trelstar and Prostatic-Hyperplasia

In 2009 Suprelorin® was released in Switzerland for the temporary suppression of fertility in male dogs. However, in practice it has also been used to treat other conditions in male dogs and in bitches. These include treatment of benign hyperplasia of the prostate, the induction or suppression of oestrus and treatment for the side effects of gonadectomy. Also in feline reproductive medicine GnRH-agonists gain increased importance. These areas of application are listed here in terms of treatment success and possible adverse effects after treatment of which owners have to be informed beforehand.

Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Enzyme Inhibitors; Estrus; Female; Fertility; Male; Ovariectomy; Prostatic Hyperplasia; Triptorelin Pamoate; Urinary Incontinence

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.

Topics: Aged; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Hormones; Humans; Male; Prostatic Hyperplasia; Time Factors; Triptorelin Pamoate; Urinary Retention

Topics: Animals; Cysts; Dog Diseases; Dogs; Drug Implants; Gonadotropin-Releasing Hormone; Male; Prostate; Prostatic Diseases; Prostatic Hyperplasia; Triptorelin Pamoate

In six German Shepherds dogs, GnRH agonist implants (Deslorelin) were inserted subcutaneously one month after histological confirmation of benign prostatic hyperplasia (BPH). Prostatic volume (PV), characteristics of ejaculate, serum testosterone concentrations and Doppler parameters of prostatic and subcapsular arteries were detected at different time intervals, for 6 month. The prostatic volume showed a significantly reduction starting at day 37. The decrease in sperm concentration, motility and increase in morphological abnormal sperm were observed from day 22 to day 37, when it was no longer possible to obtain the ejaculate. The values of peak systolic velocity and end-diastolic velocity in prostatic and subcapsular arteries showed from day 11 a gradual decrease, significant at day 22 until day 37 and reaching the lowest values at day 52 until the end of observation. The power Doppler pixel intensity of both arteries showed a gradual decrease from day 5 until day 52. In particular, a significant decrease was observed for both arteries from day 11. Testosterone serum concentration decreased to undetectable levels by day 11 until the end of the observations. All these Doppler parameters and testosterone values were positively correlated with the prostatic volume. Furthermore, testosterone values were positively correlated with peak systolic velocity, end diastolic velocity and pixel numbers. The use of implants containing GnRH analogues, even in asymptomatic subjects, is effective for the control of BPH and the application of Doppler exam of prostatic blood flow represent an non-invasive tool for monitoring the response of medical treatment.

Topics: Animals; Arteries; Blood Flow Velocity; Dog Diseases; Dogs; Drug Implants; Gonadotropin-Releasing Hormone; Male; Prostate; Prostatic Hyperplasia; Semen Analysis; Testosterone; Triptorelin Pamoate; Ultrasonography, Doppler

Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Enzyme Inhibitors; Finasteride; Hemorrhage; Histocytochemistry; Male; Prostatic Hyperplasia; Triptorelin Pamoate; Ultrasonography

Administration of GnRH agonist analogs to women may result in a hypoestrogenic state and bone mass reduction. In the present study we examined bone mineral density (BMD) and parameters of mineral metabolism in elderly men with benign prostatic hyperplasia before and during a hypoandrogenic state induced by the long-acting GnRH agonist D-Trp6-LHRH (decapeptyl). Our results showed that decapeptyl treatment caused a significant decrease in serum testosterone concentrations in all patients and resulted in a significant decrease in individual vertebral BMD in 10 of 17 patients. A significant decrease in BMD was observed in 5 patients after 6 months of treatment. Another 5 patients showed a decreased BMD only after 12 months. The mean serum concentrations of osteocalcin, phosphorus, and alkaline phosphatase activity increased after 6-12 months of treatment with decapeptyl. Serum calcium, vitamin D metabolites, and PTH concentrations remained unchanged during treatment. Urinary calcium excretion was slightly, but not significantly, increased after 6 months of treatment. These results demonstrate that long-acting GnRH agonist treatment may cause high turnover accelerated bone loss in some men during the first year of GnRH agonist treatment, as has been previously shown in women.

Topics: Aged; Alkaline Phosphatase; Bone Density; Calcium; Humans; Male; Osteocalcin; Parathyroid Hormone; Phosphorus; Prostatic Hyperplasia; Testosterone; Time Factors; Triptorelin Pamoate; Vitamin D

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.

Topics: Aged; Analysis of Variance; Animals; Biological Assay; Cells, Cultured; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Luteolytic Agents; Male; Middle Aged; Prostatic Hyperplasia; Rats; Regression Analysis; Time Factors; Triptorelin Pamoate

Using a sensitive micromethod for the determination of prolactin (PRL) binding sites based on 125I-human PRL ligand, PRL receptor levels in specimens of benign prostatic hyperplasia (BPH) and human prostate cancer were estimated by the one-point assay system. Ten of 19 BPH specimens (53%), showed significant PRL binding, four being in the 9-12 fmol/mg range. All ten of these cases had an histological diagnosis of nodular glandular hyperplasia. Of ten adenocarcinomas examined, four samples (40%) exhibited positive PRL binding, the highest receptor levels being 10.2 fmol/mg protein. To characterize the receptors from BPH membranes, samples were then separately pooled according to the results obtained in one-point assays. In the PRL-negative pool no displacement could be detected. In the PRL-positive pool, the Scatchard analysis revealed one class of receptors with an average affinity Kd = 1.1 X 10(-9) M and capacity Bmax = 287 fmol/mg protein. In the prostate cancer specimens, luteinizing hormone-releasing hormone receptors with a high affinity and a low capacity were also found. The results indicate the presence of prolactin receptors in prostate cancer and in BPH. The clinical implications of such findings are not clear, but it is possible that a certain proportion of BPH and prostate cancers might be in part PRL dependent. Further studies are necessary to ascertain this hypothesis in an attempt to improve the treatment of BPH and prostate cancer.

Topics: Gonadotropin-Releasing Hormone; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Radioligand Assay; Receptors, LHRH; Receptors, Prolactin; Triptorelin Pamoate

The hormonal effects of a delayed-release intramuscular (IM) preparation of D-Trp-6-LH-RH (TRP-6 microcapsules) were investigated in men aged 65-75 years. Six men with a prostatic adenoma (group A) received subcutaneously (SC) 500 micrograms TRP-6/day from day 0 to day 6. Seven men with a prostatic carcinoma (group B) were given the same SC treatment, but in addition received on days 7, 28 and 56 an intramuscular injection of 3 mg TRP-6 microcapsules. During SC treatment, plasma TRP-6 levels rose to 2-4 ng/ml. Plasma LH peaked on day 1, whereas high testosterone levels were maintained from day 2 to day 4, and then fell abruptly on day 6. In five subjects from group B, plasma TRP-6 was detectable in all plasma samples from day 10 to day 49. Testosterone levels were in the castrate range after day 24. Mean LH level decreased progressively from day 14 to day 56. These data provide evidence for the efficacy of periodic administration of TRP-6 microcapsules for suppressing testicular secretion.

Topics: Aged; Capsules; Carcinoma; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Injections, Subcutaneous; Luteinizing Hormone; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

D-Trp-6-LH-RH, a long acting LH-RH agonist was given in a phase II trial to 85 patients aged 52 to 88 (mean 69) with advanced prostatic carcinoma, stage B (8 pts), C (9 pts) and D (68 pts). Twenty-five patients were previously untreated, 40 had received previous hormonal therapy but none was considered has having hormone resistant tumor; 20 patients had received surgery or radiotherapy or both. D-Trp-6-LH-RH was given s.c. at a daily dose of 500 micrograms during the first seven days, followed by 100 micrograms daily. Antitumor activity was assessed after 90 days and treatment was continued in responders. The results were the following: plasmatic levels of LH were sharply decreased and those of testosterone were in all cases under 1 ng/ml by the 90th day of treatment; urinary symptoms and bone pain disappeared or were greatly improved in almost all patients; the volume of the prostate measured by ultrasonography and/or computerized tomography regressed by more than 50% of initial volume in 44% of the 34 patients for which this parameter was evaluable; bone scintiscans were improved in 18% of evaluable patients; plasmatic levels of prostatic acid phosphatases determined by radio immuno-assay were elevated in 28 patients, 61% of which presented a decrease superior to 50% or normalisation of this parameter. No disease flare up was observed on initiation of therapy. Impotence was constant but reversible on discontinuation of therapy. No other side effect could be attributed to therapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone Neoplasms; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Triptorelin Pamoate; Urination Disorders

Topics: Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Testosterone; Triptorelin Pamoate

Four geriatric male dogs of mixed breed were selected for study on the basis of palpable prostatic hyperplasia. Testosterone levels were determined by radioimmunoassay on plasma samples collected three times weekly. Prostate size was determined from lateral pneumocystograms taken at weekly intervals. Prostatic secretion was followed by ejaculating the dogs at weekly intervals. Two dogs were implanted with 125 micrograms/kg of pelleted D-Trp6-LHRH ethylamide (LHRH analog) and two were sham implanted. The pellets were removed 71 days later. Three months after the removal, one previously treated dog was sham implanted and one previously sham implanted dog was implanted with 170 micrograms/kg of pelleted analog. In each case, following analog implantation, plasma testosterone levels were elevated for up to 7 days, then declined precipitously, and were then maintained at less than 0.02 ng/ml for a prolonged period. Plasma testosterone levels returned to the pretreatment range 44 and 58 days after implantation, respectively, in two dogs, but remained low through the 60 days studied in the third. The radiographs in one treated animal were of insufficient quality for analysis. In the remaining two treated animals, prostate size progressively declined following implantation, after about a 2 wk lag time. In one animal the prostate dimensions reached a nadir of 40% of pretreatment values at five wk after implantation. In the other treated animal the prostate regressed to a position within the pelvic brim, a state resembling that seen in young dogs, and so the dimensions could not be accurately determined. After plasma testosterone levels reverted to pretreatment values, prostate dimensions slowly but progressively increased. A decline in ejaculate volume paralleled the decline in plasma testosterone and prostate size until the fifth week after implantation from when no ejaculate could be obtained. The data suggests that LHRH agonists may have utility in the therapy of hormone-responsive prostatic pathologies.

Topics: Animals; Dogs; Drug Implants; Gonadotropin-Releasing Hormone; Male; Prostate; Prostatic Hyperplasia; Semen; Sperm Count; Testosterone; Triptorelin Pamoate