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Improvement in androgenetic alopecia in 53-76-year-old men using oral finasteride.

Twenty-eight men with AGA, aged 53-76 years (mean, 65 years), were selected to participate in this trial from a double blind, placebo controlled, multicenter study of subjects with moderate symptoms of BPH. Patients received either finasteride 5 mg or placebo daily for 24 months. Hair counts were performed at entry to the study and at 6, 12, 18, and 24 months. Hair counts were made directly on the scalp in a circular target area 1 in in diameter, located in the center of a template. The template was applied in such a way that its counting window fell on the most balding scalp area, which remained the same for each patient.11 At each hair counting session, patients were asked about side-effects and questioned about their sex life. Time trend and differences between groups were examined using a one-way (treatment) MANOVA with repeated measures (baseline, 6, 12, 18, and 24 months). Additional two-tailed t-tests were performed to compare the two groups at each point of time. P < 0.05 was considered to be significant.

5-alpha Reductase Inhibitors↗

Progesterone enhances ethanol-induced modulation of mesocortical dopamine neurons: antagonism by finasteride.

The effect of endogenous 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG) on the modulation of mesocortical dopamine extracellular concentration by ethanol was investigated by microdialysis in rats. Intraperitoneal injection of progesterone (5 mg/kg, once a day for 5 days) increased the cortical content of 3alpha,5alpha-TH PROG and potentiated the biphasic effect of acute intraperitoneal administration of ethanol on dopamine content. A dose of ethanol (0.25 g/kg) that was ineffective in naïve rats induced a 55% increase in dopamine extracellular concentration in rats pretreated with progesterone. This increase was similar to that induced by a higher dose (0.5 g/kg) of ethanol in naïve rats. Administration of ethanol at 0.5 g/kg to progesterone-pretreated rats inhibited dopamine content by an extent similar to that observed with an even higher dose (1 g/kg) in naïve rats. The administration of the 5alpha-reductase inhibitor finasteride (25 mg/kg, subcutaneous), together with progesterone, prevented the effects of the latter, both on the cortical concentration of 3alpha,5alpha-TH PROG and on the modulation by ethanol of dopamine content. These data suggest that 3alpha,5alpha-TH PROG contributes to the action of ethanol on the mesocortical dopaminergic system. They also suggest that physiological fluctuations in the brain concentrations of neuroactive steroids associated with the oestrous cycle, menopause, pregnancy and stress may alter the response of mesocortical dopaminergic neurons to ethanol.

Animals↗

Impact of finasteride treatment on perioperative bleeding before transurethral resection of the prostate: a prospective randomized study.

In this preliminary, randomized study, 35 men were pretreated for 3 months with finasteride or placebo before transurethral resection of the prostate. The study was inconclusive because it did not show any benefit in terms of reducing perioperative bleeding during or after the resection but there is a need for a large, prospective, randomized study.

Aged↗

Further errors in polymorph identification: furosemide and finasteride.

Reassessment of the reported single-crystal X-ray diffraction characterization of polymorphs of furosemide and finasteride shows that, in each case, incomplete data collections have resulted in the mistaken identification of two forms that are, in fact, identical.

Crystallography, X-Ray↗

Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone.

Older men, particularly those with low serum testosterone (T) levels, might benefit from T therapy to improve bone mineral density (BMD) and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men. We hypothesized that the combination of T and finasteride (F), a 5 alpha-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate. Seventy men aged 65 yr or older, with a serum T less than 12.1 nmol/liter on two occasions, were randomly assigned to receive one of three regimens for 36 months: T enanthate, 200 mg im every 2 wk with placebo pills daily (T-only); T enanthate, 200 mg every 2 wk with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not an inclusion criterion. We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry. Prostate-specific antigen (PSA) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate. Fifty men completed the 36-month protocol. By an intent-to-treat analysis including all men for as long as they contributed data, T therapy for 36 months increased BMD in these men at the lumbar spine [10.2 +/- 1.4% (mean percentage increase from baseline +/- SEM; T-only) and 9.3 +/- 1.4% (T+F) vs. 1.3 +/- 1.4% for placebo (P < 0.001)] and in the hip [2.7 +/- 0.7% (T-only) and 2.2 +/- 0.7% (T+F) vs. -0.2 +/- 0.7% for placebo, (P < or = 0.02)]. Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip. After 6 months of therapy, urinary deoxypyridinoline (a bone-resorption marker) decreased significantly compared with baseline in both the T-only and T+F groups (P < 0.001) but was not significantly reduced compared with the placebo group. Over 36 months, PSA increased significantly from baseline in the T-only group (P < 0.001). Prostate volume increased in all groups during the 36-month treatment period, but this increase was significantly less in the T+F group compared with both the T-only and placebo groups (P = 0.02). These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months, both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men. In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy. These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels.

Aged↗

Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T.

Testosterone (T) therapy in older men with low serum T levels increases lean body mass and decreases fat mass. These changes might improve physical performance and strength; however, it has not been established whether T therapy improves functional outcome in older men. Moreover, concerns exist about the impact of T therapy on the prostate in older men. The administration of finasteride (F), which partially blocks the conversion of T to the more potent androgen, dihydrotestosterone, attenuates the impact of T replacement on prostate size and prostate-specific antigen. We hypothesized that T replacement in older, hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance, strength, and body composition. Seventy men with low serum T (<350 ng/dl), age 65 yr and older, were randomly assigned to receive one of three regimens for 36 months: 1) T enanthate, 200 mg im every 2 wk, with placebo pills daily (T-only); 2) T enanthate, 200 mg every 2 wk, with 5 mg F daily (T + F); or 3) placebo injections and pills (placebo). We obtained serial measurements of timed physical performance, grip strength, lower extremity strength, body composition (by dual-energy x-ray absorptiometry), fasting cholesterol profiles, and hormones. Fifty men completed the 36-month protocol. After 36 months, T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [4.3 +/- 1.6% (mean +/- sem, T-only) and 3.8 +/- 1.0% (T + F) vs. -5.6 +/- 1.9% for placebo (P < 0.002 for both T and T + F vs. placebo)] and increased handgrip strength compared with baseline and placebo (P < 0.05). T therapy increased lean body mass [3.77 +/- 0.55 kg (T-only) and 3.64 +/- 0.56 kg (T + F) vs. -0.21 +/- 0.55 kg for placebo (P < 0.0001)], decreased fat mass, and significantly decreased total cholesterol, low-density lipoprotein, and leptin, without affecting high-density lipoprotein, adiponectin, or fasting insulin levels. These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months, when administered alone or when combined with F, and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men.

Adiponectin↗

Inhibition of steroid 5 alpha-reductase with finasteride: sleep-related erections, potency, and libido in healthy men.

To objectively measure the effects of a 5 alpha-reductase inhibitor on erectile function, we studied 20 sexually active men (aged 41-64 yr) during double blind, randomized administration of 5 mg/day finasteride (F) or placebo (P). Serum testosterone and dihydrotestosterone (DHT) were measured every 4 weeks. Sleep-related erections were assessed with comprehensive polysomnography for 2 nights before randomization (session 1) and at week 12 (session 2). Sexual function questionnaires were administered weekly. Serum DHT levels at week 0 were 1.47 +/- 0.11 and 1.16 +/- 0.27 nmol/L (P > 0.05) in the P and F groups, respectively. F group levels fell to 31% and 28% of control values at week 4 and 12. Penile tip peak tumescence time increased on second nights more in the P than the F group at 12 weeks, producing a session main effect (P < 0.02) and a group X session interaction (P < 0.05). No significant group X session interactions were found for any sleep erection measures in a best night analysis or for self-reported sexual activity. Thus, F did not consistently suppress sleep-related erections compared to P. F primarily inhibits type 2 5 alpha-reductase activity; however, type 1 5 alpha-reductase is the major enzyme in the central nervous system. Therefore, DHT involvement in the maintenance of libido and potency is not excluded. Nonetheless, these data support the feasibility of using a type 2 inhibitor to treat benign prostatic hyperplasia without impairing erectile function.

5-alpha Reductase Inhibitors↗

Chemoprevention of prostate cancer with finasteride.

Prostate cancer is a significant cause of disease and death, making it an attractive target for chemoprevention. The association between lifetime exposure to dihydrotestosterone and risk of developing prostate cancer suggests that chemoprevention is possible with 5alpha-reductase inhibition. The recently completed Prostate Cancer Prevention Trial indicates that chemoprevention is possible with the 5alpha-reductase inhibitor finasteride. Development of a cost-effective chemoprevention strategy for prostate cancer is evolving, and is expected to have significant positive economic and public health benefits.

Animals↗

Oral testosterone in oil: pharmacokinetic effects of 5alpha reduction by finasteride or dutasteride and food intake in men.

Oral administration of 400 mg of testosterone (T) in oil, when combined with the 5alpha reductase inhibitor dutasteride (D), elevates serum T in medically castrated men to the normal range. In this study, we sought to determine the impact of 1) finasteride (F) and 2) food intake on the serum T and dihydrotestosterone (DHT) levels observed after the oral administration of T in oil. Therefore, we conducted a pharmacokinetic study of oral T in oil, alone or with D or F, in the fasting and fed states in normal men whose endogenous T production was suppressed by the GnRH antagonist acyline. After acyline administration, 7 healthy men (mean age 31 +/- 8 years) were sequentially administered five 400-mg doses of oral T in sesame oil once daily. The first dose of oral T (T-alone) in oil was given while fasting without F or D. The second (fasting) and third (fed) doses were administered after pretreatment with F (T + F). Four days later, the fourth (fasting) and fifth (fed) doses were administered after pretreatment with D (T + D). Blood samples for measurement of serum T and DHT were obtained before T dosing and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each administration. In the fasting state, 24-hour area-under-the-curve of serum T after oral T administration was significantly greater with coadministration of either D or F compared with T-alone (126 +/- 36 nmol-h/L [T-alone] vs 287 +/- 98 nmol-h/L [T + F] vs 236 +/- 82 nmol-h/L [T + D]; P < .05 for T + F and T + D vs T-alone). Administration of the T with food nonsignificantly decreased serum T levels compared with fasting administration. The administration of oral T in oil combined with either F or D results in serum T levels adequate to treat men with testicular failure. Additional studies of the combination of oral T in oil with 5alpha-reductase inhibitors as a novel form of oral T therapy are warranted.

5-alpha Reductase Inhibitors↗

Body dysmorphic disorder and life-style drugs. Overview and case report with finasteride.

The body dysmorphic disorder is the repeated preoccupation with a minimal or non-evident defect and includes a wide spectrum of imagined defects in appearance. These patients present themselves in every clinical practice and are extraordinarily difficult to treat. The focus of the preoccupation concerns head, face, chest and the genital area. Following the introduction of the new "life-style" drug, finasteride, we observed a dramatic increase in the number of patients suffering from body dysmorphic disorder attending our clinic for skin diseases in Erfurt. These patients frequently contact their doctor demanding specifically for prescription of a particular life-style drug. However, there is no indication for using life-style drugs for the treatment of a body dysmorphic disorder. The appropriate treatment includes psychotherapy and psychopharmacological treatment.

Adult↗

[With alpha blockers, finasteride and nettle root against benign prostatic hyperplasia. Which patients are helped by conservative therapy?].

Symptomatic benign prostatic hyperplasia (BPH), which a man has a 50% chance of developing during the course of his lifetime, should receive stage-related treatment. While Vahlensieck stage I disease requires no therapy, stages II and III are indications for medication. Established medications for the treatment of BPH in current use are alpha-blockers, finasteride, and the phytotherapeutic agents pumpkin seed (cucurbitae semen), nettle root (urticae radix), the phytosterols contained in Hypoxis rooperi, rye pollen and the fruits of saw palmetto (sabalis serrulati fructus). If the patient responds, these medicaments can be given life-long, or intermittently. The hard criterion for the rational use of drug treatment of BPH is, over the long term, the reduction in the number of prostate operations. In stage IV disease surgical measures--after prior compensation of renal function--are to the fore.

Adrenergic alpha-Antagonists↗

Pharmacodynamic modeling of finasteride, a 5 alpha-reductase inhibitor.

Finasteride is a 4-azasteroid inhibitor of one isoenzyme of 5 alpha-reductases that converts testosterone to dihydrotestosterone (DHT). We characterized the time course of DHT concentrations. The following model was used to assess DHT pharmacodynamics: [formula: see text] where joint fitting of three dose levels yielded kin0 = 28% change/hour, kout = 0.28 hour-1, IC50 = 0.012 ng/ml, and Emax = 0.7. The modification of a previous model with the maximum partial effect factor, Emax, may be useful in characterizing the pharmacodynamics of drugs with similar indirect mechanisms.

Dihydrotestosterone↗

[A trial of the use of finasteride and terazosin in patients with benign prostatic hyperplasia].

94 patients with obstructive urination due to benign prostatic hyperplasia received finasteride (proscar), inhibitor of 5 alpha-reductase, in a single dose 5 mg and terazosine, alpha 1 adrenoblocker, in a daily dose of 9.7 mg/day. The follow-up averaged 16.1 months. As shown by overall score of the symptoms and quality of life, rectal and ultrasonic examinations, uroflowmetry, the prostate decreased by 17%, on the average in 72% of the patients. Subjectively, urination has also improved. Maximal flow rate elevated by 55% in the majority of patients. Combination of finasterine with terazosine is well tolerated and proved optimal as a conservative therapy in patients with obstructive urination as a result of benign prostatic hyperplasia.

5-alpha Reductase Inhibitors↗

Effects of finasteride on the rat ventral prostate.

The objectives of this study were to compare changes in the ventral prostate (VP) of young adult Sprague Dawley rats after 28 days of treatment with finasteride (F), a potent 5 alpha-reductase inhibitor, with those caused by castration (Cx). VP concentrations of DHT were reduced to 20.2% and 6.6% of controls (1,947 +/- 207 pg/VP, mean +/- SE) by F (5 or 20 mg/kg/day) and to 2.6% of controls by Cx. VP weights were reduced 49% and 54% by F and 88% by Cx. DNA/VP fell 25% and 15% with F treatment and 72% after Cx, whereas RNA and protein/VP were reduced 37-51% by F and 91-93% by Cx. The RNA/DNA and the protein/DNA ratios fell to 30-36% of controls after F treatment and to 70% of controls after Cx. The mRNA concentrations of the C3 subunit of prostatein 28S ribosomal RNA fell after treatment with F (5 mg/kg/day) and after Cx, whereas the mRNA for TRPM-2, an androgen-suppressed protein associated with apoptosis, was increased only after castration. To examine further the effects of F on the rate of DNA synthesis, 7-day regressed adult rats were treated for 3 days with testosterone propionate +/- F, and incorporation of 3H-thymidine in minced ventral prostates was determined. F inhibited 3H-thymidine incorporation. We conclude that Cx causes a greater reduction in cell number/VP and a greater reduction in RNA and protein cell than F and that the differences between F treatment and castration probably result from differences in prostatic concentrations of T.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗

5 alpha-reductase activity in cultured epithelial and stromal cells from normal and hyperplastic human prostates--effect of finasteride (Proscar), a 5 alpha-reductase inhibitor.

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Dysregulation of testosterone conversion to dihydrotestosterone (DHT) by 5 alpha-reductase has been described as a key step in the development of BPH. We investigated the 5 alpha-reductase activity in primary cultures of epithelial and stromal cells from the four different regions (periurethral, transition, central and peripheral zones) of normal and hyperplastic human prostates. No significant difference in DHT production was observed among the four epithelial zones and the hyperplastic epithelial cells, or among the four normal zones and the hyperplastic stromal cells. To investigate whether the two known 5 alpha-reductase isoenzymes were expressed in prostate, we performed specific enzymatic amplification after reverse transcription which showed the presence of 274 and 383 base-pair fragments, respectively, specific for 5 alpha-reductase type 1 and 5 alpha-reductase type 2, demonstrating the expression of mRNA for both isoenzymes in BPH tissue. To pharmacologically characterize the isoenzyme present in the two cell components of hyperplastic prostate, we used finasteride, a well known inhibitor specific to 5 alpha-reductase type 2, which only slightly inhibits 5 alpha-reductase type 1. In BPH, IC50 was estimated at 62 nM and 45 nM, for stromal and epithelial cells respectively, suggesting predominately 5 alpha-reductase type 2 activity. Our results provide further evidence that 5 alpha-reductase type 2 activity is mainly responsible for DHT production by human prostatic cells.

Base Sequence↗

[Proscar (finasteride, MSD) in the treatment of patients with prostatic hyperplasia].

The drug proskar (finasteride) belongs to 5 alpha-reductase blockers breaking the steps of prostatic adenoma pathogenesis. Proskar (Merck and Co. Inc., USA) was given to 38 patients with prostatic adenoma stage I and II (residual urine < 50 ml) admitted to urological clinic of the Moscow Medical Academy in 1993-1995. Daily dose was 5 mg. In patients with associated inflammation it was treated prior to proskar administration. To reject carcinoma, patients with elevated levels of prostatic specific antigen (< 4 ng/ml) were subjected to polyfocal biopsy of the gland. In any case, these patients received antiandrogens flutamide or androkur. Subjective response was achieved in 33 of 38 patients (86.8%). Better urination was reported in 29 patients (76.3%). Abdominal and transrectal ultrasonic scanning registered a decrease in the size of the prostate in 25 (65.8%) patients. Proskar was well tolerated, sexual disturbances occurred only in 2 patients. Proskar is effective in therapy of prostatic adenoma stage I. However, its intake must be long and regular, otherwise recurrent clinical symptoms and further growth of prostatic adenoma are possible.

5-alpha Reductase Inhibitors↗