopsy and concurrent PSA tests during the 7-year study. We compared the placebo and finasteride groups for sensitivity and AUC of PSA for the detection of all prostate cancer, of Gleason grade 7 or higher prostate cancer, and of Gleason grade 8 or higher prostate cancer. All statistical tests were two-sided. Results: Of 5112 men in the placebo group, prostate cancer was detected in 1111. Gleason tumor grade was available for 1100 men, of whom 240 had grade 7 or higher and 55 had grade 8 or higher. Of 4579 men in the finasteride group, 695 had prostate cancer. Gleason grade was available for 686 men, of whom 264 had grade 7 or higher and 81 had grade 8 or higher. The AUC of PSA for all outcomes was greater for the finasteride group than the placebo group. For detecting prostate cancer versus no cancer, the AUCs were 0.757 and 0.681, respectively (P<.001); for detecting Gleason grade ≥7 versus ≤6 or no cancer, the AUCs were 0.838 and 0.781, respectively (P = .003); and for detecting Gleason grade ≥8 versus ≤7 or no cancer, the AUCs were 0.886 and 0.824, respectively (P = .071). The sensitivity of PSA was higher for men in the finasteride group than in the placebo group at all PSA cutoffs matched by specificity. Conclusions: PSA had statistically significantly better sensitivity and AUC for detecting prostate cancer in the finasteride arm of the PCPT than in the placebo arm. This bias would be expected to contribute to greater detection of all grades of prostate cancer with finasteride. [ABSTRACT FROM AUTHOR]

Background Finasteride, a competitive inhibitor of the enzyme 5α-reductase II, is widely used as a medical treatment for patients with male-pattern baldness (MPB), which is affected by the distribution of androgenic steroids. It is also notable that the androgenic effect in MPB is different for each region of the head. Objectives To study the effect of the drug finasteride, we quantified androgenic steroids in the vertex and occipital scalp hair and in the plasma of patients with MPB. Methods The patients with MPB, aged 23–52 years, were treated with finasteride 1 mg daily for 5 months. The hair and plasma samples were hydrolysed, extracted with n-pentane, and derivatized with MSTFA : NH4I : DTE (1000 : 4 : 5, v/w/w). We analysed the concentrations of dihydrotestosterone (DHT) and testosterone (T) in the hair and plasma using gas chromatography–mass spectrometry (GC-MS). Results In the hair, the ratio of DHT/T was decreased in the vertex scalp hair after the individual received finasteride ( P < 0·005). However, we found no significant difference in the ratio of DHT/T in the occipital scalp hair before and after individuals received finasteride. Like the results in the vertex scalp hair, the ratio of DHT/T in the plasma was remarkably decreased after finasteride administration ( P < 0·001). Conclusions This study supports the effect of finasteride in patients with MPB by examining the decreased level of DHT/T in scalp hair and in plasma. Thus, in view of the androgenic effect in the different hair regions, the vertex scalp hair plays a more important role for patients with MPB treated with finasteride than does the occipital hair. [ABSTRACT FROM AUTHOR]

Finasteride is a specific inhibitor of type II 5α-reductase, the enzyme that converts testosterone (T) to the more potent androgen receptor agonist dihydrotestosterone (DHT). In utero exposure to androgen receptor antagonists and T biosynthesis inhibitors have induced permanent effects on androgen-sensitive end points such as anogenital distance (AGD), nipple retention, and malformations of the male rat reproductive tract. The objectives of this study were to (1) characterize the dose response of finasteride-mediated alterations in androgen-dependent developmental end points, (2) determine whether prenatal exposure to finasteride permanently decreases AGD or results in nipple retention, and (3) evaluate whether AGD or nipple retention is predictive of adverse alterations in the male reproductive tract. Pregnant Crl:CD(SD)BR rats (n = 5-6/group) were gavaged with either vehicle or finasteride at 0.01, 0.1, 1.0, 10, or 100 mg/kg/day on gestation days 12 to 21. All male offspring were monitored individually until necropsy on postnatal day (PND) 90. The present study design has been used previously for other antiandrogens and is sensitive to perturbations of the male rat reproductive tract. Decreases in AGD on PND 1 and increases in areolae-nipple retention on PND 13 were significantly different from controls in all finasteride-exposed male rats. Finasteride-induced changes in AGD and nipple retention were permanent in male rats exposed to finasteride at and above 0.1 mg/kg/day. On PND 90, dorsolateral and ventral prostate lobes were absent in 21 to 24% of rats exposed to 100 mg/kg/day finasteride and weighed significantly less at and above 10 mg/kg/day. In the highest dose group, 73% of animals had ectopic testes, much higher than previously reported. The most sensitive malformation other than decreased AGD and nipple retention was the dose-dependent increase in hypospadias. The lowest observed adverse effect level (LOAEL) for finasteride-induced permanent effects in this study was 0.1 mg/kg/day based on permanent changes in AGD and nipple retention. Finasteride-induced changes in AGD and retention of nipples were highly predictive of hypospadias, ectopic testes, and prostate malformations even though some animals with retained nipples or decreased AGD may not have had other reproductive tract malformations. In summary, prenatal exposure to finasteride specifically inhibited DHT-mediated development with little to no change in T-mediated development. [ABSTRACT FROM AUTHOR]

Background The growth of scalp hair is a cyclical process of successive phases of growth (anagen) and rest (telogen). In previous clinical trials in men with androgenetic alopecia, treatment with finasteride increased scalp hair counts in a defined area (i.e. increased hair density). Objectives The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle. Patients/Methods Two hundred and twelve men, age 18–40 years, with androgenetic alopecia were randomized to receive finasteride 1 mg daily or placebo for 48 weeks. At baseline and at 24 and 48 weeks, macrophotographs were taken to measure total and anagen hair count in a 1-cm2 target area of the scalp. Results At baseline, mean total and anagen hair counts in the finasteride group were 200 and 124 hairs, respectively (% anagen = 62%) and the anagen to telogen ratio was 1·74 (geometric mean). In the placebo group, the respective values were 196 and 119 hairs (% anagen = 60%) and 1·57. At week 48, the finasteride group had a net improvement (mean ± SE) compared with placebo in total and anagen hair counts of 17·3 ± 2·5 hairs (8·3% ± 1·4%) and 27·0 ± 2·9 hairs (26% ± 3·1%), respectively (P < 0·001). Furthermore, treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47% (P < 0·001). In this study, treatment with finasteride 1 mg day-1 for 48 weeks increased both total and anagen hair counts, and improved the anagen to telogen ratio. Conclusions These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia is a common dermatological condition, with potentially adverse psychosocial sequelae. The present review critically examines scientific evidence concerning the effects of androgenetic hair loss on social processes and psychological functioning, as well as the psychosocial outcomes of medical treatments. Research confirms a negative but modest effect of visible hair loss on social perceptions. More importantly, androgenetic alopecia is typically experienced as a moderately stressful condition that diminishes body image satisfaction. Deleterious effects on self-esteem and certain facets of psychological adjustment are more apparent among women than men and among treatment-seeking patients. Various ‘risk factors’ vis-à-vis the psychological adversity of androgenetic alopecia are identified. Medical treatments, i.e. minoxidil and finasteride, appear to have some psychological efficacy. A conceptual model is delineated to explain the psychological effects of hair loss and its treatment. Directions for needed research are discussed. Strategies are presented for the clinical management of psychological issues among these patients. [ABSTRACT FROM AUTHOR]

The predominant form of 5α-reductase (5aR) in human scalp is 5aR1. None the less, clinical studies have shown that finasteride, a selective inhibitor of 5aR2, decreases scalp dihydrotestosterone and promotes hair growth in men with androgenetic alopecia. Immunolocalization studies were thus carried out to examine 5aR isozyme distribution within scalp and, in particular, to determine whether 5aR2 might be associated with hair follicles. 5aR2 was localized using both a rabbit polyclonal and a mouse monoclonal antibody. 5aR1 was detected with a mouse monoclonal antibody. The specificity of these reagents was demonstrated both by immunofluorescence and Western blot analyses of COS cells overexpressing human 5aR1 or 5aR2. When cryosections of scalp from men with androgenetic alopecia were stained with antibody against 5aR2, using immunoperoxidase avidin–biotin complex methodology, immunostaining was observed in the inner layer of the outer root sheath and, in more proximal regions of the follicle, in the inner root sheath. Staining was also prominent in the infundibular region of the follicle, with less intense staining extending throughout the granular layer of the epidermis. Some staining was also seen in sebaceous ducts. Similar results were obtained with both the polyclonal and monoclonal 5aR2 antibodies. In contrast, in scalp cryosections stained with antibody to 5aR1, no immunostaining was observed within hair follicles. Intense staining for the type 1 isozyme was, however, detected within sebaceous glands. Our immunolocalization data suggest that the results seen in clinical trials of men with male pattern hair loss treated with finasteride may be due, at least in part, to local inhibition of 5aR2 within the hair follicle. [ABSTRACT FROM AUTHOR]

Studies the inhibition of rat prostate carcinogenesis by finasteride, a 5alpha-reductase inhibitor. Incidence of prostate carcinoma in rats fed with finasteride-containing diets; Analysis of intrapostatic dihydrotestosterone content; Dose dependence for the chemopreventive activity of finasteride.

The authors highlight an article in the issue by Kao and colleagues which showed that finasteride use was associated with an actual increase in risk of prostate cancer. They discuss other trials investigating the use of finasteride and dutasteride for chemoprevention including The Prostate Cancer Prevention Trial (PCPT). The trials demonstrate substantial chemoprevention but at the cost of increased risk of high-grade prostate cancer. Cost-effectiveness of finasteride is also included.

The article offers information on a study which determines side-effects of finasteride use, including that of post-finasteride syndrome (PFS) in women. It mentions information on side effects of 5-alpha-reductase inhibitors and finasteride which involves depression, cognitive impairment, fatigue, suicidal ideation, and other sexual side-effects. It presents information on side-effects of finasteride use in women which includes folliculitis and menstrual irregularity.

Describes the treatment of hidradenitis suppurativa with finasteride. Clinical features; Treatment regimen; Efficacy.

The article presents a case study of a 33-year-old man who was diagnosed with rhabdomyolysis induced by exercise in combination with oral finasteride. It examines the drug history of a patient including nonprescribed medication. It notes the side effect of finasteride which is a drug for the treatment of benign prostatic hyperplasia and male pattern baldness.

The article discusses grey-scale penile ultrasound results in young men with Erectile Dysfunction (ED). Topics discussed include animal studies showing erectile tissue fibrosis after exposure to 5 alpha reductase inhibitors, use of finasteride for androgenic alopecia, and grey-scale and color duplex doppler ultrasound during maximal pharmacologic erection.

The article discusses the effects on the therapeutic response of delayed treatment in male-pattern hair loss (MPHL). Referring to a study, MPHL was monitored via hair growth assessment, wherein occurrence of hair loss has been noted depending on the individual. The use of placebos over finasteride had not reached the growth value. Moreover, a case of monozygotic twins, one had been adversely affected on the delay of treatment.

The article reports on the anomalous data regarding the published results from the Prostate Cancer Prevention Trial (PCPT) in the U.S. It is noted that the study for prostate cancer provides varying data that shows the susceptibility of the drug known as finasteride in reducing the risk of prostate cancer. However, some prostate cancer experts have suggested that finasteride prevents only insignificant tumors, the kind of cancer that would never kill and not on deadly cancer.

A letter to the editor discussing the use of finasteride in the treatment of androgenetic alopecia is presented.