Medications Mostly Associated With Ejaculatory Disorders: Assessment of the Eudra-Vigilance and Food and Drug Administration Pharmacovigilance Databases Entries.

OBJECTIVE: To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis. METHODS: The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) and the Eudra-Vigilance (EV) database were queried to identify medications more commonly associated to ejaculatory disorders from September 10, 2012 to June 1, 2023. Proportional Reported Ratios (PRRs) were computed for all the selected drugs. RESULTS: Overall, 7404 reports of ejaculatory disorders reports were identified, and of these, 6854 cases (92.6%) were attributed to ten specific medications. On FDA-FAERS and EV databases, Paroxetine and Tamsulosin were the main responsible of delayed ejaculation (103/448 events, 23.0%) and retrograde ejaculation (366/1033 events, 35.4%), respectively. Finasteride was mostly related to painful ejaculation and ejaculation failure, with 150 events (7.8%) and 735 events (38.4%) respectively. Within the group of high-risk medications, Sildenafil presented higher risk of ejaculatory disorders than Tadalafil (PRR=5.85 (95%CI 5.09-6.78), P < .01). CONCLUSION: Ten drugs were recognized to display significant reporting levels of ejaculatory disorders. Among them, Finasteride and Sildenafil were responsible for the most reports in FDA-FAERS and in EV databases, respectively. Physicians should thoroughly counsel patients treated with these drugs about the risk of ejaculatory disorders. Further integration into clinical trials is needed to enhance the applicability and significance of these results.

Androgenetic alopecia in transgender and gender diverse populations: A review of therapeutics.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

Assessment of Frailty and Association With Progression of Benign Prostatic Hyperplasia Symptoms and Serious Adverse Events Among Men Using Drug Therapy.

Importance: Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy. Objective: To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE. Design, Setting, and Participants: This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021. Exposures: A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25). Main Outcomes and Measures: Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities. Results: Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76). Conclusions and Relevance: These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.

Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial.

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.

Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia.

PURPOSE: Clinicians use tamsulosin, an α1-adrenoceptor antagonist, to manage symptomatic benign prostatic hyperplasia (BPH). Because α1-adrenoceptors are also present in the brain, the potential exists for adverse effects on cognitive functions. We explored the association between tamsulosin use and dementia risk. METHODS: We used Medicare data (2006-2012) to conduct a cohort study among patients aged ≥65 years and diagnosed with BPH. Men taking tamsulosin (n = 253 136) were matched at a 1:1 ratio using propensity-scores to each of 6 comparison cohorts: patients who used no BPH-medication (n = 180 926), and patients who used the following alternative-BPH-medications: doxazosin (n = 28 581), terazosin (n = 23 858), alfuzosin (n = 17 934), dutasteride (n = 34 027), and finasteride (n = 38 767). Assessment began following the first fill of BPH-medication to identify incident dementia by ICD-9 diagnosis codes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for dementia using Cox proportional hazard regression for each of the 6 propensity-score-matched cohort-pairs. RESULTS: The median follow-up period for all cohorts was 19.8 months. After propensity-score matching, the tamsulosin cohort had an incidence of dementia of 31.3/1000 person-years compared with only 25.9/1000 person-years in the no-BPH-medication cohort. The risk of dementia was significantly higher in the tamsulosin cohort, when compared with the no-BPH-medication cohort (HR [95% CI]: 1.17 [1.14, 1.21]) and each of the alternative-BPH-medication cohorts: doxazosin (1.20 [1.12, 1.28]), terazosin (1.11 [1.04, 1.19]), alfuzosin (1.12 [1.03, 1.22]), dutasteride (1.26 [1.19, 1.34]), and finasteride (1.13 [1.07, 1.19]). The significance of these findings persisted in sensitivity analyses. CONCLUSION: Tamsulosin may increase the risk of dementia in older men with BPH.

Assessment of Urologists' Knowledge of Intraoperative Floppy Iris Syndrome.

OBJECTIVES: To assess urologists' awareness of intraoperative floppy iris syndrome. MATERIALS AND METHODS: A questionnaire composed of 21 questions was emailed to all of the Urology residency programs in the U.S. and all members of the Western section of the American Urological Association. Responses were collected and analyzed using statistical software. RESULTS: A total of 175 responses were collected from residents, fellows, and attending physicians from a wide range of geographic locations, subspecialties, and practice settings. Thirty percent of the urologists would routinely discuss intraoperative floppy iris syndrome with patients prior to start of benign prostate hyperplasia treatment. Twenty-one percent of the respondents never asked patients about ophthalmologic conditions prior to benign prostate hyperplasia treatment. If patients had concurrent visual complaints, only 37% of the respondents would routinely encourage patients to speak to an ophthalmologist and only 13% would routinely refer patients to an ophthalmologist. A comparison among the subgroups based on training status and practice settings further showed that a significantly higher percentage of residents would not ask about visual complaints or refer patients with visual complaints to an ophthalmologist compared with fellows and attending physicians (P <.01); however, there was no significant difference between urologists in academic and nonacademic settings (P >.05). CONCLUSION: Despite continuing effort to educate physicians about intraoperative floppy iris syndrome, there still exists a knowledge gap that may compromise patient care and further education is needed.

Hormonal manipulation of benign prostatic hyperplasia.

PURPOSE OF REVIEW: We provide new viewpoints of hormonal control of benign prostatic hyperplasia (BPH). The latest treatment findings with 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride, refined indications, efficacy, and safety are discussed and compared. We also discuss potential new 5-ARIs and other hormonal treatments. RECENT FINDINGS: Finasteride and dutasteride have equal efficacy and safety for the treatment and prevention of progression of BPH. 5-ARIs are especially recommended for prostates greater than 40 ml and PSA greater than 1.5 ng/ml. Combination therapy is the treatment of choice in these patients, but with prostate volume greater than 58 ml or International Prostate Symptom Score of at least 20, combinations have no advantage over 5-ARI monotherapy. Updates on the recent developments on BPH therapy with luteinizing hormone-releasing hormone (LHRH) antagonist are also reviewed and analyzed. Preclinical studies suggest that growth hormone-releasing hormone (GHRH) antagonists effectively shrink experimentally enlarged prostates alone or in combination with LHRH antagonists. SUMMARY: New 5-ARIs seem to be the promising agents that need further study. Preclinical studies revealed that GHRH and LHRH antagonists both can cause a reduction in prostate volume. Recent data indicate that prostate shrinkage is induced by the direct inhibitory action of GHRH and of LHRH antagonists exerted through prostatic receptors. The adverse effects of 5ARIs encourage alternative therapy.

[Chemoprevention of prostate cancer - a plea]. / Chemoprävention des Prostatakarzinoms - Ein Plädoyer.

The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way.

What's wrong with chemoprevention of prostate cancer?

When prostate-specific antigen (PSA) testing was introduced, proponents expected it to cut prostate-cancer mortality and did not expect it to unleash an epidemic of unnecessary treatments. Now that evidence of a mortality benefit remains unclear while evidence of overtreatment in undeniable, there is understandable interest in reducing the human costs of the PSA system. Two related drugs, finasteride and dutasteride, both proven to reduce the incidence of prostate cancer and the "risk of diagnosis," are being promoted accordingly. However, if not for the flaws of the PSA system the use of these drugs for purposes of prevention would lose its rationale. Not only are the drugs in this sense dependent on a faulty system, but their own mortality benefits are as speculative as PSA's-in addition to which, they introduce new risks.

Finasteride for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream, straining, urgency, frequency, incomplete emptying). Finasteride, a five-alpha reductase inhibitor (5ARI), blocks the conversion of testosterone to dihydrotestosterone, reduces prostate size, and is commonly used to treat symptoms associated with BPH. OBJECTIVES: To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms (LUTS). SEARCH STRATEGY: We searched The Cochrane Library (which includes CDSR (Cochrane Database of Systematic Reviews), DARE (Database of Abstracts of Reviews of Effects), HTA (Heath Technology Assessments), and CENTRAL (Cochrane Central Register of Controlled Trials, and which includes EMBASE and MEDLINE), LILACS (Latin American and Caribbean Center on Health Sciences Information) and Google Scholar for randomized, controlled trials (RCTs). We also handsearched systematic reviews, references, and clinical-practice guidelines. SELECTION CRITERIA: Randomized trials in the English language with placebo and/or active arms with a duration of at least 6 months. DATA COLLECTION AND ANALYSIS: JT extracted the data, which included patient characteristics, outcomes, and harms. Our primary outcome was change in a validated, urinary symptom-scale score, such as the AUA/IPSS. A clinically meaningful change was defined as 4 points. We also categorized outcomes by trial lengths of ≤ 1 year (short term) and > 1 year (long term). MAIN RESULTS: Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration, and significantly lowered the risk of BPH progression (acute urinary retention, risk of surgical intervention, ≥ 4 point increase in the AUASI/IPSS). In comparison to alpha-blocker monotherapy, finasteride was less effective than either doxazosin or terazosin, but equally effective compared to tamsulosin. Both doxazosin and terazosin were significantly more likely than finasteride to improve peak urine flow and nocturia, versus finasteride. Versus tamsulosin, peak urine flow and QoL improved equally well versus finasteride. However, finasteride was associated with a lower risk of surgical intervention compared to doxazosin, but not to terazosin, while finasteride and doxazosin were no different for risk of acute urinary retention. Two small trials reported no difference in urinary symptom scores between finasteride and tamsulosin. Finasteride + doxazosin and doxazosin monotherapy improved urinary symptoms equally well (≥ 4 point improvement).For finasteride, there was an increased risk of ejaculation disorder, impotence, and lowered libido, versus placebo. Versus doxazosin, finasteride had a lower risk of asthenia, dizziness, and postural hypotension, and versus terazosin, finasteride had a significant, lower risk of asthenia, dizziness, and postural hypotension. AUTHORS' CONCLUSIONS: Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.

[Finasteride: 10 years of clinical use. Systematic review of the literature]. / Finasterida: diez años de uso clínico. Revisión sistemática de la literatura.

INTRODUCTION: After ten years of clinical use of Finasteride in patients with BPH, we carried out a systematic review of the literature including the assessment of their quality and grading the level of evidence for clinical recommendations. METHODS: Using Medline, Embase, Healthstar and Cochrane Library from 1990 until 2002, we select all the studies referring patients between 50 to 85 with symptoms of BPH, metrics of flow, prostatic volume, postmictional residue, detrusor pressure, adverse effects, cost-effectiveness and quality of life. RESULTS: We found out 135 references, of which 36 accomplish the inclusion criteria. Of those, 3 have got level I of evidence, 12 level II, 6 level III and 10 level IV. Three are economic studies and two evaluate the quality of life. DISCUSSION: With a high level of evidence and after ten years of clinical use, Finasteride shows its effectiveness in reducing the symptoms of patients with prostate bigger than 40 ml and/or PSA of more than 1.4 ngr/ml, with scarce adverse effects with a clear improvement of quality of life. Therefore, it is recommended (grade A) for clinical use. CONCLUSIONS: Finasteride, through prostate volume reduction, modify natural evolution of BPH, decreasing the risk of acute urine retention and surgery.

Finasteride and tamsulosin used in benign prostatic hypertrophy: a review of the prescription-event monitoring data.

OBJECTIVE: To review the results of non-interventional observational cohort studies of 14 772 patients treated with finasteride and 12 484 patients treated with tamsulosin, both studies being of national proportions and undertaken in general medical practice in England. METHODS: Both studies were undertaken by prescription-event monitoring (PEM), whereby the exposure data are derived from information provided in strict confidence by the Prescription Pricing Authority of the National Health Service. The outcome data are derived from 'green form' questionnaires completed by the prescribing general practitioners (GPs). Additional data are obtained by medical follow-up with the attending practitioners. Adverse experience was measured in three ways; as reports of events which the doctors considered to represent adverse drug reactions; as reports of reasons for stopping the drug; and by studying the incidence density of each reported event. For these purposes a computerized dictionary containing 1430 higher level terms was used. The duration of exposure in the finasteride study was approximately 1 year and was approximately 6 months in the tamsulosin study. RESULTS: The outcome data on the 14 772 and 12 484 patients treated in the finasteride and tamsulosin studies were derived from the 63% and 57.4% of the green forms sent out and returned, respectively. The finasteride cohort included two women and the tamsulosin cohort 70 women. The mean (SD) age of the men in the two cohorts was, respectively, 69.0 (9.2) and 66.2 (11.7) years. Both drugs were well tolerated on long-term therapy and 69.6% (10 274 patients) of the total finasteride and 62.0% (7739 patients) of the total tamsulosin cohort were still receiving the drug at the end of 6 months. In the finasteride study, impotence or ejaculatory failure was reported in 2.0% of the patients still receiving the drug; there were reports of decreased libido in 1.0% and gynaecomastia was reported whilst the drug was still being prescribed in 39 patients (0.3% of the cohort). With tamsulosin, uncommon cases of dizziness, headache, malaise and hypotension (89 reports in 12 484 patients, i.e. 0.7% of the cohort) were common to the findings of reported adverse reactions, reasons for stopping the drug and events of highest incidence density. None of the deaths which occurred in either of these large cohorts was attributed by either the reporting GPs or the PEM medical staff to the drugs examined. Conclusion The GPs rated the drugs effective in most patients; tolerance and adverse experience was consistent with the known pharmacology of the two drugs. No serious, unexpected adverse effects were identified.

Economic analysis of finasteride: a model-based approach using data from the Proscar Long-Term Efficacy and Safety Study.

Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in older men in the United States. BPH is often associated with a reduction in quality of life and may progress to acute urinary retention (AUR), the inability to pass any urine. Recently, a 4-year placebo-controlled clinical trial known as the Proscar Long-Term Efficacy and Safety Study (PLESS) demonstrated that finasteride use reduces the risk of developing AUR by 57% and the need for BPH-related surgery by 55%. The economic implications of these findings were investigated using a model-based decision-analytic approach to compare finasteride with both watchful waiting and alpha-blocker therapy. The modeling used the longest-term published controlled data concerning alpha-blockers, which were for the alpha-blocker terazosin. The base case considered a 64-year-old man (the mean age of a PLESS patient) with prostatic enlargement on digital rectal examination and moderate-to-severe symptoms of BPH. The model suggested savings in surgical and AUR costs with finasteride versus watchful waiting, with an estimated 25% of total finasteride costs recouped in savings on surgical events avoided in the first year. Over 2 years, the expected cost per patient starting finasteride therapy was $2304, whereas the expected cost per patient starting terazosin was $2334. Analyses also explored the variation in economic results by baseline levels of prostate-specific antigen (PSA), a proxy for prostate volume. For patients with PSA levels > or =1.4 ng/mL, expected 2-year costs with finasteride and terazosin were $2342 and $2479, respectively. For patients with PSA levels > or =3.3 ng/mL, expected 2-year costs with finasteride were $373 less than with terazosin ($2347 vs $2720). Results were robust over a range of model assumptions and cost estimates. The analyses illustrate that all medical interventions, including watchful waiting, have associated costs. Finasteride shows cost offsets compared with watchful waiting and cost savings compared with terazosin over 2 years. Finasteride appears to be more economical in men with higher PSA levels.

Finasteride: an update of its use in the management of symptomatic benign prostatic hyperplasia.

UNLABELLED: Finasteride inhibits type 25alpha-reductase activity, significantly reducing dihydrotestosterone levels. Consequent reductions in prostate volume, increases in urinary flow rates and improvements in symptoms compared with placebo have been observed in trials of up to 4 years' duration and in noncomparative extensions (for up to 6 years). Results from the 4-year placebo-controlled PLESS trial show finasteride to significantly reduce the risk of benign prostatic hypertrophy (BPH)-related acute urinary retention and the requirement for surgical intervention. Finasteride has significantly greater efficacy in patients with a large prostate (> or = 40 ml) than in patients with a small prostate. However, the predictive value of prostate size has been questioned. Results of an earlier comparative 1-year trial show terazosin monotherapy and terazosin plus finasteride therapy to be significantly more effective than both finasteride monotherapy and placebo in reducing symptom scores and improving maximum urinary flow rates. Prostatic volume was significantly reduced by finasteride monotherapy and combination therapy only. The overall efficacy of finasteride in patients with mild to moderate symptomatic BPH tended to be greater than that of serenoa repens (Permixon) in a 6-month trial. A US cost analysis model indicates that finasteride and terazosin are less expensive than transurethral resection of the prostate (TURP) during the first 2 years of initiation. Canadian cost-effectiveness and cost-utility analyses using decision analysis modelling have shown primary intervention with finasteride to provide more quality-adjusted life years (QALYs) at lesser cost than watchful waiting or TURP in patients with moderate symptoms who receive the drug for < or = 3 years and < or = 14 years, respectively, but fewer QALYs at a higher cost in patients with severe symptoms needing therapy for > or = 4 years. Confirmatory prospective economic studies are required. Finasteride appears to improve overall quality of life to a similar extent to serenoa repens; patient satisfaction appears similar with finasteride and TURP. Finasteride is generally well tolerated. Most commonly reported adverse effects are sexually related (1 to 2.1 %). Gynaecomastia has been reported in 0.4% of patients. CONCLUSIONS: Despite modest improvements in maximum urinary flow rates and symptom scores, finasteride is a first-line treatment option in those with moderate uncomplicated BPH, especially in patients with a large prostate (> or = 40 ml). It is also an option in patients with more severe symptoms who are unable or unwilling to undergo surgery and in those awaiting surgery. Importantly, finasteride appears to reduce disease progression, significantly decreasing the incidence of acute urinary retention and the requirement for surgical intervention; to date, no other pharmacological agent has been shown to reduce these outcomes.

Treatment of benign prostatic hyperplasia. A pharmacoeconomic perspective.

Men with moderate symptoms of benign prostatic hyperplasia (BPH) are the best candidates for medical treatment, while surgery is usually indicated for patients with severe symptoms. Men with mild symptoms do not usually need treatment, but they might be re-evaluated annually if desirable. Finasteride, which produces selective hormonal deprivation, is now established as a well tolerated drug for the long term medical therapy of BPH. Recent studies suggest that finasteride is most effective in men with large prostates (> 40 ml), and the drug should probably be reserved for these patients. alpha-Blockers work in men with small or large prostates, and their rapid onset of action facilitates the identification of responders. alpha-Blockers are more effective than finasteride during the first year of treatment, but only finasteride induces regression of the prostate and offers increased efficacy over time. Even if drug therapy reduces the need for prostate surgery, the total economic cost of BPH treatment is likely to rise because of the increasing application of medical treatment. The magnitude of this increase depends largely on what percentage of the male population embark on long term therapy, at what age treatment is started, and how successful it is. At present, the answers to these questions are largely unknown. The personal economic expenses for men who begin long term medical therapy will probably be an important factor in deciding how common drug treatment for BPH will become in the future. For many men, the main benefit of drug treatment will be the relief of urinary symptoms, but whether this improvement is substantial enough to improve their overall quality of life has not yet been clearly demonstrated in controlled studies.

Assessment of the pharmacokinetic-pharmacodynamic interaction between terazosin and finasteride.

The pharmacokinetic-pharmacodynamic interaction between terazosin and finasteride was evaluated in an 18-day, parallel, open-label, randomized study. Forty-eight non-smoking, healthy, adult male volunteers entered the study. One third of the participants received terazosin alone, one third received terazosin and finasteride, and one third received finasteride alone. Multiple-dose coadministration of terazosin and finasteride did not alter the central values of steady-state pharmacokinetic parameters of either drug in a statistically significant manner. Compared with the single-agent groups, however, the group taking finasteride and terazosin had higher variability in the pharmacokinetic parameters of both drugs. Testosterone concentrations were not altered after administration of finasteride and terazosin alone or in combination. Terazosin administered alone did not affect the dihydrotestosterone concentrations. The significant reduction in dihydrotestosterone concentrations induced by administration of finasteride was not affected by coadministration of terazosin. Mean changes in blood pressure and pulse rate in these normotensive volunteers were generally slight; therefore, concurrent administration of multiple doses of terazosin and finasteride did not produce significant clinical concern.

Healthcare resources should be targeted to chemoprevention: the argument against.

Chemoprevention of prostate cancer is an attractive idea that appeals to many struggling with the treatment of this disease. Many details inherent in any preventive strategy must be considered before embarking on this course, no matter how seductive it may appear. Critical issues of effectiveness, cost, difficulties in implementation, side effects, duration of the preventive cycle, and public acceptance may thwart prevention of prostate cancer from being implemented in the near future.