ay-25-205 and Prostatic-Neoplasms

This paper first reports the results of 12 patients with sex hormone-dependent neoplasms, including 9 women with breast cancer, 2 men with osteosarcoma and 1 man with prostate carcinoma, treated by LRH agonist, (D-Ala6, des-Gly-NH2(10))-LRH-ethylamide (LRH-A) 100-200 micrograms, IM, QD. After 15-30 days of administration, the concentrations of plasma mean estradiol, progesterone, testosterone, serum luteinizing hormone and follicle-stimulating hormone were lowered significantly in the peripheral blood of all patients, associating with improvement of the patients' general condition and reduction of the tumors and/or metastatic foci. No serious side effects were observed except vaginal irregular bleeding in isolated patients. Three patients died and the others were alive in follow-up of 4-30 months. The results suggest that LRH-A be useful in the treatment of the sex hormone-dependent tumors and worth further study.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Breast Neoplasms; Female; Fibula; Gonadotropin-Releasing Hormone; Hormones; Humans; Male; Middle Aged; Orbital Neoplasms; Osteosarcoma; Prostatic Neoplasms

In an attempt to determine whether the chronic administration of GnRH agonist (GnRH-A) has a direct inhibitory effect on testicular steroidogenesis in the human, the testes of four men with disseminated prostatic cancer who were treated with GnRH-A daily for at least 1 yr were assayed for intratesticular pregnenolone (5-pregnen-3 beta-ol-20-one), progesterone, dehydroepiandrosterone, 17 alpha-hydroxypregnenolone (5-pregnen-3 beta 17 alpha-diol-20-one), 17 alpha-hydroxyprogesterone, androstenedione, and testosterone (T). In addition, testicular 17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase enzyme activities of the delta 4 pathway were measured. These intratesticular steroids and enzyme activities from four GnRH-A-treated patients were compared to those in five men (controls) who were orchiectomized as the primary treatment for their disseminated prostatic cancer and in three other men who were treated for 3-12 months with GnRH-A daily but received, in addition to the daily GnRH-A, 1000 IUhCG, im, every other day for 3 days immediately before their salvage orchiectomy, which was performed when their disease progressed. In the control group, the delta 5-steroids, particularly dehydroepiandrosterone and pregnenolone, represented the majority of the intratesticular steroids. Compared to control values, all intratesticular steroids except delta 4-P (for which there was no difference) were significantly lowered by treatment with GnRH-A. Intratesticular T was reduced by 98% from 328 +/- 139 (+/- SEM) ng/g testis in the control group to 8 +/- 3 in the GnRH-A-treated group (P less than 0.01). The additional treatment with hCG for 3 days in the GnRH-A-treated group reversed the inhibition of all steroids to either control or above control levels, with intratesticular T rising to 1144 +/- 273 ng/g testis. A similar trend was found for all three enzymatic activities, i.e., GnRH-A alone inhibited each of the enzymatic activities, whereas the addition of hCG reversed this inhibition by GnRH-A. These data indicate that the chronic administration of GnRH-A to elderly men results in inhibition in both the delta 4 and delta 5 pathways, with a subsequent decrease in the intratesticular T concentration. The ability of exogenous hCG to reverse both the reduction in delta 4 and delta 5 intratesticular steroid content and the intratesticular enzyme activities induced by GnRH-A treatment supports the concept that GnRH-A does not have a direct inh

Topics: 17-Hydroxysteroid Dehydrogenases; Adult; Aldehyde-Lyases; Chorionic Gonadotropin; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Steroid 17-alpha-Hydroxylase; Testicular Hormones; Testis

The effect of daily injections of D-Ser-(TBU)6-LRH-EA10 (GnRH analogue (GnRH-A) 100 micrograms sc) on serum testosterone (T), 17 alpha-hydroxyprogesterone (17OHP) and oestradiol-17 beta (E2) was studied in 4 men. During GnRH-A therapy T, 17OHP and E2 were markedly decreased by the end of the second month. Continuous long-term administration of GnRh-A inhibited testicular function. To test whether the biosynthetic pathway was affected by the regimen, a bolus of 2000 U hCG was given to each subject after 10 months of therapy. Evaluation of the kinetics of steroid responsiveness showed a significant release of T in response to the trophic stimulus, with little or no elevation of serum 17OHP and E2. The response seen in these treated men appeared similar to that found in hypogonadotrophic men and prepubertal boys.

Topics: 17-alpha-Hydroxyprogesterone; Aged; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Estradiol; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydroxyprogesterones; Luteinizing Hormone; Male; Prostatic Neoplasms; Testis; Testosterone; Time Factors