Effects of long term treatment with finasteride (MK-906), a 5-alpha reductase inhibitor, on circulating LH, FSH, prolactin and estradiol.
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5-alpha Reductase Inhibitors↗
Biomedical subjects
Z Braf
Publications and source records attributed to Z Braf.
Prolonged treatment with finasteride (a 5 alpha-reductase inhibitor) does not affect bone density and metabolism.
OBJECTIVE: Since it is not clear whether testosterone or dihydrotestosterone is the active hormone in bone metabolism, we wished to assess the effect of finasteride, a 5 alpha-reductase inhibitor, or vertebral bone mineral density and parameters of bone and mineral metabolism. DESIGN: Patients were treated in a randomized, double-blind controlled study with either placebo, 1 or 5 mg/day finasteride. PATIENTS: Twenty-three men with benign prostatic hyperplasia (BPH) were included in this study; eight received placebo, seven were allocated to treatment with 1 mg/day, and eight to 5 mg/day finasteride for 12 months. MEASUREMENTS: Vertebral bone mineral density was measured at the lumbar spine by dual energy X-ray bone densitometry. Serum calcium, phosphorus, parathyroid hormone, osteocalcin and vitamin D metabolites were measured regularly. Urinary calcium and creatinine excretion were monitored as well. RESULTS: Finasteride caused a significant decrease in serum dihydrotestosterone after 6 and 12 months, but no effect on serum testosterone. Vertebral bone mineral density remained unaltered. None of the other parameters monitored were affected except for a small unexplained increase in 1.25-dihydroxyvitamin D in the group receiving 5 mg finasteride/day. CONCLUSIONS: Testosterone is probably the active hormone in bone metabolism. However, oestradiol, the product of testosterone aromatization (which remains unaltered under finasteride) may yet be another possible responsible steroid in the maintenance of bone density. We can also not rule out that the small amount of dihydrotestosterone remaining under finasteride administration is sufficient for maintaining normal bone metabolism.
5-alpha Reductase Inhibitors↗
T lymphocyte subsets and function in the peripheral blood of patients with urological cancer.
The phenotypic distribution and immune reactivity of T lymphocyte subpopulations from peripheral blood of 50 patients with urological cancer were determined. Included were 36 patients with bladder transitional cell carcinoma, 7 patients with renal cell carcinoma and 7 patients with prostatic carcinoma. Thirty-eight age-matched patients with benign urological disease served as controls. A depression in immune competence was found in the group of male patients with infiltrating bladder cancer. In more than 50% of the patients with infiltrating bladder carcinoma, the T helper (CD4) subset was reduced with a concomitant inversion in the CD4/CD8 ratio and impairment in the T cell function as determined by the ability to proliferate upon phytohemagglutinin and concanavalin stimulation. Patients with superficial bladder carcinoma, as well as those with renal cell carcinoma had an immune profile similar to that of the control group. The group of patients with prostatic carcinoma had higher mean CD4/CD8 ratios than the control group, resulting from decreased suppressor/cytotoxic cells. Our results have indicated that the characterization of T cell subset and lymphocyte activity correlated well with the histopathologic state of patients with bladder carcinoma. Thus, the determination of the CD4/CD8 ratio may prove a valuable method for monitoring patients with bladder carcinoma, in addition to serial urine cytology, random urothelial biopsies and flow cytometry.
Adenocarcinoma↗
Laboratory monitoring of androgenic activity in benign prostate hypertrophy treated with a 5 alpha-reductase inhibitor.
Testosterone and androstenedione are metabolized by 5 alpha- and 5 beta-reductases to androsterone (A) and etiocholanolone (E), respectively. These are excreted in the urine as conjugates, and the A/E ratio in normal men is usually greater than or equal to 1.5 (as opposed to 1 in women) because of the high 5 alpha-reductase activity in the prostate. The A/E ratio can be determined simply by gas chromatography after acid hydrolysis of a urine sample, extraction of steroids, and formation of trimethylsilyl derivatives. A timed collection of urine is unnecessary because the ratio of A/E is used rather than absolute values. In men suffering from benign prostate hypertrophy who are treated with Finasteride (a 5 alpha-reductase inhibitor), the A/E ratio decreases to less than 0.5. The A/E ratio decrease can be detected long before there is clinical improvement.
5-alpha Reductase Inhibitors↗
Characterization of peripheral blood T-cell subpopulation of bladder cancer patients.
The levels of immune reactivity of peripheral and blood T-lymphocytes were evaluated in 37 bladder cancer patients and 31 age-matched controls. T-lymphocyte subsets were quantified by monoclonal antibodies, and the immune reactivity was measured using stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM). Comparing the patients before and after treatment revealed significant changes in the stimulation index of proliferative response to PHA, PWM, in the PWM% (the patient response compared to the control), and in the percent of T8 cells from the total count of blood lymphocytes. Further significant differences were found among the disease stages in the numbers of T3, T4 lymphocytes subpopulations and the total lymphocyte count. A significant interaction was found between the treatment and patient's sex regarding the T4:T8 ratio. Also, a higher prevalence of T4:T8 less than 1 was found among the patients compared to the controls before and after treatment regardless of the disease stage. This T4:T8 less than 1 ratio can serve as an indicator of immune competence in bladder transitional cell carcinoma patients.
Aged↗
The role of oxygen free radicals and prostaglandins in reperfusion injury to warm ischemic kidneys.
The present study was designed to determine whether the administration of superoxide dismutase (SOD) can alleviate ischemic kidney damage and whether there is a relationship between oxygen free radicals and thromboxane (Tx). In 17 dogs, the right kidney was removed and the vascular pedicle of the left kidney was clamped for 75 min. Prior to reperfusion, the ischemic kidney was rinsed with 5 mg SOD and an additional 20 mg SOD was infused systemically. Blood samples were drawn from the renal vein before ischemia and after reperfusion to determine serum levels of thromboxane B2 (TxB2). All eight untreated dogs died within 1 week of renal failure, and the nine treated dogs demonstrated transient renal failure, with a significant difference (P less than 0.001) being found between the two groups. A significant difference (P less than 0.001) in TxB2 levels was found in the untreated dogs before and after ischemia and between the two groups following reperfusion. Animals that are treated with SOD after the ischemic event has occurred but before reperfusion exhibit a favorable clinical course in terms of survival and renal function. Tx synthesis in the kidney can be blocked by the administration of SOD.
Animals↗
Endocrine treatment of benign prostatic hypertrophy: current concepts.
To summarize the endocrine approach for the treatment of BPH: much clinical data have accumulated over the past forty years. Until recently, scientists and physicians mainly concentrated on the reduction of androgens as a possible solution. We have come a long way from surgical castration, through the administration of hormones such as estrogen and progesterone, gonadotropin-releasing hormone agonists to the inhibition of an enzymatic reaction reducing testosterone to DHT--the now recognized active intracellular androgen metabolite. Recently, the role of estrogens has been emphasized with the finding that stromal hyperplasia is the main change occurring in BPH. Lately, research has been initiated to examine the clinical effect aromatase inhibitors would have in the treatment of human BPH. Since there is enough evidence that both the epithelial and stromal components of the human prostate undergo hyperplasia in BPH, and individuals vary with respect to their relative epithelial/stromal components, both structures would have to be reduced for therapy to be successful. Therefore, the combination of an antiandrogenic and antiestrogenic effect is theoretically promising. Indeed, prostates of beagles shrunken after treatment with an aromatase inhibitor, further decreased in weight after additional treatment with cyproterone acetate, an antiandrogen. We are now approaching the stage where these "antihormones" are both enzyme inhibitors with actually no side effects that preclude the use of the earlier generation's "antihormonal" hormonal drugs. Furthermore, it has recently been reported that the aromatase inhibitor, 4-hydroxy-androstenedione also inhibits human prostatic 5-alpha reductase, at least in vitro. The in vivo relevance of this finding awaits further classification. Thus, a good hormonal treatment that will be both scientifically sound, and clinically safe and effective, seems feasible in the near future. Two main factors have encouraged our interest and research into methods of inhibiting prostatic growth or reducing its obstructive symptomatology: the enormous cost of prostatic operations for outlet obstruction secondary to BPH, and the natural aging process of the population accompanied by deteriorated health precluding anesthesia and prostatic surgery. Medical treatment of BPH has to result in symptomatic improvement, elimination of residual urine, and improvement of flow to be considered successful. These are usually accomplished by surgery and results at least as good as those obtained by operation should be aimed at, if medical treatment is to replace surgery. Although indications for surgery and outcome of operations are well-defined, this is not the case when alternatives to prostatectomy are chosen.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Treatment of benign prostatic hypertrophy by a long-acting gonadotropin-releasing hormone analogue: 1-year experience.
Benign prostatic hypertrophy, a common ailment among elderly men, usually is treated by surgery. Since androgens enhance prostatic hypertrophy, their withdrawal seems a logical way to treat this condition. Recently gonadotropin-releasing hormone analogues, known to produce "chemical castration," have been tried in cases of benign prostatic hypertrophy. We report our experience with 20 men treated by a monthly injection of gonadotropin-releasing hormone for prolonged periods. In 17 men treated for 6 months the prostatic volume decreased to an average of 63% of the initial volume; however, this did not correlate with clinical objective improvement. Only 6 men attained normal flow rates. Residual urine volume remained unaltered. Ten patients experienced subjective amelioration, while only 7 (40%) reported objective and subjective improvement. Maximal decrease in prostatic volumes was reached at 9 months of treatment and further treatment did not cause additional shrinkage. At 3 months after discontinuation of treatment prostatic volumes returned to 95 +/- 10.5% of pre-treatment values. A similar decrease in flow rates also was noted. Symptoms remained improved for longer periods. We conclude that this mode of treatment offers little to the majority of men with benign prostatic hypertrophy. Proper patient selection, based perhaps on serum prostate specific antigen, might augment positive results. This therapy should be restricted to patients considered high risk for any surgical and anesthetic intervention, and then it will have to be continued indefinitely.
Aged↗
Serum bioactive and immunoreactive follicle stimulating hormone during chronic treatment with gonadotropin releasing hormone agonist in elderly men.
Chronic administration of GnRH agonists "down regulates" the pituitary and decreases LH and FSH serum levels. Changes in the bioactivity of FSH have not been adequately assessed under such treatment, for lack of a proper test. We examined serum changes under GnRH agonist treatment among 12 healthy elderly men suffering only from benign prostatic hypertrophy, for up to one year, using a modification of a granulosa cell bioassay for the determination of FSH bioactivity. While radioimmunoassay-FSH decreased, we noticed a significant increase in the bioactivity of this hormone. The clinical importance of this increase is discussed.
Aged↗
Does age influence the bioactivity of follicle-stimulating hormone in men?
We measured follicle-stimulating hormone (FSH) by both standard radio-immunoassay (RIA) and bioassay (Bio) methods in 56 men, using a modification of a previously described in vitro granulosa cell bioassay for the determination of the bioactivity of FSH. Thirty-four were young (mean age 25 years), and 22 elderly (mean age 72). No interfering factors such as disease or alcoholism could be identified. The elderly men had higher RIA-FSH levels compared with the younger ones. Bio-FSH demonstrated a similar trend and therefore the Bio/Immuno ratio was practically constant (3.3 +/- 0.6 vs. 2.7 +/- 0.4). We conclude that the age-associated decline in testicular function seen in normal ageing cannot be attributed to a chronic change in FSH activity. Not only is the RIA-FSH elevated among the elderly, it is of the same biological quality as in the younger men. The underlying cause for the testicular function decline is probably at the level of the testis itself.
Adult↗
[Urolithiasis: B. Pharmacological and instrumental treatment of stones].
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Humans↗
[Urolithiasis: I. Prevention and related pharmacotherapy].
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Humans↗
Clinical importance of prostatic measurements in follow-up of GnRH analogue-treated prostatic carcinoma patients.
Thirteen patients with advanced adenocarcinoma of the prostate were treated with buserelin-a gonadotropin-releasing hormone (GnRH) analogue. Follow-up period extended to thirty-six months during which 8 patients were considered either responsive or stabilizing, in terms of pain relief and clinical tumor regression, and 5 were categorized as suffering from progressive disease. Urinary symptoms were ameliorated in the majority of cases (11/12). Prostatic size was measured by rectal ultrasound, an accepted accurate new modality. In 12 patients a decrease in size was demonstrated, and only in 1 progressive case the prostate grew larger on a six-month follow-up. Thus prostatic size and clinical responsiveness are not correlated. The clinical value of recording urinary symptomatology and measuring prostatic size in prostatic carcinoma patients is discussed with regard to the latest communications that GnRH analogues acting by decreasing testosterone levels, can cause amelioration in benign prostatic hypertrophy (BPH) cases, too. It is suggested that prostatic size has little clinical value concerning tumor responsiveness in the follow-up of patients with prostatic carcinoma.
Adenocarcinoma↗
Complications in hyperthermia treatment of benign prostatic hyperplasia.
Of 435 patients treated with local hyperthermia to the prostate 27 had 29 complications, for an over-all complication rate of 6.6%. Urinary tract infections (7 cases), hematuria (6), and epididymitis (2) accounted for roughly half of the complications and could be attributed to the insertion of a catheter rather than the treatment itself but this remains to be proved. Most of the complications occurred within the first 3 treatment sessions. Despite the complication, 9 patients continued and completed the treatment course. Mean age of the study group was 73 +/- 8.3 years. Given the age of these patients, high incidence of accompanying diseases and low rate of complications, local hyperthermia should be considered a viable low risk treatment option in patients with benign prostatic hyperplasia.
Aged↗
Local hyperthermia of the prostate gland for the treatment of benign prostatic hypertrophy and urinary retention.
Local hyperthermia of the prostate was used to treat 72 patients who had an indwelling catheter because of urinary retention caused by benign prostatic hypertrophy. One month after completion of treatment 50% of patients were able to dispense with the catheter and 1 year later 40% remained catheter-free. The best results were achieved in patients who underwent 6 to 10 treatment sessions in conjunction with cyproterone acetate 50 mg tid administered during the treatment period only.
Aged↗
Local microwave hyperthermia in the treatment of benign prostatic hypertrophy.
Local deep microwave hyperthermia has been introduced recently for the treatment of benign prostatic hypertrophy (BPH). We report the results of treatment in 114 patients divided into 2 groups. The first group included 83 patients with severe obstructive symptoms. Although some improvement was found in the scoring of both subjective and objective parameters, the number of patients benefiting was small, with only 28% showing improvement in both parameters. Approximately 50% reported subjective improvement but in only 25% was this significant. In 42% there was objective evidence of improvement. Prostatic volumes did not change as a result of treatment. The second group comprised 31 patients with indwelling catheters because of acute urinary retention. After treatment, 19 patients (61%) were able to dispense with the catheter. The difficulties of interpreting an open trial of treatment for BPH and assessing its impact on objective parameters and symptomatology are discussed. Our results should be regarded cautiously in view of these reservations.
Aged↗
Local thermotherapy of the benign prostate: a 1-year follow-up.
Local hyperthermia to the prostate has initially been found to be of considerable beneficial value in cancer of the gland and later also in benign prostatic hypertrophy (BPH) and in chronic prostatitis. The Prostathermer has been especially developed and used for this purpose. 124 patients with BPH, who have been treated by this method, were reevaluated after 1 year. This thermotherapy was well tolerated, and no noticeable complications were encountered. A sustained definite improvement in objective and subjective obstructive symptoms and signs was seen in 51% of the cases. Such definite and persistent improvement was best obtained when treatments were performed twice weekly for 60 min over a period of 3 weeks. Those patients with the more severe obstructive symptoms fared best. A full explanation for the effectiveness of this treatment of BPH has yet to be found. Although local hyperthermia cannot, at this stage, be considered as a radical form of treatment of BPH, it may offer definite relief to about 50% of the cases, particularly to those unwilling or unsuitable for surgery.
Androgen Antagonists↗
Short-term effect of a new portable extracorporeal lithotripter on renal function.
Extracorporeal shock wave lithotripsy has become the treatment of choice for upper urinary tract stones. We evaluated the impact of a new lithotripter on the kidneys of 14 nonobstructed patients treated for renal stones, using several physiological parameters and renal ultrasonography. Glomerular filtration rates (GFR) were estimated from the renal scan. Complete disintegration of the stone was accomplished in all but one patient. Treatment did not alter the serum parameters or the renal ultrasonography. Also, no changes were found in the GFR on the follow-up renal scans in both kidneys. The implications of these findings are discussed.
Adult↗