M.R. Pandian

Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal male range

OBJECTIVE To examine the relationship between serum T levels and sexual function when T levels are varied in the normal male range by pharmacological means. Two groups of healthy men were treated with a depot form of GnRH agonist leuprolide acetate (Lupron depot; TAP Pharmaceuticals, Chicago, IL) on days 1 and 31 to suppress endogenous T production and either 4 (n = 6) or 8 (n = 5) mg/d T replacement by a sustained release, long-acting T microcapsule formulation on day 1. OUTCOME MEASURES Sexual function was evaluated by daily logs of sexual activity and electroencephalogram-coupled nocturnal penile tumescence recording before and after 9 weeks of treatment. RESULTS Serum T levels in 4 and 8 mg/d groups were at low and high ends of the normal male range, respectively (10.5 +/- 1.7 versus 26.5 +/- 3.4 nmol/L). The number and duration of rapid eye movement (REM) periods, latency to REM sleep, erections/REM period, magnitude, and duration of tumescence were not significantly different between the 4 and 8 mg groups. Sexual logs also did not show significant differences in overall scores or in subcategories of intensity of sexual feelings (libido) and sexual activity between the two doses. CONCLUSIONS These data indicate that erectile function and sexual activity and feelings are restored by relatively low T levels. These data may help explain why some partially hypogonadal men continue to have normal sexual function and the absence of good correlation between serum T levels in the normal range and sexual function.

DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients

SummarySeveral potential prognostic factors are available today for patients with breast cancer, and many more are being identified and studied. To evaluate the clinical utility of these factors, it will be necessary to measure them on a large number of patients, and then follow these patients so that multivariate survival analyses can be performed.The Oncology Research Network was established in 1986 by the University of Texas Health Science Center at San Antonio and Nichols Institute Reference Laboratories in order to evaluate the clinical utility of new prognostic factors for patients with primary breast cancer. The first generation of prognostic factors included steroid receptors, along with DNA ploidy and S-phase fraction determined by flow cytometry. Currently, laboratory results have been obtained from more than 127,000 patients, and follow-up information is available on a subset of more than 25,000 of these patients.S-phase fraction was related to the ploidy status of the tumor. An increased incidence of aneuploidy and higher S-phase fractions were found in estrogen and progesterone receptor negative tumors, tumors from patients with positive axillary lymph nodes, tumors greater than 2 cm in diameter, and patients younger than 35 years of age. Preliminary survival analyses suggest that S-phase fraction and DNA ploidy, in combination with other prognostic factors, are powerful predictors of early disease relapse.The Oncology Research Network provides an important resource for examining the clinical significance of new laboratory assays and for expediting improvements in existing laboratory techniques.

Is physiologic sympathoadrenal catecholamine release exocytotic in humans

In cultured cells and isolated perfused organs, catecholamines are coreleased with chromogranin A (CgA) from adrenal chromaffin cells and sympathetic neurons. The corelease suggests that exocytosis is the mechanism of catecholamine secretion. To investigate whether physiologic catecholamine secretion is exocytotic in humans, we measured plasma norepinephrine, epinephrine, and CgA responses to differentiated stimuli of sympathoadrenal discharge. The CgA radioimmunoassay antibody recognized authentic CgA in normal human adrenal chromaffin vesicles. Insulin-induced hypoglycemia and caffeine ingestion, in decreasing order of potency, selectively stimulated epinephrine release from the adrenal medulla. During hypoglycemia, plasma levels of epinephrine and CgA rose, and peak plasma levels of epinephrine and CgA correlated, suggesting that gradations in epinephrine release represented gradations in exocytosis. However, significant increments in plasma CgA were not observed after caffeine ingestion. Furthermore, the rise of CgA levels during hypoglycemia lagged 60 minutes behind those of epinephrine. A less-pronounced temporal dissociation between CgA and epinephrine release was also shown in isolated chromaffin cells in vitro. Selective adrenal vein catheterization suggested a barrier to CgA transport across the adrenal capillary wall. Short-term, high-intensity dynamic exercise, assumption of the upright posture, prolonged low-intensity dynamic exercise, and smoking, in decreasing order of potency, stimulated norepinephrine release from sympathetic nerve endings. Only the first sympathetic neuronal stimulus resulted in significant increments in plasma CgA, increments considerably less than those attained during adrenal medullary activation by insulin hypoglycemia. During high-intensity exercise, peak plasma norepinephrine and CgA levels correlated, suggesting that gradations in norepinephrine release represented gradations in exocytosis. The human adrenal medulla was a far more prominent tissue source of CgA than human sympathetic nerves--adrenal medullary homogenates contained 97-fold more CgA (micrograms/g) than sympathetic nerve homogenates. In conclusion, catecholamine secretion during selective stimulation of either sympathetic nerves or the adrenal medulla is, at least in part, exocytotic. Furthermore, stimulation of the former results in comparatively modest changes in plasma CgA compared with changes attained during stimulation of the latter. CgA appears to be transported by a route different from that of catecholamines from adrenal medullary chromaffin cells to the circulation in vivo.

How to integrate steroid hormone receptor, flow cytometric, and other prognostic information in regard to primary breast cancer

A large group of patients with node‐positive breast cancer was divided into a training set (n = 851) and a validation set (n = 432) to demonstrate techniques for integrating steroid hormone receptor status, DNA flow cytometric findings, and other prognostic factors to predict patient survival. Multivariate analyses showed that estrogen receptor status, the number of involved axillary lymph nodes, patient age, S‐phase fraction, progesterone receptor status, and tumor size were significant predictors of survival in patients with node‐positive breast cancer. Techniques for optimizing and validating a cut point for a new prognostic factor and for examining alternative representations of prognostic factors were demonstrated. Prognostic indexes were created that could be used to identify patients with very good or very poor prognoses.

Leptin and IGF-I levels in unconditioned male volunteers after short-term exercise.

We have previously shown that serum gonadotropins, particularly LH, decline after acute exercise in male volunteers. The mechanism for this decline is unknown. Plasma leptin and IGF-I concentrations were measured in seven male volunteers after acute exercise to exhaustion using the Bruce protocol. Leptin concentrations declined following exercise reaching nadir values 30-120 min after exercise. As anticipated, plasma IGF-I concentrations showed a transient rise immediately after exercise falling thereafter to nadir levels 60-90 min after exercise before returning towards baseline levels. In view of the previously described decline in gonadotropin release after acute exercise, the decline in plasma leptin levels, perhaps related to the rise in IGF-I, may play a role in exercise-induced inhibition of gonadotropin release presumably by inhibition of GnRH secretion.

Effects of Blood pH and Blood Lactate on Growth Hormone, Prolactin, and Gonadotropin Release after Acute Exercise in Male Volunteers

Abstract It has recently been found that prevention of the acidosis of anaerobic exercise blocks β-endorphin release. Because heavy exercise affects secretion of other anterior pituitary hormones, we studied the results of alkali infusion and ingestion upon blood levels of four hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). Eight male subjects were studied after either 2 mEq/kg placebo (NaCl) or alkali (NaHCO3) administered before and during exercise to exhaustion. Blood samples were obtained before exercise and then 15, 30, 60, 90, 120, and 180 min postexercise. GH and PRL but not FSH or LH increased significantly postexercise, with a peak at 60 min, and subsequently declined back to baseline by 180 min. Base treatment reduced GH at baseline and postexercise (except at 60 min) and increased PRL significantly, particularly at 60 min. While the precise mechanisms on how acid/base changes affect hormone release remain to be defined, there are possible consequences on gonadal function and substrate availability during exercise.

Melatonin and gonadotropin secretion after acute exercise in physically active males

SummarySerum concentrations of luteinizing hormone (LH), follicle stimulating hormone, testosterone (T) and melatonin were measured in seven physically active male volunteers after exercise on a treadmill using the Bruce protocol. Measurements were made on blood samples obtained before exercise, within 30 s after exercise, at 15 min after exercise, and subsequently at 30-min intervals after exercise for a total duration of 180 min. Serum LH concentration fell from a peak post-exercise level of 15.7 (4.7) IU·l−1 [mean (SD)] to a nadir of 10.3 (2.4) IU·l−1 (P<0.004). Nadir values in individual volunteers were seen between 60 and 150 min after exercise. This fall in serum LH was paralleled by a similar fall in the concentration of serum T. Serum melaonin concentrations did not change significantly after exercise. It is concluded that melatonin, despite is reported anti-gonadotropic properties, does not play a role in the depression of serum LH after acute strenuous exercise in physically active males

Corticotropin releasing hormone and gonadotropin secretion in physically active males after acute exercise

SummaryPlasma concentrations of corticotropin releasing hormone (CRH) and the serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, adrenocorticotropic hormone (ACTH) and cortisol were measured in seven physically active males after acute exercise on a treadmill using the Bruce protocol. Measurements were made in the basal pre-exercise state, immediately after exercise, and at 30-min intervals for 3 h after exercise. Serum LH concentrations declined following exercise reaching nadir values between 60 and 180 min after exercise (90 min post exercise in the group). The nadir values in individual volunteers were significantly lower than both the baseline and post-exercise levels. This fall in serum LH concentration appeared to follow a slight but significant elevation of the plasma concentration of CRH which reached peak levels when measured immediately post exercise. Plasma ACTH concentrations paralleled the rise in CRH, but fell to undetectable levels of below 13.8 nmol · l−1 (< 5 ng · l−1) 60 min after exercise. Plasma cortisol concentrations peaked approximately 30 min after the rise in ACTH, after which they gradually declined to baseline levels. Plasma testosterone concentrations paralleled the concentrations of LH. The data suggest that CRH, on the basis of its previously described gonadotropin-depressant property, may be the hormone involved in the exercise-mediated decline in serum LH. Alternatively, some as yet unidentified factor(s), may be involved in producing the altered concentrations of both LH and CRH.

Serum levels of androstenedione, testosterone and dehydroepiandrosterone sulfate in patients with premature ovarian failure to age-matched menstruating controls.

Serum concentrations of androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were measured in 29 patients with premature ovarian failure (POF) and an identical number of age-matched normal control subjects. The study was aimed at determining possible differences in androgen concentrations of ovarian and adrenal origin in POF patients and age-matched normal menstruating controls. Serum testosterone and DHEAS concentrations in the 2 populations were not significantly different. The serum androstenedione concentration in the POF patient group (3,077.50 +/- 1,122.33 pmol/l) was significantly lower than in age-matched normal control subjects (4,167.70 +/- 1,381.09 pmol/l, p < 0.005), possibly reflecting the loss of ovarian androstenedione secretion and/or a subtle defect in adrenal steroidogenic capacity.

Atrial natriuretic peptide and arginine vasopressin in pregnancy and pregnancy-induced hypertension.

Atrial natriuretic peptide (ANP) and arginine vasopressin concentrations were measured in 9 patients with pregnancy-induced hypertension. The results were compared to those found in 7 normal pregnant women matched for age, duration of pregnancy, and parity. Plasma ANP levels were significantly higher in the pregnancy-induced hypertension patients than in the control group. Plasma arginine vasopressin concentrations, however, were not significantly different in the two populations. The mechanism of the observed rise in ANP concentrations in the patients with pregnancy-induced hypertension is not known. However, it may be related to a rise in intra-atrial pressures secondary to hypertension, an increase in baroreceptor discharge as a result of hypertension, or, less likely, the ANP may be released from extracardiac sites.