Neither author has a financial or proprietary interest in any material or method mentioned.
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The purpose of this review is to highlight the most important developments in the diagnosis, prevention, and management of prostate cancer reported in the past year that have been published in the medical literature.
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Finasteride increased sexual dysfunction only slightly and its impact diminished over time; the increase in the Sexual Activity Scale score relative to placebo of 3.21 points (95% confidence interval [CI] = 2.83 to 3.59 points; P<.001) at the first assessment decreased to 2.11 points (95% CI = 1.44 to 2.81 points; P<.001) at the end of study. These Sexual Activity score values were small on a scale of 0-100, the range observed in the study, and in comparison with individual variation. After adjustment for all covariates, mean sexual dysfunction increased in both arms from baseline (6 months after randomization) by 1.26 Sexual Activity points (95% CI = 1.16 to 1.36 points; P<.001) per year, corresponding to a cumulative increase of 8.22 points (95% CI = 7.52 to 8.92 points; P<.001) over the study period.
There were similar effects of finasteride administration to the amygdala to attenuate antianxiety behavior in naturally receptive and ovx, hormone-primed rats. Finasteride administration significantly decreased central entries in the open field, decreased open arm time in the elevated plus maze, increased defensive freezing in response to footshock, and increased time spent immobile compared to vehicle.
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These recent developments in the field of AGA hold some promise and may play a role in the future management.
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It has long been suspected that sex steroids play a key role in the pathogenesis of benign prostatic hyperplasia (BPH). Prostatic diseases do not occur in males castrated before puberty or in males with heritable disorders of androgen production or action. Both estrogens and androgens have been shown to induce BPH in experimental animals.
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).
Nationwide random sample of PCPs and urologists, selected from the American Medical Association Registry.
Published studies were identified in a search of MEDLINE. Information about ongoing studies was provided by author access to protocols.
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Caffeine is the main treatment for apnoea in preterm neonates, but its interactions with other respiratory stimulants like progesterone are unknown. We tested the hypothesis that the addition of progesterone to caffeine treatments further stimulates ventilation. Newborn rats were treated with water (control) or caffeine (15 mg kg(-1)) by daily gavage between postnatal day (P)3 and P12. At P4 and P12, we measured apnoea frequency, ventilatory responses and metabolic parameters under both normoxia and hypoxia (12% O2, 20 min) following an acute administration of either saline or progesterone (4 mg kg(-1); i.p.). Progesterone injection increased the serum levels of both progesterone and its neuroactive metabolite allopregnanolone. Progesterone had no effect on ventilation in control rats under normoxia. Progesterone depressed ventilation in P12 caffeine-treated rats under normoxia and hypoxia and increased apnoea frequency in both P4 and P12 rats. Because allopregnanolone is an allosteric modulator of GABAA receptors and caffeine may enhance GABAergic inhibition in newborns, we studied the effects of the GABAA receptor antagonist bicuculline at 0, 1, 2 and 3 mg kg(-1) doses and allopregnanolone (10 mg kg(-1) dose) in P12 rats. In caffeine-treated rats, bicuculline enhanced ventilation, while allopregnanolone decreased ventilation and increased total apnoea time. Progesterone had no effect on ventilation and apnoea frequency in caffeine-treated rats injected with finasteride, which blocks the conversion of progesterone to allopregnanolone. We conclude that combining progesterone and chronic caffeine therapy is not an option for the treatment of persistent apnoea in preterm neonates, unless the effects of allopregnanolone can be counteracted.
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Senescence is associated with hormonal imbalance and prostatic disorders. Angiogenesis is fundamental for the progression of malignant lesions and is a promising target for prostate cancer treatment. The aim was to characterize matrix metalloproteinase-9 (MMP-9) and insulin-like growth factor receptor-1 (IGFR-1) responses in the prostate during senescence and following antiangiogenic and/or androgen ablation therapies, comparing them to cancer progression features in TRAMP mice. Aged male mice (52-week-old FVB) were submitted to antiangiogenic treatments with SU5416 (6 mg/kg; i.p.) and/or TNP-470 (15 mg/kg; s.c). Finasteride (20 mg/kg; s.c.) was administered alone or associated to both inhibitors. Dorsolateral prostate was collected for light microscopy, and immunohistochemistry and Western blotting collected for MMP-9 and IGFR-1. Senescence led to inflammation and different proliferative lesions in the prostate, as well as to increased MMP-9 and IGFR-1, resembling TRAMP mice prostatic microenvironment. Antiangiogenic therapies promoted recovery and/or interruption of age-associated alterations, presenting differential effects on the molecules studied. SU5416 acted mainly on MMP-9, whereas TNP-470 showed its best influence on IGFR-1 levels. Finasteride administration, alone or in combination with antiangiogenic agents, also resulted in regression of inflammation and neoplastic lesions, besides having a negative modulatory effect on both MMP-9 and IGFR-1. We concluded that stimulated tissue remodeling and proliferative processes during senescence predisposed the prostate to malignant disorders. The combination of different agents was more effective to minimize prostatic imbalance during this period, probably due to the differential action of each drug on factors involved in cell proliferation and extracellular matrix remodeling, resulting in a broader spectrum of effects following the combined treatment.
A total of 5090 patients met selection criteria. After 1 year of 5ARI therapy, the AUR rate was lower for dutasteride (12%) when compared with finasteride (14.7%) (odds ratio [OR], 0.79; P = .0042). Risks for prostate-related surgeries were also lower among dutasteride-treated patients (3.9% vs 5.1%, respectively; OR, 0.77; P = .03).
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In an attempt to maximize the quality of life of advanced prostate cancer patients on prolonged total androgen ablation and to minimize side effects, we have devised a strategy of 'sequential androgen blockade'. Animal studies have demonstrated that the combination of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide was as effective as a luteinizing hormone-releasing hormone analog and flutamide in inhibiting the growth of the prostate. In a pilot trial, 10 potent patients with clinical stage C and D1 prostate cancer were given the combination of finasteride (5 mg b.i.d.) and flutamide (125-250 mg t.i.d.). Eight of ten men remained potent. At 3 months the mean prostate-specific antigen level of all patients was 3.8 ng/ml (34 ng/ml prior to therapy). In all patients serum testosterone increased and those with the highest increase demonstrated gynecomastia. The combination was easily tolerable and side effects were few. This treatment regime appears to offer the benefits of total androgen blockade, is less expensive and has fewer side effects. Further trials are warranted.
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Botulinum toxin A (BoNT-A) injections into the prostate have been reported to be effective and durable in the treatment of small benign prostatic hyperplasia (BPH). This study evaluated the effectiveness of BoNT-A in patients with large BPH with an unsatisfactory response to combined alpha-blocker and 5-alpha-reductase inhibitor therapy.
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The aim of this study was to: (1) determine effects of finasteride on transition zone (TZ) volume, TZ ratio (TZ volume/total prostate volume), and total prostate volume; (2) analyze differences in TZ and total volume reduction among patients who improve peak urinary flow rates following finasteride therapy with those who do not; (3) investigate which parameters correlate with improvement in peak urinary flow rate and urinary symptom score; and (4) establish if there is any predictive value of these parameters for response to therapy.
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We conducted a nested case-control study using medical administrative databases. All men older than 65 years of age who had filled at least one prescription for nonselective nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors (coxibs), aspirin, or acetaminophen between January 1999 and December 2002 were eligible. Among this group, we identified men who underwent prostate biopsy between January 2000 and June 2002 and did not have a diagnosis of any cancer in the preceding 2-year period. Cases were those with a diagnosis of prostate cancer. Controls were those who did not receive a diagnosis of any cancer. Logistic regression models were used to determine associations between prostate cancer occurrence and frequent exposure (more than 4 months) to nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors or aspirin during the prior 2 years in comparison with no exposure to any of these drugs, adjusting for age and prior finasteride use.
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Of the 850 questionnaires sent, 302 were returned, and 277 of those were included in the final analysis (response rate 32.6%). Korean urologists preferred urethral catheterization as the initial management. Of respondents, 154 (55.6%) and 109 (39.4%) started their patients on alpha-blockers and alpha-blockers with finasteride, respectively. Nearly half (50.2%) used a trial without catheter 7 days after catheterization. One failed trial without catheter was an indication for surgery for only 69 (24.9%) of the respondents. A second trial without catheter was advocated by 108 (39.0%). Most urologists (82.3%) expected to be successful with the above management in 50% or greater. Physician's demographics or types of initial management did not influence physician's perception of expected success rate when the expected success rate was divided as < or =50% and >50.
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This exploratory study establishes that karyometric monitoring can track the results of subtle nuclear changes induced by preventive interventions in men with CaP, thus allowing assessment of agent activity in a cost-effective manner.
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Finasteride significantly improved hair growth at one year compared to placebo (p < 0.05) based on analysis of photographs of the vertex and superior-frontal scalp. These results were consistent with the hair count change measured in the finasteride group, which was superior (p < 0.05) to the change measured in the placebo group. Patient self-assessment demonstrated that treatment with finasteride, in comparison to placebo, led to improvements in scalp hair growth and patients' satisfaction with appearance of hair. No drug-related adverse events were reported during the study.