A new human chromogranin 'A' immunoradiometric assay for the diagnosis of neuroendocrine tumours.

We investigated whether plasma chromogranin A (CgA), measured by a new immunoradiometric assay, may be a sensitive and specific marker of phaeochromocytoma and of other neuroendocrine tumours. This study involved 121 patients of whom 20 with phaeochromocytoma, 28 with other neuroendocrine tumours (19 gastroenteropancreatic tumors, 3 medullary thyroid and 6 small cell lung carcinomas), 25 with solid nonfunctioning adrenocortical tumours and 48 with essential hypertension. In addition, 130 normal subjects were taken as controls. Plasma catecholamines were measured by using high-performance liquid chromatography, and CgA by a two-site sandwich immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245) of human CgA. Plasma CgA in controls (49.0 +/- 3.1 ng ml(-1), mean +/- SE) and in essential hypertensives (50.8 +/- 3.5 ng ml(-1)) was lower (P< 0.0001) than in adrenocortical tumours (91.8 +/- 13.2 ng ml(-1)), in phaeochromocytomas (254 +/- 49 ng ml(-1)) and in patients with other neuroendocrine tumours (469 +/- 84 ng ml(-1)). Plasma CgA and catecholamines identified 13 and 18 out of 20 phaeochromocytomas with sensitivity of 65% and 90%, respectively. Combined measurement of both markers improved sensitivity up to 100%. In the other neuroendocrine tumours, CgA was abnormal in 23/28 cases (sensitivity 82%) and in 6 it was the only circulating marker of disease. In gastroenteropancreatic tumours, CgA measurement identified all cases (sensitivity 100%). Specificity of CgA in patients with essential hypertension was 98%. In conclusion, CgA determination showed high sensitivity in identifying gastroenteropancreatic tumours and, in association with catecholamines, in detecting patients with phaeochromocytoma. CgA sometimes appeared to be the only circulating marker of disease. Since the specificity of CgA proved to be excellent, this assay may be useful for diagnosis both of functioning and non-functioning neuroendocrine tumours.

Influence of endogenous androgens on carotid wall in postmenopausal women.

OBJECTIVE: There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. DESIGN: Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). RESULTS: Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03-0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. CONCLUSIONS: Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may benefit the carotid artery wall.

Endogenous androgens and carotid intimal-medial thickness in women.

The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P < 0.03-0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P < 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P < 0.02), while A was negatively associated with body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.

Utility of plasma dehydroepiandrosterone sulphate determination in adrenal incidentalomas.

To evaluate whether low DHEA-S levels are predictors of cortical origin, benignity and hormonal activity in incidentally detected adrenal masses, thirty-five patients with adrenal incidentalomas were studied. All patients were operated on and the diagnosis was histologically confirmed. Basal endocrine workup included plasma determination of cortisol before and after dexamethasone (1 mg overnight), plasma ACTH (08:00 h), 17-OH-progesterone, testosterone and potassium, standing plasma renin activity and aldosterone, supine and standing plasma noradrenaline and adrenaline. If necessary, we performed dexamethasone suppression tests at low (2 mg) and high (8 mg) doses, or the loperamide test (16 mg os) for evaluation of glucocorticoid activity and the glucagon test (1 mg i.v.) for exploring adrenal medulla function. Plasma DHEA-S was measured in all patients and the results were compared to those obtained in controls matched for age, sex and menopausal status. Suppression of DHEA-S was found in 11 out of 35 patients (31.5%). However, this hormonal finding occurred in 50% of the extracortical adrenal lesions, while in proven cortical adenomas (no. = 19) it was detected in only 5 patients (26.3%). Sensitivity, specificity, diagnostic accuracy and positive predictive value of low DHEA-S in indicating a cortical origin of the mass were 0.27, 0.0, 0.25, and 0.80. In malignancies (no. = 6) low DHEA-S levels were found in 1 out of 2 metastases and never in cortical carcinomas. Sensitivity, specificity, diagnostic accuracy and positive predictive value of low DHEA-S in indicating a benign form were 0.34, 0.83, 0.42, and 0.91. Six out of 19 patients with cortical adenomas showed signs of hypothalamic-pituitary adrenal (HPA)-axis dysfunction. Low DHEA-S levels were found in 50% of adenomas with HPA-axis abnormality and in 15.3% of adenomas without hormonal activity. Sensitivity, specificity, diagnostic accuracy, and positive predictive value of low DHEA-S levels in indicating hormonal activity of the mass were 0.50, 0.84, 0.73, and 0.60. Our data indicate that the association between low DHEA-S levels and adrenal incidentalomas is frequent. Low DHEA-S appears to be a poor predictor of hormonal activity with low sensitivity and specificity in respect of cortical origin and benignity of the mass. In conclusion, our results show that DHEA-S measurement does not offer relevant clinical information in the management of adrenal incidentalomas.

Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and testicular steroidogenesis in male hypercholesterolemic patients.

To evaluate the influence of an hydrophilic statin, pravastatin, on adrenal and testicular steroidogenesis and spermatogenesis, eight male hypercholesterolemic patients were studied. All patients observed a hypocholesterolemic diet and received placebo for 4 weeks followed by pravastatin (20 mg/die) for 6 months. Before, during (4th-5th week) and at the end (23th-24th week) of active treatment, CRH (1 microgram i.v.), ACTH (Synacthen 250 micrograms i.v.) and human CG (HCG 3000 IU i.m.) tests were performed in addition to semen analysis. Pravastatin significantly reduced total cholesterol (20.3%), calculated LDL-cholesterol (24.6%) and apolipoprotein B (10.5%, increased apolipoprotein A1 (16.1%) and did not influence plasma HDL-cholesterol and triglycerides. Basal plasma cortisol, aldosterone, androstenedione, testosterone and oestradiol did not change under active treatment. Pravastatin administration affected neither adrenal hormone responses to CRH and ACTH or testicular response to HCG nor spermatogenesis in respect of motility, morphology and sperm count. In conclusion, long-term pravastatin treatment, at doses effective in improving lipid profile, did not influence testicular reproductive and endocrine function and did not interfere with basal and stimulated adrenal activity of male hypercholesterolemic patients.

Frequency of pheochromocytoma in adrenal incidentalomas and utility of the glucagon test for the diagnosis.

To investigate the frequency of pheochromocytoma in patients with incidentally discovered adrenal masses (incidentalomas) and to evaluate the sensitivity, specificity and diagnostic accuracy of the Glucagon test in comparison with resting plasma catecholamines, 89 patients with adrenal incidentalomas (age range 23-80 yr; 41 males and 48 females) were studied. Fifty-seven patients were normotensive (SBP 130+/-1.8 mmHg; DBP 80+/-0.7 mmHg, mean+/-SE) and 32 had stable hypertension (SBP 155+/-3.3 mmHg, DBP 93+/-1.4 mmHg): no patient complained of typical signs or symptoms of pheochromocytoma. Resting plasma samples for noradrenaline and adrenaline determination and, at appropriate intervals, the Glucagon test (1 mg i.v.), were performed in all subjects. Diagnosis of pheochromocytoma was made on the basis of humoral evaluations and/or surgical intervention in 6 patients (6.7%), of whom 3 hypertensives and 3 normotensives. Resting plasma catecholamines revealed 5 out of 6 patients with pheochromocytoma: in 3 cases both catecholamines were above the normal range, in 1 only adrenaline was elevated and in 1 case only noradrenaline. Similarily, the glucagon test identified 5/6 pheochromocytomas: in 3 patients the response was abnormal for both catecholamines, in 1 only for adrenaline and in 1 case only for noradrenaline. The sensitivity, specificity, and diagnostic accuracy of resting plasma catecholamines and of the glucagon test were comparable: 83.3%, 96.3%, and 95.5%, respectively. In conclusion, the frequency of pheochromocytoma in adrenal incidentalomas is not negligible, and since the diagnostic accuracy of the Glucagon test is the same of that of resting plasma catecholamines, the former does not appear to offer additional advantages in the diagnosis of incidentally discovered pheochromocytomas.

17-Hydroxyprogesterone response to ACTH in bilateral and monolateral adrenal incidentalomas.

The aim of our study was to assess the frequency of 21-hydroxylase deficiency, a cause of congenital adrenal hyperplasia (CAH), in incidentally discovered asymptomatic adrenal masses (incidentalomas) and to compare the prevalence of this enzymatic disorder in monolateral (M) and bilateral (B) forms. Twenty-seven patients with incidentalomas (12 M and 15 B) and 16 sex and age-matched controls (C) received synthetic adrenocorticotropin (ACTH, 250 micrograms i.v.). Plasma 17-OHprogesterone (17-OHP) and cortisol were collected in basal conditions and after 30, 60, 90 minutes. Basal plasma 17-OHP in C [1.25 +/- 0.15 (0.61) ng/ml, mean +/- SE (SD)] was not significantly different from that in patients with M [0.85 +/- 0.13 (0.44) ng/ml] or B [0.94 +/- 0.23 (0.90) ng/ml] incidentalomas. After ACTH, 17-OHP levels significantly (p < 0.05) increased in C, in M and B incidentalomas. However, the rise in plasma 17-OHP in C both in terms of peak [2.5 +/- 0.28 (1.1) ng/ml] and of AUC values [174 +/- 16 (64) ng/ml/min] was significantly lower than that observed in M [peak 6.32 +/- 1.66 (5.7) ng/ml, p < 0.01; AUC 410 +/- 111 (385.5) ng/ml/min, p < 0.01] and in B [peak 8.84 +/- 1.98 (7.65) ng/ml, p < 0.001; AUC 613 +/- 149 (579.3), ng/ml/min, p < 0.001] incidentalomas. Individual data indicated that while 17-OHP response to ACTH in C never reached 5 ng/ml (cut-off for normal response), 16 out of 27 patients with incidentalomas (59.2%) exceeded this value. Moreover, the abnormal response was more frequently observed in B (66.6%) than in M (50%) incidentalomas. Basal and stimulated plasma cortisol did not differ among the three groups. In conclusion, our data indicate that in adrenal incidentalomas the endocrine pattern of 21-hydroxylase deficiency is very common and that this enzymatic defect is more frequent in bilateral than in monolateral lesions.

Comparison between the suppressive effects of dexamethasone and loperamide on cortisol and ACTH secretion in some pathological conditions.

Since in patients with Cushing's disease, unlike in normal subjects, tonic inhibitory opioid control of ACTH secretion does not operate, use of the opiate agonist loperamide (LOP) has recently been proposed in the diagnosis of hypercortisolemic states. We compared the sensitivity, specificity and diagnostic accuracy of the LOP test (16 mg orally) with corresponding results of the dexamethasone test (DXM, 1 mg orally overnight) in 23 normal subjects and in a total of 42 patients, affected by Cushing's disease (n = 8), incidentally discovered adrenal masses with impaired function of the hypothalamic-pituitary-adrenal (HPA) axis (n = 6), obesity (n = 21) and depression (n = 7). While in controls both DXM and LOP strongly suppressed plasma cortisol and ACTH, in Cushing's disease and in incidentalomas no patient showed a decrease in cortisol levels below 50 ng/ml or a reduction in plasma cortisol greater than 50% of basal values in response to LOP and DXM. In obese subjects both drugs significantly reduced plasma cortisol and ACTH without giving false positive results. In the depressed group only 3/7 patients showed a decrement in cortisol levels below 50 ng/ml after LOP in contrast to 6/7 after DXM. Thus, in patients with impairment of the HPA-axis, i.e. in Cushing's disease and in patients with adrenal incidentalomas and hormonal abnormalities, LOP and DXM test sensitivity was 100%. In controls and in obese patients specificity was 100% both with LOP and DXM, while in depressed patients it was 43% and 86% with LOP and DXM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term simvastatin treatment on testicular and adrenal steroidogenesis in hypercholesterolemic patients.

Simvastatin is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the synthesis of cholesterol, recently introduced in the therapy of hypercholesterolemic patients. Cholesterol is the precursor of the biosynthesis of steroid hormones; thus, a reduction of the availability of cholesterol in the adrenal and testicular cells may reduce the synthesis of corticosteroids and androgens. To establish whether chronic therapy with simvastatin interferes with the integrity of the hypothalamic-pituitary-adrenal axis and with the adrenal and testicular reserve, we administered simvastatin orally in a single-day 10 mg dose for 6 months in 8 mildly hypercholesterolemic male patients. At weeks 0, 6 and 24 of treatment we evaluated the lipids, the activity of the hypothalamic-pituitary-adrenal axis by means of the Corticotropin-Releasing Hormone (CRH) test, the adrenal reserve by means of the Corticotropin rapid test and, finally, the testicular reserve by means of the Human Chorionic Gonadotropin (HCG) test. Total cholesterol and LDL-cholesterol were significantly reduced by Simvastatin, while the HDL-cholesterol and triglycerides did not change significantly. The hormonal responses to CRH, ACTH and HCG tests at weeks 6 and 24 of treatment were comparable to those obtained in basal conditions. We conclude that Simvastatin, while effective in reducing total and LDL-cholesterol in hypercholesterolemic male patients, did not interfere with hypothalamic-pituitary-adrenal axis activity or with basal and stimulated adrenal and testicular steroidogenesis.

Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects.

To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 microgram/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d-FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 microgram/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 +/- 11.2 ng/mL v 104.1 +/- 9.5 ng/mL). This response was lower (P less than .005) than in the controls, in whom the basal cortisol value of 120.6 +/- 11.8 ng/mL reached a peak value of 221.2 +/- 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P less than .0001) plasma cortisol (peak value 170.6 +/- 18.0 ng/mL v 111.5 +/- 10.8 ng/mL) and the response was enhanced (P less than .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 +/- 1.7 pg/mL v 9.6 +/- 1.1 pg/mL), but the hormonal response was lower (P less than .005) than in controls (peak value 38.1 +/- 5.5 pg/mL v 13.8 +/- 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P less than .05) in plasma ACTH at 30 minutes (20.4 +/- 3.7 pg/mL v 10.9 +/- 0.9 pg/mL) and 45 minutes (18.0 +/- 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Naloxone does not modify fenfluramine-induced prolactin increase in obese patients.

OBJECTIVE: To evaluate whether the supposed physiological interaction between serotoninergic and opioidergic pathways in the modulation of PRL release is preserved in human obesity, a pathological condition in which these two systems are greatly impaired. DESIGN: According to a single-blind randomized procedure, three tests were performed: test A (oral placebo + saline infusion over 5 hours), test B (fenfluramine, a well known serotoninergic drug, 60 mg orally + saline infusion over 5 hours) and test C (fenfluramine at the same dose + naloxone, an opiate receptor antagonist, infusion over 5 hours at a dose of 3 mg/h). PATIENTS: Ten obese women (body mass index 34.4 +/- 2.3 kg/m2, mean +/- SE) and ten normal-weight sex and age-matched subjects (body mass index 22.3 +/- 2.4 kg/m2) volunteered for the study. MEASUREMENTS: At each test, blood samples for PRL determination were collected in basal conditions (time 0) and every hour for 5 hours. Plasma PRL was determined by radioimmunoassay. RESULTS: In controls, naloxone significantly reduced the clear-cut PRL increase induced by fenfluramine. In obese patients, serotoninergic stimulation caused an increment in PRL levels similar to that in the controls, but opioid receptor blockade by naloxone did not affect this response. CONCLUSIONS: These findings confirm that there is a physiological relationship between the serotoninergic and the opioidergic systems in the control of PRL secretion and show that this interaction is not present in obese subjects. Our data provide indirect proof of the functional impairment of these two systems in human obesity.

Blunted growth hormone (GH) responsiveness to GH-releasing hormone in obese patients: influence of prolonged administration of the serotoninergic drug fenfluramine.

The aim of the present study was to ascertain if reduced central serotoninergic activity might contribute to the well-known blunted growth hormone (GH) response to GH-releasing hormone (GHRH) in obese patients. Thus, we studied the effect of prolonged stimulation of the serotoninergic system by fenfluramine (FF; 60 mg twice daily for 7 days) on GHRH-induced GH release in nine obese and seven normal subjects. In controls, GHRH (100 micrograms intravenously [IV]) injection increased GH levels from 2.3 +/- 1.8 (+/- SE) to 18.5 +/- 2.8 mU/L, P less than .002. FF administration enhanced both basal and GHRH-stimulated GH levels (peak, 38.4 +/- 8.3 v 6.9 +/- 2.6 mU/L, P less than .002). This response was significantly higher (P less than .02) than in pretreatment. In obese patients, GH responsiveness to GHRH was slight (peak, 7.1 +/- 2.0 v 0.6 +/- 0.18 mU/L, P less than .01) and lower (P less than .01) than in controls. FF administration did not affect this response. In controls, the enhanced FF-induced GH release after a maximal dose of GHRH indicates that serotoninergic activation influences GH secretion and that the mechanism involved is independent of endogenous GHRH. In obese patients, we found a blunted GH responsiveness to GHRH that was not affected by FF, thus supporting the hypothesis that the serotoninergic control on GH release is impaired.

Impaired growth hormone response to insulin-induced hypoglycaemia in obese patients: restoration blocked by ritanserin after fenfluramine administration.

The aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin-induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal-weight control women underwent three IIH tests, at 14-day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5-HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2.2 mmol/l. In the controls, the expected GH increase to IIH (peak value 56 +/- 13.4 mU/l, AUC 234.4 +/- 55 mU/min/ml) was unaffected by FF administration (peak value 43 +/- 11.4; AUC 216.8 +/- 34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak value 21.4 +/- 4.6 mU/l, P less than 0.02; AUC 93.2 +/- 18.6, P less than 0.02). However, in comparison with the basal test, FF administration significantly (P less than 0.001) enhanced GH response to insulin hypoglycaemia (peak value 33.4 +/- 4; AUC 150 +/- 14.6), reaching values not significantly different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of fenfluramine and ritanserin on prolactin response to insulin-induced hypoglycemia in obese patients: evidence for failure of the serotoninergic system.

In order to study the hypothesized impairment of the serotoninergic system in human obesity, an insulin tolerance test (ITT) was carried out on 12 obese normoprolactinemic women and on 6 normal-weight women before (A) and after (B) the administration of a serotoninergic drug, fenfluramine (60 mg twice a day per os for 7 days). After a washout period, a new ITT (C) followed the administration of fenfluramine at the same dose, associated with a specific S2 blocker receptor agent, ritanserin (30 mg/day for the first 2 days and 20 mg/day for a further 5 days). In obese subjects, the prolactin (PRL) response to ITT A was reduced as compared to the controls: in 6 patients ('nonresponders') the PRL levels did not change, while in the other 6 ('responders') they increased (p less than 0.003) but less than in the controls (p less than 0.02). In normal-weight subjects, the administration of fenfluramine alone or with ritanserin did not modify the PRL response to ITT. In the responders, the serotoninergic drug normalized the PRL response to ITT while significantly improving it in the nonresponders; these effects were not antagonized by ritanserin. In conclusion, our data suggest that the serotoninergic system of obese patients is impaired and that the different secretory pattern observed in the two groups before and after fenfluramine may reflect differing degrees of this impairment.

Influence of conjugated oestrogens on circulating oestradiol, oestrone, LH, FSH and prolactin levels in postmenopausal women.

The effects on plasma 17-beta-oestradiol (E2), oestrone (E1), LH, FSH and prolactin (PRL) levels of 1.5 mg conjugated oestrogen, administered daily per os for 20 consecutive days, was investigated in six postmenopausal women aged 60-68. Both E2 and E1 increased progressively and significantly (p less than 0.001) from 18 and 28 pg/ml to 32 and 108 pg/ml, respectively, at the end of treatment; five days after the last dose both E2 and E1 had fallen to pretreatment levels (p greater than 0.05). LH and FSH decreased progressively and significantly (p less than 0.001) from 114 and 105 mlU/ml (before therapy) to 43 and 36 mIU/ml, respectively, after oestrogen administration. One week after interruption of treatment, both LH and FSH were significantly higher (p less than 0.001) than that obtained at the end of therapy. No significant variation (0.05 greater than p greater than 0.02) was observed for plasma PRL during and after oestrogen administration. Such results indicate that in postmenopausal women the specific enzymatic mechanism of oestrogen interconversion are maintained and that there is no increase of prolactin. IN this was, the possible effects on the development of breast cancer by elevated levels of this hormone, usually observed during long-term oestrogen therapy, would be avoided.

Amplification of LH response to LHRH by dopamine infusion in eugonadal women.

Although the role of biogenic amines in the regulation of gonadotropin release has been studied extensively, the precise role of dopamine (DA) in stimulating LHRH and/or LH release is still controversial. In the present study 6 eugonadal women, aged 20-30, were given an LHRH infusion on day 6 of the menstrual cycle and the pattern and magnitude of LH and FSH responses were estimated. On day 6 of the next cycle, the experiment was repeated and DA was also infused beginning 60 min after the start of the LHRH infusion. Following LHRH infusion plasma LH showed a marked and significant rise with a mean peak increment at 4 h, and with a cumulative response (CR) of 9136 +/- 955 mIU/ml/6h. The pattern of FSH response tended to parallel that of LH; however, mean peak increment at 4 h and a CR of 2640 +/- 169 mIU/ml/6h were markedly lower. Plasma prolactin levels remained unchanged. Addition of DA to LHRH at 60 min evoked a significantly greater mean peak LH increment at 4 h and a CR of 15514 +/- 1836 mIU/ml/6h (p less than 0.001). There were no significant changes in either mean FSH peak at 4 h or in the CR (3257 +/- 309 mIU/ml/6h). As expected, a highly significant (p less than 0.001) decrease in circulating PRL from 12.1 +/- 3.1 to 3.0 +/- 1.5 ng/ml was seen during DA infusion. In conclusion, DA given by iv infusion enhancement LH response to LHRH in eugonadal women under the conditions of the present investigation, supporting a role for a dopaminergic component in the control of LH release in women.