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S Micic

Publications and source records attributed to S Micic.

At least 37 records · Page 2Linked to original sources

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease.

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.

Aged↗

Screening for familial hypercholesterolaemia by measurement of apolipoproteins in capillary blood.

A total of 3025 families with schoolchildren aged 6-8 years were offered pilot screening for familial hypercholesterolaemia by measurement of the concentrations of apolipoproteins A-1 and B in the children's capillary blood and by analysis of their family histories of early ischaemic heart disease. The concentrations of the apolipoproteins were determined by double rocket immunoelectrophoresis of an eluate of blood spotted on filter paper. Results were available from 2085 children. Because their B:A-1 ratio was above the 97.5 centile and their concentration of B was above the 99th centile, 54 children (2.6%) were selected to have their apolipoprotein concentrations reassessed. The 17 children (0.8%) whose values were persistently above the chosen cut off points, and all of their available first and second degree relatives, had fasting determinations of serum lipid concentrations carried out. Raised serum concentrations of low density lipoprotein cholesterol and an autosomal dominant pattern of hypercholesterolaemia were found in 12 children and 10 families, respectively, suggesting a higher incidence of familial hypercholesterolaemia than the reported 1:500. Further investigations among family members disclosed hypercholesterolaemia in 29 relatives. A family history of early ischaemic heart disease was elicited by questionnaire, and was positive in only five of the 12 schoolchildren with hypercholesterolaemia. We conclude that analysis of apolipoproteins from capillary blood spotted on filter paper is suitable for screening for familial hypercholesterolaemia, and that this method is more efficient than screening based on family history.

Apolipoproteins A↗

Comparison of the effect of cortisol on aromatase activity and androgen metabolism in two human fibroblast cell lines derived from the same individual.

The effect of preincubation with cortisol on estrogen and androgen metabolism was investigated in human fibroblast monolayers grown from biopsies of genital and non-genital skin of the same person. The activity in the cells of aromatase, 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase and 3 alpha-hydroxysteroid oxidoreductase was investigated by isolating estrone, estradiol, estriol, dihydrotestosterone, androstanedione, androsterone, 3 alpha-androstanediol, testosterone and androstenedione after incubation of the cells with [14C]testosterone or [14C]androstenedione. For experiments with 14C-labeled substrate the cells were incubated in medium, charcoal stripped of steroids without Phenol Red. Preincubation from 6 to 36 h with cortisol in concentrations of 10(-8) - 10(-6) M showed maximal stimulation of aromatase activity after 12 h preincubation with cortisol in concentrations of 0.5-1.0 x 10(-6) M in both cell lines. When preincubation with cortisol was omitted no estrogen synthesis was detected. The formation of androgen was not altered after preincubation with cortisol. Pronounced differences were found in estrogen and in androgen metabolism in the two cell lines suggesting a local regulation of the hormonal environment. The aromatase activity, which is low in many tissues could be stimulated by cortisol without altering the androgen metabolism was found to be a suitable system for investigations of the cellular interconversion of androgens and estrogens and for investigations of the in vitro regulation of the enzymes involved.

Androgens↗

[A study of percutaneous absorption of estradiol and progesterone in absolute alcohol in postmenopausal women].

Absorption of solutions containing 17-beta-oestradiol (E2) in absolute alcohol and progesterone (P) in absolute alcohol was investigated in six postmenopausal women. These preparations were applied to the skin of the forearm and the abdomen. 1 mg E2 was applied twice daily to the left forearm (RAS) for 28 days. After an interval of one week, the treatment was continued with 1 mg E2 twice daily for 28 days in the epigastric region (RE). From the 14th to the 28th day, this treatment was supplemented by 10 mg P twice daily partly on the right forearm and partly on the epigastrium. The 24-hour absorptions of E2 and P were investigated: E2 on the first and fourteenth days and P on the fourteenth day in both periods. On days 1, 7, 14, 21 and 28, plasma E2, oestrone (E1) and oestrone sulphate (E1SO4) were investigated for hormone application. Statistically significant absorption of E2 was found after 24 hours (p less than 0.05) and significantly greater absorption from RAS than RE (p less than 0.005). No systematic variation in plasma E2 was found during the period of investigation on RAS or RE. P was not absorbed. No local side effects were registered. It is concluded that E2 dissolved in absolute alcohol is clinically employable for treatment of postmenopausal women but that P is of no value in the dosage employed here. Further investigations of transcutaneous absorption of P are desirable.

Administration, Cutaneous↗

Effect of oestrogen and progestagen on gonadotrophins and sex hormones in oophorectomized women.

Five premenopausal women were followed with measurements of androgens, oestrogens, gonadotrophins and sex hormone binding globulin (SHBG) after ovariectomy for benign disease. After a period of 6 weeks without treatment the women were treated with oestradiol 4 mg daily for 8 weeks, oestradiol 4 mg plus norethisterone acetate (NETA) 2 mg daily for 8 weeks and finally oestradiol 4 mg daily for another 8 weeks. The levels of androgens did not change during the various periods. As usual during oral treatment oestrone and oestrone sulphate were elevated while oestradiol levels were in the pre-operative range during treatment, regardless of the addition of NETA. SHBG was elevated during oestrogen-only treatment, while addition of NETA normalized the concentration of SHBG. In the combined NETA period concentrations of free oestradiol and non-SHBG-bound oestradiol were significantly elevated, and gonadotrophins returned to premenopausal levels, in contrast to the high levels in the oestrogen-only periods. Using oral oestrogen therapy it may be preferable to add a progestagen rather than elevate the oestrogen dose. Progestagen will result in more free oestradiol and give greater relief of symptoms, but the potentially harmful effect of progestagens on blood lipids must be considered.

Adult↗

Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females.

During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers (aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione and dehydroepiandrosterone-sulphate levels decreased 6-48%, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68% Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.

Adult↗

Effect of oral testosterone treatment on serum concentrations of sex steroids gonadotrophins and prolactin in alcoholic cirrhotic men. Copenhagen Study Group for Liver Diseases.

The aim of this study was to examine the serum concentrations of sex steroids and pituitary hormones in a randomly selected group of alcoholic cirrhotic men participating in a randomized, placebo-controlled study on the efficacy of oral testosterone treatment on the liver. Before treatment, patients (n = 25) had median serum concentrations of testosterone, oestradiol, non-protein bound oestradiol, non-sex hormone binding globulin (SHBG) bound oestradiol and oestrone sulphate which did not differ significantly from those of healthy controls (n = 16), but the patients had significantly (P less than 0.01) higher median serum concentrations of oestrone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. The patients were randomized to treatment with either oral micronized testosterone (200 mg t.d.s.) or placebo for a median duration of 1 year. In the placebo group (n = 8), hormone concentrations at follow-up were not significantly different from those at entry apart from a significant (P less than 0.05) increase in FSH concentrations. Median concentrations of testosterone, oestrone, and oestrone sulphate increased significantly (P less than 0.05) in the testosterone-treated group (n = 17) when compared with concentrations at entry and concentrations in the placebo group. The testosterone-treated group had significantly (P less than 0.05) higher serum concentrations of non-protein bound and non-SHBG bound oestradiol when compared with concentrations at entry, but no significant changes were observed regarding serum oestradiol and prolactin concentrations. Both LH and FSH concentrations decreased significantly (P less than 0.05) in the testosterone-treated group when compared with concentrations at entry and concentrations in the placebo group.

Adult↗

Simultaneous quantification by double rocket immunoelectrophoresis of apolipoproteins A-I and B in blood spotted on filter paper.

We describe double rocket immunoelectrophoresis for simultaneous quantification of apolipoprotein A-I (apo A-I) and B (apo B) in blood on filter paper. The apolipoproteins from blood spots on filter paper were eluted with detergents (sodium dodecyl sulfate and Triton X-100). The eluates were subjected to electrophoresis on agarose gel containing antisera against both apolipoproteins. Within- and between-assay CVs for apo B/A-I ratios were less than 5.5% and 7.2%, respectively. The apo B/A-I ratio was influenced by length and temperature of storage. In results for 121 venous blood samples, the apo B/A-I ratios in dried blood spots correlated well with those in serum (r = 0.92) and correlated somewhat with the ratios for low-density lipoprotein/high-density lipoprotein cholesterol in serum (r = 0.87). Of these specimens, 68 were from patients with known familial hypercholesterolemia, all of whom had an apo B/A-I ratio greater than 0.90. We think this method will be of value for detecting familial hypercholesterolemia and possibly familial hyperapobeta- and hypoalphalipoproteinemia.

Adolescent↗

Dopaminergic regulation of gonadotropin levels and pulsatility in normal women.

This study was done to define the concentration of dopamine (DA) that inhibits gonadotropin secretion and to study the effect of DA D-2 receptor blockade during the infusions. Normal women received 5-hour infusions of either glucose (n = 14) or DA at rates of 0.04 (n = 6), 0.4 (n = 6), and 4.0 micrograms/kg X minute (n = 9). After 3 hours, metoclopramide (MTC) was administered. Mean serum luteinizing hormone (LH) concentration declined during 0.4 (P less than 0.01) and 4.0 micrograms/kg X minute (P less than 0.05) infusion doses of DA. This effect of DA was not consistently (P greater than 0.05) antagonized by MTC. Six women received DA (4.0 micrograms/kg X minute) or glucose for 18 hours. After 17 hours, MTC was given. Blood samples were collected every 10 minutes during the last 8 hours. No significant effect on LH pulse frequency and pulse amplitude was observed (P greater than 0.05). A marked (P less than 0.01) rise in LH occurred after MTC administration. The authors conclude that (1) physiologic doses of DA may inhibit LH secretion with only little, if any, effect on the pulsatile release; and (2) low-affinity DA receptors responsive to DA D-2 antagonists may regulate LH secretion.

Adult↗

Abnormal androgen and oestrogen metabolism in men with steroid sulphatase deficiency and recessive X-linked ichthyosis.

Serum levels of sex hormone binding globulin (SHBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulphate, oestradiol, oestrone, oestrone sulphate, FSH, and LH were measured in 20 steroid sulphatase-deficient men with recessive X-linked ichthyosis and in normal men. The serum oestrone sulphate level was significantly higher than normal in the patients (P less than 0.0001). In affected men, there was a tendency towards higher dehydroepiandrosterone sulphate levels and no decline with age was seen in the patients as opposed to normal men (interaction: P less than 0.025). Serum androstenedione, and oestradiol levels were lower than normal in the patients (P less than 0.0005 and P = 0.055, respectively), while their LH level was higher than normal (P less than 0.0005). The serum levels of SHBG, total and free testosterone, dihydrotestosterone, oestrone, and FSH were not significantly different from normal in the icthyotic patients. We suggest that the observed abnormalities in these patients are a consequence of the enzyme deficiency which severely impairs the ability of tissues to hydrolyse steroid sulphates.

Adult↗

Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis.

Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed no significant differences from the controls. Serum concentrations of oestrone and oestradiol were significantly (P less than 0.05) increased in all patient groups, and serum oestrone increased with decreasing liver function. No significant differences were observed concerning SHBG concentrations in the three groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH and LH concentrations was observed after dexamethasone suppression. The mean percentage increase of FSH and LH was higher the greater the severity of liver cirrhosis.

Adult↗

Pituitary-testicular function in patients with alcoholic cirrhosis of the liver.

In forty-two patients with alcoholic liver cirrhosis and without recent alcohol ingestion the pituitary-testicular function was studied in an effort to relate the endocrine abnormalities with the degree of liver cell dysfunction, evaluated on a quantitative basis. Compared with values in twenty-one healthy controls, we found significantly elevated serum oestrone, oestradiol, follicle-stimulating hormone, luteinizing hormone and prolactin (P less than 0.01). Serum dehydro-epiandrosterone and dehydroepiandrosterone sulphate were significantly reduced in the cirrhotics (P less than 0.01), whereas serum testosterone was not significantly different from that in the controls. Raised levels of sex-hormone binding globulin were found in 71% (22/31) of the patients (median 8 x 10(-18) mol/l, range 3-17 x 10(-8) mol/l). The incidence of gynaecomastia (38%), cutaneous spiders (67%), testicular atrophy (24%) and reduced axillary hair (71%) was without significant relation to raised levels of sex-hormone binding globulin or progressively reduced liver function. In the presence of clinical or hormonal hypo-gonadism we found evidence of a state of primary hypogonadism together with an inadequate secretion of gonadotropins. The state of hyperoestrogenaemia and the concentration of gonadotropins were significantly correlated to the hepatic synthesis of coagulation factors.

Adult↗

Lack of effect of intravenous LHRH on plasma noradrenaline in man.

One hundred microgram of LHRH was given intravenously to two male and two female subjects. Plasma noradrenaline did not change following LHRH, in contrast to findings reported by others. There was no change in heart rate and systolic arterial blood pressure. LH increased significantly as expected.

Adult↗

Treatment of hyperprolactinemic luteal insufficiency with bromocriptine.

Twelve patients with infertility and insufficent luteal function were studied during a control cycle, and during a cycle when 2.5 mg of bromocriptine was given twice daily. Serum levels of prolactin, progesterone, estradiol-17-beta, FSH and LH were determined during both cycles. Endometrial biopsies were taken from most patients during the late luteal phase. Two patients had persistent hyperprolactinemia, approximately 35-45 ng/ml, and both had repeated insufficient luteal function, which completely reverted to normal during treatment. Five of the 10 normoprolactinemic patients achieved a normal luteal function during bromocriptine therapy. No pregnancies were achieved during the study but one patient later conceived during bromocriptine therapy.

Adult↗

Correlation between rises of gonadotrophins and rises of sex steroids during clomiphene test in men.

Serum FSH, LH and testosterone and urinary excretion of androsterone, aetiocholanolone, dehydroepiandrosterone and total oestrogens were measured in normal and oligospermic men before and after clomiphene stimulation. Responses in all parameters were highly variably from one individual to another and this great variation formed the basis for investigating the correlations between responses. There was no correlation between increase of FSH and LH or increase of LH and steroids. Also there was no correlation between rises of FSH and rises of androgens. But a significant correlation existed between rises of FSH and rises of oestrogens. This confirms that one action of FSH is to stimulate production of testicular oestrogens which presumably takes place in the Sertoli cells.

Adolescent↗

Luteinizing hormone and follicle stimulating hormone and the response to luteinizing hormone releasing hormone in relation to sex and age.

Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) before and after intravenous injection of luteinizing hormone releasing hormone (LHRH) were studied in 71 male and female subjects of various ages. Mean basal FSH and LH levels were not significantly different in the male groups, except that FSH was significantly higher in the very old subjects. Postmenopausal female subjects had much higher concentrations of both hormones than had premenopausal women. LH was higher in female subjects shortly after the menopause than in very old female subjects. The serum concentrations of both FSH and LH 30 min. after intravenous injection of 200 mug LHRH were not different from the 60 min. values. There was no significant difference in the response of LH in the male groups. The peak FSH concentration was higher in the very old male subjects. Postmenopausal women had a much higher peak concentration of both FSH and LH than had younger subjects. The increment of LH, but not of FSH, was larger in female subjects shortly after the menopause than in very old female subjects. In both sexes there was a significant correlation between the basal FSH/LH ratio and age. In younger male subjects there was a close positive correlation between basal LH and serum testosterone, in older male subjects this correlation was negative and significant.

Adult↗