Use Of Finasteride Research Articles

MP64-05 SELF-REPORTED FINASTERIDE USE IS ASSOCIATED WITH DECREASED INCIDENCE OF BLADDER CANCER: DATA FROM THE PROSTATE, LUNG, COLORECTAL, & OVARIAN CANCER STUDY

You have accessJournal of UrologyBladder Cancer: Natural History and Pathophysiology1 Apr 2015MP64-05 SELF-REPORTED FINASTERIDE USE IS ASSOCIATED WITH DECREASED INCIDENCE OF BLADDER CANCER: DATA FROM THE PROSTATE, LUNG, COLORECTAL, & OVARIAN CANCER STUDY Edwin E. Morales, Sonja Grill, Nicholas A. Freidberg, Ian M. Thompson, Robert S. Svatek, Dharam Kaushik, Donna P. Ankerst, and Michael A. Liss Edwin E. MoralesEdwin E. Morales More articles by this author , Sonja GrillSonja Grill More articles by this author , Nicholas A. FreidbergNicholas A. Freidberg More articles by this author , Ian M. ThompsonIan M. Thompson More articles by this author , Robert S. SvatekRobert S. Svatek More articles by this author , Dharam KaushikDharam Kaushik More articles by this author , Donna P. AnkerstDonna P. Ankerst More articles by this author , and Michael A. LissMichael A. Liss More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2316AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The androgen receptor (AR) has been increasingly implicated in the incidence and progression of bladder cancer (BC) based largely on animal models. Androgen deprivation therapy (ADT) has been suggested for prevention and/or additionally treatment in BC. While ADT is not a practical option to prevent bladder cancer, Finasteride (FST) is a 5-α reductase inhibitor, which competitively inhibits the production of dihydrotestosterone (DHT) and is the most potent natural androgenic AR activator. In order to investigate the effect of FST on BC, we obtained the self-reported use of FST at any time during the Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) trial and noted the outcome of new BC diagnosis. METHODS The PLCO Trial is a landmark nationwide database of nearly 76,685 men with a 13+ year study follow-up. The primary predictor was any FST use and the primary outcome was BC diagnosis. Cox proportional hazard regression analysis was performed to determine the association of FST use with time to diagnosis of BC and time to BC mortality, controlling for confounding factors, including age and tobacco use. RESULTS Of the 72,370 male participants who met inclusion criteria, 6,069 (8.4%) had reported the use of FST. BC was diagnosed in 1.07% (65/6069) of those who reported FST compared to 1.46% (966/66,301) (p=0.018). Mortality rates from BC did not differ between groups (0.18% vs. 0.19%, p=0.61). In a multiple Cox regression analysis self-reported usage of FST was associated with a decreased risk of development of BC with a hazard ratio (HR) of 0.634 (95% CI: [0.493, 0.816], p=0.0004), controlling for age and smoking (age: 1.073 [1.060, 1.085], p < 0.0001; former smoker: 2.282 [1.951, 2.669], and current smoker: 3.634, [2.974, 4.441], p <0.0001). There was no statistically significant effect of self-reported FST use in time to BC mortality. CONCLUSIONS Reported usage of FST by PLCO participants resulted in a nearly 30% reduction in the development of BC. While animal modes have been suggestive, our findings are the first to report the potential use of FST as a preventative or therapeutic target in BC. A limitation of these results is their basis on an observational comparison of self-reported use of FST during the PLCO and further investigation is currently underway. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e799 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edwin E. Morales More articles by this author Sonja Grill More articles by this author Nicholas A. Freidberg More articles by this author Ian M. Thompson More articles by this author Robert S. Svatek More articles by this author Dharam Kaushik More articles by this author Donna P. Ankerst More articles by this author Michael A. Liss More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Combination of tadalafil and finasteride for improving the symptoms of benign prostatic hyperplasia: critical appraisal and patient focus.

The evidence suggests that combination therapy for benign prostatic hyperplasia (BPH)-lower urinary tract symptoms (LUTS) using an α-blocker and a 5α-reductase inhibitor has become well accepted. The combination of daily tadalafil and an α-blocker has also demonstrated benefit. This paper addresses combination therapy with daily tadalafil and finasteride for the treatment of BPH-LUTS. Our results demonstrate that use of tadalafil and finasteride represents a logical extension of combination therapies. We analyze a landmark study by Casabé et al that demonstrates improved voiding symptoms as assessed by International Prostate Symptom Scores with a combination of tadalafil and finasteride compared with finasteride and placebo. Study patients had moderate to severe LUTS and prostate volumes >30 g. The additional benefit of improved erectile function as assessed by International Index of Erectile Function-erectile function domain scores with the addition of tadalafil was a secondary benefit. We propose that the ideal patient for combination therapy with tadalafil and finasteride has a prostate volume >30 g and desires additional benefit over monotherapy. For these men, improved erectile function without sexual side effects was a secondary benefit.

Physical activity and benign prostatic hyperplasia-related outcomes and nocturia.

Benign prostatic hyperplasia (BPH) and its associated lower urinary tract symptoms (LUTS), including nocturia, are extremely common among middle- and older-age American men. Although studies on physical activity (PA) and prevalent BPH-related outcomes suggest that PA may protect against the development of this common condition, only a few studies have examined the relation between PA and incident BPH-related outcomes and LUTS with mixed findings. In addition, although nocturia is the most commonly reported and most bothersome LUTS in men with or without evidence of BPH, few studies have examined the association of PA and nocturia independent of BPH. The purpose of this analysis was to examine the association of PA with BPH-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. We examined this association with both prevalent (n = 28,404) and incident (n = 4710) BPH-related outcomes (measured by self-report of physician diagnosis, BPH surgery, finasteride use, and clinical indicators) and nocturia. Poisson regression with robust variance was used to calculate prevalence ratios and relative risks. PA was weakly positively associated with several prevalent BPH-related outcomes and was strongly inversely associated with prevalent nocturia. In incident analyses, PA was only associated with nocturia. Men who were active ≥1 h·wk(-1) were 13% less likely (95% confidence interval, 2%-22%) to report nocturia and 34% less likely (95% confidence interval, 15%-49%) to report severe nocturia as compared with men who reported no PA. The associations were similar for men with and without additional BPH-related outcomes, except for prevalent nocturia, where the association was stronger for men without other BPH-related outcomes. Combined with other management strategies, PA may provide a strategy for the management of BPH-related outcomes, particularly nocturia.

Topical minoxidil fortified with finasteride: An account of maintenance of hair density after replacing oral finasteride.

Background:Finasteride acts by reducing dihydrotestosterone levels, thereby inhibiting miniaturization of hair follicles in patients with androgenetic alopecia (AGA). Oral finasteride is associated with side effects such as decreased libido, sexual dysfunction, and gynecomastia.Aim:The aim of the following study is to assess the efficacy of maintaining hair growth with 5% topical minoxidil fortified with 0.1% finasteride in patients with AGA after initial treatment with 5% topical minoxidil and oral finasteride for two years.Materials and Methods:A retrospective assessment was done in 50 male patients aged 20-40 years with AGA. All the patients had been initially treated with topical minoxidil and oral finasteride for a period of two years, after which the oral finasteride was replaced with topical minoxidil fortified with finasteride. Five of 50 patients had discontinued the treatment for a period of 8-12 months and were then resumed with only topical minoxidil fortified with finasteride. The patients’ case sheets and photographs were reviewed by independent observers and the efficacy of minoxidil-finasteride combination was assessed.Results:Of the 45 patients who underwent a continuous treatment for AGA, 84.44% maintained a good hair density with topical minoxidil-finasteride combinatio. Of the five patients who discontinued oral finasteride for 8-12 months, four demonstrated good improvement in hair density when treatment was resumed with topical minoxidil-finasteride combination.Conclusion:Topical finasteride can be considered for hair density maintenance after initial improvement with oral finasteride, thereby obviating the indefinite use of oral finasteride.

A population-based nested case-control study: the use of 5-alpha-reductase inhibitors and the increased risk of osteoporosis diagnosis in patients with benign prostate hyperplasia.

5-alpha-reductase inhibitors (5ARIs) are the potent androgen responsible for the development and enlargement of the prostate gland by decreasing dihydrotestosterone (DHT). This results in inhibition of the conversion of testosterone to dihydrotestosterone and markedly suppresses serum dihydrotestosterone levels. Testosterone replacement therapy improves bone density in men with hypogonadal osteoporosis. This study explores the possible association between the use of two typical 5ARIs (finasteride and dutasteride) and the subsequent risk of osteoporosis diagnosis. We identified 1352 osteoporosis diagnosis cases and 5387 control cases without osteoporosis diagnosis from the claims data for patients with benign prostate hyperplasia (BPH), which are collected in the Taiwanese National Health Insurance Research Database (NHIRD). Four controls were frequency matched to each case according to age (every 5years) and diagnosis date. We measured the effect of 5ARIs and determined the adjusted odds ratios (ORs) with 95% confidence intervals (CIs). We observed a 1·52-fold increase in osteoporosis diagnosis among patients with BPH using finasteride (95% CI, 1·01-2·30). Furthermore, a dosage analysis showed that higher doses of finasteride were associated with higher osteoporosis diagnosis risk (OR=1·68; 95% CI, 1·01-2·81), relative to the patients not using 5ARIs. This population-based nested case-control study suggests that the use of finasteride can increase the risk of osteoporosis diagnosis among patients with BPH. The effects were more prominent in patients using higher doses of finasteride.

Oral fluoroquinolone use and risk of peripheral neuropathy: a pharmacoepidemiologic study.

To quantify the risk of peripheral neuropathy (PN) with oral fluoroquinolone (FQ) use. We conducted a case-control study within a cohort of men aged 45 to 80 years in the United States followed from 2001 to 2011. Cases were defined as those with the first physician visit diagnosis of PN, polyneuropathy, or drug-induced polyneuropathy. Four controls were matched to each case by age, follow-up, and calendar time using density-based sampling. As a sensitivity analysis, we also quantified the risk of PN with finasteride use, a drug that is not expected to increase the risk of PN. Rate ratios (RRs) for current users of FQs were computed using conditional logistic regression, which was adjusted for chronic renal failure, chronic liver disease, hypothyroidism, postherpetic neuralgia, and the use of nitrofurantoin and metronidazole. We identified 6,226 cases and 24,904 controls. Current users of FQs were at a higher risk of developing PN (RR = 1.83, 95% confidence interval [CI] 1.49-2.27). Current new users had the highest risk (RR = 2.07, 95% CI 1.56-2.74). No risk was observed for current users of finasteride (RR = 1.21, 95% CI 0.97-1.51). Current users, especially new users of FQs, are at a higher risk of developing PN. Despite the increase in the use of FQs, clinicians should weigh the benefits against the risk of adverse events when prescribing these drugs to their patients.

Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia.

Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (AGA). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against AGA. Cases were 8 males (aged 29–43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23–49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.

Evaluation of the clinical indications, adverse drug reactions, and finasteride use in patients with benign prostatic hyperplasia in Poland

BackgroundBenign prostatic hyperplasia (LUTS/BPH) is one of the most common urinary disorders in elderly men. The symptoms of the disease include prostate gland enlargement, bladder outlet obstruction, and lower urinary tract symptoms (LUTSs). BPH predisposes patients to bladder infections and bladder stone formation and increases their risk of urinary retention, which in turn causes renal failure. Hence, the disease requires surgical treatment. However, over the recent years, the number of surgical interventions performed in pharmacotherapy has significantly reduced because of the increased efficacy of conservative therapy, including combination treatment mostly with 2 groups of drugs, namely, alpha-1-adrenolitics and other 5-alpha-reductase blockers, with a different pharmacological activity [5].The aim of this study was to evaluate the clinical indications, adverse drug reactions, and finasteride use in patients with diagnosed BPH in Poland. Materials and methodsWe conducted a clinical trial from November 2009 to November 2010 that included 5751 patients who were enrolled in 46 urological centres in Poland. The researchers who conducted the clinical trial were urologists from different regions of Poland. The clinical trial involved 6 follow-up visits. The mean age of the patients was 67 years (range, 45–93 years; median, 67.00; SD, 8.507). The inclusion criteria were as follows: LUTSs, finasteride therapy for at least 2 weeks, age>40 years, and BPH. ResultsPatients self-reported data on LUTSs, the symptom frequency, concurrent diseases, and intensification of urinary system symptoms. In addition, additional examinations were performed, including prostate-specific antigen test, urinary tract ultrasonography with evaluation of residual urine and prostate, and uroflowmetry. The study did not exclude data on the combined treatment with finasteride and alpha-1-adrenolitics. ConclusionFinasteride was demonstrated to be effective, as evidenced by the significant decrease in TPV by 40% even after 12 months. It was also found to contribute to the attenuation of LUTSs, improvement in maximum flow rate, decrease in nocturia, and improvement in QoL.

PD21-01 SEXUALLY TRANSMITTED INFECTIONS, BENIGN-PROSTATIC HYPERPLASIA AND NOCTURIA: RESULTS FROM THE PROSTATE, LUNG, COLORECTAL, AND OVARIAN CANCER SCREENING TRIAL

INTRODUCTION AND OBJECTIVES: The exact pathogenesis of benign prostatic hyperplasia (BPH) and related lower urinary tract symptoms (LUTS) remain unclear; however evidence supports a role of inflammation. One possible source of prostatic inflammation is sexually transmitted infections (STIs), which have been found to be positively related to subsequent LUTS in several small case-control studies. The objective of our analysis is to examine whether a history of STIs or positive STI serology is associated with prevalent and incident BPHrelated outcomes in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). METHODS: Self-reported history of STIs (gonorrhea, syphilis) was ascertained at baseline, and serological STIs (Chlamydia trachomatis, Trichomonas vaginalis, HPV-16, HPV-18, HSV-2, CMV and HHV-8) were detected using baseline serum specimens. We used data collected on the baseline questionnaire, as well as results from the baseline PSA test and digital rectal exam (DRE), to define prevalent BPH-related outcomes as evidence of LUTS (self-reported diagnosis of an enlarged prostate/BPH, BPH surgery, or nocturia (waking iÝ2times/night to urinate)) and evidence of prostate enlargement (PSA>1.4 ng/mL or prostate volume iÝ30 mL) in men without prostate cancer. We created a similar definition of incident BPH using data from the follow-up questionnaire completed 5-13 years after enrollment ((self-reported diagnosis of an enlarged prostate/BPH or nocturia), data on finasteride use during follow-up, and results from the follow-up PSA tests and DREs. We used Poisson regression with robust variance estimation to calculate prevalence ratios in our cross-sectional analysis of self-reported (n1⁄432,900) and serological STIs (n1⁄41,143) with prevalent BPH, and risk ratios in our prospective analysis of self-reported STIs with incident BPH (n1⁄45,226). RESULTS: Generally null results were observed for a self-reported history of STI or positive STI serologies with prevalent and incident BPH related outcomes, with the possible exception of T. vaginalis. CONCLUSIONS: Our findings do not support a causal role of STIs in the pathogenesis of BPH related outcomes, although T. vaginalis infection may warrant further study. Prevalent BPH-related outcomes Incident BPH-related outcomes

Hormonal manipulation of lower urinary tract symptoms secondary to benign prostatic obstruction.

Although the etiology of lower urinary tract symptoms (LUTS) is often multifactorial, a significant proportion of men over the age of 50 suffer from benign prostatic obstruction (BPO) secondary to benign prostatic hyperplasia. Prostate, being an androgen responsive organ is dependent on the male sex hormone, testosterone, for growth. Thus, treatment strategies that manipulate the levels of circulating hormones that influence the level of testosterone and/or prostatic growth represent an important potential option for patients suffering with troublesome LUTS due to BPO. Despite this, the only hormonal treatment that is currently used in daily clinical practice is the 5-alpha reductase inhibitor. In this article, we review the current evidence on the use of the 5-alpha reductase inhibitors finasteride and dutasteride. We also discuss new emerging hormonal manipulation strategies for patients with LUTS secondary to BPO.

Clinical effects and economical impact of dutasteride and finasteride therapy in Italian men with LUTS

To investigate differences in the risk of benign prostatic hyperplasia (BPH)- related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients under dutasteride or finasteride treatment. A retrospective cohort study was conducted using data from record-linkage of administrative databases. Men aged ≥ 40 years old who had received a prescription for at least 10 boxes/year (index years: 2004-06) were included. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score matched analysis and a 5-to-1, greedy 1:1 matching algorithm were performed. The budget impact analysis of dutasteride vs finasteride in BPH-treated patient was performed. From an initial cohort of about 1.5 million of Italian men, 19620 were selected. The overall hospitalization for BPH-non surgical reasons, for BPH-related surgery and for new detection of PCa incidence rates (IRs) were 8.20 (95% CI, 7.62-8.23), 18.0 (95% CI, 17.12-18.93) and 8.62 (95% CI, 8.03-9.26) per 1000 person-years, respectively. The multivariate analysis after the propensity score-matching showed that dutasteride was associated with an independent reduced likelihood of hospitalization for BPH-related surgery (HR 0.82; 95% CI 0.73-0.93; p = 0.0025) and of newly detected PCa (HR: 0.76,95% CI, 0.65-0.85; p = 0.0116). The IR for BPH-non surgical reasons was 8.07 (95% CI, 7.10-9.17) and 9.25 (95% CI, 8.19-10.44) per 1000 person-years, respectively. The IR for BPH-related surgery was 18.28 (95% CI, 17.17-20.32) and 21.28 (95% CI, 19.24-23.06) per 1000 person-years among patients under dutasteride compared with those under finasteride, respectively. For new-onset PCa, the IR was 8.01 (95% CI, 7.07-9.08) and 9.38 (95% CI, 8.32-10.58) per 1000 person-years The pharmacoeconomical evaluation showed that the net budget impact of the use of dutasteride vs. finasteride in 1000 BPH-treated patient for 1 year induces a saving of 3933 €. The clinical effects of dutasteride and finasteride are slightly different. The likelihood of hospitalization for BPH-related surgery and of newly detected PCa seems to be in favor of dutasteride. The budget impact analyses showed a slightly benefit for dutasteride. Comparative prospective studies are necessary to confirm these results.

Risk factors for intraoperative floppy iris syndrome: One year prospective study

AbstractPurpose Intraoperative Floppy Iris Syndrome (IFIS) was associated with a‐blockers use. Our purpose was to evaluate risk factors for IFIS in patients undergoing phacoemulsification.Methods Participants in our study were 1024 patients, who underwent routine phacoemulsification cataract surgery. The following data were recorded and evaluated as possible risk factors for IFIS: ophthalmological conditions (glaucoma, pseudoexfoliation, age‐related macular degeneration), sociodemographic features, axial length, hypertension, diabetes mellitus and medications being taken at the time of surgery. Cases were characterized intraoperatively as IFIS and non‐IFIS. Univariate and multivariate logistic regression was performed with SPSS 19.0.Results IFIS was observed in 61/1024 eyes (5.9%, 95%CI: 4.3%‐7.2%). Current use of tamsulosin, alfuzosin, terazosin, benzodiazepines, quetiapine and finasteride were all independently associated with IFIS. Borderline associations were noted for rivastigmine. Hypertension and short axial length were also significantly associated with IFIS. It is worthy to note that IFIS was not associated with the duration of a‐blockers intake.Conclusion Apart from the well‐established associations with alpha1‐adrenergic receptor antagonists, this prospective study points to benzodiazepines, quetiapine, hypertension and short axial length as potential risk factors for IFIS.

Should Finasteride Be Routinely Given Preoperatively for TURP?

Objective. The aim of the review was to compare the use of finasteride to placebo in patients undergoing TURP procedures. Material & Methods. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966–November 2011), EMBASE (1980–November 2011), CINAHL, Clinicaltrials.gov, Google Scholar, reference lists of articles, and abstracts from conference proceedings without language restriction for studies comparing finasteride to placebo patients needing TURPs. Results. Four randomised controlled trials were included comparing finasteride to a placebo. A meta-analysis was not conducted due to the disparity present in the results between the studies. Three of the studies found that finasteride could reduce either intra- or postoperative bleeding after TURP. One study found finasteride to significantly lower the microvessel density (MVD) and vascular endothelial growth factor (VEGF). None of the studies reported any long-term complications related to either the medication or the procedure. Conclusion. finasteride reduces bleeding either during or after TURP.

Aspirin Use is Associated with Lower Prostate Cancer Risk in Male Carriers of BRCA Mutations

Previous studies have shown that male BRCA mutation carriers stand at increased risk of developing prostate cancer and have concerns about developing cancer. Genetic counseling practitioners often discuss strategies for reducing the risk of cancer for patients at high risk due to their genetic background. Addressing modifiable health habits is one such strategy. Unfortunately, modifiable risk factors for prostate cancer have only been documented in the general population and have not yet been studied in the BRCA carrier subpopulation. Therefore, this study aimed to identify modifiable risk factors for prostate cancer in BRCA carriers. We examined prostate cancer risk factors in 74 men who were part of families with a BRCA mutation. This study examined nine dichotomous variables including: exercise, history of vasectomy, smoking history, alcohol use, finasteride use, statin use, aspirin use, coffee use, and vitamin use. The survey was sent to all cases of prostate cancer in the Hereditary Cancer Center Database at Creighton University with a known BRCA status. This study confirmed the protective benefits of daily aspirin use, which have been observed in previous studies of the general population, and suggests its benefit in BRCA carriers. Protective benefits from regular vigorous exercise and daily coffee use trended towards significance, but neither factor withstood the Bonferroni Correction for multiple comparisons.

Decreased Alcohol Consumption Among Former Male Users of Finasteride with Persistent Sexual Side Effects: A Preliminary Report

There is a robust literature in rodents, but not in humans, on the interaction between finasteride and alcohol, particularly as it relates to neurosteroids. Finasteride has been shown to reduce alcohol intake and suppress alcohol preference in male mice. This study examines the role of finasteride in alcohol consumption in humans with male pattern hair loss. The subjects were 83 otherwise healthy men who developed persistent sexual side effects associated with finasteride, despite the cessation of this medication for at least 3 months. Information from standardized interviews was collected regarding medical histories, sexual function, and alcohol consumption before and after finasteride use. Of the 63 men who consumed at least 1 alcoholic beverage/wk prior to starting finasteride, 41 (65%) noted a decrease in their alcohol consumption after stopping finasteride. This reduction typically began before discontinuing finasteride. Twenty men (32%) reported no change in their alcohol consumption, and 2 men (3%) reported an increase in their alcohol consumption. For the 63 consumers of alcohol, the mean number (± SE) of alcoholic beverages/wk declined from 5.2 ± 0.7 before finasteride to 2.0 ± 0.3 after finasteride (p < 0.0001). A major study limitation is the lack of a comparison group. In former male users of finasteride who developed persistent sexual side effects, 65% noticed a decline in their alcohol consumption as compared to baseline. This finding is consistent with finasteride's ability to modulate alcohol intake in rodents. Further research is needed on the central nervous system effects of finasteride in humans.

228 THE ASSOCIATION BETWEEN FINASTERIDE USE AND HIGH-GRADE OR LETHAL PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History (I)1 Apr 2013228 THE ASSOCIATION BETWEEN FINASTERIDE USE AND HIGH-GRADE OR LETHAL PROSTATE CANCER Mark A. Preston, Katherine Wilson, Sarah Coseo-Markt, Rongbin Ge, Edward Giovannucci, Christopher Morash, Meir Stampfer, Massimo Loda, Lorelei A. Mucci, and Aria F. Olumi Mark A. PrestonMark A. Preston Boston, MA More articles by this author , Katherine WilsonKatherine Wilson Boston, MA More articles by this author , Sarah Coseo-MarktSarah Coseo-Markt Boston, MA More articles by this author , Rongbin GeRongbin Ge Boston, MA More articles by this author , Edward GiovannucciEdward Giovannucci Boston, MA More articles by this author , Christopher MorashChristopher Morash Ottawa, Canada More articles by this author , Meir StampferMeir Stampfer Boston, MA More articles by this author , Massimo LodaMassimo Loda Boston, MA More articles by this author , Lorelei A. MucciLorelei A. Mucci Boston, MA More articles by this author , and Aria F. OlumiAria F. Olumi Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1608AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Despite the widespread use of 5-alpha reductase inhibitors (5-ARIs) for benign prostatic hyperplasia (BPH), there is much controversy regarding the potential risk of high-grade prostate cancer when 5-ARIs are used for prostate cancer chemoprevention. Our objective was to determine the association between finasteride use, including duration of use, and the development of total, high-grade or lethal prostate cancer. METHODS The Health Professionals Follow-up Study is a prospective cohort of United States male health professionals who were 40 to 75 years old at baseline in 1986. Finasteride use was assessed on questionnaires every two years from 1996, and 38,430 men who were cancer-free in 1996 were followed for prostate cancer diagnosis until 2010. Cox proportional-hazard models were used to estimate risk associated with finasteride use, adjusting for possible confounders including age, time period, recent smoking history, race, family history of prostate cancer, vigorous physical activity, BMI, height, history of diabetes mellitus, history and intensity of PSA testing, history of physical examinations, history of prostate biopsy or rectal ultrasound, statins, digoxin, alpha-blockers, saw palmetto use, and vasectomy. RESULTS During 452,576 person-years of follow-up, we ascertained 3710 prostate cancer cases, 578 of which were advanced and 463 of which were high-grade. Of 38,419 men at baseline in 1996, 2920 (7.6%) reported use of Finasteride between 1986-2010. The age-adjusted relative risk for ever-use of Finasteride compared with never-use was 1.04 (95% CI=0.89-1.22) for total disease. After adjusting for confounders, ever use of Finasteride was associated with significantly lower risk of total disease, Gleason 7 and low-grade disease. The multivariable-adjusted relative risk was 0.77 (95% CI=0.65-0.90) for total disease, 0.66 (95% CI=0.49-0.89) for Gleason 7 disease, and 0.73 (95% CI=0.57-0.94) for low-grade disease. Finasteride use was not associated with risk of high-grade (RR=1.00, 95% CI=0.67-1.49) or lethal disease (RR=0.95, 95% CI=0.56-1.63). CONCLUSIONS Finasteride use was associated with a decreased risk of overall, low-grade, and Gleason 7 prostate cancer. Finasteride use, however, was not associated with either lowering or increasing the risk of high grade, or lethal prostate cancer as may have been suggested by previously published studies. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e94 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mark A. Preston Boston, MA More articles by this author Katherine Wilson Boston, MA More articles by this author Sarah Coseo-Markt Boston, MA More articles by this author Rongbin Ge Boston, MA More articles by this author Edward Giovannucci Boston, MA More articles by this author Christopher Morash Ottawa, Canada More articles by this author Meir Stampfer Boston, MA More articles by this author Massimo Loda Boston, MA More articles by this author Lorelei A. Mucci Boston, MA More articles by this author Aria F. Olumi Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Major role for 5-alpha reductase inhibitors in the aging male

The Canadian consensus meeting, held in Toronto in May 2006, represents an important initiative in sorting out much of the confusion surrounding the use of 5-alpha reductase inhibitors (5ARIs) in clinical practice. The impact of the Medical Therapy of Prostatic Symptoms study and the Prostate Cancer Prevention Trial (PCPT) are quite dramatic as they confirm that 5ARIs, a class of drugs that never gained much market share in urologic practice, have significant impact on both benign prostatic hyperplasia (BPH) and prostate cancer- related outcomes. It is quite ironic that these pivotal trials, funded not by industry but by tax payers, have come to fruition at a time when finasteride is soon to be genericized in the United States. Commercial interests aside, this consensus summary provides useful information for urologists and primary care physicians. With respect to BPH-related outcomes, the 5ARIs have clearly demonstrable benefits in reducing long-term complications and lower urinary tract symptoms (LUTS). There is little debate on this topic. The impact of 5ARIs on prostate cancer prevention remains controversial and, in my mind, these recommendations have some limitations that deserve mention. With respect to the grade and volume bias, this observation, internationally led by our group, is real, and many other centres are now reporting it. We must emphasize that these recommendations report that this bias explains the PCPT grade issue “with a high degree of confidence.” While I truly believe this is the case, a small but lingering doubt must still exist within us all. It is essentially now unprovable! Perhaps more relevant than the grade issue is the clinical significance of the prevented cancers. Indeed, in the PCPT the relative risk reduction in “for-cause” biopsies, those that mirror clinical practice, is only 10%. I believe that future pivotal trials, such as REDUCE (the Reduction by Dutasteride of Prostate Cancer Events study; dutasteride v. placebo among men with negative prostate biopsy and elevated prostate-specific antigen), will help us clarify some of these issues. With respect to class effect and use of 5ARIs, I believe that both 5ARIs are good agents and that there are theoretical advantages to dutasteride in cancer prevention. Further trials will bear this out. What are clinicians to do? Consider the cancer prevention properties as an added benefit to complication reduction and symptom improvement for men with large-volume BPH and LUTS. In my view, either 5ARI is appropriate. Consider primary prevention with 5-ARI in ultra-high risk men, those in whom a cancer is likely to be clinically significant (e.g., men with strong family history, African-Canadians or both). In this setting, the best evidence would support the use of finasteride.

Crystallization Engineering in Aza-Steroid: Application in the Development of Finasteride

Novel and robust crystallization approach based on solid solution formation was developed for the purification of finasteride. This is an unprecedented approach that describes the use of pure finasteride 1 to purify different lots of finasteride 1 (impure) contaminated with dihydrofinasteride 2.

Persistent Sexual Side Effects of Finasteride: Could They Be Permanent?

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. To prospectively study whether the persistent sexual side effects associated with finasteride resolve or endure over time. 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. Scores from the Arizona Sexual Experience Scale (ASEX). 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. 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.

Secondary infertility due to use of low-dose finasteride

Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.