Biomedical subjects

A Belanger

Publications and source records attributed to A Belanger.

At least 55 records · Page 3Linked to original sources

PubMed1990

Longer life but worse health? Measurement and dynamics.

A number of recent cross-sectional studies of longevity and health among the elderly have concluded that recent positive trends in the prolongation of life have not been matched by similar trends in the extension of healthy life. This paper challenges that pessimistic conclusion by examining conceptual issues related to the measurement and dynamics of the mortality-disability process. It uses data from the 1986 Longitudinal Study of Aging (U.S. Department of Health and Human Services, 1988) to illustrate its principal points.

Aged↗

PubMed1990

Hormonal and biochemical changes during treatment of endometriosis with the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6,des-Gly-NH2(10)]LH-RH ethylamide.

The effect of medical oophorectomy induced by treatment with the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6,des-Gly-NH2(10)]LH-RH ethylamide was studied in 34 patients with laparoscopically proven endometriosis. Tamoxifen was administered during the 1st month of therapy to prevent flare-up of the disease during the estrogen surge. Fifteen women had a decrease of their laparoscopy scores translated into an improvement in the stage of disease, whereas in 12 others, the decrease in their scores was not enough to allow a change of disease stage. The 2nd laparoscopy was not performed in 7 women. Medical oophorectomy, after daily injection of the LH-RH agonist (LH-RH-a), was accompanied by low levels of circulating estradiol. The serum concentration of all delta 4-3-ketosteroids was significantly decreased during medical oophorectomy, whereas the level of circulating delta 5-3 beta-hydroxysteroids was not altered except for pregnenolone. The present data indicate that medical oophorectomy induced by an LH-RH-a in association with tamoxifen is a very efficient and well tolerated therapy in endometriosis.

Adrenal Cortex Hormones↗

PubMed1989

Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate.

Androgens play a major role in the development, growth, and function of accessory sexual organs, especially the prostate. However, the testis is not the sole source of circulating androgens in man, since the adrenal gland secretes dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (delta 4-dione) in large quantities. The aim of the present study was to investigate the effect of plasma concentrations of DHEA and delta 4-dione similar to those found in adult man on sensitive and specific markers of androgen action in the rat ventral prostate. In addition to ventral prostate weight, we have measured the steady state levels of the mRNAs encoding the C1 component of rat prostatic binding protein (PBP-C1) and spermine-binding protein (SBP) using 35S-labeled cDNA probes for in situ hybridization. One week after castration, ventral prostate weight fell 84%, while prostatic 5 alpha-dihydrotestosterone (DHT) and androgen-dependent mRNAs were undetectable. When administered via Silastic implants to castrated adult rats for 1 week, plasma concentrations of 1.37 +/- 0.06 ng/ml DHEA or 0.43 +/- 0.08 ng/ml delta 4-dione independently caused increases in ventral prostate weight to 33% and 65% of normal values, respectively. The same plasma levels of DHEA and delta 4-dione resulted in high intraprostatic levels of DHT to 1.19 +/- 0.34 and 3.66 +/- 0.89 ng/g tissue, respectively. Furthermore, DHEA caused an increase in the steady state levels of PBP-C1 and SBP mRNAs to 50% and 57% of the normal state, respectively, while delta 4-dione caused increases corresponding to 80% and 119% of control values, respectively. Castrated adult rats receiving testosterone at a concentration of 1.66 +/- 0.37 ng/ml plasma maintained normal ventral prostate weight and gene expression levels. The present results demonstrate that circulating levels of the adrenal steroids DHEA and delta 4-dione comparable to those found in man cause an important stimulation of androgen-dependent gene expression in the rat, probably after their conversion to DHT in the prostatic tissue itself.

Adrenal Glands↗

PubMed1989

Active life among the elderly in the United States: multistate life-table estimates and population projections.

Calculations of multistate life expectancy not only measure how long a population may live beyond a certain age, but also what fractions of this continuing lifetime will be spent in an independent or dependent status. Many Americans aged 70 and over are leading long, active lives; large numbers of individuals who become dependent, moreover, do so temporarily and return to independent status. Men and women have disparate total and active life expectancies, however, reflecting differential survival patterns and varying rates of transition among statuses. Policy makers must consider the increased size of the future elderly population, and changes in its age composition and functional status, when planning relevant health services.

Activities of Daily Living↗

PubMed1988

Determinants of isolated systolic hypertension.

Isolated systolic hypertension (ISH), defined as systolic blood pressure of 160 mm Hg or greater when the diastolic pressure is less than 95 mm Hg, is a common form of hypertension among the elderly. We collected incidence and prevalence data on ISH and evaluated several potential factors for its occurrence in the Framingham Heart Study during 16 biennial examinations. The factors evaluated were age, sex, all components of the blood pressure (systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure), Metropolitan relative weight, serum cholesterol level, serum uric acid level, cigarette smoking, ventricular heart rate, glucose intolerance, and hematocrit. The population at risk (1687 men and 1992 women) were those members of the Framingham cohort with a systolic blood pressure less than 160 mm Hg in the first four biennial examinations. Results showed ISH in 14.4% of the men and 22.8% of the women. Cumulative incidence rates were 418 per 1000 in men and 533 per 1000 in women. Significant risk factors for ISH were age, sex, all components of the blood pressure, and increased relative weight in women. We conclude that ISH is a highly prevalent disorder. Its major determinants are age, sex, increasing levels of blood pressure, and obesity in women.

Age Factors↗

PubMed1988

Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in previously untreated patients with clinical stage D2 prostate cancer: today's therapy of choice.

One hundred and ninety-nine patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 26 months (3-59 months). The objective response to the treatment was assessed according to the criteria of the U.S. NPCP. There was a 5.7-fold increase (26.3 vs 4.6%) in the percentage of patients who achieved a complete response compared with the results obtained in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 12 of the 186 evaluable patients (6.5%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in the same five studies using monotherapy. The duration of response was also significantly improved in the patients who received the combination therapy while the death rate was decreased by approximately two-fold during the first 4 yr of treatment. In fact, while an approximately 50% death rate is observed at 2 yr in all studies using monotherapy, the same 50% death rate is delayed by 2 yr in the present study. It should be mentioned that at the time of relapse under combination therapy, the treatment is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide. The marked (5.7-fold) improvement in the rate of complete objective responses coupled with the three-fold decrease in the number of non-responders, the increased duration of the positive responses and the two-fold decrease in the death rate during the first 4 yr of treatment are obtained with the combination therapy using Flutamide and castration, thus improving the quality and duration of life with no or minimal side-effects. By blocking the androgen receptors in the prostatic cancer tissue, the antiandrogen decreases the action of the androgens of adrenal origin and thus inhibits the growth of a large number of tumors which, otherwise, would continue to be stimulated by the adrenal androgens left after medical or surgical castration.

Aged↗

PubMed1988

The rise in testicular androgens during the first days of treatment with an LHRH agonist in the dog can be blocked by aminoglutethimide or ketoconazole.

Up to day 6 of treatment of adult dogs, daily subcutaneous administration of 50 micrograms of the LHRH agonist [D-Trp6, des-Gly-NH2-10]LHRH ethylamide causes up to a 3-fold increase in serum testosterone (T) concentration which is followed by a progressive decrease to castration levels (less than or equal to 0.2 ng/ml) at later time intervals (up to 21 days, the last time interval studied). Both aminoglutethimide and ketoconazole, two inhibitors of steroid biosynthesis, cause a 30-40% rise in serum T when administered alone. However, either drug administered in combination with the LHRH agonist completely blocks the transient rise in serum T observed when the LHRH agonist is administered alone. On the other hand, the LHRH agonist prevents the secondary rise in steroid secretion observed when either of the two inhibitors of steroid secretion is used alone. Administration of the pure antiandrogen Flutamide alone or in combination with LHRH-A and an inhibitor of steroid biosynthesis does not influence serum T levels. When the serum levels of pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone, dehydroepiandrosterone (DHEA), androstenedione (delta 4-dione), androst-5-ene-3 beta, 17 beta-diol (delta 5-diol), T, dihydrotestosterone (DHT), androstane-3 alpha, 17 beta-diol, androstane-3 beta. 17 beta-diol and 17 beta-estradiol (E2) are analyzed in detail, it can be seen that both aminoglutethimide and ketoconazole not only prevent the rise in serum steroids observed during the first 8 days of treatment with the LHRH agonist but that both compounds enhance the inhibitory effect of the LHRH agonist at later time intervals. A predominant inhibitory effect of ketoconazole is exerted on 17,20-desmolase activity. Aminoglutethimide has little influence on the loss of serum LH bioactivity induced by the LHRH agonist while ketoconazole stimulates the concentration of serum bioactive LH in the absence or presence of simultaneous treatment with the LHRH agonist. The present data clearly demonstrate that aminoglutethimide or ketoconazole can prevent the rise in serum androgens accompanying the first days of treatment with an LHRH agonist in the dog. Moreover, after 3 weeks of treatment, the inhibitory effect of the LHRH agonist on serum androgen levels is enhanced by addition of aminoglutethimide or ketoconazole. Moreover, Flutamide does not interfere with the inhibitory action of the LHRH agonist, aminoglutethimide or ketoconazole, thus suggesting that maximal inhibition of androgen action is likely to be achieved by a combination of these drugs.

Aldehyde-Lyases↗

PubMed1988

Combination therapy with flutamide and [D-Trp6]LHRH ethylamide for stage C prostatic carcinoma.

Sixty-seven previously untreated patients presenting with clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average duration of treatment of 23.5 months. Only five patients have so far shown treatment failure with 91.8% of the patients still in remission at 2 years. Three patients have died from prostate cancer while three have died from other causes, 93.5% of the patients being alive at 2 years. Local control was achieved rapidly in all except one patient. Urinary obstruction and hydronephrosis were corrected in all cases. When comparing to recent data obtained after single endocrine therapy (orchiectomy or estrogens), or radiotherapy, the rate of treatment failure at 2 years is 3.5-fold lower after combination therapy (8.2%) than monotherapy (28.4%). The death rate at 2 years following start of the combination therapy is 6.5% while it is on average 22.2% (3.4-fold higher) in the studies using monotherapy (orchiectomy or estrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of the disease permits a better response which is possibly explained, at least in part, by the lower degree of dedifferentiation and heterogeneity of the tumors.

Acid Phosphatase↗

PubMed1988

Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate.

In order to assess the androgenic potency of physiological plasma concentrations of the adrenal steroids dehydroepiandrosterone (DHEA) and androstenedione (delta 4-dione) in the rat prostate, these two steroids were released from Silastic tubings of appropriate length and size in castrated male rats. Implants of DHEA led to plasma levels of DHEA and 5-androsten-3 beta,17 beta-diol covering the range of concentrations found in adult men while no significant change was observed in plasma levels of delta 4-dione, testosterone and dihydrotestosterone (DHT). delta 4-Dione implants, on the other hand, led to a parallel increase in plasma delta 4-dione and testosterone levels at all doses used while plasma DHT only increased at supraphysiological doses of delta 4-dione. At plasma concentrations comparable to those found in adult men; delta 4-dione (0.8 ng/ml) and DHEA (3.4 ng/ml) stimulated prostate weight 3.7- and 2.1-fold, respectively. In the same groups, prostatic DHT levels were elevated at 4.48 +/- 0.05 and 2.70 +/- 0.73 ng/g tissue, respectively. A close parallelism was observed between prostatic DHT levels and prostatic weight in all groups. The present data show that in the rat, a species having no significant secretion of adrenal androgens, plasma concentrations of DHEA and delta 4-dione maintained within the range of those found in adult men are efficiently converted into DHT and act as potent androgenic stimuli in prostatic tissue. The castrated rat bearing Silastic implants releasing constant and predetermined amounts of adrenal steroids offers a good model to study the recently identified role of adrenal steroids in peripheral tissues.

Androgens↗

PubMed1987

Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients.

Patients (154) with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 22 months (3-49 months). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 vs 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy. The death rate was decreased by approximately 2-fold between 2 and 3 yr of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non-responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2-3 yr of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects.

Adenocarcinoma↗

PubMed1987

Flutamide eliminates the risk of disease flare in prostatic cancer patients treated with a luteinizing hormone-releasing hormone agonist.

Although chronic treatment with luteinizing hormone-releasing hormone agonists achieves castration levels without side effects other than those related to hypoandrogenism, a limitation to their use alone for the treatment of prostatic cancer is the transient increase in serum androgens that lasts for 5 to 8 days at the start of treatment with the risk of disease flare. Our data show that the concomitant administration of the pure antiandrogen flutamide in association with the luteinizing hormone-releasing hormone agonist (D-Trp6) luteinizing hormone-releasing hormone ethylamide caused a 64 to 78 per cent decrease in serum prostatic acid phosphatase on days 3 and 7 after the start of treatment in 70 patients with previously untreated stage D2 prostatic cancer. Pain, which was present in 41 patients at the start of treatment, did not increase in any patient, it decreased in 7 at 1 week and it disappeared or decreased in 27 at 2 weeks. Performance, which originally was abnormal in 34 patients, became normal in 7 within 1 week and in 20 within 1 month (59 per cent). These data show that the addition of flutamide completely eliminates the risks of disease flare associated with the use of the otherwise exceptionally well tolerated luteinizing hormone-releasing hormone agonists in patients treated for prostatic cancer.

Acid Phosphatase↗

PubMed1987

Increase in plasma steroid glucuronide levels in men from infancy to adulthood.

We studied the relationships between circulating steroid glucuronide concentrations and the changes in adrenal as well as testicular C-19 steroid secretion during pubertal development in men. Plasma levels of dehydroepiandrosterone and its sulfate, androst-5-ene-3 beta,17 beta-diol, androstenedione, testosterone, dihydrotestosterone, androstane-3 alpha,17 beta-diol and its glucuronide, and androsterone and its glucuronide were measured in 56 boys (aged 3-16 yr) and in normal men. There was a progressive and parallel increase in plasma dehydroepiandrosterone sulfate and dehydroepiandrosterone concentrations from age 7 to 15 yr, while plasma androstenedione and androst-5-ene-3 beta,17 beta-diol concentrations increased only at 11-12 yr. From age 13 yr to adulthood, a dramatic rise of testosterone was observed while there was no marked change in dihydrotestosterone or androstane-3 alpha,17 beta-diol. Between 3 and 11 yr of age, androsterone glucuronide increased from 0.68 +/- 0.24 (+/- SEM) to 2.25 +/- 0.59 ng/mL (P less than or equal to 0.01) and androstane-3 alpha,17 beta-diol glucuronide from 0.17 +/- 0.02 to 0.41 +/- 0.09 ng/mL (P less than or equal to 0.01). A further rise of both 5 alpha-reduced steroid glucuronides occurred when testosterone levels increased during puberty. Our data indicate that 5 alpha-reduced steroid glucuronides are good markers of peripheral transformation of adrenal and testicular C-19 steroids. In addition, since 5 alpha-reduced steroid glucuronides are detected before puberty, there must be a peripheral conversion of adrenal C-19 steroids into testosterone during prepubertal development.

Adolescent↗

PubMed1986

Physical activity and physical demand on the job and risk of cardiovascular disease and death: the Framingham Study.

Cardiovascular events over 24 years of surveillance were examined in 1166 men participating in the Framingham Study, classified by physical demands of their work and by a 24-hour index of physical activity. Findings are based on 303 noncardiovascular, 220 coronary, and 325 cardiovascular deaths in men aged 45 to 64 years at time of physical activity assessment. For level of physical activity over 24 hours, there is a clear trend of improved overall, cardiovascular, and coronary mortality with increased level of physical activity at all ages, including the elderly. The effect is sustained with a more pronounced effect with the passage of time, despite presumed decrease in level of activity. The mortality benefits apply both in those with and without intervening overt cardiovascular disease, making it unlikely that the physical inactivity-mortality relationships reflects already existent myocardial damage. For physical demands of the job, there is only a suggestion (not statistically significant) of benefit for cardiovascular mortality including coronary deaths. In sharp contrast, noncardiovascular mortality was positively related to both physical demand of the job and 24-hour physical activity index.

Cardiovascular Diseases↗

PubMed1986

Advantages of the combination therapy in previously untreated and treated patients with advanced prostate cancer.

In order to achieve a more complete blockade of androgens of both testicular and adrenal origin at the start of treatment, we have administered the pure antiandrogen Flutamide in association with orchiectomy (13 patients) or the LHRH agonist [D-Trp6]LHRH ethylamide (118 patients) to previously untreated patients with clinical stage D2 prostate cancer. The mean duration of treatment was 491 days (102-1208 days). The response was assessed according to the criteria of the U.S. National Prostatic Cancer Project. A complete response has been observed in 30 patients (23%) while partial and stable responses have been achieved in 50 (38%0 and 45 (34%) patients, respectively. A positive objective response has thus been observed in 125 of 131 patients (95%). Serum PAP became normal before 6 months in all except 8 (6.1%) of patients. Quite remarkably, 23 of 48 patients treated for 2 years (47.9%) have achieved a complete response. Of the 20 deaths, 12 (9%) were due to prostate cancer, while 8 (6%) resulted from other causes. The probability of continuing a positive response after 2 years of treatment (according to Kaplan and Meier) is 60% while the probability of survival at the same time interval is 89%. This survival should be compared to values of approx 50% achieved with previous treatments limited to inhibition of testicular androgen secretion or action. The present data demonstrate that the combined blockade of androgens achieved with Flutamide and castration provides an objective response in approx 95% of patients, and markedly prolongs the period of remission while the death rate within the first 2 years is lower than that obtained with previous treatments. The important prolongation of survival is achieved with an excellent quality of life. Two-hundred and three patients have clinical stage D2 prostate cancer previously treated by orchiectomy, estrogens or LHRH agonists alone received, at the time of relapse, the same combination therapy. Patients already castrated received only Flutamide while, for those previously treated with DES, the estrogen was replaced by the LHRH agonist [D-Trp6]LHRH ethylamide in association with Flutamide. Flutamide was given as additional medication to those already receiving an LHRH agonist alone. Complete, partial and stable objective responses assessed according to the criteria of the U.S. National Prostatic Cancer Project were obtained in 11 (5.4%), 17 (8.4%) and 38 (18.7%) patients, respectively, for a total objective response rate of 32.5%. Progression continued in 137 (67.5%) patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists↗

PubMed1986

Loss of luteinizing hormone bioactivity in patients with prostatic cancer treated with an LHRH agonist and a pure antiandrogen.

Chronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5 alpha-dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D-Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2 +/- 0.3 (SEM) to 1.1 +/- 0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43 +/- 0.04 to 0.030 +/- 0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26 +/- 0.03 to 0.03 +/- 0.01. In the same patients, serum testosterone levels were decreased from 3.91 +/- 0.51 to 0.14 +/- 0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032 +/- 0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with LHRH agonists.

Adenocarcinoma↗

PubMed1985

Long term treatment with luteinising hormone releasing hormone agonists and maintenance of serum testosterone to castration concentrations.

Serum concentrations of luteinising hormone and testosterone were measured by radioimmunoassay one, two, four, seven, and 24 hours after the subcutaneous administration of 500 micrograms of the luteinising hormone releasing hormone agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide in patients who had previously received daily treatment with these peptides for 0, 1, 6, 12, 18, and 24 months. No increase in the serum concentrations of luteinising hormone or testosterone were detected at any time between one and 24 months' treatment. The data show that daily subcutaneous administration of the two luteinising hormone releasing hormone agonists used at the appropriate dose can maintain concentrations of serum androgens equivalent to those after castration during long term treatment.

Bone Neoplasms↗

PubMed1985

Changes in plasma steroid levels after single administration of hCG or LHRH agonist analogue in dog and rat.

The present study was designed to investigate the effect of acute administration of gonadotropin on testicular steroid secretion in dog and rat. Animals received a subcutaneous injection of 25 IU/kg of hCG or 1.5 microgram/kg of [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A). Testosterone is the predominant steroid measured, in dog plasma, under basal conditions. After LHRH-A injection, testosterone levels are not significantly changed while dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol (delta 5-steroids) levels are stimulated by almost 20-fold (P less than 0.01). When dogs were injected with hCG, we also observed a marked stimulation of dehydroepiandrosterone levels (20-fold; P less than 0.01) accompanied by a small increase of plasma testosterone concentration (2-fold, P less than 0.01). In rats injected with either hCG or the LHRH analogue, an increment of plasma testosterone (7-fold, P less than 0.01) is detected in the first hour while plasma dehydroepiandrosterone levels are slightly stimulated. Moreover, in rats injected with hCG, low plasma steroid levels are present between 4-12 h after injection due to testicular desensitization. This marked decrease is then followed by a second peak of steroid secretion 24 h later. Acute testicular steroidogenic responsiveness to hCG on the dog is, however, different: after stimulation, the levels of plasma dehydroepiandrosterone are maintained at a plateau and slowly decline after 24-48 h. Our data indicate that in dogs, stimulation of testicular steroidogenesis leads to an increase of plasma delta 5-steroid levels while the same stimuli cause, in the rat, a stimulation of delta 4-androgen, particularly testosterone.

1-Methyl-3-isobutylxanthine↗

PubMed1985

Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in advanced prostate cancer: a marked improvement in response and survival.

Eighty-seven previously untreated patients with clinical stage D2 (bone metastases) prostate cancer have received the combination therapy with a pure antiandrogen and an LHRH agonist (or orchiectomy) as first treatment in a multicentre study for up to 34 months (average = 16.2 months). A positive objective response assessed according to the criteria of the US NPCP has been observed in all cases. Pain disappeared in all patients within 1 month and performance become normal in all (including 2 bedridden patients) within 4 months. Progression of the disease after a period of remission has been observed in only 8 patients. Only one patient has died from prostate cancer while 3 have died from other causes. The probability of continuing response and survival at 2 years for the patients who receive the combination treatment (Kaplan-Meier's method) is 81 and 91%, respectively. By contrast, in the randomized group who had orchiectomy alone, 4 of 7 have died from prostate cancer (P less than 0.05 as compared to combination therapy). In addition to a marked improvement in the remission rate and survival, combination therapy maintains a good quality of life, hot flashes and a decrease or loss of libido being the only side-effects.

Acid Phosphatase↗