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PubMed1987

Alternating tamoxifen and medroxyprogesterone acetate in postmenopausal advanced breast cancer patients--short and long term endocrine effects.

The endocrine effects of alternating tamoxifen and medroxyprogesterone acetate have been evaluated in 26 post-menopausal patients with metastatic breast cancer. Endocrine evaluations included the RIA determination of plasma levels of sex-hormone binding globulin, follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, cortisol, and testosterone. The evaluation of the study parameters at different intervals during therapy indicates that with this schedule an alternate sequential effect on the endocrine system is achievable because each drug exerts its own endocrine activity that is completely reversed when the other drug is administered. We can hypothesize that the same alternate activity as seen on the endocrine system could be obtained also on other tissues and organs including tumors.

Breast Neoplasms↗

PubMed1976

Endocrine effects of vasectomy.

In order to provide information on the endocrine effects of vasectomy, unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were analysed in the blood plasma of twenty Mexican men on two occasions before and 1, 3, 6 and 12 months after vasectomy. Vasectomy appeared to be associated with a significant decrease in the plasma levels of pregnenolone, dehydroepiandrosterone and androstenedione and a significant increase in the levels of dihydrotestosterone and oestrone. A probably significant increase in oestradiol levels took place 12 months after vasectomy but not before. No consistent changes were found in testosterone (up to 12 months) or in FSH and LH levels (up to 6 months) after vasectomy. The unconjugated steroids indicated above, except oestrone, were also estimated, whenever possible, in seminal plasma specimens obtained from thirty-nine subjects (including the twenty indicated above) on the same occasions. Vasectomy was associated with a highly significant decrease of seminal plasma dihydrotestosterone levels on all occasions and a significant decrease in androstenedione levels after 6 and 12 months. After 12 months there was a decrease in dehydroepiandrosterone and an increase in oestradiol; these changes were both probably significant. In another preliminary study, the levels of pregnenolone sulphate, dehydroepiandrosterone sulphate, testosterone glucuronide, testosterone sulphate and dihydrotestosterone sulphate were estimated before and 1 month after vasectomy in the seminal plasma of fourteen to seventeen subjects. Testosterone glucuronide fell, probably significantly, but other conjugates were unchanged. The data indicate that vasectomy may be associated with significant changes in the circulating and in seminal plasma levels of several steroids. The gradual nature of some of the changes observed suggests the necessity of conducting in several centres large-scale, long-term studies on vasectomized subjects and on a carefully matched control group. During the last decade vasectomy has been widely practised in several parts of the world as a method of fertility control. However, information on the endocrine effects of this intervention appears to be scanty. In most of the human studies reported, a small number of individuals were investigated and the studies have been confined to the assessment of the short-term effects of the operation. Moreover, the hormonal indices assessed by the various investigators have been limited, in most cases, to gonadotrophins and testosterone in blood. The present study was designed to assess in the same subjects the levels of a number of unconjugated steroids, FSH and LH on two occasions before and 1, 3, 6 and 12 months after vasectomy. The studies were extended to include steroid analyses in seminal plasma in the hope that such assays might yield information as to the effects of vasectomy on the distribution of steroids in the fluids of the male reproductive tract.

Adult↗

PubMed1990

The clinical and endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer.

The aromatase inhibitor, 4-hydroxyandrostenedione (4OHA) is an effective treatment for advanced post-menopausal breast cancer. The clinical and endocrine effects of 4OHA treatment were studied in five pre- and perimenopausal women with metastatic breast cancer. Serum oestradiol levels were not significantly reduced as a result of treatment with 500 mg of 4OHA by weekly i.m. injections and no patient had a tumour response. Four patients were subsequently treated with the luteinising hormone releasing hormone (LHRH) analogue, gosereline, and three had objective responses. The endocrine effects of combined treatment with goserelin (Zoladex), and 4OHA were studied in a further five premenopausal women. Serum oestradiol levels after treatment with goserelin alone were typical of post-menopausal women. Addition of 4OHA led to a further suppression of oestradiol to within the range observed in post-menopausal patients treated with further suppression of oestradiol to within the range observed in post-menopausal patients treated with 4OHA. Six patients whose tumours had regressed as a result of goserelin treatment and who subsequently relapsed were then given combined treatment. Four of the six experienced a second remission. We conclude that while 4OHA alone is unlikely to be a satisfactory treatment for premenopausal patients with advanced breast cancer, 4OHA in conjunction with goserelin leads to profound suppression of oestradiol. The combination of LHRH analogue and aromatase inhibitor may prove to be a superior treatment to LHRH analogue alone in these patients.

Adult↗

PubMed1991

Cardiovascular and endocrine effects of clonidine premedication in neurosurgical patients.

The present study was conducted to examine the haemodynamic and endocrine effects of clonidine, given as sole preanaesthetic medication, in neurosurgical patients. Nineteen patients of ASA physical status I and II, subjected to craniotomy, randomly received po premedication of either clonidine (300 micrograms, n = 9) or placebo (n = 10). Blood pressure and heart rate were monitored continuously, while arterial blood samples were collected at specific times, from induction of anaesthesia to recovery, for the measurement of plasma concentrations of epinephrine, norepinephrine, cortisol, aldosterone, and glucose. Clonidine treatment led to a decrease in mean arterial blood pressure (MABP), heart rate (HR), and plasma cortisol and aldosterone concentrations throughout the study, compared with placebo (P less than 0.05). Clonidine, however, did not prevent increases in MABP (16 +/- 5 mmHg, mean +/- SE, P less than 0.05) and HR (18 +/- 4 bpm, P less than 0.05) during induction of anaesthesia, which was comparable to the placebo group. Plasma catecholamine concentrations did not differ between the two groups. Plasma glucose concentrations increased in both groups at the end of the study (P less than 0.05), but were lower in clonidine-treated patients (P less than 0.05). Though statistically significant, the observed inhibitory haemodynamic and endocrine effects of clonidine seem to be of minor clinical importance. As the action of clonidine on cerebral blood flow regulation is not well known, we see no advantage in the preanaesthetic administration of clonidine to neurosurgical patients with normal cardiovascular status.

Administration, Oral↗

PubMedDate not supplied

Endocrine effects of oral contraception.

Numerous well-documented endocrine effects of oral contraceptives (OCs) can be subdivided into two groups: (a) those relating to the hypothalamic and pituitary-ovarian system, the breast and the genital tract of the human female and (b) those related indirectly to laboratory testing of other endocrine glands. Benefits from OC use include marked decreases in the incidence of menorrhagia, benign breast disease, dysmenorrhea, iron deficiency anemia, premenstrual tension and ovarian cyst formation--all of which will be discussed only briefly. Of much concern are two suggested adverse effects of OCs: (a) the development of amenorrhea or menstrual disturbance associated with anovulation after discontinuing OCs, thereby possibly influencing the future fertility of former OC users, and (b) the suggested relationship between hyperprolactinemia and the development of micro- and eventually macropituitary adenomas. A review of the literature, along with our own findings, is presented.

Adenoma↗

PubMed1989

Pharmacokinetics and endocrine effects of the LHR analogue buserelin after subcutaneous implantation of a slow release preparation in prostatic cancer patients.

The pharmacokinetics and endocrine effects of the LHRH analogue buserelin [D-Ser(TBU)6-LHRH], released from biodegradable implants, were studied in 14 patients with stage C and D prostate cancer. Six patients received a subcutaneous implant of 3.3 mg buserelin monthly, and 8 patients received a subcutaneous implant of 6.6 mg buserelin every two months. Serum levels of buserelin decreased rapidly immediately after implantation. After 1-2 weeks a more gradual decline occurred, while in the two-monthly treated group a third phase of the elimination curve started after 5 weeks. Mean serum buserelin levels just before the next implantation in the two groups were not different. Urinary excretion of buserelin followed the same pattern. Serum LH levels in both groups became non-detectable 2 weeks after the first implant. This decrease of LH levels was accompanied by a suppression of serum testosterone to concentrations below 1 nmol/l (castration level). Side effects were not different from those observed with the intranasal application of buserelin. It is concluded that the subcutaneous application of buserelin is an easily administered form of treatment which has more profound and more reliable endocrine effects when compared with the intranasal administration of the drug. The greatest advantage of the new preparation is that the intervals between applications may be prolonged to at least 2 months.

Aged↗

PubMed1991

[Endocrine effects of hypotension induced by diltiazem in rabbits].

Endocrine effects of hypotension induced by diltiazem, a calcium antagonist, were studied in 16 male rabbits under the inhalation of 0.7% halothane in oxygen. They were randomly allocated to one of two groups. Group C (n = 8) received no vasodilator therapy and served as control and group D (n = 8) received infusion of diltiazem. Mean arterial pressure was decreased and was maintained at 60 mmHg for 60 minutes in group D. No change was noted in plasma catecholamines measured in group C throughout the experiment but plasma renin activity decreased progressively. During and after induced hypotension in group D plasma epinephrine showed a dramatic rise compared with the control value. The maximum increase occurred 30 minutes after induction of hypotension but this change was not statistically significant. Plasma norepinephrine in group D was significantly higher than the control value. Compared with the control value (0.19 +/- 0.04 ng.ml-1), plasma norepinephrine was activated 30 and 60 minutes after induction of hypotension (0.71 +/- 0.16 ng.ml-1, P less than 0.05, 0.82 +/- 0.20 ng.ml-1, P less than 0.05, respectively). Plasma renin activity in group D was significantly higher than the control value. The highest level of plasma renin activity was three times the control value 30 minutes after induction of hypotension. In conclusion, our data show that induced hypotension by diltiazem activates the renin-angiotensin-sympathetic nervous system.

Animals↗

PubMed1990

[Endocrine effects of hypotension induced by nicardipine in rabbits].

Endocrine effects of hypotension induced by nicardipine, a calcium antagonist, were studied in 18 male rabbits under halothane anesthesia. They were randomly divided into two groups; nicardipine (group N; n = 10) and controls (group C; n = 8). No change was noted in plasma catecholamines in group C throughout the experiment, but plasma renin activity decreased progressively. During and after induced hypotension, in group N, plasma epinephrine was significantly higher than the control value. The highest level of plasma epinephrine was seven times of the control value during 30 minutes after induction of hypotension. Plasma norepinephrine of group N was significantly higher than the controls. The maximum increase occurred 60 minutes after induction of hypotension. Plasma renin activity of group N was significantly higher than the control value. Compared with the control value (15.1 +/- 1.8 ng.ml-1.hr-1), plasma renin activity was activated 30 and 60 minutes after induction of hypotension (55.5 +/- 6.0 ng.ml-1.hr-1, P less than 0.001, 50.3 +/- 7.1 ng.ml-1.hr-1, P less than 0.01, respectively). In conclusion, our data show that hypotension by nicardipine activates the renin-angiotensin-sympathetic system.

Animals↗

PubMedDate not supplied

Endocrine effects of human recombinant interleukin-3 in cancer patients.

It is known that several cytokines can exert hormonal effects. At present, no data are available about the possible influence of IL-3 on the endocrine system. In order to investigate the endocrine effects of IL-3 in humans, we have evaluated serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and melatonin in response to intravenous injection of IL-3 at a dose of 1 mcg/kg b.w. at 6.00 p.m. The study was performed in 5 non-small cell lung cancer patients. GH increased significantly in response to IL-3. PRL showed a progressive decrease after IL-3 injection, but its variations were not statistically significant. All other hormones, including cortisol, were not affected by IL-3. This preliminary study shows that IL-3 may exert endocrine effects in humans, which would seem at variance with previously reported results on most other cytokines.

Biomarkers, Tumor↗

PubMed1978

Endocrine effects of alcohol.

A variety of effects of alcohol on endocrine function are now well documented. Clinically, the most important of these are alcohol-induced 'pseudo-Cushing's syndrome' and a syndrome of hypothalamic-pituitary-adrenocortical unresponsiveness, both of which result from long-term over-indulgence, and impairment of testosterone secretion which may occur following relatively short-term drinking. Evidence indicates that a number of different mechanisms are responsible for mediating the effects of alcohol on endocrine function. In a few instances (e.g. inhibition of vasopressin secretion and impairment of steroidogenesis resulting in a fall in testosterone production rate), alcohol appears to influence directly the release or synthesis of individual hormones. However, the majority of the endocrine effects of alcohol are probably indirect, resulting from either the stress of intoxication (stimulation of cortisol, catecholamines and possibly GH and prolactin), changes in the level of intermediary metabolites (e.g. a fall in circulating FFA stimulating GH secretion) or changes in the metabolism of hormones (e.g. catecholamines, oestrogens, androgens) resulting from alteration in intracellular redox state or tissue damage.

Adrenal Cortex↗

PubMed1987

Endocrine effects of 5-methoxytryptoline, 5-hydroxytryptoline and tryptoline, putative modulators of rat serotonergic system.

The effects of tryptolines (TH beta Cs), putative endogenous compounds acting on the serotonergic function, have been studied on endocrine parameters in rats. In particular, graded doses of 5-methoxytryptoline (5-MeOT), 5-hydroxytryptoline (5-OHT) and tryptoline (Tp) were ip or iv administered to the animals and the circulating titers of prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) were assayed either at 20 min or at various times after the injection of the compounds. The data herein reported show that TH beta Cs exert endocrine effects, at least in a pharmacological condition. However, the three compounds unequally affect anterior pituitary function. In fact, while 5-MeOT, 5-OHT and Tp all enhance plasma PRL concentrations in a quick, short lasting and dose-related manner, 5-MeOT and Tp induce also decreases of serum LH levels in ovariectomized rats, and 5-MeOT only is able to diminish plasma GH titers. These findings underline an endocrine effect for TH beta Cs in pharmacological conditions and may suggest a functional role for these compounds in the control of anterior pituitary function.

Animals↗

PubMed1991

The endocrine effects of long-term treatment with mifepristone (RU 486).

Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.

Adrenocorticotropic Hormone↗

PubMed1988

Hemodynamic, renal and endocrine effects of atrial natriuretic peptide infusion in severe heart failure.

The cardiac release and total body and renal clearances and the hemodynamic, renal and endocrine effects of increasing doses of atrial natriuretic peptide were investigated in 12 patients with severe chronic congestive heart failure. Immunoreactive arterial plasma levels of atrial natriuretic peptide were 10-fold higher than normal and there was no correlation between aortic atrial natriuretic peptide and cardiac filling pressures. The heart released atrial natriuretic peptide into the coronary sinus. The kidney, though a major clearance site, accounted for only 33% of the total body clearance. Administration of 0.3 micrograms/kg per min atrial natriuretic peptide produced significant changes in heart rate (95 +/- 4 to 85 +/- 4 beats/min) and mean arterial (92 +/- 8 to 77 +/- 9 mm Hg), right atrial (13 +/- 3 to 8 +/- 2 mm Hg) and mean pulmonary artery occluded (27 +/- 3 to 14 +/- 3 mm Hg) pressures. Atrial natriuretic peptide increased cardiac index (2.25 +/- 0.18 to 2.83 +/- 0.3 liters/min per m2) and stroke work index (21 +/- 1.5 to 29 +/- 3.4 g/m2), whereas systemic vascular resistance (1,424 +/- 139 to 1,033 +/- 97 dynes.s.cm(-5)) decreased. Infusion of 0.1 microgram/kg per min atrial natriuretic peptide increased urinary flow 128%, fractional excretion of sodium 133% and fractional excretion of potassium 35%. The filtration fraction increased from 29 +/- 2 to 31 +/- 4%. This represented a disproportionate rise in glomerular filtration rate over renal plasma flow. Plasma aldosterone and norepinephrine decreased whereas plasma renin activity remained unchanged. In association with these hemodynamic, excretory and endocrine changes, the urinary excretion of cyclic guanosine monophosphate doubled. Placebo had no effect. These results showed that, despite high circulating levels of atrial natriuretic peptide, administration of this hormone in heart failure is associated with potentially beneficial hemodynamic, renal and endocrine effects.

Adult↗

PubMed1986

Endocrine effects of low dose aminoglutethimide with hydrocortisone--an optimal hormone suppressive regimen.

The endocrine effects of aminoglutethimide 125 mg twice daily and hydrocortisone 20 mg twice daily were assessed in 45 postmenopausal women with advanced breast cancer. Oestrone and oestradiol levels were suppressed by 60% within 2 weeks and suppression was maintained for more than 6 months of chronic treatment. In contrast to conventional dose AG with hydrocortisone, or low dose AG without hydrocortisone, delta 4 androstenedione was suppressed by 65%. This effect may contribute to optimal oestrogen suppression.

Aminoglutethimide↗

PubMed1989

The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects.

The pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio-hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio-hGH administration and safety parameters were monitored over a 3-week period. Growth hormone levels reached a mean (+/- SD) peak of 106 +/- 10 mIU/l at 3.3 +/- 0.5 h following the first dose and resulted in a significant rise of somatomedin C. free fatty acids, fasting blood glucose and insulin concentrations. Bio-hGH administration resulted in a significant increase in body weight (80.0 +/- 4.5 to 81.1 +/- 4.3 kg; P less than 0.01) which was associated with a marked reduction in urinary sodium excretion (196 +/- 38 to 45 +/- 20 mmol/day; P less than 0.025). Serum T3 increased during bio-hGH administration and was associated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio-hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40 U/m2/week) or more in patients with GH responsive short stature.

Adult↗

PubMed1975

Endocrine effects of chronic administration of psychoactive drugs to prepubertal male rats. II. LSD.

The endocrine effects of chronic D-lysergic acid diethylamide (LSD) administration to prepubertal animals were studied by injecting intraperitoneally three times a week for a month either 100 mug or 500 mug of the psychoactive drug per kilogram or the vehicle to groups of Sprague-Dawley male rats starting at 21 days of age. Animals injected with either dosage of LSD had smaller body weights than controls and tail length was significantly reduced in the high dosage group, plasma levels of growth hormone (GH) were decreased in the high dosage group, and pituitary levels in the low dosage group. Plasma levels and pituitary concentrations of luteinizing hormone and follicle stimulating hormone were not significantly modified by the drug. The low dosage of LSD decreased the brain levels of noradrenaline and increased those of dopamine, while the high dosage decreased those of 5-hydroxyindoleacetic acid. These data suggest that LSD, when administered chronically to developing animals, can inhibit body growth probably by altering the secretion of GH through modifications of its neuroendocrine control.

Animals↗

PubMed1991

Renal and endocrine effects of physiological variations of atrial natriuretic factor in normal humans.

The renal and endocrine effects of incremental infusions of 3 and 6 ng.kg-1.min-1 of exogenous atrial natriuretic factor (ANF)-(99-126) or placebo were investigated in 10 normal subjects. A 90-min basal period was followed by two 2-h infusion periods with urine collection in the last 90 min of each period. Plasma ANF concentration increased by 50 and 150%, respectively, from a basal value of 6.2 +/- 3.1 pmol/l. Plasma guanosine 3',5'-cyclic monophosphate concentration increased in parallel with ANF. Blood pressure and heart rate were unchanged, whereas hematocrit was stepwise increased. 51Cr-EDTA clearance (GFR) did not change, but ANF caused an increase in Li clearance (a measure of end-proximal fluid delivery), Na clearance, and urine flow compared with time-matched control values. These excretory effects of ANF were mainly due to prevention of the 20- to 50% decreases occurring in the placebo series. Calculated values of fractional proximal and distal tubular Na reabsorption decreased significantly. ANF caused a decrease in plasma concentrations of active renin and aldosterone, whereas renin substrate, angiotensin I, and angiotensin II concentrations were unaltered. A subtle increase in plasma concentrations of norepinephrine and epinephrine was observed during the ANF infusions. These data suggest that the natriuretic effect of ANF is caused by an increased fluid delivery from the proximal tubule in addition to a fall in fractional distal Na reabsorption.

Adult↗

PubMed1989

Diazepam: endocrine effects and hypothalamic binding sites in the developing male and female rat.

The ontogeny of diazepam's endocrine effects in male and female rats, and of 3H-diazepam binding in the hypothalami of both sexes was studied. Diazepam inhibited basal prolactin levels in 38 day-old male rats and, if prolactin levels were stimulated by Haloperidol the inhibition occurred in 28 day-old males, indicating that the hypoprolactinemic effect of the drug could be evidenced earlier if prolactin titers were high. The prolactin inhibition in females did not reach statistical significance at any studied age. Diazepam significantly released LH only in male rats at 12 days, showing thus, a period of special sensitivity of LH release to the drug. Benzodiazepine-hypothalamic binding sites increased in number from birth to puberty, reaching a plateau at 20 days of age. No sexual differences or changes in affinity were found throughout the studied period. These results suggest that the maturation of diazepam's hypoprolactinemic effect could be partially related to the increase in hypothalamic binding sites, whereas the sexual differences observed in diazepam's endocrine actions could be due to sexual differentiation of endocrine control mechanisms.

Animals↗