Deprivation In Men Research Articles

ANDROGEN DEPRIVATION USE WITH EXTERNAL BEAM RADIATION FOR PROSTATE CANCER: RESULTS FROM CaPSURE™

Recent data support the role of androgen deprivation in men undergoing external beam radiotherapy for prostate cancer. The benefits of neoadjuvant, concurrent or adjuvant treatment have been limited to men at intermediate and high risk. We examined the patterns and predictors of androgen deprivation in men undergoing external beam radiation therapy in CaPSURE. CaPSURE is an observational, longitudinal disease registry, from which 932 men met study inclusion criteria. Androgen deprivation was classified as neoadjuvant-within 9 months of radiation or adjuvant-from the start of radiation to 6 months after completion. Time trends in androgen deprivation as well factors associated with combined therapy were elucidated using multivariate analyses. In this study 40%, 39% and 21% of men could be categorized into high, intermediate and low risk groups, respectively. Overall 42% and 33% of patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. Between 1997 and 2002 neoadjuvant hormone use increased significantly in all risk groups, including patients at low risk. On multivariate analyses only the year of diagnosis and clinical risk group were associated with receiving androgen deprivation with radiation. A significant increase in combined androgen deprivation and external radiation was observed in the last decade in men with intermediate and high risk disease. Nevertheless, more widespread acceptance is necessary since a substantial minority continue to receive radiation alone. Many patients with low risk disease that is amenable to radiation monotherapy also receive androgen deprivation. No clinical or sociodemographic features predicted the use of androgen deprivation with external radiation.

Estradiol and cognition during androgen deprivation in men with prostate carcinoma

Salminen et al.1 present evidence that LHRH analogs, by lowering endogenous estradiol levels, impair certain cognitive processes in prostate cancer (PCa) patients. Others have shown that estradiol cognitively protects spatial memory in older men.2 Currently, estrogens are used as secondary, rather than primary, hormonal therapies for PCa patients. We propose that estradiol is likely to be more protective of cognition if it is used before patients start on an LHRH agonist. Salminen et al. do not cite data that has shown no cognitive benefits of estradiol treatment in PCa patients.3 To reconcile those differences, we suggest that estradiol's cognitive benefits are likely to be greatest in patients who have not already experienced cognitive decline—either from LHRH agonists or aging. We base this suggestion on data from menopausal women, which reveal a critical window of time at menopause when estrogenic compounds are protective of cognition.4 After cognitive decline has set in, exogenous estrogens may actually play a negative role. Extending these results to men, we should expect that estradiol will be most beneficial to PCa patients if used earlier rather than later. Estradiol lowers patients' risk of osteoporosis and incidences of hot flashes, while costing less than LHRH agonists. So, then, why not use estradiol as primary hormonal therapy for PCa? The risk of thromboembolism is real, but it can be greatly reduced if estradiol is applied transdermally. Supposedly, gynecomastia can be reduced with prophylactic radiotherapy; however, its effectiveness has not been proven in prospective studies, nor does it significantly reduce the incidence of breast complaints from patients on estradiol. Again, extrapolating from postmenopausal women, physicians should be aware that estrogens may increase urinary incontinence in patients already experiencing incontinence secondary to a prostatectomy and radiotherapy for localized PCa.5

Estradiol and cognition during androgen deprivation in men with prostate carcinoma

The adverse effects of hormonal manipulation in prostate carcinoma need to be established in view of its increasing use as an adjuvant treatment. This prospective study investigated the association of androgen deprivation-induced estradiol decline with cognition in prostate carcinoma. Cognitive testing of prostate carcinoma patients was carried out at baseline and at 6 and 12 months on androgen deprivation (AD). Cognitive performances were evaluated with standardized measures of information processing, including working memory and attention, visual and verbal skills, and memory performances in 31 tests. Testosterone and estradiol changes during AD were measured with the DELFIA (PerkinElmer, Inc., Wellesley, MA) system. Associations between changes in cognitive performances and estradiol decline were studied. Cognitive performances, which were significantly associated with decline in estradiol, included visual memory of figures (r = -0.52; P = 0.022) and recognition speed of numbers, which were impaired, (r = -0.57; P = 0.030) at 6 months, and improvement in verbal fluency (r = -0.52; P = 0.019) at 12 months. Other cognitive domains appeared unaffected by estradiol decline. The character of change (impairment or improvement) depended on the magnitude of estradiol decline. The cognitive domains of verbal fluency, visual recognition, and visual memory were associated with decline in estradiol during androgen deprivation. The results suggest selective associations among testosterone decline, estradiol, and cognitive performance. Documentation of these associations has implications for informed patient support in hormonally treated prostate carcinoma.

Alanine infusion during hypoglycaemia partly supports cognitive performance in healthy human subjects.

To investigate the potential for the non-glucose metabolic substrate alanine to support brain function during glucose deprivation in man. Seven healthy men were studied on two occasions using a hyperinsulinaemic glucose clamp to lower arterialized plasma glucose to 2.5 mmol/l, in the presence of either 2 mmol/kg/h alanine infusion or saline, measuring counter-regulatory hormonal responses, symptoms generated and cognitive function with a mini-battery of tests sensitive to hypoglycaemia. Alanine infusion elevated plasma alanine (peak value 1481 +/- 1260 vs. 138 +/- 32 micro mol/l, P = 0.02 alanine vs. saline) and lactate (peak value 3.09 +/- 0.14 vs. 2.05 +/- 0.12 mmol/l, P = 0.02). Cognitive function assessed by the Stroop word and colour subtests deteriorated less with alanine than saline (P < 0.01 for both). Other cognitive function tests deteriorated equally and counter-regulatory hormones rose equally during hypoglycaemia in both studies (P > 0.34) except for increased glucagon with alanine (peak 260 +/- 53 vs. 91 + 8 ng/l, P = 0.03). There was no significant effect of alanine on either autonomic or neuroglycopenic symptom scores. Some, but not all, aspects of cognitive performance may be supported by an alanine infusion during hypoglycaemia. It is not clear whether alanine supports brain function directly or via increased availability of lactate. These data contribute to the growing evidence that regional metabolic differences exist in the brain's ability to use non-glucose fuels during hypoglycaemia.

Androgen deprivation in men with prostate cancer is associated with an increased rate of bone loss.

The objective of this work was to determine the effect of androgen deprivation therapy (ADT) on rates of bone mineral density (BMD) loss in men with prostate cancer. It was a prospective study comparing men receiving ADT to age matched controls for 2 y. Subjects received a history, physical exam, bone mineral density measurement, and laboratory evaluation every 6 months. Thirty-nine subjects receiving continuous ADT for prostate cancer (subjects) were compared to 39 age-matched controls not receiving ADT (controls). Twenty-three subjects and 30 controls completed the study through 24 months. Men in the ADT group demonstrated greater rates of bone mineral density loss than men in the control group at every site except the lumbar spine. Twenty-four month per cent of bone mineral density loss is presented as mean+/-standard error (s.e.). At the distal forearm, the ADT group value was -9.4%+/-1.0% and -4.4%+/-0.3% for controls (P<0.0005). The ADT group femoral neck values were -1.9%+/-0.7% and 0.6%+/-0.5% in the control group (P=0.0016). The ADT group total hip value was -1.5%+/-1.0% and 0.8%+/-0.5% in the control group (P=0.0018). The ADT group trochanter value was -2.0%+/-1.3% and -0.1%+/-0.5% in the control group (P=0.0019). The ADT group lumbar spine value was -0.2%+/-0.8 % and 1.1%+/-0.6% in the control group (P=0.079). Our data demonstrate greater rates of bone mineral density loss in men receiving androgen deprivation therapy for prostate cancer.

Intermittent androgen deprivation.

Intermittent androgen deprivation is a controversial approach to management of prostate cancer. Preclinical models have demonstrated delay in time to prostate-specific antigen (PSA) progression in athymic mice bearing LNCaP tumors and a delay in time to androgen independence in androgen-dependent Shionogi carcinoma tumors in castrated animals exposed to intermittent androgen. Phase II clinical trials have demonstrated improved sexual function and quality of life in men discontinuing androgen deprivation. The average percentage of time spent off androgen deprivation ranges from 37% to 58%. Most men respond to retreatment with hormonal therapy. Current ongoing phase III clinical trials of intermittent versus continuous androgen deprivation in men with metastatic disease or recurrent disease after localized therapy will assess the comparative impact on quality of life and survival. Final analyses of these critical trials will define the ultimate role of this approach in prostate cancer. In the interim, intermittent androgen deprivation should be considered an experimental approach.

Additional treatments and reimbursement rates associated with prostate cancer treatment for patients undergoing radical prostatectomy, interstitial brachytherapy, and external beam radiotherapy

Objectives. To define patterns of treatment among contemporary patients undergoing radical prostatectomy, interstitial radiation, and external beam radiation for prostate cancer. Methods. We analyzed 291 consecutive patients (Stage T1-T3NXM0) who underwent definitive local treatment for prostate cancer with radical prostatectomy, interstitial seed implantation, or external beam radiation. Patients were stratified into three risk groups based on clinical T stage, serum prostate-specific antigen level at diagnosis, and biopsy Gleason score. The frequency of additional treatments, including androgen deprivation and external beam radiation, given within 3 months of initial local therapy was assessed. Patterns of care were compared and adjusted for risk. Results. Of the 291 patients, 107 (36.8%) underwent radical prostatectomy, 94 (32.3%) underwent interstitial seed implantation, and 90 (30.9%) underwent external beam radiation. Use of combination therapy differed significantly according to the type of initial local treatment and risk category. No patient in the low-risk group received combination therapy. For patients in the intermediate and high-risk groups, the frequency of combination therapy was significantly lower in the radical prostatectomy group when compared with either the interstitial seed implantation ( P <0.001 and P <0.02, respectively) or external beam radiation group ( P <0.001 and P <0.001, respectively). Conclusions. There are significant differences in resource utilization for contemporary patients undergoing definitive local therapy for prostate cancer. These differences may have a significant effect on treatment cost and morbidity, and they will likely make short-term comparisons between different treatment modalities difficult because of the high use of androgen deprivation in men treated with radiation therapy.

Cold thermoregulatory changes induced by sleep deprivation in men.

The aim of this study was to evaluate the thermoregulatory changes induced by 27-h of sleep deprivation (SD) in men at rest both in a comfortable ambient temperature and in cold air. A group of 12 male subjects were placed in a comfortable ambient temperature (dry bulb temperature, Tdb = 25 degrees C, relative humidity, rh = 40%-50%, clothing insulation = 1 clo) for 1 h and then they were submitted to a standard cold air test in a climatic chamber for 2 h (Tdb = 1 degree C, rh = 40%-50%, wind speed = 0.8 m.s-1, nude), before and after 27 h of sleep deprivation. Thermoregulatory changes (rectal temperature, Tre; mean skin temperature. Tsk; metabolic heat production M) were monitored continuously. At comfortable ambient temperature, no significant change was observed after SD for Tre, Tsk and M. During the cold test, Tre did not change but Tsk and M were higher after SD (P < 0.05). Increased M (+ 6%, P < 0.05) was related to earlier and higher shivering, with a possible increase in the sensitivity of the thermoregulatory system as shown by the shorter time to onset of continuous shivering (d): 8.66 (SEM 1.33) min versus 28.20 (SEM 1.33) min (P < 0.001) and by a higher Tsk observed at d: 27.60 (SEM 1.40) degrees C versus 21.40 (SEM 0.60) degrees C (P < 0.001). These results were associated with higher cold sensations and shivering following SD. They also suggested that SD modified thermoregulatory responses at a central level especially in a cold environment.

The Effect of Nafarelin Acetate, a Luteinizing-Hormone-Releasing Hormone Agonist, on Benign Prostatic Hyperplasia

We examined the influence of androgens on benign prostatic hyperplasia, using nafarelin acetate, a potent luteinizing-hormone-releasing hormone agonist, to achieve reversible androgen deprivation in men with benign prostatic hyperplasia. Nine patients with bladder-outlet obstruction due to benign prostatic hyperplasia were treated with subcutaneous nafarelin acetate (400 micrograms per day) in an open trial for six months. In all patients, serum testosterone decreased to castrate levels. Objective observations included uroflowmetry, measurement of residual urine volume, determination of prostatic size by ultrasonography, and prostatic biopsy. In all patients, the prostate regressed to a mean (+/- SEM) of 75.8 +/- 3 percent of the initial size (range, 52 to 86; P less than 0.005); the regression reached a plateau after four months. Morphologic analysis of biopsy specimens showed regression of glandular epithelium. Three of nine patients had clinical improvement with treatment. Six months after the cessation of treatment, plasma testosterone levels had returned to normal and the size of the prostate had increased to 99 +/- 5.5 percent of the initial size. These findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients. However, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.

The Effect of Nafarelin Acetate, a Luteinizing-Hormone–Releasing Hormone Agonist, on Benign Prostatic Hyperplasia

We examined the influence of androgens on benign prostatic hyperplasia, using nafarelin acetate, a potent luteinizing-hormone-releasing hormone agonist, to achieve reversible androgen deprivation in men with benign prostatic hyperplasia. Nine patients with bladder-outlet obstruction due to benign prostatic hyperplasia were treated with subcutaneous nafarelin acetate (400 micrograms per day) in an open trial for six months. In all patients, serum testosterone decreased to castrate levels. Objective observations included uroflowmetry, measurement of residual urine volume, determination of prostatic size by ultrasonography, and prostatic biopsy. In all patients, the prostate regressed to a mean (+/- SEM) of 75.8 +/- 3 percent of the initial size (range, 52 to 86; P less than 0.005); the regression reached a plateau after four months. Morphologic analysis of biopsy specimens showed regression of glandular epithelium. Three of nine patients had clinical improvement with treatment. Six months after the cessation of treatment, plasma testosterone levels had returned to normal and the size of the prostate had increased to 99 +/- 5.5 percent of the initial size. These findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients. However, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.

Normalization of binocular VERs after early onset visual deprivation in man

Visually evoked responses (VERs) were elicited by a reversing checkerboard target from a patient who suffered early onset bilateral deprivation of form vision as a result of a high refractive error, large amplitude strabismus, and congenital nystagmus. Monocular and binocular steady-state VERs were abnormal in amplitude and wave form even when a correction for the patient's large refractive error (compound hyperopic astigmatism) was worn. Although monocular VERs could not be normalized, a normal wave form and amplitude were restored to the binocular VER by the addition of horizontal prisms to the patient's ophthalamic prescription. The initially degraded binocular VER gradually acquired a normal morphology and amplitude as the magnitude of compensating base-out prisms in the patient's habitual ophthalmic prescription was systematically increased. The relationship between the binocular VER amplitude and the correcting prisms derived by the method described in this paper was subsequently used to arrive at a practical clinical solution for the patient's unusual and debilitating visual symptoms. This electrophysiological evaluation of binocular function at the cortical level proved to be a very useful diagnostic procedure with prognostic value; standard clinic procedures were ineffective in elaborating the patient's sensory and oculomotor disorders. The theoretical and practical implications of managing patients with history of early onset visual deprivation are discussed.

Effect of acute zinc deprivation on plasma zinc and platelet aggregation in adult males

In view of earlier results obtained with rodents, the present study was designed to investigate the effect of acute zinc deprivation in man on plasma zinc concentration and the response of platelets to aggregating agents. Three adult men consumed a formula diet based largely on soybean protein for 12 to 14 days. During the control period the diet was supplemented with 12 mg zinc per day. Without supplementation the diet supplied approximately 0.5 mg zinc per 3.0 Mcal; it contained 0.7 ppm zinc, and 0.2% phytate. After removal of the zinc supplement plasma zinc dropped rapidly and reached a minimum by the 5th day. There was a wide diurnal variation in plasma zinc concentration in one subject with the overnight fasting value being the highest and decreasing soon after the morning meal. Platelet aggregation in response to ADP and arachidonate was impaired when plasma zinc was 60 micrograms/dl or less and was restored to normal within 19 h of oral zinc supplementation. These results demonstrate that plasma zinc can be rapidly decreased by dietary zinc deprivation and that extracellular zinc plays an important role in platelet aggregation.

Rapid-eye-movement sleep deprivation decreases the density of 3H-dihydroalprenolol and 3H-imipramine binding sites in the rat cerebral cortex

The high affinity binding sites for 3H-imipramine ( 3H-IMI) and 3H-dihydroalprenolol ( 3H-DHA) in the rat cerebral cortex were studied after 24, 48 and 72 h of rapid-eye-movement (REM) sleep deprivation. Both the K d and B max values for 3H-IMI and 3H-DHA binding remained unaffected after 24 or 48 h of REM sleep deprivation. After 72 h of REM sleep deprivation there was a significant reduction in the B max for 3H-IMI and 3H-DHA binding with a concomitant increase in the apparent affinities. The reduction in high affinity 3H-IMI and 3H-dihydroalprenolol binding sites observed 72 h after REM sleep deprivation could be related to the antidepressant effects of REM sleep deprivation in man.

Potentiation of sulpiride-induced prolactin secretion by sodium deprivation in man.

Abstract. Previous studies suggest that prolactin is not an important osmoregulatory hormone in man, while aldosterone is well known to be important in osmoregulation. The present investigation was undertaken to ascertain whether serum osmotic changes affect pituitary prolactin secretion following sulpiride administration. Five normal subjects were placed on a constant isocaloric diet with different sodium content. Serum prolactin and aldosterone level were measured by specific radioimmunoassay. The basal serum level of prolactin was unaffected by changes in sodium content of the diet, in contrast to the basal level of aldosterone. On the other hand, the maximum levels of serum prolactin in response to sulpiride (50 mg, im) were significantly higher on a low sodium diet (3 g of salt/day) than on a control diet (12– 15 g of salt/day). When the content of diet changed from low salt to high salt (25 g of salt/day), sulpiride-induced prolactin response decreased, though it was not significantly lower than that on a control diet. However, sulpiride administration could not stimulate aldosterone secretion under any of the various sodium contents of the diet. The present study provides evidence that lowering of serum osmolarity stimulates serum prolactin response to sulpiride administration in man and this response is not modulated by aldosterone secretion.

A review of the biological effects of total sleep deprivation in man

This biologically oriented review attempts to complement earlier and more psychological performance based reviews of total sleep deprivation. Also, the effects of total sleep deprivation are interpreted, here, from a function of human sleep perspective, rather than from the more usual stress viewpoint. It would appear that total sleep deprivation does not produce any major changes in biochemical and physiological measures of somatic functioning. Such a conclusion would not seem to support an hypothesis that human sleep is for body restitution. Although there are equivocal results amongst several of the more psychophysiological measures, EEG does show a pronounced change. This latter finding, together with many reports of psychological performance detriment, would appear to sustain a CNS or cerebral restitutional role for human sleep. However, before definitive conclusions can be drawn from the biochemical and physiological findings of total sleep deprivation, the following qualifications of experimental methodology are made: 1. (1) Apart from sleep loss, many studies have provided unnatural regimes which may have ameliorated p possible effects of total sleep deprivation. 2. (2) Most studies are of relatively short duration and may not have been sufficiently long for effects to develop. 3. (3) Measures are often limited in range and depth of analysis. 4. (4) Subjects are mostly fit, young adult, intelligent males and there is little constitutional variability. 5. (5) Reported changes of statistical significance may be of no physiological significance and changes of possible physiological significance may be obscured by statistical procedures. 6. (6) Intervening behavioural variables, such as novelty and anticipation of the sleep deprivation situation, may confound real effects.

Bromocriptine: lack of effect on the angiotensin II and aldosterone responses to sodium deprivation.

Five normal subjects took a low sodium diet for four days on two occasions, one with and one without added bromocriptine 2.5 mg three times a day by mouth. Daily measurements of urinary electrolytes and the concentrations of plasma renin (PRC), angiotensin II (AII), aldosterone, 18-hydroxycorticosterone, cortisol, electrolytes and prolactin were made in both phases of the study. Deprivation of sodium without bromocriptine resulted in progressive and highly significant increases in the plasma concentration of aldosterone from 230 +/- 50 to 418 +/- 44 (SEM) pmol/l, 18-hydroxycorticosterone from 627 +/- 138 to 1420 +/- 478 pmol/l, PRC from 108 +/- 38 to 166 +/- 14 muU/ml and AII from 16 +/- 3 to 29 +/- 4 pmol/l. Similar changes were found during bromocriptine administration despite suppression of prolactin secretion. Sodium deprivation together with bromocriptine resulted in increases in the plasma concentrations of aldosterone from 230 +/- 47 to 416 +/- 72 pmol/l, 18-hydroxycorticosterone from 630 +/- 99 to 1629 +/- 552 pmol/l, PRC from 105 +/- 12 muU/ml and AII from 14 +/- 3 to 26 +/- 5 pmol/l. Plasma cortisol did not change either in response to sodium deprivation or bromocriptine. Mean cumulative negative sodium balance was 101 +/- 14 mmol on bromocriptine and 118 +/- 14 mmol in the control period. We conclude that prolactin is not necessary for the steroidogenic response to sodium deprivation in man.

Role of Growth Hormone in the Regulation of Aldosterone Biosynthesis*

Experimental evidence indicates that a non-ACTH pituitary hormone (s) is essential for a normal aldosterone response to ACTH and sodium deprivation in man and animals. The present study was designed to evaluate the role of somatotropin in the regulation of aldosterone biosynthesis in human beings. The aldosterone response to ACTH was determined in 8 intact human beings before and after dietary sodium restriction and compared with the aldosterone response observed in 3 patients with panhypopituitarism and 3 patients with isolated GH deficiency. Plasma aldosterone concentration, plasma cortisol concentration, and plasma renin activity were determined by radioimmunoassay. A normal aldosterone,cortisol, and renin response to dietary sodium restriction and ACTH was observed in the subjects with isolated GH deficiency. Plasma aldosterone concentration was normal under resting conditions in the patients with panhypopituitarism, but failed to increase in response to ACTH or sodium deprivation. A normal response o...

Energy deprivation in man--methodological problems and possibilities.

Various approaches to the study of physiological and behavioural effects of energy deprivation are presented and discussed. An experimental, total energy deprivation in 20 healthy human volunteers during an 11-day period, preceded and followed by 4-day control periods, is described. Potentially pathogenic reactions which occurred in spite of precautions are analysed. It is concluded that the present controlled real-life model with acute total energy deprivation serves the purpose of studying hypotheses concerning potentially pathogenic mechanisms occurring in deprivational situations under conditions of natural and man-made catastrophes.

Recovery sleep following different visual conditions during total sleep deprivation in man

The findings of visual impairment during total sleep deprivation were used as a basis for a possible link between vision and sleep. It was proposed that the level of visual load imposed during sleep deprivation was an important variable, and would have a substantial effect upon recovery sleep. Six young male subjects underwent two conditions of 64 h of sleep deprivation on separate occasions. One condition incorporated a high visual load, and the other a low load. Exercise and sound were balanced. All night sleep EEGs were taken for two baseline nights, and also for two recovery nights following each condition. There was a significant increase of stage 4 on all recovery nights and a REM rebound on the second recovery night. SWS, particularly stage 4, TST and REM density, were significantly greater following the high load. Implications of these findings for sleep theories and for sleep deprivation research are discussed.

The Influence of Age on the Renal Response to Water Deprivation in Man

Alterations in urine concentrating ability with age were examined in 98 active community-dwelling volunteers (aged 20-79 years) who were free from evidence of diseases known to adversely affect renal function. There was a significant decrease in urine osmolality reached after 12 h dehydration with advancing age, which could not be correlated with the age-related decline in creatinine clearance. A significant age-related diminution in the ability to conserve solute was also observed. This inability to conserve solute may result in diminished medullary tonicity and impaired urinary concentrating ability.