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Browsing by Author "Prelević, G.M. (7004326204)"

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    24-hour serum cortisol profiles in women with polycystic ovary syndrome
    (1993)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Balint-perić, L. (6701858516)
    We studied the 24-h blood profiles of Cortisol in obese and non-obese women with polycystic ovary syndrome (PCOS), for comparison with the levels in healthy women (controls). The levels of other hormones, such as androgens, which are known to be disturbed in PCOS, were also compared. Luteinizing hormone (LH) and androgen (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)) concentrations were significantly (p < 0.005) raised in patients with PCOS, compared to those in control women. Sex hormone binding globulin (SHBG) concentration was significantly lower in women with PCOS, particularly in those who were overweight. There was a significant negative correlation between body mass index (BMI) and SHBG concentrations (r = -0.59;p = 0.006). Mean 24-h Cortisol concentrations were similar in women with PCOS and controls, as well as in the obese and non-obese PCOS patients. However, the 24-h blood Cortisol profile pattern was significantly different in women with PCOS as compared to the controls (p - 0.0039). Significantly lower Cortisol levels were observed during the night (levels were determined between 20.00 and 04.00 and are expressed as the area under the curve) in subjects with PCOS, compared to the control women (p = 0.02). These changes were most marked in the non-obese women with PCOS who had lower blood Cortisol levels during the night than either the controls or the obese PCOS subjects. Our finding of significantly lower Cortisol concentrations during the night could reflect a subtle abnormality of adrenal steroid secretion in women with PCOS. © 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    24-hour serum cortisol profiles in women with polycystic ovary syndrome
    (1993)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Balint-perić, L. (6701858516)
    We studied the 24-h blood profiles of Cortisol in obese and non-obese women with polycystic ovary syndrome (PCOS), for comparison with the levels in healthy women (controls). The levels of other hormones, such as androgens, which are known to be disturbed in PCOS, were also compared. Luteinizing hormone (LH) and androgen (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)) concentrations were significantly (p < 0.005) raised in patients with PCOS, compared to those in control women. Sex hormone binding globulin (SHBG) concentration was significantly lower in women with PCOS, particularly in those who were overweight. There was a significant negative correlation between body mass index (BMI) and SHBG concentrations (r = -0.59;p = 0.006). Mean 24-h Cortisol concentrations were similar in women with PCOS and controls, as well as in the obese and non-obese PCOS patients. However, the 24-h blood Cortisol profile pattern was significantly different in women with PCOS as compared to the controls (p - 0.0039). Significantly lower Cortisol levels were observed during the night (levels were determined between 20.00 and 04.00 and are expressed as the area under the curve) in subjects with PCOS, compared to the control women (p = 0.02). These changes were most marked in the non-obese women with PCOS who had lower blood Cortisol levels during the night than either the controls or the obese PCOS subjects. Our finding of significantly lower Cortisol concentrations during the night could reflect a subtle abnormality of adrenal steroid secretion in women with PCOS. © 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Acute effects of L-dopa and bromocriptine on serum PRL, LH and FSH levels in patients with hyperprolactinemic and normoprolactinemic polycystic ovary syndrome
    (1987)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Perić, Lj.A. (57017746600)
    We have investigated the importance of the dopaminergic control of gonadotropin secretion by studying LH, FSH and PRL responses to L-dopa and bromocriptine in patients with polycystic ovary syndrome (PCOS). Both L-dopa and bromocriptine administration were followed by a statistically significant decrease in LH in the hyperprolactinemic PCO patients (compared to the normoprolactinemic subgroup — p < 0.01 and control group — p < 0.05); the decline was proportional to the basal level of LH. A significant positive correlation between basal LH levels and maximum net decrease of LH was observed after administration of both agents (p < 0.01). Although both subgroups of PCO patients showed a similar decrease in PRL levels it was statistically significant only in the normoprolactinemic patients,(p < 0.01). Prolactin sensitivity to the inhibitory effect of bromocriptine and L-dopa showed a significant correlation with the basal PRL level (p < 0.01). The response of serum FSH was variable and not significant. These results suggest that a reduction of an inhibitory influence of hypothalamic dopamine might be a cause of inappropriately elevated LH and PRL levels found in patients with polycystic ovary syndrome and hyperprolactinemia. © 1987, Italian Society of Endocrinology (SIE). All rights reserved.
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    Acute effects of L-dopa and bromocriptine on serum PRL, LH and FSH levels in patients with hyperprolactinemic and normoprolactinemic polycystic ovary syndrome
    (1987)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Perić, Lj.A. (57017746600)
    We have investigated the importance of the dopaminergic control of gonadotropin secretion by studying LH, FSH and PRL responses to L-dopa and bromocriptine in patients with polycystic ovary syndrome (PCOS). Both L-dopa and bromocriptine administration were followed by a statistically significant decrease in LH in the hyperprolactinemic PCO patients (compared to the normoprolactinemic subgroup — p < 0.01 and control group — p < 0.05); the decline was proportional to the basal level of LH. A significant positive correlation between basal LH levels and maximum net decrease of LH was observed after administration of both agents (p < 0.01). Although both subgroups of PCO patients showed a similar decrease in PRL levels it was statistically significant only in the normoprolactinemic patients,(p < 0.01). Prolactin sensitivity to the inhibitory effect of bromocriptine and L-dopa showed a significant correlation with the basal PRL level (p < 0.01). The response of serum FSH was variable and not significant. These results suggest that a reduction of an inhibitory influence of hypothalamic dopamine might be a cause of inappropriately elevated LH and PRL levels found in patients with polycystic ovary syndrome and hyperprolactinemia. © 1987, Italian Society of Endocrinology (SIE). All rights reserved.
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    Changes in prolactin levels with the menopause: The effects of estrogen/androgen and calcitonin treatment
    (1997)
    Balint-Perić, L.A. (6701858516)
    ;
    Prelević, G.M. (7004326204)
    Prolactin levels were evaluated over a 2-year period in three groups of postmenopausal women: group A consisted of 35 untreated women distributed according to time since the menopause; group B consisted of 17 women on a combined estrogen/androgen preparation (Gynodian depot®) intramuscularly at monthly intervals; and group C consisted of 12 women on 100 units of salmon calcitonin intranasally on alternate days and 1500 mg calcium daily. The control group (group D) consisted of 11 healthy premenopausal women. Serum prolactin, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at the onset and 6-month intervals over 24 months. Mean serum prolactin concentrations decreased significantly during the second postmenopausal year in untreated women (p = 0.0001 and p = 0.0000 after 18 and 24 months, respectively) when compared to either the levels in premenopausal women or those at the beginning of the menopause (p = 0.0007). Neither combined estrogen/androgen nor calcitonin therapy significantly influenced prolactin levels which were similar throughout the observed period. In the group on a combined estrogen/androgen preparation, physiological estradiol concentration together with a suppression of gonadotropins during the first 6 months of therapy were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH and LH levels were unchanged. Our results show that prolactin levels decrease significantly during the second year of the menopause. Neither combined estrogen/androgen, nor salmon calcitonin therapy had any effect on serum prolactin concentrations in post menopausal women.
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    Changes in prolactin levels with the menopause: The effects of estrogen/androgen and calcitonin treatment
    (1997)
    Balint-Perić, L.A. (6701858516)
    ;
    Prelević, G.M. (7004326204)
    Prolactin levels were evaluated over a 2-year period in three groups of postmenopausal women: group A consisted of 35 untreated women distributed according to time since the menopause; group B consisted of 17 women on a combined estrogen/androgen preparation (Gynodian depot®) intramuscularly at monthly intervals; and group C consisted of 12 women on 100 units of salmon calcitonin intranasally on alternate days and 1500 mg calcium daily. The control group (group D) consisted of 11 healthy premenopausal women. Serum prolactin, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at the onset and 6-month intervals over 24 months. Mean serum prolactin concentrations decreased significantly during the second postmenopausal year in untreated women (p = 0.0001 and p = 0.0000 after 18 and 24 months, respectively) when compared to either the levels in premenopausal women or those at the beginning of the menopause (p = 0.0007). Neither combined estrogen/androgen nor calcitonin therapy significantly influenced prolactin levels which were similar throughout the observed period. In the group on a combined estrogen/androgen preparation, physiological estradiol concentration together with a suppression of gonadotropins during the first 6 months of therapy were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH and LH levels were unchanged. Our results show that prolactin levels decrease significantly during the second year of the menopause. Neither combined estrogen/androgen, nor salmon calcitonin therapy had any effect on serum prolactin concentrations in post menopausal women.
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    Effect of two different progestins (cyproterone acetate and norgestrel), administered in a cyclical estradiol valerate regimen, on markers of bone turnover
    (1994)
    Prelević, G.M. (7004326204)
    ;
    Beljic, T. (6603356288)
    ;
    Balint-perić, L. (6701858516)
    ;
    Petrović, J. (7101898533)
    ;
    Elliesen, J. (6508074199)
    It has been suggested that some progestogens could have a stimulating effect on bone formation. This study was therefore undertaken in order to compare the influence of cyproterone acetate and norgestrel on bone metabolism when administered in a discontinuous, sequentially combined regimen with estradiol valerate. Twenty healthy early postmenopausal women were randomly assigned to treatment with either Cyclo-Progynova® containing 0.5 mg of norgestrel, or Climen® containing 1 mg of cyproterone acetate (CPA), over two 28-day cycles. Markers of bone resorption -fasting urinary hydroxypro-line / creatinine and calcium / creatinine ratios - and of bone formation - serum alkaline phosphatase and osteocalcin - were determined initially, before the start of treatment and thereafter twice weekly (a total of 17 assessments for each woman) during the 8-week treatment period. Serum osteocalcin concentrations were slightly but not significantly higher throughout the study period in women receiving Climen, compared to those taking Cyclo-Progynova. Cyclical fluctuation of serum osteocalcin levels were more pronounced in women with a high baseline level of osteocalcin. During the period of progestogen administration, osteocalcin concentrations were either similar to or even lower than those in the phase of administration of estradiol valerate alone. Serum calcium and alkaline phosphatase concentrations were relatively stable during the study period with both treatment regimens. Urinary excretion of calcium and hydroxyproline varied during the cycle but the variation was unrelated to either type or time of progestogen administration. Mean urinary hydroxyproline excretion during the 8-week study period was similar for both preparations, although the mean decrease in the urinary hydroxyproline /creatinine ratio was insignificantly higher for the CPA-containing preparation. Women with a high baseline osteocalcin level, however, showed significantly lower hydroxyproline excretion when treated with Climen than with a norgestrel-containing preparation. The significantly lower hydroxyproline excretion suggests a favorable effect on bone turnover of the preparation containing CPA. This effect was particularly obvious in women with a high bone turnover and was most probably the result of a potentiating effect of CPA on the anti-resorptive effect of estradiol valerate. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Effect of two different progestins (cyproterone acetate and norgestrel), administered in a cyclical estradiol valerate regimen, on markers of bone turnover
    (1994)
    Prelević, G.M. (7004326204)
    ;
    Beljic, T. (6603356288)
    ;
    Balint-perić, L. (6701858516)
    ;
    Petrović, J. (7101898533)
    ;
    Elliesen, J. (6508074199)
    It has been suggested that some progestogens could have a stimulating effect on bone formation. This study was therefore undertaken in order to compare the influence of cyproterone acetate and norgestrel on bone metabolism when administered in a discontinuous, sequentially combined regimen with estradiol valerate. Twenty healthy early postmenopausal women were randomly assigned to treatment with either Cyclo-Progynova® containing 0.5 mg of norgestrel, or Climen® containing 1 mg of cyproterone acetate (CPA), over two 28-day cycles. Markers of bone resorption -fasting urinary hydroxypro-line / creatinine and calcium / creatinine ratios - and of bone formation - serum alkaline phosphatase and osteocalcin - were determined initially, before the start of treatment and thereafter twice weekly (a total of 17 assessments for each woman) during the 8-week treatment period. Serum osteocalcin concentrations were slightly but not significantly higher throughout the study period in women receiving Climen, compared to those taking Cyclo-Progynova. Cyclical fluctuation of serum osteocalcin levels were more pronounced in women with a high baseline level of osteocalcin. During the period of progestogen administration, osteocalcin concentrations were either similar to or even lower than those in the phase of administration of estradiol valerate alone. Serum calcium and alkaline phosphatase concentrations were relatively stable during the study period with both treatment regimens. Urinary excretion of calcium and hydroxyproline varied during the cycle but the variation was unrelated to either type or time of progestogen administration. Mean urinary hydroxyproline excretion during the 8-week study period was similar for both preparations, although the mean decrease in the urinary hydroxyproline /creatinine ratio was insignificantly higher for the CPA-containing preparation. Women with a high baseline osteocalcin level, however, showed significantly lower hydroxyproline excretion when treated with Climen than with a norgestrel-containing preparation. The significantly lower hydroxyproline excretion suggests a favorable effect on bone turnover of the preparation containing CPA. This effect was particularly obvious in women with a high bone turnover and was most probably the result of a potentiating effect of CPA on the anti-resorptive effect of estradiol valerate. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Effects of a iow-dose estrogen-antiandrogen combination (diane-35) on lipid and carbohydrate metabolism in patients with polycystic ovary syndrome
    (1990)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Trpković, D. (6507143317)
    ;
    Balint-Perić, L. (6701858516)
    This study was undertaken in order to evaluate the effect of an oral contraceptive containing 35 μg of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Twentythree patients with PCOS were treated with Diane-35 for between 9 and 18 cycles without interruption (a total of 318 treated cycles). Metabolic evaluations, which included measurements of fasting blood glucose, insulin, C-peptide, total cholesterol, triglyceride, total lipids, HDL-cholesterol, LDL-cholesterol and apolipoproteins (Apo A1, Apo A2 and Apo B), were performed before treatment and every 3rd cycle during the treatment period. In the case of 5 women an oral glucose tolerance test (oGTT) was performed before and after the 12th cycle of Diane-35 treatment, with blood samples taken for glucose, insulin and C-peptide measurements. Total cholesterol showed a significant increase after the 6th cycle (p < 0.001) and reached the mean maximal value after the 9th cycle. A similar increasing trend was observed with LDL-cholesterol, which also reached the maximal mean level after the 9th cycle of treatment (p < 0.05). There were no significant changes in HDL-cholesterol levels. Significant increases in serum triglyceride (p < 0.01) and total lipids (p < 0.001) were observed after the 3rd cycle. Apo A2 concentrations increased significantly after the 6th cycle (p < 0.001) and showed an increasing trend thereafter. A significant increase was also observed in Apo B concentrations after the 6th cycle but these decreased after the 12th cycle. In spite of these observed increases in serum lipids and lipoproteins, the mean levels remained within the normal range throughout the treatment period. Fasting serum glucose, insulin and C-peptide concentrations did not show any significant changes during the study. Higher insulin and C-peptide responses during the oGTT were observed after the 12th cycle but the differences in the areas under the curve before and after treatment were not significant. A deterioration of blood glucose was observed after treatment with Diane-35, a significant difference in mean values being noted 150 minutes after the glucose overload (p < 0.005). However, the areas under the curve in blood glucose response before (34.92 ± 4.12) and after (43.45 ± 3.61) treatment were not significantly different. The results of this study show that a low-dose estrogen-antiandrogen combination could cause deterioration of carbohydrate and lipid metabolism in PCO patients and strongly suggest a need for continuous monitoring of such patients having long-term estrogen-antiandrogen treatment. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Effects of a iow-dose estrogen-antiandrogen combination (diane-35) on lipid and carbohydrate metabolism in patients with polycystic ovary syndrome
    (1990)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Trpković, D. (6507143317)
    ;
    Balint-Perić, L. (6701858516)
    This study was undertaken in order to evaluate the effect of an oral contraceptive containing 35 μg of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Twentythree patients with PCOS were treated with Diane-35 for between 9 and 18 cycles without interruption (a total of 318 treated cycles). Metabolic evaluations, which included measurements of fasting blood glucose, insulin, C-peptide, total cholesterol, triglyceride, total lipids, HDL-cholesterol, LDL-cholesterol and apolipoproteins (Apo A1, Apo A2 and Apo B), were performed before treatment and every 3rd cycle during the treatment period. In the case of 5 women an oral glucose tolerance test (oGTT) was performed before and after the 12th cycle of Diane-35 treatment, with blood samples taken for glucose, insulin and C-peptide measurements. Total cholesterol showed a significant increase after the 6th cycle (p < 0.001) and reached the mean maximal value after the 9th cycle. A similar increasing trend was observed with LDL-cholesterol, which also reached the maximal mean level after the 9th cycle of treatment (p < 0.05). There were no significant changes in HDL-cholesterol levels. Significant increases in serum triglyceride (p < 0.01) and total lipids (p < 0.001) were observed after the 3rd cycle. Apo A2 concentrations increased significantly after the 6th cycle (p < 0.001) and showed an increasing trend thereafter. A significant increase was also observed in Apo B concentrations after the 6th cycle but these decreased after the 12th cycle. In spite of these observed increases in serum lipids and lipoproteins, the mean levels remained within the normal range throughout the treatment period. Fasting serum glucose, insulin and C-peptide concentrations did not show any significant changes during the study. Higher insulin and C-peptide responses during the oGTT were observed after the 12th cycle but the differences in the areas under the curve before and after treatment were not significant. A deterioration of blood glucose was observed after treatment with Diane-35, a significant difference in mean values being noted 150 minutes after the glucose overload (p < 0.005). However, the areas under the curve in blood glucose response before (34.92 ± 4.12) and after (43.45 ± 3.61) treatment were not significantly different. The results of this study show that a low-dose estrogen-antiandrogen combination could cause deterioration of carbohydrate and lipid metabolism in PCO patients and strongly suggest a need for continuous monitoring of such patients having long-term estrogen-antiandrogen treatment. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Effects of a low-dose estrogen-antiandrogen combination (diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome
    (1989)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Balint-perić, L. (6701858516)
    ;
    Puzigaća, Z. (6506601852)
    This study evaluates the effect of an oral contraceptive containing 35 ug of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on hormone dynamics, clinical signs of androgenization and ovarian size in patients with polycystic ovary syndrome (PCOS). Forty-six patients with PCOS were treated with Diane-35 for between 9 and 30 cycles without interruption (a total of 688 cycles). Clinical and hormonal evaluations were performed before treatment and every 3rd cycle during the treatment period while ultrasonographic assessment of ovaries was carried out every 6th cycle. A highly significant decrease in the LH/FSH ratio (p < 0.001) as well as testosterone levels (p < 0.001) was noticed after the 3rd cycle of Diane-35 administration. The mean serum androstenedione level decreased significantly (p < 0.025) after the 3rd cycle, and showed a lowering trend thereafter. A significant reduction in serum DHEA-S levels was observed after the 6th cycle of treatment and they also showed a subsequent lowering trend. A highly significant increase in SHBG concentrations (p < 0.001) was noticed after the 3rd cycle. Most of the patients noticed improvement in hirsutism between the 8th and 12th cycles of treatment. Mean ovarian size decreased significantly (p < 0.001) after the 6th cycle, the normal size being reached after the 12th cycle of treatment. After the 4th cycle treatment was discontinued in 1 patient due to secondary amenorrhea, and in another 3 patients because of an increase in diastolic blood pressure. In a few patients side-effects such as weight gain, breast tenderness and mood changes in mild form were reported. Three out of 7 patients conceived in the 2nd or 3rd cycle after discontinuing Diane-35 therapy. The results of this study show that a combination of low-dose estrogen and cyproterone acetate (Diane-35) successfully reduces the hormonal disturbances which characterize PCOS. Apart from the normalization of the hormonal profile and the decrease in ovarian size, beneficial effects of Diane-35 were also observed on acne, hirsutism and regulation of the menstrual cycle. Favourable effects were also seen in terms of the pregnancy rate after dicontinuation of Diane-35 therapy. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Effects of a low-dose estrogen-antiandrogen combination (diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome
    (1989)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Balint-perić, L. (6701858516)
    ;
    Puzigaća, Z. (6506601852)
    This study evaluates the effect of an oral contraceptive containing 35 ug of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on hormone dynamics, clinical signs of androgenization and ovarian size in patients with polycystic ovary syndrome (PCOS). Forty-six patients with PCOS were treated with Diane-35 for between 9 and 30 cycles without interruption (a total of 688 cycles). Clinical and hormonal evaluations were performed before treatment and every 3rd cycle during the treatment period while ultrasonographic assessment of ovaries was carried out every 6th cycle. A highly significant decrease in the LH/FSH ratio (p < 0.001) as well as testosterone levels (p < 0.001) was noticed after the 3rd cycle of Diane-35 administration. The mean serum androstenedione level decreased significantly (p < 0.025) after the 3rd cycle, and showed a lowering trend thereafter. A significant reduction in serum DHEA-S levels was observed after the 6th cycle of treatment and they also showed a subsequent lowering trend. A highly significant increase in SHBG concentrations (p < 0.001) was noticed after the 3rd cycle. Most of the patients noticed improvement in hirsutism between the 8th and 12th cycles of treatment. Mean ovarian size decreased significantly (p < 0.001) after the 6th cycle, the normal size being reached after the 12th cycle of treatment. After the 4th cycle treatment was discontinued in 1 patient due to secondary amenorrhea, and in another 3 patients because of an increase in diastolic blood pressure. In a few patients side-effects such as weight gain, breast tenderness and mood changes in mild form were reported. Three out of 7 patients conceived in the 2nd or 3rd cycle after discontinuing Diane-35 therapy. The results of this study show that a combination of low-dose estrogen and cyproterone acetate (Diane-35) successfully reduces the hormonal disturbances which characterize PCOS. Apart from the normalization of the hormonal profile and the decrease in ovarian size, beneficial effects of Diane-35 were also observed on acne, hirsutism and regulation of the menstrual cycle. Favourable effects were also seen in terms of the pregnancy rate after dicontinuation of Diane-35 therapy. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Inhibitory effect of sandostatin on secretion of luteinising hormone and ovarian steroids in polycystic ovary syndrome
    (1990)
    Prelević, G.M. (7004326204)
    ;
    Wurzburger, M.I. (6603925241)
    ;
    Balint-Perić, L. (6701858516)
    ;
    Nešić, J.S. (59843749000)
    Hyperinsulinism accompanies the raised luteinising hormone (LH) concentrations in women with the polycystic ovary syndrome (PCOS). Somatostatin inhibits insulin and LH secretion in healthy adults, so the effect of treatment with a long-acting somatostatin analogue ('Sandostatin') on gonadotropin and androgen secretion in PCOS was investigated. LH pulsatility, androgen concentrations, and hormonal responses to an oral glucose load and to administration of a GnRH agonist (buserelin) were measured before and after 7 days' treatment with sandostatin 100 μg subcutaneously twice a day in 10 amenorrhoeic women with classic features of PCOS. Sandostatin significantly reduced integrated LH concentrations and LH pulse amplitudes, oestradiol, testosterone, and androstenedione concentrations, and LH responses to buserelin; it also suppressed insulin and C-peptide responses to an oral glucose load. Thus sandostatin inhibits pituitary and ovarian hormonal responses in part by a direct influence on pituitary activity, and the possibility of an indirect effect mediated by changes in insulin concentrations requires investigation. These findings have implications for the treatment of infertility in women with PCOS. © 1990.
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    LH pulsatility and response to a single S.C. Injection of buserelin in polycystic ovary syndrome
    (1990)
    Prelević, G.M. (7004326204)
    ;
    Wiirzburger, M.I. (56355880900)
    ;
    Balint-Peric, L. (6701858516)
    The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am-PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am-PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 μg of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p < 0.02 and p < 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p < 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p < 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p < 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p < 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis ofPCOS. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    LH pulsatility and response to a single S.C. Injection of buserelin in polycystic ovary syndrome
    (1990)
    Prelević, G.M. (7004326204)
    ;
    Wiirzburger, M.I. (56355880900)
    ;
    Balint-Peric, L. (6701858516)
    The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am-PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am-PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 μg of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p < 0.02 and p < 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p < 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p < 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p < 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p < 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis ofPCOS. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    Metoclopramide effect on serum prolactin, LH and FSH in patients with polycystic ovary syndrome
    (1988)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Perić, Lj.A. (57017746600)
    In order to investigate the DA activity in polycystic ovary syndrome (PCOS) we studied the response of LH, FSH and PRL to a dopamine receptor antagonist metoclopramide (MCP-10 mg iv) in 12 PCO subjects (7 with normal and 5 with elevated levels of prolactin). The prolactin and LH responses to metoclopramide were compared to those obtained in 6 normal cycling women. Although a significant increase in PRL levels was documented after MCP administration in all PCO patients and normal cycling women (p< 0.01 ), the highest increment in PRL levels was observed in normoprolactinemic PCO subjects. In contrast a blunted PRL response was observed in hyperprolactinemic PCO patients. There was a negative correlation between basal PRL levels and the maximum net increase in PRL after MCP. In both groups of PCO subjects MCP administration caused initial decrease in LH levels followed by an increase after 4 h. In hyperprolactinemic PCO patients this observed MCP effect on LH was more pronunced and significantly different in comparison with normoprolactinemic PCO patients (p < 0.01). MCP administration did not cause significant acute alterations in LH levels in normal cycling women and no significant FSH changes in either PCO or control subjects. A relative dopamine deficiency might cause hypersecretion of PRL and LH in patients with PCOS and hyperprolactinemia. © 1988, Italian Society of Endocrinology (SIE). All rights reserved.
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    Metoclopramide effect on serum prolactin, LH and FSH in patients with polycystic ovary syndrome
    (1988)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Perić, Lj.A. (57017746600)
    In order to investigate the DA activity in polycystic ovary syndrome (PCOS) we studied the response of LH, FSH and PRL to a dopamine receptor antagonist metoclopramide (MCP-10 mg iv) in 12 PCO subjects (7 with normal and 5 with elevated levels of prolactin). The prolactin and LH responses to metoclopramide were compared to those obtained in 6 normal cycling women. Although a significant increase in PRL levels was documented after MCP administration in all PCO patients and normal cycling women (p< 0.01 ), the highest increment in PRL levels was observed in normoprolactinemic PCO subjects. In contrast a blunted PRL response was observed in hyperprolactinemic PCO patients. There was a negative correlation between basal PRL levels and the maximum net increase in PRL after MCP. In both groups of PCO subjects MCP administration caused initial decrease in LH levels followed by an increase after 4 h. In hyperprolactinemic PCO patients this observed MCP effect on LH was more pronunced and significantly different in comparison with normoprolactinemic PCO patients (p < 0.01). MCP administration did not cause significant acute alterations in LH levels in normal cycling women and no significant FSH changes in either PCO or control subjects. A relative dopamine deficiency might cause hypersecretion of PRL and LH in patients with PCOS and hyperprolactinemia. © 1988, Italian Society of Endocrinology (SIE). All rights reserved.
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    The effect of intranasal salmon calcitonin on biochemical parameters of bone turnover in postmenopausal women
    (1994)
    Balint-Perić, L.A. (6701858516)
    ;
    Prelević, G.M. (7004326204)
    ;
    Bešlagić, Z. (57199583579)
    ;
    Petrović, J. (7101898533)
    This study aims to evaluate the effect of intranasal salmon calcitonin on variables of bone metabolism in 12 postmenopausal women during 24 months of treatment. A treatment regime of 100 U of intranasal salmon calcitonin on alternate days and 1500 mg daily of oral elementary calcium was applied. The control group consisted of 35 postmenopausal women distributed according to time since menopause. Biochemical and hormonal evaluations of calcium metabolism were performed at the start of treatment and after 6, 12, 18 and 24 months of treatment. Mean serum osteocalcin concentration was unchanged during the 1st year of treatment but was significantly elevated during the 2nd year (p = 0.03 and p = 0.005 after 18 and 24 months, respectively) when compared to levels at 12 months. Similar elevation of osteocalcin levels was observed in untreated women during the first 12 postmenopausal months. Mean 24-h hydroxyproline excretion decreased during the first 12 months of therapy but increased in the subsequent 6 months. The observed rise in serum osteocalcin concentration and urinary hydroxyproline excretion during the 2nd year of treatment with calcitonin was accompanied by a significant rise in serum calcitonin level. No significant differences in serum calcium, phosphorus, alkaline phosphatase or parathormone concentration, or urinary calcium excretion, were observed between treated and untreated women during the 24-month period. This study shows that 12 months' treatment with intranasal salmon calcitonin decreases bone resorption in early postmenopausal women, while bone formation remains unchanged. Longer treatment with intranasal salmon calcitonin, however, seems to be ineffective, most probably due to secondary resistance to calcitonin. This justifies intermittent treatment schedules: the most appropriate ones have yet to be established. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    The effect of intranasal salmon calcitonin on biochemical parameters of bone turnover in postmenopausal women
    (1994)
    Balint-Perić, L.A. (6701858516)
    ;
    Prelević, G.M. (7004326204)
    ;
    Bešlagić, Z. (57199583579)
    ;
    Petrović, J. (7101898533)
    This study aims to evaluate the effect of intranasal salmon calcitonin on variables of bone metabolism in 12 postmenopausal women during 24 months of treatment. A treatment regime of 100 U of intranasal salmon calcitonin on alternate days and 1500 mg daily of oral elementary calcium was applied. The control group consisted of 35 postmenopausal women distributed according to time since menopause. Biochemical and hormonal evaluations of calcium metabolism were performed at the start of treatment and after 6, 12, 18 and 24 months of treatment. Mean serum osteocalcin concentration was unchanged during the 1st year of treatment but was significantly elevated during the 2nd year (p = 0.03 and p = 0.005 after 18 and 24 months, respectively) when compared to levels at 12 months. Similar elevation of osteocalcin levels was observed in untreated women during the first 12 postmenopausal months. Mean 24-h hydroxyproline excretion decreased during the first 12 months of therapy but increased in the subsequent 6 months. The observed rise in serum osteocalcin concentration and urinary hydroxyproline excretion during the 2nd year of treatment with calcitonin was accompanied by a significant rise in serum calcitonin level. No significant differences in serum calcium, phosphorus, alkaline phosphatase or parathormone concentration, or urinary calcium excretion, were observed between treated and untreated women during the 24-month period. This study shows that 12 months' treatment with intranasal salmon calcitonin decreases bone resorption in early postmenopausal women, while bone formation remains unchanged. Longer treatment with intranasal salmon calcitonin, however, seems to be ineffective, most probably due to secondary resistance to calcitonin. This justifies intermittent treatment schedules: the most appropriate ones have yet to be established. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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    The effect of residual beta cell activity on menstruation and the reproductive hormone profile of insulin-dependent diabetics
    (1989)
    Prelević, G.M. (7004326204)
    ;
    Würzburger, M.I. (6603925241)
    ;
    Perić, L.A. (57017746600)
    To investigate the cause of secondary amenorrhoea in insulin-dependent diabetes gonadotrophins, sex steroid hormone levels and residual beta cell activity (C-peptide index) were estimated in a group of 43 women with IDDM. Among 26 women with residual insulin secretion, the C-peptide positive (CpP) group, 5 had secondary amenorrhoea (CpP-Am); among 17 women without endogenous beta cell activity, the C-peptide negative (CpN) group 6 had secondary amenorrhoea (CpN-Am). In this study two different types of secondary amenorrhoea in insulin-dependent diabetics were observed. All CpP-Am women have the classical hormone profile of the polycystic ovary syndrome (increased (LH/FSH ratio, increased serum testosterone, decreased SHBG) together with a history of oligomenorrhoea and excess weight before the onset of diabetes. On the other hand, all CpN-Am women had decreased LH levels as well as low LH/FSH ratio and testosterone levels. These results strongly suggest that a lack of residual pancreatic beta cell activity influences hypothalamus-pituitary function in insulin-dependent diabetes. It might be concluded that PCOS is independent of diabetes while low LH amenorrhoea seems to be the consequence of diabetes and is strongly associated with a lack of residual insulin secretion. © 1989 Springer-Verlag.
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