leuprolide and Prostatic-Hyperplasia

Benign Prostatic Hyperplasia (BPH) usually occurs in males 45-50 old and progressively involves 75% of the male population over 75 years of age. The clinical manifestations of BPH are related primarily to bladder outlet obstructions resulting from enlargement (mechanical component) of the prostate gland, and from extrinsic and intrinsic sympathetic activation of alpha-adrenoceptors (dynamic component) present in the prostatic muscle tissue, prostatic urethra, bladder base and neck. Several drugs have been employed in the last decades: LHRH analogs (Leuprorelin and Goserelin) which can reduce the testicular production of androgens with reduction in prostate size; Serenoa repens for its anti-androgenic and anti-estrogenic activities; Finasteride (5-alpha-reductase inhibitor) which blocks the conversion of testosterone into the more active dihydrotestosterone. Finally, the alpha 1 blocking agents (Terazosin, Doxazosin, Tamsulosin) that improve urinary symptoms by acting on dynamic component. Clinical improvements derive from their antagonist action on alpha 1 adrenergic receptors which mediate contraction of the prostate gland, proximal urethra, bladder base and neck, with the consequent reduction of urethral pressure, bladder outlet resistance, and increase of urinary flow. Due to its pharmacodynamic and pharmacokinetic properties, as well as the clinical results obtained, Terazosin, alpha 1 blocker, appears to be particularly useful in the treatment of patients with mild- to moderate symptomatic BPH.

Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Aged; Androgen Antagonists; Doxazosin; Enzyme Inhibitors; Finasteride; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Muscle, Smooth; Plant Extracts; Prazosin; Prostatic Hyperplasia; Receptors, Adrenergic, alpha-1; Serenoa; Sulfonamides; Tamsulosin; Urinary Bladder Neck Obstruction; Urodynamics

Topics: Adrenergic alpha-Antagonists; Cholestenone 5 alpha-Reductase; Clinical Trials as Topic; Drug Therapy, Combination; Finasteride; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oxidoreductases; Prazosin; Prostatic Hyperplasia; Sulfonamides; Tamsulosin

This study was designed to determine whether androgen ablation (AA) affects expression of alpha1A-adrenergic receptors (AR) in the human prostate.. Concentrations of alpha1A-AR mRNA were determined in benign prostatic tissue from patients undergoing surgery after a 3-month course of combined androgen ablation (CAD) therapy with leuprolide and flutamide, and a matched group of untreated patients with clinical BPH.. Mean concentration of alpha1A-AR in the AA group was 0.53 +/- 0.53 SD (range 0.026-1.55) attomol/mg. Control mean was 0.29 +/- 0.22 SD (range 0.02-0.69; P = 0.3, two tailed t-test). Tissue composition did not statistically differ between the two groups. Expression of alpha1A-AR correlated with concentration of smooth muscle myosin heavy chain (SMMHC) (r = 0.84, P = 0.001). No significant differences were observed after adjusting for SMMHC content.. A 3-month course of CAD does not appear to have a significant effect on alpha1A-AR mRNA expression in the human prostate.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Humans; Leuprolide; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Adrenergic, alpha-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

This prospective, randomized, multicenter comparative trial studied the effect of neoadjuvant hormonal treatment (NHT) prior to radical, prostatectomy.. Histopathologic tissue specimens were obtained from 91 consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for stage B prostate adenocarcinoma. The patients had received NHT for three months. Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy.. Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant interglandular connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic figures were seen in any treated tumors.. Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone Acetate; Diagnosis, Differential; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms

In the last few years, the role of neoadjuvant hormonal treatment (NHT) prior to radical prostatectomy has been largely debated and investigated in randomized multicenter trials as well as in large single-institution studies. We have initiated a prospective randomized comparative trial with parallel groups in patients with clinically limited disease to contribute to the clarification of the possible role of NHT; to evaluate the efficacy of NHT with leuprolide plus cyproterone acetate in 'maintaining' the stage of the disease; to reduce the percentage of pathological overstaging, and mainly to accurately assess the pathological modifications induced by NHT. The present paper is an interim report of the results.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma in Situ; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cyproterone Acetate; Delayed-Action Preparations; Diagnosis, Differential; Disease-Free Survival; Drug Administration Schedule; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatectomy; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

Hormonal changes resulting from long-term use of the luteinizing hormone-releasing hormone agonist leuprolide depot were studied in a randomized placebo-controlled study comprising 50 evaluable patients with benign prostatic hyperplasia (BPH). A total of 26 patients received 3.75 mg leuprolide depot intramuscularly every 28 days for 24 weeks and 24 received a placebo. The patients were followed up for a further 24-week period. Serum concentrations of luteinizing hormone decreased by 90% and follicle-stimulating hormone by 55% during the treatment period. Mean testosterone levels decreased by 96% to 0.7 nmol l-1 and dihydrotestosterone decreased by 90%. The adrenal androgens androstenedione and dehydroepiandrosterone sulphate decreased by 48 and 24%, respectively. In most patients, estradiol decreased to non-detectable values, while the decrease in estrone was 35%. There was no change in prolactin and sex hormone-binding globulin as compared to the placebo group. Hormonal changes were reversible, but the suppression of testicular hormone production was not completely normalized in all patients 24 weeks after discontinuation of the treatment.

Topics: Aged; Androstenedione; Dehydroepiandrosterone Sulfate; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Male; Placebos; Prostatic Hyperplasia

We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent androgen suppressive therapy for 24 weeks with the luteinizing hormone releasing hormone (LHRH) agonist leuprolide depot for symptomatic benign prostatic hyperplasia (BPH). Before treatment started, the prostates consisted of 88.4% stroma, 9.0% epithelium and 2.6% glandular lumen. After completion of therapy, the percentages were 94.7, 3.0 and 2.3, respectively. The absolute reductions of volume were 27% for stroma, 77% for epithelium and 40% for lumen. Correlations between pretreatment parameters (epithelial content, stromal epithelial ratio and prostate specific antigen density (PSAD)) and the clinical outcome parameters (prostate volume reduction, improvement in maximum flow rate, reduction of symptom score and reduction in outflow resistance) were not statistically significant, indicating that the histological composition of BPH tissue or PSAD are poor parameters to predict differences in response for individual patients during hormonal therapy for BPH. By comparing morphometry results of the core biopsies with morphometry performed on corresponding TURP tissue, it appeared that the lumen content of the biopsies was somewhat underestimated.

Topics: Aged; Androgen Antagonists; Biopsy; Double-Blind Method; Humans; Leuprolide; Male; Prostate; Prostatic Hyperplasia

Between December 1991 and December 1993, 74 BPH patients with an increased operative risk and concomitant diseases such as diabetes mellitus and hypertension were submitted to a transurethral incision of the prostate (TUIP). After TUIP, patients were randomized to two different groups: group 1 was followed without additional treatment and group 2 received an LHRH analogue for the first 6 months of follow-up. With respect to transurethral resection of the prostate (TURP), TUIP has been shown to demonstrate a lower perioperative morbidity. This advantage has lent further support to this technique as a valid alternative for patients in poor general conditions who are at high risk with more invasive procedures. One of the limits of TUIP is the long-term effectiveness. Aim of this study was to ascertain whether in patients with BPH and an increased operative risk who require immediate and definitive treatment but with a low perioperative morbidity, the long-term effectiveness of TUIP can be stabilized by the administration of an LHRH analogue. At present postoperative follow-up ranges from a minimum of 24 months to a maximum 48 months (mean 38.4 months). Perioperative morbidity rate associated with TUIP was 8.1%. In the group randomized to combination therapy (TUIP + LHRH analogue), the clinical condition of the patients was not modified by LHRH analogue treatment and none of the patients withdrew from treatment. Loss of sexual potency occurred in all patients on LHRH analogue, however, none of these patients discontinued treatment for this reason. At the end of the cycle of hormone treatment, sexual potency returned to pretreatment values in 69.5% of patients after a mean of 3.2 months. In this study the objective efficacy of the treatment was evaluated using flow rate measurements, and the subjective assessment of outcomes, using the International Prostate Symptom Score. Statistically significant differences between the two groups (TUIP alone or TUIP + LHRH analogue) (p < 0.01) were reported at 6 months and were still maintained at 24 months of follow up. Results emerging from this investigation confirm that TUIP may be considered extremely safe procedure with low operative risk. In selected BPH patients who are at high risk, with a more invasive procedure and who must be submitted to immediate and definitive treatment, the association of an LHRH analogue seems to increase the long-term effectiveness of TUIP. Five year follow-up studies are still in progress

Topics: Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Erectile Dysfunction; Follow-Up Studies; Humans; Leuprolide; Male; Postoperative Complications; Prostatic Hyperplasia; Urodynamics

The impact of chronic administration of the luteinizing hormone-releasing hormone agonist leuprolide depot on cardiovascular risk factors was investigated in a controlled double-blind study comprising 50 evaluable patients with benign prostatic hyperplasia. In the 26 patients receiving leuprolide the mean total cholesterol level increased by 10.6%, high density lipoprotein cholesterol by 8.2% and triglycerides by 26.9% (p = 0.003, 0.052 and 0.050, respectively). Low density lipoprotein cholesterol levels were unchanged. Apolipoprotein A1 increased by 13.2% (p = 0.001), while apolipoprotein B, fibrinogen, thrombocytes and plasminogen activator inhibitor were unchanged. Hemoglobin decreased by 1.2 gm./100 ml. without a concomitant decrease in serum erythropoietin concentration. These changes act in different directions with regard to cardiovascular risk and the overall effect is difficult to assess.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Blood Platelets; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Erythropoietin; Estradiol; Fibrinogen; Hemoglobins; Humans; Leuprolide; Lipoproteins; Male; Placebos; Plasminogen Activator Inhibitor 1; Prostatic Hyperplasia; Testosterone; Triglycerides

The luteinizing hormone releasing hormone agonist leuprolide was investigated in a double-blind, randomized, placebo-controlled study comprising 50 evaluable patients with moderate to severe symptoms resulting from benign prostatic hyperplasia. Patients received 3.75 mg. leuprolide depot or placebo as an injection every 28 days for 24 weeks. Hemoglobin level decreased by 0.8 gm/100 ml. (p = 0.0052) for patients receiving leuprolide. Mean testicular volume decreased by 28.9% (p < 0.001) compared to placebo. Of 26 patients receiving leuprolide 5 had a weight gain of more than 3 kg. Almost all patients receiving leuprolide experienced hot flushes. Breast changes, and loss of energy and vigor were not more pronounced than for patients receiving placebo. Erectile function and sexual activity were lost during treatment. Libido also decreased but was still partially retained. Despite this, patients receiving leuprolide were generally contented with their sexual life during treatment. Side effects were bothersome for some patients but were reversible. Of the patients in our study 73% expressed that they could repeat or continue treatment if that had been possible. The high cost of these drugs will limit their use for a benign condition, such as benign prostatic hyperplasia.

Topics: Aged; Aged, 80 and over; Climacteric; Double-Blind Method; Humans; Leuprolide; Libido; Male; Middle Aged; Prostatic Hyperplasia; Testis

Several physicians have used luteinizing hormone-releasing hormone agonists for small, selected groups of patients with benign prostatic hyperplasia but their clinical role in this indication is still not well defined. We investigated the effect of the luteinizing hormone-releasing hormone agonist leuprolide given as an injection every 28 days for 24 weeks in a double-blind, placebo-controlled trial with 50 evaluable patients along an extensive protocol with the main emphasis on objective parameters for outcome assessment. Prostate volume decreased by 34.5% (2.6% in the placebo group). Maximum flow rate at spontaneous micturition and after instillation of saline improved by 2.0 ml. per second (32%) and 3.0 ml. per second (54%) more than with placebo. Detrusor pressure during micturition decreased by approximately 24% for patients who received leuprolide compared to placebo and was accompanied by a 25% increase in flow rate, which indicated decreased bladder outlet resistance. Improvement in urodynamic parameters generally was of statistical significance. Symptom scores improved significantly for both groups throughout the study when compared to those before treatment. At between group comparison, the improvement for irritative symptoms in favor of leuprolide reached statistical significance at week 48. With few exceptions, leuprolide patients tolerated the treatment well even if they had side effects, such as flushing and decreased sexual function.

Topics: Aged; Double-Blind Method; Humans; Leuprolide; Male; Prospective Studies; Prostate; Prostatic Hyperplasia; Urodynamics

Gonadotropin-releasing hormone receptors (GnRHR) have been found in extrapituitary tissues, including the prostate, where they might exert a local effect on tissue growth. Degarelix is a GnRHR antagonist approved for use in patients with prostate cancer (PCa) who need androgen deprivation therapy. The slowing of prostate cell growth is a common goal shared by PCa and benign prostate hyperplasia (BPH) patients, and the effect of degarelix on BPH cells has not yet been investigated. We wanted to evaluate the direct effect of degarelix on human BPH primary cell growth. Gene expression studies performed with BPH (n=11), stage 0 (n=15), and PCa (n=65) human specimens demonstrated the presence of GNRHR1 and GNRHR2 and their respective endogenous peptide ligands. BPH-isolated epithelial and stromal cells were either cultured alone or co-cultured (1:4 or 4:1 ratio of epithelial to stromal cells) and subsequently treated with increasing concentrations of degarelix. Degarelix treatment induced a decrease in cell viability and cell proliferation rates, which occurred in parallel to an increase in apoptosis. Both epithelial and stromal BPH cells are sensitive to degarelix treatment and, interestingly, degarelix is also effective when the cells were growing in a co-culture microenvironment. In contrast to degarelix, the GnRHR agonists, leuprolide and goserelin, exerted no effect on the viability of BPH epithelial or stromal cells. In conclusion, (i) prostate tissues express GNRHR and are a potential target for degarelix; and (ii) degarelix directly inhibits BPH cell growth through a decrease in cell proliferation and an increase in apoptosis. Supporting information for this article is available online at http://www.thieme-connect.de/products.

Topics: Apoptosis; Cell Proliferation; Cells, Cultured; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oligopeptides; Prostatic Hyperplasia

Methods for quantification of bladder outlet obstruction (BOO) are still controversial. Parameters such as detrusor opening pressure (p(det.open)), maximum detrusor pressure (p(det.max)), minimum voiding pressure (p(det.min.void)), and detrusor pressure at maximum flow rate (P(det.Qmax)) separate obstructed from nonobstructed patients to some extent, but two nomograms, the Abrams-Griffiths nomogram and the linearized passive urethral resistance relation (LinPURR), are more accepted for this purpose, along with the urethral resistance algorithm. In this retrospective, methodologic study, we evaluated the properties of these parameters with regard to test-retest reproducibility and ability to detect a moderate (pharmacologic) and a pronounced (surgical) relief of bladder outlet obstruction. We studied the pressure-flow charts of 42 patients who underwent 24 weeks of androgen suppressive therapy, 42 corresponding patients who received placebo, and 30 patients who had prostate surgery. The patients performed repeat void pressure-flow examinations before and after treatment or placebo. The various parameters were compared. Among the bladder pressure parameters, P(det.Qmax) seemed to have some advantages, supporting the belief that it is the most relevant detrusor pressure parameter to include in nomograms to quantify BOO. In assessment of a large decrease in urethral resistance, such as after TURp, resistance parameters that are based on maximum flow rate as well as detrusor pressure are preferable.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Controlled Clinical Trials as Topic; Diagnostic Techniques, Urological; Humans; Leuprolide; Male; Medical Records; Middle Aged; Muscle Hypertonia; Nitriles; Pressure; Prostatic Hyperplasia; Reproducibility of Results; Retrospective Studies; Tosyl Compounds; Treatment Outcome; Urinary Bladder Neck Obstruction; Urodynamics

To investigate any differences in changes in serum prostate specific antigen (PSA) levels in patients with benign and malignant prostatic disease in response to the testosterone surge after administering a luteinizing hormone-releasing hormone (LHRH) analogue.. The study included 54 patients referred to the urology clinic with intermediate PSA levels (4-10 ng/mL) or an abnormal digital rectal examination. Forty-five patients received a single injection of LHRH analogue depot each at one week before prostate biopsy and nine served as a control group. Changes in PSA levels in response to the testosterone surge from the LHRH analogue were recorded after 5 and 7 days, and were correlated with the biopsy results. The PSA changes were compared with basal PSA levels and the free/total PSA ratio(f/tPSA).. Of the 45 patients who underwent prostate biopsy, histopathology showed prostate cancer in 11, benign prostatic hyperplasia in 33 and prostatic intraepithelial neoplasia in one. Patients with cancer had a significantly greater increase in serum PSA levels during the first week after LHRH injection than those in the benign and control groups. Receiver operating characteristic curves showed that the percentage change in PSA level on day 5 was more diagnostic than total PSA and f/tPSA.. There was a marked difference in the PSA response of patients with benign or malignant disease to the testosterone surge produced by the LHRH analogue. Although a larger study would be needed before LHRH-induced provocation could be proposed as a clinical test, in this small series the response was better than that for total PSA or f/tPSA in differentiating benign and malignant disease.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Humans; Leuprolide; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; ROC Curve; Testosterone

There are large interindividual differences in response to medical therapy for men with benign prostatic hyperplasia. Selection of patients for alpha-blocker versus hormonal treatment is often based more on assumptions than on well-documented knowledge. A more scientifically based decision of therapy has a potential for economical savings and increased effectiveness.. We performed morphometry on prostate biopsy specimens and determined the amount of stroma, epithelium, and glandular lumen (pretreatment characteristics) in 34 men with benign prostatic hyperplasia before 24 weeks of androgen suppressive therapy. Androgen suppressive therapy consisted of either the luteinizing hormone-releasing hormone agonist leuprolide depot (3.75 mg intramuscularly every 28 days) or the nonsteroidal antiandrogen bicalutamide (50 mg/day orally). The evaluation of the clinical response (effectiveness parameters) was based on changes in prostate volume, peak urinary flow rate, symptom score, and bladder outlet obstruction.. A large prostate volume before treatment was associated with more pronounced symptom score improvement, but neither prostate-specific antigen nor any of the parameters of tissue composition used (percentage of epithelium, epithelial volume, and stromal/epithelial ratio) predicted a favorable response to hormonal treatment.. The pretreatment variables that are readily available at present have a limited role in helping clinicians to decide the optimal medical treatment for patients with benign prostatic hyperplasia.

Topics: Aged; Androgen Antagonists; Anilides; Biopsy; Delayed-Action Preparations; Epithelium; Humans; Leuprolide; Male; Nitriles; Probability; Prostate; Prostatic Hyperplasia; Tosyl Compounds; Treatment Outcome; Ultrasonography; Urodynamics

The discovery of a novel estrogen receptor (ER), ER-beta, has given rise to new possibilities regarding estrogen's roles in the prostate. Although ER-beta is reported to be expressed preferentially in the rat prostate, its expression in the human prostate and relationship to cancer development has not been investigated. Thus the purpose of the study was to examine mRNA levels of ER-alpha and ER-beta in benign prostatic hyperplasia and prostate carcinoma.. Samples of 15 prostate cancers obtained at radical prostatectomy were examined. All the patients had been maintained on androgen withdrawal therapy for at least 3 months. ER-alpha and ER-beta mRNAs were measured with a competitive PCR technique.. Both ER-alpha and ER-beta mRNAs were detected in all of the prostate cancer tissues examined, as well as in PC3 and LNCap cells, although the levels varied among specimens. Interestingly, both types were significantly decreased in cases with lymph node metastasis. However, there was no correlation between ER mRNA levels and any other clinicopathological parameters.. (1) Both ER-alpha and ER-beta mRNAs are expressed in prostate cancer and (2) expression of ER mRNA may not be related to cancer progression but may be negatively correlated with metastasis.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Estrogen Receptor alpha; Estrogen Receptor beta; Gene Expression Regulation, Neoplastic; Humans; Leuprolide; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Estrogen; RNA, Messenger

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.. Clinical studies utilizing hormonal therapies to treat BPH were reviewed. Studies that used total medical castration therapy via the use of a long-acting gonadotropin-releasing hormone (GnRH agonist), partial androgen blockade via the use of the 5 alpha-reductase inhibitor finasteride, and estrogen blockade (via the use of aromatase inhibitors) were analyzed.. Both the GnRH agonists and finasteride result in prostatic size reduction and alleviate symptoms in some patients. Both therapies are more effective in men with larger prostates (> 40 cc). Finasteride is less efficacious in terms of size reduction than the GnRH agonists but also has fewer side effects. To date, clinical trials with aromatase inhibitors have not yielded dramatic positive results in the treatment of BPH.

Topics: Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Estrogen Antagonists; Estrogens; Finasteride; Humans; Leuprolide; Male; Prostatic Hyperplasia; Testosterone

Topics: Humans; Leuprolide; Male; Prostatic Hyperplasia

A total of 4 men with benign prostatic hypertrophy who underwent medical castration therapy with a long-acting gonadotropin-releasing hormone agonist (leuprolide) for more than 6 months elected to add an estrogen transdermal patch (0.05 mg. to the skin biweekly) to the leuprolide regimen. The average prostatic size (transrectal ultrasound), serum prostate specific antigen (PSA) levels and symptoms of prostatism were dramatically decreased with leuprolide alone. The addition of estrogen for 6 months did not result in any change in prostate size, symptoms or serum PSA levels over that seen with leuprolide alone. The development of squamous metaplasia was noted in 1 man with leuprolide alone and in 1 man after the addition of estrogen. Immunohistochemical staining with anticytokeratin 903 antibodies reveals that squamous metaplasia appears to arise from prostatic basal cells. We postulate that the target cell for estrogen action in the prostate is the prostatic basal cell. In the absence of androgen the only direct effect of estrogens is the induction of squamous metaplasia.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Drug Therapy, Combination; Estradiol; Estrogens; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Testis; Testosterone

Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists; Androgen Antagonists; Androstenes; Azasteroids; Buserelin; Finasteride; Goserelin; Humans; Leuprolide; Male; Prostatic Hyperplasia

We studied serum prostate-specific antigen levels in 12 men with benign prostatic hypertrophy treated with a long-acting GnRH analogue, leuprolide, 1 mg (0.2 mL) sc. daily for six months. The average decrease in prostate size measured by ultrasound was 45 percent after six months with concomitant improvement in the obstructive symptoms of prostatism. There was a steady decline in serum PSA levels which paralleled the decrease in prostate size. One patient who discontinued treatment after six months demonstrated both a regrowth of his prostate and a rise in serum PSA levels to pretreatment levels four months post-discontinuation of treatment. We conclude that treatment with a GnRH analogue caused reversible involution of prostatic epithelial cells with parallel effects on serum PSA levels. Consideration of the initial prostate size together with the serum PSA levels can help predict the response to medical castration in men with BPH.

Topics: Antigens, Neoplasm; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia

To determine the effects of reversible medical castration on prostatic size and symptoms we treated 15 patients with benign prostatic hypertrophy with a long-acting GnRH analog, leuprolide (1 mg/day sc), for a minimum of 4 months. The men's serum testosterone, dihydrotestosterone, and estradiol concentrations fell to very low levels within 4-6 weeks after the initiation of treatment. Transrectal ultrasonography of the prostate demonstrated an average shrinkage of 40% after 4 months of treatment (n = 15) and 46% after 6 months of treatment (n = 11). All 15 men had improvement in urinary flow and, to a lesser extent, in nocturia and frequency. The side-effects of the therapy were decreased potency and flushing. The most dramatic improvement occurred in 4 of the 5 men who had complete urinary obstruction before treatment. One man had a suprapubic cystotomy tube removed during the fifth treatment month. Two other men who had Foley catheters before treatment are voiding well without catheters since their third treatment month. Another man who had a very large prostate (300 g) before treatment had one successful voiding trial, although he still has a suprapubic cystotomy tube. One man decided to stop treatment after 6 months. Two months later his hormone values and prostate size had returned to pretreatment levels. One man treated during the fourth and fifth months with fluoxymesterone in addition to leuprolide had regrowth of his prostate while receiving this androgen. We conclude that leuprolide treatment of men with benign prostatic hypertrophy results in shrinkage of prostatic size and concomitant improvement in the obstructive symptoms of prostatism. The prostatic shrinkage reverses when treatment is discontinued or combined with androgen.

Topics: Aged; Aged, 80 and over; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Middle Aged; Prostate; Prostatic Hyperplasia

A common affliction of older men is bladder outlet obstruction secondary to benign prostatic hyperplasia for which the standard treatment is surgical prostatectomy. We report on six men with urinary retention from benign prostatic hyperplasia who were not medically able to undergo surgical prostatectomy but were successfully treated with the luteinizing hormone-releasing hormone (LH-RH) agonist, leuprolide acetate. This therapy is exemplified by the case of a sixty-six-year-old man with hemophilia B and urinary retention. The patient was treated with daily subcutaneous injections of 1 mg of leuprolide acetate, and prostatic size decreased from 132 g to 42 g, with initiation of spontaneous micturition while on treatment. For patients with symptomatic benign prostatic hyperplasia who are not candidates for surgery, treatment with an LH-RH agonist, such as leuprolide acetate, should be considered as a possible alternative.

Topics: Aged; Aged, 80 and over; Drug Evaluation; Gonadotropin-Releasing Hormone; Hemophilia B; Humans; Leuprolide; Male; Middle Aged; Organ Size; Prostate; Prostatic Hyperplasia; Ultrasonography; Urination Disorders

To determine the effects of reversible medical castration on prostatic size in patients with benign prostatic hypertrophy (BPH), 3 patients with BPH were treated with a GnRH analogue, leuprolide, for six months at a dosage of .2ml (1 mg) s.c. daily. Serum testosterone, dihydrotestosterone and estradiol fell to castration levels 4-6 weeks after the initiation of treatment and remained low throughout the study period. Transrectal ultrasonography of the prostate demonstrated an average decrease in prostatic volume of 58% at 6 months, with the greatest rate of decrease occurring during the 2nd to 5th months of treatment. One man who had acute urinary retention before treatment was subsequently able to void extremely well. In a second man the symptoms of prostatism diminished but in the third urinary frequency and nocturia persisted in spite of a reduction in prostatic size, presumably because his symptoms were due to renal insufficiency.

Topics: Aged; Aged, 80 and over; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Male; Pituitary Hormone-Releasing Hormones; Prostatic Hyperplasia; Urination Disorders