Search PubMed⌕ Search

Biomedical subjects

L Hellman

Publications and source records attributed to L Hellman.

At least 91 records · Page 5Linked to original sources
PubMed1977

The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins.

Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.

Aged↗
PubMed1977

Comparative effects of a series of prolactin inhibitors, 17beta-estradiol and 2alpha-methyldihydrotestosterone propionate, on growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas.

Eight ergot alkaloids and ergoline derivatives, effective prolactin inhibitors, were tested for activity against DMBA-induced rat mammary carcinomas. Compounds were administered daily, 5 times/week for 4 weeks, and rats were observed for an additional 4 weeks. Groups treated with androgen and estrogen were used as positive controls. Those ergot compounds and ergolines that proved to be highly effective in reducing tumor size or in inducing regression of tumors to nonpalpability were Deprenon (D-6-methyl-8-ergolin-I-ylacetic acid amide) and ergocryptine; effective to an intermediate degree were Dironyl [N-(D-6-methyl-8-isoergolin-I-yl)-N',N'-diethylurea], ergocornine, and Lysenyl [N-(D-6-methyl-8-isoergolenyl)-N',N'-diethyl-urea]; and effective to a minimal degree were Lergotrile (2-chloro-6-methylergoline-8beta-acetonitrile), CB-154, and 6605-VUFB (D-6-methyl-8-cyanomethylergolin-I). Remission of many individual carcinomas was brief, and duration of complete regression (all tumors in the rat were nonpalpable) was less than 10 weeks.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Radioimmunoassay of androsterone and androsterone-3-sulfate in plasma.

Details of a sensitive and specific radioimmunoassay for androsterone (1) and androsterone sulfate in plasma have been presented. Benzene extracts of plasma were chromatographed on alumina to isolate the androsterone fraction either (a) directly after extraction (A) or (b) after solvolysis (AS). Following treatment with rabbit anti-A-17-BSA, antibody bound steriod was precipitated by ammonium sulfate. Androsterone concentrations in normal male plasma averaged 57 +/- 24 (S.D.) ng/dl, range 35-135 ng/dl and for normal women, 44 +/- 21 (S.D.) ng/dl, range 18-98 ng/dl. Androsterone sulfate concentrations were: males 55 +/- 28 mug/dl (range 10-114 mug/dl); premenopausal females 52+/- 31 mug/dl (range 16-318 mug/dl).

Adolescent↗
PubMed1976

7beta,17alpha-Dimethyltestosterone (calusterone)-induced changes in the metabolism, production rate, and excretion of estrogens in women with breast cancer: a possible mechanism of action.

The metabolism of estradiol, its production rate and the urinary excretion rate of its metabolites were studied in 5 women patients with breast cancer, 2 of whom were postmenopausal and 3 were ovariectomized, both before and after a period of 7beta,17alpha-dimethyltestosterone (calusterone) therapy. In all cases calusterone caused a profound decrease in the transformation to estriol and an increase in the formation of estrone and 2-hydroxyestrone. The production rate of estrogens was diminished by calusterone in the three overiectomized patients but not in the postmenopausal subjects. The possible participation of the above changes in the chemotherapeutic action of calusterone is discussed.

Adult↗
PubMed1976

Androsterone sulfate concentrations in plasma in hypo- and hyperthyroidism.

Androsterone sulfate concentrations have been measured in the plasma of 16 hypothyroid women and 14 hyperthyroid women by a gas-liquid chromatographic technique and in 23 hypothyroid and 18 hyperthyroid women by radioimmunoassay. In obth studies androsterone sulfate concentrations were significantly higher in the hyperthyroid groups. In one hypothyroid subject, blood was obtained at 20-minute intervals over 24 hours before and after the administration of triiodothyronine; plasma androsterone sulfate, initially 25 mug per dl, increased three-fold as a consequence of treatment.

Adult↗
PubMed1976

The influence of age and sex on the metabolism of testosterone.

The influence of age and sex on the peripheral metabolism of testosterone was studied by giving intravenous tracers of 14C-testosterone to 21 prepubertal children (13 boys and 8 girls), 39 young adults 18-43 years old (23 men and 16 women), and 10 elderly adults 68-86 years old (6 men and 4 women). Studies were also carried out in 2 sexually immature young adults, one 18-year-old 45 XO phenotypic female with gonadal agenesis and one 18-year-old 45 XO, 46 XX mosaic female with gonadal dysgenesis; the latter was restudied after prolonged estrogen-progestagen therapy. Age and sex influences were observed only with respect to the androsterone/etiocholanolone (A/E) ratio; a sex difference in diol metabolite formation was not observed. Prepubertal children showed no sex difference in A/E ratio, which averaged 1.7 +/- 0.28 in boys and 1.9 +/- 0.42 in girls. Young adult men showed a slightly lower A/E ratio, averaging 1.5 +/- 0.10, while females showed a much greater decrease in A/E ratio, to 0.9 +/- 0.09, so that there was a highly significant (P less than .001) sex difference in this age group. The decreased averages were due to disappearance of the higher end of the ranges seen in prepubertal children; the lower limit of the ranges remained the same. Elderly adult men showed a further fall in the A/E ratio, to 1.0 +/- 0.11, and elderly women also showed a further fall, to 0.4 +/- 0.04; a highly significant (P less than .005) sex difference remained. Once again, the fall in average A/E ratio from young adults to elderly adults was due to disappearance of the higher end of the ranges in the former, the lower limits of the ranges were the same in both groups. Of the 2 sexually immature young women, one showed an A/E ratio of 1.3, just below the upper limit for young adult women, and the other showed a ratio of 1.8, well above that limit and thus typical of prepubertal girls. Estrogen-progestagen therapy of the second girl decreased the A/E ratio to 1.4, the upper limit for young adult women. It was concluded that there is a fundamental aging effect in both sexes which causes a gradual progressive decrease of the mean A/E ratio as a result of progressive disappearance of the higher individual A/E values while the lower end of the range of values remains constant; superimposed on this gradual decrease is an acute pubertal decrease in females, probably mediated by the development of the estrogen-progestagen milieu characteristic of sexually mature women.

Adolescent↗
PubMed1976

The effect of medroxyprogesterone acetate on the pituitary-adrenal axis.

Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.

Adrenocorticotropic Hormone↗
PubMed1976

The relationship of luteinizing hormone secretion to sleep in women during the early follicular phase: effects of sleep reversal and a prolonged three-hour sleep-wake schedule.

The relationship of luteinizing hormone (LH) secretion to sleep in adult women was investigated in two ways: an acute 180 degrees sleep-wake cycle reversal in a group of six women and a schedule in which a young woman engaged in a three hour sleep-wake cycle (two hours awake, one hour allowed for sleep continuously for ten days--the study was carried out on the eighth day). Each subject in the reversal study had a baseline period during which plasma samples were collected every twenty minutes for twenty-four hours and nocturnal sleep was monitored electrophysiologically during the early follicular phase of the menstrual cycle. During a succeeding cycle, the study was repeated after sleep-wake reversal. LH secretory patterns were analyzed by comparing the 24-hour mean plasma LH concentration with the hourly averages in percentage terms, using Stage 2 sleep onset as the zero point. LH secretion was depressed to approximately the same degree in both the baseline and reversal studies. The average hourly percentage difference from the 24-hour mean for the four-hour period following sleep onset was -13.4% and -13.1% for the baseline and reversal, respectively. These percentage deviations represented practically the entire negative deviation for the 24-hour period in both studies. The difference between the first four-hour period after sleep onset and the second was significant. The subject on a three-hour cycle had a baseline in which a large decrease in LH secretion occurred after sleep onset (-52.2% during the third hour). Her LH secretory pattern during the three-hour sleep-wake schedule was characterized by a fall during sleep periods, particularly when slow wave sleep (SWS) predominated. However, no correlation was found between specific sleep stages and LH secretion in the six women of the reversal study. These results confirm a relationship of LH secretion to sleep in adult women, one which is different from that described during puberty.

Adult↗
PubMed1976

Effect of 7beta, 17alpha-dimethyltestosterone (calusterone) on cortisol metabolism in women with advanced breast cancer.

It was demonstrated that oral administration of 7beta, 17alpha-dimethyltestosterone (Calusterone) reversibly alters cortisol production and metabolism in women with advanced breast cancer. There was a 30% decrease in cortisol production rate, a 50% decrease in transformation to tetrahydrocortisone (THE) glucuronide, a 50% prolongation of plasma cortisol half-life and decreased conversion to C-19 metabolites. The plasma cortisol concentrations (means and 24-hour profiles) remained unchanged by Calusterone despite the reduction in adrenocortical function. We have concluded that the beneficial effect of Calusterone in breast cancer is probably not due to its effects on cortisol production.

Adult↗
PubMed1976

Endocrine studies in a phenotypic girl with XY gonadal agenesis.

An 18-year-old phenotypic girl with XY gonadal agenesis had endocrine studies. The patient had a small amount of sexual hair, a slightly enlarged clitoris, normal labia and no posterior fusion. Her vagina was of normal length, but no cervix was palpable. At laparoscopy, no gonads, uterus or fallopian tubes were identified. The buccal smear was chromatin negative and the karyotype was 46XY. The 24 h LH plasma pattern was qualitatively similar to that found in normal late pubertal subjects, but the values were in the castrate range. The 24h mean plasma concentrations of testosterone and dihydrotestosterone were 16.4 ng/dl and 14.2 ng/dl, respectively. Urinary estrogen excretion was 15 and 19 mug/day. These clinical and endocrine findings suggest that the patient was a genetic male in whom Mullerian regression occurred normally; however, the testes probably ceased functioning early in gestation preventing normal development of the Wolffian system. This set of events resulted in agenesis of the gonaductal system and female external genitalia. The patient represents the second example of this variation of male pseudohermaphroditism associated with XY gonadal agenesis.

Adolescent↗
PubMed1976

Hypothyroid-like alterations in testosterone metabolism in anorexia nervosa.

The metabolism of 14C-testosterone was studied in 8 severely underweight young women with anorexia nervosa. The urinary androsterone/etiocholanolone (A/E) ratio was uniformly low, in a range characteristic of hypothyroidism; the patients also showed low plasma concentrations of triiodothyronine (T3). Clinical remission as manifested by weight gain was accompanied by concomitant increases of the A/E ratio and the plasma T3 concentration to or toward normal. The administration of T3 also resulted in a shift of the A/E ratio toward normal. These data demonstrate that the low plasma T3 concentrations in patients with anorexia nervosa may be related to the development of one of the characteristic biochemical abnormalities found in clinical hypothyroidism, namely a decreased A/E ratio. These data suggest that the "low T3 syndrome" may be associated with biochemical hypothyroidism.

Adolescent↗
PubMed1976

Clinical and laboratory heterogeneity in idiopathic hypogonadotropic hypogonadism.

Six young men with idiopathic hypogonadotropic hypogonadism had 24-h frequent blood sampling studies for measurement of LH, FSH and testosterone. Five of the patients had LH and FSH measured after administration of 100 mug LH-RH during waking and then during sleep. Four of the patients had testicular biopsies performed. The results of the present studies showed that 4 of the patients had no evidence of episodic LH, FSH, or testosterone secretion. The two patients who showed significant sleep related pulses of LH had the highest 24 h mean testosterone concentrations, the best responses to exogenous LH-RH and the most differentiated testicular biopsies. Sleep had no effect on the release of LH or FSH in response to LH-RH. These sutdies suggest that the clinical and laboratory heterogeneity of idiopathic hypogonadotropic hypogonadism may be the result of differences in the degree of endogenous LH-RH deficiency.

Adult↗
PubMed1976

Human puberty: 24-hour estradiol in pubertal girls.

Plasma luteinizing hormone, follicle-stimulating hormone, and estradiol were measured at 20-minute intervals for 24-hours in seven pubertal premenarchal girls whose sleep was monitored polygraphically. A circadian variation in plasma estradiol was demonstrated with the highest values occurring during the day (1400-1600 hours) and lowest values during sleep, a time when gonadotropin secretion was augmented.

Adolescent↗
PubMed1975

Direct analysis of dehydroisoandrosterone in plasma.

DHA (1) has been measured in plasma by a radioimmunoassay procedure using an antiserum to DHA-7-BSA whose specificity is such that the procedure is carried out directly on diluted, unextracted plasma. The method has been used to obtain plasma DHA secretory patterns and mean concentrations and the data are in accord with those determined by related but more laborious techniques.

Adrenalectomy↗