Biomedical subjects

K Carlström

Publications and source records attributed to K Carlström.

At least 37 records · Page 2Linked to original sources

PubMed2001

A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.

OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105

Adipose Tissue↗

PubMed2000

Tissue concentrations of tissue polypeptide antigen (TPA) and prostatic specific antigen (PSA) in 42 patients with prostatic carcinoma.

BACKGROUND: Following development of methods to quantitate biochemical markers in aspiration biopsies we showed that tissue concentration of prostate specific antigen (T-PSA) decreased with increasing malignancy while serum PSA increased. We also found that T-PSA predicts the clinical outcome better than earlier used prognostic markers. METHODS: In order to further study biochemical markers in prostatic cancer a membrane protein, tissue polypeptide antigen (TPA), which is a complex of polypeptide fragments of cytokeratins 8, 18, and 19, was quantitated in 42 patients with newly diagnosed carcinoma of the prostate. The samples had previously been analyzed for T-PSA. RESULTS: Correlation to TGM classification showed that higher malignancy is correlated to lower tissue TPA values. There is a significant positive correlation (r(s) = 0.49, P < 0.01) between T-TPA and T-PSA. Pretreatment values of T-PSA, but not T-TPA, had association to time to progression or time to death. CONCLUSIONS: Increasing prostatic malignancy is correlated to decreasing values of T-TPA. This indicates that the concentrations of membrane and secretory proteins are changed in the same direction in tissue during cancer development. Tissue TPA seem to have no prognostic value in endocrine treatment of prostatic carcinoma.

Aged↗

PubMed2000

Estrogens increase the endothelial nitric oxide synthase (ecNOS) mRNA level in LNCaP human prostate carcinoma cells.

BACKGROUND: The endothelial cell-specific form of nitric oxide synthases (ecNOS) may play an important role in vascular development, maintenance of vascular tone, and tumor growth in human prostate cancer. Estrogens have been shown to upregulate ecNOS expression in different human cell culture systems. Estrone sulfate (E1S) is the most abundant circulating estrogen, and may serve as a prehormone for the terminal biologically active estrogen estradiol-17beta (E2) in men. METHODS: The effects of E1S and E2 on mRNA expression of ecNOS were studied in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative, LNCaP-r. The cells were grown in steroid-depleted medium and incubated for 2-4 or 48 hr with 0-100 nM of E1S and E2, respectively. ecNOS mRNA levels were determined using RT-PCR and are expressed as arbitrary units after correction for control HGPRT gene mRNA levels. RESULTS: Treatment for 48 hr with 10 and 100 nM E1S significantly (P<0.05) increased ecNOS mRNA levels in LNCaP-FGC cells. Significantly higher (P<0.05) ecNOS mRNA levels also were found in LNCaP-FGC cells treated with E2 for 2-4 hr, irrespective of E2 concentration. The level of ecNOS mRNA was significantly lower (P<0.05) in untreated LNCaP-r than in LNCaP-FGC. LNCaP-r cells incubated with 100 nM E2 for 48 hr had a significantly higher (P<0.05) level of ecNOS mRNA than control LNCaP-r cells. CONCLUSIONS: The results indicate that ecNOS mRNA expression in LNCaP-FGC can be induced by E2, but also by its prehormone E1S, probably after conversion to E2. However, the different stimulation patterns observed for E2 and E1S in LNCaP-FGC and LNCaP-r cells also could indicate stimulatory as well as inhibitory effects of estrogens in this model system, and this could depend on time of exposure and the concentration of active estrogen.

Endothelium↗

PubMed2000

Cortisol axis abnormalities early after stroke--relationships to cytokines and leptin.

OBJECTIVE: To assess the relationships between circulating levels of proinflammatory cytokines and adrenocortical hormones and leptin early after stroke. DESIGN: Blood samples were collected four times daily the first two days after stroke, twice daily the next 4 days and four times at day 7. Cognitive function and functional outcome was measured at admittance and at day 7. SETTING: Consecutive inclusion of patients admitted to the stroke unit at Umeâ University Hospital. SUBJECTS: Eight men and 4 women with acute stroke and 10 healthy volunteers. MAIN OUTCOME MEASURES: Levels and diurnal variations of plasma proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), serum adrenocortical hormones (cortisol and DHEA) and leptin, and MMSE, SSS, and ADL scores. RESULTS: A significant correlation was present between IL-6 and cortisol levels the first two days after stroke (P < 0.05). In patients with a disturbed diurnal rhythm of cortisol, cortisol and leptin levels were increased (68% and 81% increase, respectively), whilst DHEA levels were unaltered. Half of the patients displayed an abnormal diurnal rhythmicity of leptin at the end of the week. Median TNF-alpha levels for the first two days after stroke also correlated to median leptin levels at the end of the week (P < 0.05). Median IL-6 levels correlated to severity of paresis on days 1 and 7 and to MMSE scores on day 7 (P < 0.05). CONCLUSIONS: Neuroendocrine disturbances are common and often profound early after stroke. Cytokines seem to be important modulators of these disturbances, including diurnal rhythmicity of cortisol and leptin.

Adrenocorticotropic Hormone↗

PubMed2000

Impact of hypoxaemia on neuroendocrine function and catecholamine secretion in chronic obstructive pulmonary disease (COPD). Effects of long-term oxygen treatment.

The aim of the study was to investigate the effects of chronic hypoxaemia on neuroendocrine function in hypoxaemic chronic obstructive pulmonary disease (COPD). The stress level was assessed by measurement of daytime plasma catecholamine and nocturnal urinary catecholamine levels and endocrine function was assessed by measuring serum gonadotropins, peripheral sex hormones and peripheral thyroid hormones, and by measuring thyroid stimulating hormone (TSH), prolactin and growth hormone before and after thyroid releasing hormone challenge in 12 male, stable, hypoxaemic COPD patients before and after at least 4 months of long-term oxygen treatment (LTOT). Mean pre-treatment PaO2 was 7.39 +/- 0.78 kPa and mean nocturnal arterial oxygen saturation (MSaO2) was 86.6 +/- 3.2%. Plasma norepinephrine (NE) levels were higher than normal, while all other pre-treatment hormone levels were within normal range. Low forced expiratory volume in 1 sec (FEV1) was associated with low basal and stimulated TSH (P < 0.01). Urinary NE excretion correlated positively to nocturnal time spent with SaO2<85% (P<0.05). In similarity with normal controls, positive correlations were found between sex hormone binding globulin and testosterone both before and after LTOT (P<0.01). No significant hormonal changes were noted following an average of 8 months of LTOT for the entire study group. However, in a subgroup (n = 6) with an increase in MSaO2 exceeding 7% points following LTOT, nocturnal excretion of NE and epinephrine were reduced by 30% (P<0.05) and S-free thyroxin by 20% (P<0.05). In conclusion, patients with chronic hypoxaemia secondary to COPD exhibit elevated plasma NE levels but otherwise normal endocrine levels, including a normal hypothalamic-pituitary testicular axis. The severity of airway obstruction is associated with reduced basal and stimulated TSH. The endocrine function is not significantly changed following LTOT except for a subgroup with severe nocturnal hypoxaemia, where elevated nocturnal NE excretion was noted, which was reduced only if whole night oxygenation was normalized during oxygen therapy.

Adult↗

PubMed2000

Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon) in patients with rheumatoid arthritis.

CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated podophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and increased serum levels of sex hormone-binding globulin (SHBG). Significant positive correlations were found between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-alpha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes decreased ACTH stimulation, resulting in a reduced adrenocortical steroid secretion. Accumulation of the drug in the adrenal cortex may also affect adrenal steroidogenesis. The elevated SHBG levels may be caused by a weak estrogenic activity of the drug.

Adrenocorticotropic Hormone↗

PubMed2000

Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions.

The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from women without fibroid disease. Women with menstrual periods were classified according to the phase of the cycle. In tissues from non-treated premenopausal women, IGF-I mRNA expression was significantly higher in fibroids than in myometrium, with no differences related to phase of the menstrual cycle. In post-menopausal women and in GnRH agonist-treated women responding to treatment, similar mRNA expression was seen in myometrium and fibroids but the concentrations were lower than in untreated premenopausal women. The IGF-I mRNA value in fibroids from pregnant women was higher than in any other group and myometrium from pregnant women exhibited higher mRNA expression than myometrium from non-treated premenopausal women. The IGF-I protein was more abundant in fibroids than in myometrium of non-treated premenopausal and of pregnant women and in both tissues the concentration was significantly higher in the group of pregnant women. The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women. High sex steroid concentrations in pregnant and non-pregnant women of fertile age seem to be associated with a higher expression of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the selective growth advantage of these tumours.

Adult↗

PubMed2000

Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy.

Metabolic-endocrine dysfunctions, including hyperinsulinemia, hypertriglyceridemia, increased fat mass, and dysregulation of the hypothalamic-pituitary-adrenal axis, are common in myotonic dystrophy (MD). We hypothesized that increased production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may be important underlying mechanisms. We studied the diurnal rhythmicity of cytokines and cortisol, ACTH, and dehydroepiandrosterone in 18 men with adult onset MD and 18 controls. Morning levels of androstenedione, 17-hydroxyprogesterone, testosterone, and insulin were also determined. Genetic analyses were performed, including calculation of allele sizes. Median circulating 24-h levels of IL-6 (P < 0.001), TNF-alpha (P = 0.05), ACTH (P < 0.05), and cortisol (P < 0.05) were all significantly increased in MD, whereas dehydroepiandrosterone levels were decreased (P < 0.001). The diurnal rhythms of these cytokines/ hormones were disturbed in patients. Morning testosterone levels were decreased and insulin levels increased (P < 0.01 for both). Patients with high body fat mass had significantly increased insulin levels and decreased morning levels of cortisol, ACTH, and testosterone. IL-6 and TNF-alpha levels are increased and adrenocortical hormone regulation is disturbed in MD. Adiposity may contribute to these disturbances, which may be of importance for decreased adrenal androgen hormone production and metabolic, muscular, and neuropsychiatric dysfunction in MD.

Adipose Tissue↗

PubMed2000

Bone mass and body composition of adult women with congenital virilizing 21-hydroxylase deficiency after glucocorticoid treatment since infancy.

AIM: To study bone mass, body composition and androgenic/anabolic activity in adult women with virilizing congenital adrenal hyperplasia (CAH) treated with glucocorticoids since infancy and to relate this to the postmenarcheal glucocorticoid impact. PATIENTS AND METHODS: Thirteen adult women with virilizing CAH treated with gluco- and mineralocorticoids but otherwise medicine-free were investigated with respect to bone mineral content, body composition by dual energy X-ray absorptiometry and endocrine status. In addition an index of accumulated postmenarcheal exogenous glucocorticoid impact was calculated. Seven of the patients had regular menstrual periods, and six were oligomenorrheic but responded with withdrawal bleedings on cyclic progestagens. The data for the patients were compared with those of age-matched healthy reference subjects. RESULTS: In spite of their shorter stature, CAH patients were significantly heavier and had a significantly higher body mass index and fat/lean body mass ratio than the controls. Their bone mineral area density (BMD) was significantly lower than that of the controls. Serum concentrations of androgens were subnormal in all except two of the patients. Strong negative associations were found between BMD and the calculated index of accumulated postmenarcheal glucocorticoid dose but not between BMD and circulating androgen levels. CONCLUSION: The results indicate that glucocorticoids were administered in excess in most of the patients, resulting in subnormal levels of adrenocortical androgens, increased body fat and bone demineralization. Increased catabolic activity due to hypercortisolism rather than decreased androgenic/anabolic steroids is probably the major cause of the subnormal BMD in the treated CAH patients.

Absorptiometry, Photon↗

PubMed2000

Prognostic significance of tissue prostate-specific antigen in endocrine-treated prostate carcinomas.

Fine-needle aspiration biopsy is a minimally invasive technique for obtaining sample material suitable not only for cytological grading but also for flow cytometry and for biochemical analyses. The prognostic value of tissue prostate-specific antigen (T-PSA) from fine-needle aspiration biopsies was compared with serum total and free prostate-specific antigen, the ratio of free:total serum prostate-specific antigen, tumor stage, cytological grade, and DNA ploidy in 179 patients with stage T2-T4 prostate cancer (CAP). The patients, who were free from bone metastases at the time of diagnosis, were treated by either orchidectomy or medical castration with GnRH analogues or high-dose parenteral depot estrogens. They were followed for at least for 71 months or until death, and the different variables were correlated to time to progression and time to death from CAP. Using Cox univariate analysis, T-PSA was shown to be the most important factor in predicting time to progression and time to death. When the patients were divided into three groups with respect to T-PSA, 56 of 60 (93%) of the patients with low T-PSA levels developed progressive disease, and 52 of 60 (87%) died of CAP. For patients with intermediate T-PSA levels, the corresponding figures were 9 of 60 (15%) and 6 of 60 (10%). None of the 59 patients with high T-PSA values developed progressive disease. Similar but less pronounced relationships were found between tumor progress and CAP-specific death on the one hand and clinical stage, cytological grade, and DNA ploidy on the other. In a Cox multivariate stepwise analysis, T-PSA was the only important factor for time to progression and death. This was also true for the subgroup of patients with stages T2 and T3 disease only. The study shows that T-PSA is superior to other hitherto routinely used markers for the prediction of outcome of hormone-treated patients with newly diagnosed CAP.

Aged↗

PubMed2000

Prognostic value of serial tissue prostate-specific antigen measurements during different hormonal treatments in prostate cancer patients.

To reveal the effects of different hormonal treatments directly on the prostate during treatment, the concentration of prostate-specific antigen in the tissue (T-PSA) was studied in 63 patients with untreated newly diagnosed carcinoma of the prostate (CaP). T-PSA measurements were performed in fine-needle aspiration biopsies at the time of diagnosis and 6, 12, and 24 months after initiation of treatment. Treatments modalities were bilateral orchidectomy, gonadotropin-releasing hormone (GnRH) agonists, or parenteral estrogens. Thirty-one (49%) of the patients died of CaP and 18 (29%) of other diseases. Fourteen of the patients (22%) were still alive at the end of the observation period (median follow-up time, 111.5 months; range, 98-128 months). In all of the 31 patients who died of CaP, T-PSA values increased during treatment. This increase was observed long before clinical signs of progression appeared (median of interval, 14 months). Twenty of these 31 patients showed an increase in T-PSA from pretreatment values at 6 months. At 12 months this increase was observed in 30 of 31 patients. In contrast, in all of the patients who responded to the hormonal regimen, T-PSA values decreased and remained low during treatment. Furthermore, the patients who did not die of CaP and received estrogen treatment had significantly higher T-PSA values compared with those who were treated with bilateral orchidectomy or GnRH agonists. This indicates that estrogens may stimulate PSA synthesis in tumor tissue in vivo in the presence of castration levels of testosterone. Statistical evaluation showed that the T-PSA ratio between month 12 and month 0 had the most significant prognostic value for predicting the clinical outcome. This ratio was superior to clinical classifications, e.g., tumor stage and cytological grade, and also was higher than T-PSA at the time of diagnosis. This study has shown that aspiration biopsy material can be used to reveal biochemical changes in the tissue during treatment and that one specific marker (T-PSA) can predict the clinical outcome of endocrine treatment of CaP patients better than previously used methods. We believe that selected tissue markers or the protein pattern can help us to characterize the tumors and predict the clinical outcome so an optimal treatment can be chosen for every patient.

Aged↗

PubMed1999

Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen.

BACKGROUND: The present pilot study tested the clinical performance of a new pharmacokinetically guided dosing regimen of parenteral estrogen in patients with advanced prostatic carcinoma. The aim was to accelerate endocrine effects and to avoid cardiovascular side effects. METHODS: Seventeen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (five doses), followed by a maintenance dose of 240 mg every month; and 16 patients were randomized to bilateral orchidectomy. The estrogen dosing was calculated by pharmacokinetic modelling to achieve a rapid increase in serum estradiol and thereby a fast decrease in testosterone. RESULTS: The predicted increment in serum estrogen was achieved, together with a subsequent decrease in testosterone in the PEP group. In addition, there were no signs of an increased cardiovascular morbidity. This was probably due to a minimal estrogenic influence on the liver and was reflected by unchanged levels of coagulation factor VII. Clinical effects, during the first 2 years of treatment, were similar in the two treatment arms, with 12 patients in the orchidectomy group and 14 patients in the PEP group responding to treatment. CONCLUSIONS: The present parenteral regimen is an efficient and time-saving estrogen regimen with a favorable side-effect profile. PEP seems to offer a potential for revival of the most cost-effective endocrine treatment of cancer of the prostate, i.e., estrogen.

Aged↗

PubMed1999

In vitro evaluation of aromatase enzyme in granulosa cells using a [11C]vorozole binding assay.

An in vitro method for measuring aromatase cytochrome P450 enzyme (P450AROM) in human granulosa cells (GC) has been developed, based on binding of the 11C-labeled aromatase inhibitor vorozole. GC were obtained following superstimulation during in vitro fertilisation. The method revealed a binding affinity (Kd) of 0.4 nM and a maximum binding (Bmax) at 11 fmol/4000 cells which is equal to 1.6 million binding sites per cell. Linear Scatchard plots indicated a single type of binding site. P450AROM concentrations measured by [11C]vorozole binding correlated positively with aromatisation of [1beta-3H]androst-4-ene-3,17-dione measured as [3H]water release, and a positive association was also found with the ovarian in vivo response to follicle-stimulating hormone (FSH) stimulation expressed as 1000 times the ratio of the number of oocytes recovered from a patient and the total dose of recombinant FSH administered. Frozen cells could be used for P450AROM quantitation, provided the correct freezing procedure was used. Quantitation of P450AROM, based on binding of [11C]vorozole is an accurate and sensitive in vitro method, which might be extended to the measurement of aromatase expression by a noninvasive technique in the intact ovary in vivo using positron emission tomography.

Aromatase↗

PubMed1999

Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP).

We studied the effects of chronic nocturnal hypoxaemia due to obstructive sleep apnoea syndrome (OSAS) on the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-testicular axes and on catecholamine and cortisol secretion. We investigated whether hormones other than catecholamines may serve as markers for chronic hypoxic stress and the possible effects of nasal continuous positive airway pressure (nCPAP) treatment on endocrine status. Nocturnal oximetry was performed in 16 male patients with OSAS diagnosed by polysomnography, immediately before nCPAP treatment and in 11 of the patients the oximetry was repeated after 7 months of nCPAP therapy. Plasma and urinary catecholamines, luteinizing hormone (LH) testosterone, cortisol, thyroid stimulating hormone (TSH), prolactin (PRL), and the response of TSH and PRL to a thyroid releasing hormone (TRH) challenge test were measured immediately before and after 7 months of nCPAP treatment. Subnormal LH and TSH and elevated serum cortisol as well as increased nocturnal urinary norepinephrine levels were found in patients prior to treatment; otherwise endocrine values were normal. There was a significant correlation between low pretreatment nocturnal arterial oxygen saturation and high plasma and urinary norepinephrine levels. The nCPAP treatment caused significant reduction in serum prolactin and TSH, and significant reduction in plasma epinephrine and urinary norepinephrine. The reduction in serum TSH and urinary norepinephrine was most pronounced in the subjects with the worst pretreatment nocturnal hypoxaemia. No other significant changes were found in basal hormone levels. The response to TRH challenge was normal before and after treatment and was not influenced by CPAP therapy. OSAS is associated with elevated catecholamine and cortisol and decreased TSH and LH levels but a normal response to TRH challenge and a normal androgen status. Apart from catecholamines, none of the hormones studied is likely to serve as a specific marker for chronic hypoxic stress.

Adult↗

PubMed1999

Tissue PSA is the best predicting variable for the outcome of endocrine treatment of prostatic carcinoma.

In order to evaluate the prognostic value of tissue-PSA (prostatic-specific protein, measured in aspiration biopsies) 231 hormonally treated patients with verified carcinoma of the prostate (CaP) but without metastasis were studied retrospectively. T-PSA was determined at the time of diagnosis in all patients and in 52 of these also at 6, 12 and 24 months after diagnosis. Of the 231 patients, 79 died of prostatic carcinoma and 152 were still alive or had died of other diseases at the end of the observation period (more than 71 months). In a first set of evaluations the predictive value of a single analysis at the time of diagnosis was studied in 179 patients. It was found that tissue PSA was the most important factor for predicting both time to progression and time to death in CaP. Other competing factors were S-PSA, free S-PSA, age, clinical stage, grade and DNA-ploidy. Further evaluations regarding serial PSA determinations were performed in 52 patients. Tissue PSA increased during treatment in all patients who died of CaP. In all patients who survived or died for other reasons, tissue PSA decreased during treatment and remained low. The change of tissue PSA seen between 0, 6 and 12 months could in all cases predict the clinical outcome. It is concluded that a single analysis of tissue PSA at the time of diagnosis can predict the clinical outcome in most cases and that serial determinations can predict the outcome in almost all cases of a CaP without metastasis at the time of diagnosis. This requires that we use this assay when selecting between patients who will survive on hormonal treatment and those who most probably would benefit from a more aggressive treatment.

Aged↗

PubMed1999

Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization.

Increased androgen concentrations are thought to be detrimental to oocyte quality and reproductive potential. Adjuvant treatment with glucocorticoids has been tried to suppress androgens in women undergoing infertility treatment. In the present study 20 infertile women with polycystic ovary syndrome were prospectively randomized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night, during standard in-vitro fertilization (IVF) treatment. Serum samples for assays of gonadotrophins, steroids and sex hormone-binding globulin (SHBG) were collected before treatment, at down-regulation, and at oocyte retrieval. Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes, the rest according to the clinic's routines. In the placebo group, serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S) did not change between down-regulation and oocyte retrieval, whereas adjuvant prednisolone resulted in a significant decrease. In follicular fluid, adjuvant prednisolone resulted in significantly lower concentrations of DHEA-S as compared to placebo, no other significant differences were found. No significant differences were found in embryo characteristics or pregnancy rates between the groups.

Adult↗

PubMed1999

Is carbohydrate metabolism altered among women who have undergone a preeclamptic pregnancy?

OBJECTIVE: To compare women after a preeclamptic pregnancy with women after a normal pregnancy with respect to androgenic-anabolic status and carbohydrate and lipid profiles. METHOD: Twenty-one patients and 22 controls were followed up to 26-119 weeks after delivery. Blood was sampled for analyses of insulin, glucose, insulin growth factor-1, lipids, androgens, sex hormone-binding globulin (SHBG) and uric acid. Anthropometric data and blood pressure were recorded. Data are presented as median and ranges (within parentheses) or mean +/- SEM where appropriate. Comparisons were made by unpaired t test or Mann-Whitney U test, respectively. RESULTS: Significantly higher values were found in the preeclampsia than in the control group for fasting insulin, fasting glucose, fasting insulin resistance index (FIRI, fasting glucose x fasting insulin/25), serum triglycerides, uric acid and blood pressure. There were no differences in androgen status and IGF-1 levels. CONCLUSION: Patients with a recent history of preeclampsia demonstrate signs of relative insulin resistance, hypertriglyceridemia and hyperuricemia as well as increased blood pressure as compared with women who had a normal pregnancy. However, in contrast to other women with insulin resistance, they have a normal androgen status.

Adult↗

PubMed1999

Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with the polycystic ovary syndrome.

The influence of weight reduction and female sex hormones on the regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 20 obese hyperandrogenic women with polycystic ovary syndrome (PCOS). Nine PCOS women were reinvestigated after 8-12 weeks of weight reduction therapy (WR) with a very low calorie diet, inducing a mean loss of 8 +/- 3 kg, and 8 PCOS women were reinvestigated after 12 weeks of treatment with combined oral contraceptives (OC), containing ethinyl estradiol and norethisterone; the remaining 3 subjects were drop-outs. Both WR and OC normalized hyperandrogenicity. WR caused a 50% reduction of basal lipolysis rate and a 5- to 7-fold increased noradrenaline and terbutaline sensitivity (P < 0.02); the latter could be ascribed to a 2-fold increased beta2-adrenoceptor density (P < 0.02) as determined with radioligand binding. There was no change with regard to dobutamine (beta1-adrenoceptor sensitivity) or clonidine, (alpha2-adrenoceptor sensitivity) or to beta1-adrenoceptor density. OC treatment did not influence the basal lipolysis rate or beta2- or alpha2-adrenoceptor sensitivity, but lowered the beta1-adrenoceptor sensitivity 7-fold (P < 0.03) without a reduction in beta1-adrenoceptor density. The OC treatment effect was not observed when forskolin and dibutyryl cAMP, acting on adenylate cyclase or protein kinase A, respectively, were used, suggesting a partial uncoupling of beta1-adrenoceptors. WR therapy, but not OC therapy, caused, in addition to changes in lipolysis function, improved in vivo insulin sensitivity and lower plasma noradrenaline levels. These findings suggest that factors other than hyperandrogenicity modulate lipolysis regulation in obese subjects with PCOS. Disturbances in sympathetic pathways could be of pathogenic importance.

Adipocytes↗