Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of long term GnRH treatment with the biodegradable depot formulation of ICI 118.630 on hormone levels and spermatogenesis were investigated in 18 males with advanced prostate cancer. Plasma levels of FSH, LH, testosterone, DHEA-S and SHBG were monitored at regular intervals. The drug suppressed FSH, LH and testosterone significantly and did not affect DHEA-S and SHBG plasma levels. Tissue specimens for histologic assessment and quantitative analysis of germinal cell types were obtained at secondary orchidectomy in 16 patients immediately following GnRH analogue treatment. Germinal cell maturation was arrested at the spermatogonial stage. In two patients discontinuing treatment histologic assessment of secondary orchidectomy specimens 9 and 10 months after the last GnRH analogue depot injection resulted in germinal cell maturation to late spermatids in part of the tubule cross sections. These results indicate that long term administration of the GnRH analogue fails to produce complete testicular sclerosis and spermatogenic arrest might be reversible.
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PMID:Effects of long term GnRH analogue treatment on hormone levels and spermatogenesis in patients with carcinoma of the prostate. 297 2

Seven patients suffering from prostatic cancer were treated with a slow-release D-Trp-6-LHRH preparation for a period of 24-32 months. LH, FSH, PRL and testosterone levels were evaluated before and at the end of treatment and then 40 days later. Baseline and GnRH-, TRH-, and HCG-stimulated hormonal values decreased after treatment. The possibility that a long-term treatment with GnRH analogues induces a sustained suppression of pituitary and testicular function is suggested.
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PMID:Sustained impairment of pituitary and testicular function in prostatic cancer patients treated with a depot form of a GnRH agonist. 297 31

Ninety patients with advanced prostatic cancer (15 with stage B, 23 with stage C, and 52 with stage D) were randomized to receive 0.9, 1.8, or 3.6 mg, respectively, of Zoladex depot subcutaneous injection every 28 days for 12 weeks. The serum levels of LH, FSH, and testosterone were elevated after the first injection, and followed by a significant decrease. The suppression of testosterone levels in the blood to castrate levels was observed in all patients except two treated with 0.9 mg. Objective response (CR and PR) was seen in 63.6% (0.9 mg), 47.8% (1.8 mg), and 68% (3.6 mg) of patients according to the Japanese Prostatic Group Criteria. Subjective improvement (performance status, analgesic consumption) was also observed in 75-88% of patients but without a statistically significant difference between each dose group. Only minor adverse effects were found during the treatments. The drug was detected dose dependently in the blood by radioimmunoassay. These results suggest that endocrine therapy with Zoladex depot in doses of 3.6 mg subcutaneously every 4 weeks is a useful alternative to surgical castration in patients with prostatic cancer.
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PMID:LH-RH agonist, Zoladex (Goserelin), depot formulation in the treatment of prostatic cancer. Randomized dose-finding trial in Japan. 297 62

Six patients with advanced prostatic cancer were treated with a potent GnRH agonist analog (buserelin, Hoechst; 600 micrograms, intranasally, three times a day) for 6 months. The first 2-6 days of treatment were associated with a 50% elevation (P less than 0.01) in serum testosterone (T) and a simultaneous elevation of 20% (P less than 0.01) in serum prostate-specific acid phosphatase (PAP). Serum T fell to the castrate range (less than 1 nmol/liter) in all patients in 2-3 weeks, and PAP decreased concomitantly in five of the six patients. Serum LH progressively decreased by about 80% during the treatment, whereas a secondary rise of FSH levels occurred after the first month of treatment. The patients were orchiectomized after 6 months of treatment. No differences were found between the pre- and postsurgical levels of serum T or in comparison with those of six patients orchiectomized as the first therapeutic measure. Testicular endogenous T concentrations, LH and FSH receptors, and in vitro T production were measured in three testis samples and compared with those values in testis tissue obtained from five control patients. The endogenous levels and in vitro production of T were depressed by over 95% in testes from agonist-treated patients. The small residual T production responded to hCG stimulation as in control patients. Interestingly, no change was found in testicular LH receptor content, but FSH receptors decreased by 80%. The elevation in serum PAP at the beginning of the agonist treatment and the small residual testicular T production after 6 months may not be clinically important. However, they indicate the necessity of comparative long term studies between orchiectomy and GnRH agonists in the treatment of patients with prostatic cancer.
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PMID:Treatment of prostatic cancer with a gonadotropin-releasing hormone agonist analog: acute and long term effects on endocrine functions of testis tissue. 299 45

Clinical and experimental studies are described on the effects of a gonadotropin-releasing hormone (GnRH) agonist (A) and antagonist (Ant.) on testicular endocrine function. Testicular effects of long-term gonadotropin suppression by GnRH-A were assessed during treatment of prostatic cancer patients. The testis tissue removed after 6 months of A treatment had less than 5% of the testosterone(T)-producing capacity in comparison to testis tissue removed from untreated control patients. However, the LH receptors (R) and responsiveness of T output to LH stimulation in vitro were unchanged. FSH-R decreased by 70%. Hence, despite suppression of gonadotropins and testicular androgen production during long-term GnRH-A treatment the responsiveness to exogenous gonadotropins is maintained. The testicular effects of a gonadotropin suppression induced with GnRH-Ant. and testicular GnRH-R blockade were studied in rats. Besides decreases of gonadotropins and testicular T, systemic Ant. treatment decreased testicular Prl-R, but had no effect on LH-R or FSH-R. Bromocriptine-induced hypoprolactinemia, in contrast, decreased LH-R but had no effect on Prl-R. The results indicate reciprocal regulation of LH-R and Prl-R, and that testicular steroidogenesis and LH-R are under differential regulation, the former by LH, the latter by Prl. In another study, testicular GnRH-R, and consequently the action of a putative testicular GnRH-like factor, were blocked by unilateral intratesticular infusion of Ant. (1 week, Alzet osmotic pumps). The treatment resulted in 90% occupancy of testicular GnRH-R in the Ant.-infused testes, and this was associated with decreased levels of R for LH, FSH and Prl, and of T. The results indicated that the testicular GnRH-R have a physiological function in subtle stimulation of Leydig cell functions.
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PMID:Regulation of testicular steroidogenesis by gonadotropin-releasing hormone agonists and antagonists. 300 72

We have observed that familial factors have a decided influence on the plasma content of sex steroids in men both in the general population and in men of families with prostatic cancer. The contribution of genetic and nongenetic familial factors on the variation of plasma sex steroid content and action has now been investigated in 75 pairs of normal male monozygotic (MZ) twins and 88 pairs of dizygotic (DZ) twins. Zygosity was determined by measuring ten blood proteins and enzymes. The mean plasma values for testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and 3 alpha-androstanediol glucuronide (3 alpha-diol G), free T, LH, FSH, SHBG, age, and degree of adiposity were all similar between the groups of twins. Familial factors (P less than 0.01) accounted for 50% or more of the variation in plasma hormone levels in MZ twins (3 alpha-diol G, 84%; T/DHT, 70%; T, 63%; E1, 63%; free T, 61%; E2, 57%; DHT, 56%; LH, 55%; and FSH, 54%) except for SHBG, which was 30%. The familial influence was greater in MZ twins than in DZ twins for all measurements except for SHBG. The heritability of the variation of hormone levels in plasma was determined from the equation: 2[rMZ(intraclass correlation) - rDZ]. Genes regulate 25% to 76% of the total variation of plasma content of the hormones except for DHT (12%) and SHBG (less than 1%). Genetic regulation of tissue DHT formation was suggested by observing a 48% genetic effect on the plasma content of 3 alpha-diol G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins. 309 56

Endogenous testosterone (T), LH and FSH receptors, and in vitro production of cyclic adenosine-3':5'-monophosphate (cAMP), T and some of its steroid precursors were measured in testicular tissue obtained at orchiectomy from seven prostatic cancer patients treated for 6 months with a potent gonadotropin-releasing hormone (GnRH) agonist analog (buserelin, Hoechst, 600 micrograms 3 times a day intranasally). In addition, histologic and morphometric studies were carried out on the testicular tissue. Testicular tissue from age-matched prostatic cancer patients (n = 14), whose first therapy was orchiectomy, served as controls. The peptide treatment decreased intratesticular T by 95% (P less than 0.01) and FSH receptors by 57% (P less than 0.01), but had no effect on LH receptors. The in vitro production of T decreased by 94% (P less than 0.01), but that of cAMP was unaffected. Besides T, the in vitro production of testicular 17-hydroxyprogesterone (17-OHP-4), androstenedione and 5 alpha-dihydrotestosterone (5 alpha-DHT) dropped by 71 to 90% (P less than 0.01 to 0.05) during buserelin treatment, but those of pregnenolone, progesterone and dehydroepiandrosterone (DHEA) were not affected. Histologic studies revealed considerable variation in the seminiferous epithelium of the control group, but spermatogenesis was highly suppressed in nearly all of the buserelin-treated group. The number of Sertoli cells was unaffected, but tubular diameters were reduced (P less than 0.05) by buserelin treatment. Leydig cells appeared dedifferentiated in this group, although their number per testis was not altered. These data indicate that gonadotropin suppression by GnRH agonist most likely affects testicular steroidogenesis by inhibiting 3 beta-hydroxysteroid dehydrogenase and a step(s) prior to pregnenolone formation. The treatment does not impair testicular LH binding or cAMP production, but clearly suppresses FSH receptors. Spermatogenesis in general is suppressed but with considerable variation.
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PMID:Pituitary-testicular function of prostatic cancer patients during treatment with a gonadotropin-releasing hormone agonist analog. II. Endocrinology and histology of the testis. 312 46

Serum bioactive and immunoreactive FSH levels were measured in five prostatic cancer patients during treatment for 6 months with the GnRH agonist analog buserelin (Hoechst; 600 micrograms, intranasally, 3 times per day) and for up to 12 weeks after subsequent orchidectomy. FSH bioactivity was measured using a sensitive specific in vitro granulosa cells aromatase bioassay. Before buserelin treatment, mean serum FSH bioactivity and immunoreactivity were 19.7 +/- 4.1 (+/- SE) IU/L (n = 5) and 13.7 +/- 3.8 IU/L, respectively, with a bioactivity to immunoactivity (B/I) ratio of 1.7 +/- 0.2. After the initiation of treatment with the GnRH agonist, FSH bio- and immunoactivities both transiently increased for 1-3 days. The increase in bioactivity was greater and prolonged, and the B/I ratio increased nearly 7-fold in 2 weeks. Serum FSH immunoreactivity declined to below the pretreatment level in 5 days and remained low for the rest of the treatment period. In contrast, serum FSH bioactivity did not decrease significantly below the pretreatment level during the 6-month treatment period, although the B/I ratio returned slowly toward the pretreatment value. After orchidectomy, both FSH activities increased dramatically, and the B/I ratio rose transiently from 1.5 to 7 in 2 weeks. Interestingly, serum FSH bioactivity and immunoreactivity decreased significantly (P less than 0.05) 1 day after orchidectomy in the buserelin-treated patients. In contrast, serum FSH immunoreactivity increased during the same period (P less than 0.05) in patients treated only by orchidectomy (FSH bioactivity was not measured). In conclusion, serum FSH bioactivity increases acutely more than FSH immunoreactivity after initiation of GnRH agonist treatment or orchidectomy. In the former case, serum FSH bioactivity subsequently returned to the pretreatment range. A clear decline during long term agonist treatment occurred only in serum FSH immunoreactivity, in contrast to the concomitant decline in serum LH bio- and immunoreactivities reported previously. The persistence of bioactive FSH may explain the inconsistent effects of GnRH agonist treatment on the suppression of spermatogenesis. The acute decrease in serum FSH after orchidectomy in the buserelin-treated men suggests that the testes may produce a factor that stimulates pituitary FSH secretion.
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PMID:Serum bioactive and immunoreactive follicle-stimulating hormone in prostatic cancer patients during gonadotropin-releasing hormone agonist treatment and after orchidectomy. 312 10

In order to clarify the effects of androgen blockade on the hypothalamic-pituitary-testicular axis in man, four patients with advanced prostate cancer, not previously treated, were given oral flutamide, 250 mg three times daily for 9 days. Before, and 7, 8 and 9 days after starting flutamide treatment, on separate days, the following tests were performed: a gonadotrophin pulsatility study, with 20 min interval blood sampling for 12 h, a naloxone test and a GnRH test. Flutamide induced a significant increase in both LH and FSH pulse frequency, while pulse amplitudes and plasma integrated concentrations (IC) of LH and FSH were unaffected. Plasma integrated concentrations of testosterone and oestradiol rose significantly, while that of prolactin was unaffected. The increase in plasma LH concentration induced by naloxone injection was abolished by flutamide treatment. On the other hand, the small FSH response to naloxone was unaffected by flutamide treatment. Response to GnRH was unaffected by flutamide. These results suggest that flutamide exerts effective androgen blockade at the hypothalamic level, since, despite increased plasma testosterone concentrations, gonadotrophin pulse frequency increased and the LH response to naloxone was abolished.
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PMID:The effect of androgen blockade on pulsatile gonadotrophin release and LH response to naloxone. 312 93

The effect of short term administration of flutamide on the hypothalamic-pituitary-gonadal axis was studied in six patients with advanced prostate cancer (C2 stage). Flutamide significantly increased LH pulse frequency in all patients (p less than 0.05 by Wilcoxon's test). The FSH pulse analysis disclosed a similar pattern of LH. Plasma IC-T clearly increased following flutamide therapy; mean IC-T values were 2.67 +/- 0.47 ng./ml. and 4.67 +/- 0.62 ng./ml. before and after flutamide administration, respectively (p less than 0.05 by paired Student's t test). Our study demonstrates that flutamide acts in humans as a selective and specific antiandrogen compound.
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PMID:Short term effects of flutamide administration on hypothalamic-pituitary-testicular axis in man. 312 48


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