Behavior modification.
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Biomedical subjects
Publications and source records attributed to G E Abraham.
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OBJECTIVES: Because dehydroepiandrosterone may protect against neoplasia, osteoporosis, and cardiac disease, we investigated the bioavailability of oral micronized dehydroepiandrosterone, anticipating its adjunctive use in postmenopausal steroid replacement. STUDY DESIGN: Eight postmenopausal women randomly received either a placebo or 150 or 300 mg of oral micronized dehydroepiandrosterone in a lipid matrix. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and estradiol were measured periodically over the 12 hours after each dose. All treatments, all doses, and mean serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone were compared with analysis of variance for repeated measures and Newman-Keuls a posteriori test of statistical significance. RESULTS: Mean peak steroid concentrations after 150 mg (300 mg) doses were dehydroepiandrosterone 1617 (2639) ng/dl, 7 (11.5)-fold above placebo; dehydroepiandrosterone S 1185 (1688) micrograms/dl, 14 (20)-fold above placebo; and testosterone 183 (311) ng/dl, 4 (7)-fold above placebo. Estradiol concentrations remained less than 20 pg/ml, but androgen concentrations rose by 1 hour and remained elevated through the twelfth hour. Peak androgen concentrations and areas under the curves exhibited proportionality with both doses. A testosterone radioimmunoassay with celite chromatography revealed a 300% overestimation for testosterone in the direct-assay method used in this study. Thus after appropriate readjustment maximum testosterone concentrations were observed consistently within physiologic premenopausal ranges after the 150 mg dose. CONCLUSIONS: Micronized dehydroepiandrosterone may provide a steroidal postmenopausal replacement that is adjunctive to estrogens and worthy of further investigation.
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The use of calcium supplementation for the management of primary postmenopausal osteoporosis (PPMO) has increased significantly in the past few years. A review of the published data does not support calcium megadosing during postmenopause. Controlled studies showed no significant effect of calcium intake on mineral density of trabecular bone and a slight effect on cortical bone. Since PPMO is predominantly due to demineralization of trabecular bone, there is no justification for calcium megadosing in postmenopausal women. Soft tissue calcification is a serious risk factor during calcium megadosing under certain conditions. A total dietary program emphasizing magnesium instead of calcium for the management of PPMO takes into account the available data on the effects of magnesium, life-style and dietary habits on bone integrity and PPMO. When this dietary program was tested on 19 postmenopausal women on hormonal replacement therapy who were compared to 7 control postmenopausal women, a significant increase in mineral bone density of the calcaneous bone (BMD) was observed within one year. Fifteen of the 19 women had had BMD below the spine fracture threshold before treatment; within one year, only 7 of them still had BMD values below that threshold.
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The clinical, biochemical and endocrine effects of a total dietary program were evaluated in patients with the premenstrual tension syndromes (PMTS). The program consisted of dietary guidelines and nutritional supplementation. Open trials suggested that an initial dosage of the supplement consisting of six tablets daily gave the best symptomatic relief during the first three to six months. Double-blind studies confirmed that a daily average of six tablets decreased PMTS symptom scores to significantly lower levels than did the placebo. A significantly higher percentage of PMTS patients reported feeling better on the dietary program than did those on the placebo. Although significant changes were observed in some liver function tests, the values were within the normal ranges. The dietary program, implemented for three to six months, decreased serum estradiol 17-beta and increased serum progesterone levels during the midluteal phase in PMTS patients. Nonresponders using the program should be reevaluated and treated according to the results of the reevaluation and the PMTS symptoms.
Rat Graafian follicles were dissected from ovaries during the morning of proestrus and incubated in various media. After an 8 h incubation period, ovarian follicles were collected and analyzed, by radioimmunoassay, for progesterone, 17 alpha-hydroxyprogesterone, androstenedione, estradiol-17 beta, and dihydrotestosterone. Following incubation in proestrus (a.m.) serum, preovulatory follicles secreted all these steroids and the output of progesterone, 17 alpha-hydroxyprogesterone and androstenedione was markedly stimulated following the addition of LH to the media. Follicle-enclosed oocytes resumed meiosis when incubated in proestrus serum without added LH. However, germinal vesicle break-down (GVBD) under these conditions was considerably slower than that observed following addition of LH to the medium. "Spontaneous" maturation of oocytes in proestrus serum was associated with increased production of steroids. Oocyte maturation and steroidogenesis both occurred following incubation of ovarian follicles in serum obtained from hypophysectomized rats. Addition of LH to the media markedly accelerated these responses. These results suggest that oocyte maturation and steroidogenesis also occur in cultured ovarian follicles in the absence of gonadotrophic hormones. The relationship between steroidogenesis and/or spontaneous oocyte maturation are discussed.
A procedure utilizing co-chromatography and complementary antiserum comparisons was employed to assess the specificity of a cortisol radioimmunoassay for use in the chronically catheterized fetal sheep preparation. Complementary antiserum comparisons is a technique by which two different cortisol antisera, prepared from conjugates attached at opposite ends of the cortisol molecule, were used to determine cortisol concentrations in the same ovine fetal plasma specimens. Results were not significantly different between the two groups, each measured by a different antiserum. This procedure may be used to assess assay specificity in any species in which steroid radioimmunoassays are being adapted.
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This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation.
The peripheral levels of 17-hydroxypregnenolone (17delta5P), progesterone (P), 17-hydroxyprogesterone (17P), testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), androst-5-ene-3beta,17beta-diol (delts5diol), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), estradiol-17beta (E2), and cortisol (F) were measured in peripheral and right adrenal venous blood of an amenorrheic patient with a right virilizing adrenal adenoma. Urinary 17-ketosteroids were markedly elevated and were not suppressed on a low dose of dexamethasone (Dex) for 7 days. Peripheral T level was 1.2 ng/ml and DHEA-S was 13,500 ng/ml. Calculations of the ratios of adrenal venous gradients for delta5 and delta4 steroids suggest that the predominant pathway of steroid secretion used by the tumor was as follows: pregnenolone (delta5P) leads to 17delta5P leads to DHEA leads to A leads to T. Following removal of the adenoma, T returned to normal levels but DHEA-S was still above normal at 4100 ng/ml. The patient became eumenorrheic with marked improvement at her hirsutism and virilization.
The ovarian-peripheral gradients of various delta4 and delta5 steroids were determined for a patient with virilizing arrhenoblastoma. The high peripheral testosterone level accompanying this tumor results from increased precursor supply from both the delta4 and delta5 pathways, with the delta5 pathway predominating, and from negligible aromatase activity. A review of 45 cases of androgen-producing ovarian tumors with measurement of peripheral venous testosterone, and of 24 cases with measurement of ovarian venous testosterone, and a comparison with findings in 159 patients with hirsutism of functional origin reveal the following 1) An androgen-producing tumor must be ruled out when peripheral testosterone exceeds 2 ng/ml; 2) an ovarian venous testosterone level exceeding 20 ng/ml generally accompanies a tumor, particularly when the tumor is less than 5 cm in diameter; and 3) virtually all (98%) of the tumors reviewed were accompanied by virilization, regardless of the peripheral concentration of testosterone.
A patient with the cholestasis of Hodgkin's disease was investigated. Our studies failed to relate the cholestasis to endocrine abnormalities. The patient had severely abnormal aminopyrine metabolism, suggesting more profound hepatocellular dysfunction than had previously been appreciated.
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