The median electrophoretic mobility of FSH in serum (S-FSH) was determined in 14 girls, aged 9-14 yr, with Turner's syndrome before and after iv administration of GnRH. The basal S-FSH level varied almost 100-fold between patients. Less negatively charged forms of FSH appeared in serum in all patients after GnRH stimulation. The aim of the study was to determine if the change in electrophoretic mobility of S-FSH after GnRH treatment was related to the basal S-FSH level, the absolute or relative increase in the S-FSH level after GnRH, or the electrophoretic mobility of S-FSH present in the basal state. A highly significant (r = 0.94; P less than 0.001) correlation was found between the relative increase in S-FSH 60 min after GnRH treatment and the decrease in electrophoretic mobility. A selective survival of different forms of FSH in the circulation is proposed as the most likely explanation for the appearance in serum of the less negatively charged forms of FSH after GnRH stimulation.

Serum concentrations of calcium, magnesium, potassium and phosphate can be lowered experimentally by adrenaline, which also can stimulate the secretion of parathyroid hormone (PTH). In order to evaluate the possible clinical importance of these mechanisms serial blood samples were drawn during the first three hospital days in 26 patients with acute myocardial infarction (AMI), a condition known to increase plasma catecholamine levels. During the study period there were no consistent significant changes of the serum electrolytes. The serum PTH levels, however, were significantly raised in the AMI patients already on admission and did not normalize during the observation time. The PTH concentrations were unexplained by infarct size, concomitant diseases or medication. These findings suggest that PTH could be an independent risk factor for AMI.

Infusions with stepwise increasing concentrations of epinephrine (from 2.5 to 10 micrograms/min) and norepinephrine (0.5-2.0 micrograms/min) were given to normal subjects. During infusion of epinephrine there was a clear rise of the serum parathyroid hormone (PTH) levels already at the lowest concentration. Concomitantly there was a fall in the serum concentrations of calcium. The PTH levels returned to baseline promptly after termination of infusion whereas hypocalcaemia persisted up to 30 minutes, indicating a primary response of PTH to epinephrine. When propranolol was given prior to and during the epinephrine infusion no significant changes occurred for either PTH or calcium. During infusion of norepinephrine no consistent significant changes were noted for either PTH or serum calcium. Thus, our data do not support any concept of a basal adrenergic tone which normally modulates the secretion of PTH. However, during conditions of stress the beta-adrenergic stimulation night be of importance.

Serum ferritin was measured in two groups of alcoholics; one comprised 71 individuals on ambulatory control and with varying current alcohol intake and the other 19 alcoholics followed with serial determinations during two weeks of abstinence Serum ferritin was elevated in 26 subjects in the larger group, and 22 of them had elevated ASAT and ALAT values. Low-grade but significant correlations were found between serum levels of ferritin and serum concentrations of some variables used to detect liver affection (ASAT, ALAT, bilirubin and gamma-GT). Serum ferritin and ASAT declined in a parallel fashion in the 19 patients studied longitudinally, so that the ferritin:ASAT ratio described a straight line. No correlation was found between serum ferritin or the serum ferritin:ASAT ratio and serum iron. Neither was any correlation observed between the magnitude of the changes in serum ferritin and the changes in serum iron, serum transferrin or circulating platelets or reticulocytes observed in the serially followed alcoholics. These data indicate that elevated serum ferritin in alcoholics is associated with the degree of liver affection and not with the degree of erythropoietic activity.

Several previous observations from animal and in-vitro studies indicate that both the acute and chronic ingestion of ethanol could affect calcium regulation but little data is available concerning the effects of ethanol in man. Twelve healthy male subjects drank 0.8 g ethanol/kg body weight in the form of whisky so that the serum ethanol concentrations reached an average of 17.4 +/- 2.5 (SD) mmol/l. At this time there were no significant differences for the serum concentrations of parathyroid hormone, calcium or phosphate. Thus, it appears that there is little acute effect on calcium homeostasis in man of a moderate rise of serum ethanol levels.

Aims. We investigated the association between preoperative serum levels of follicle stimulating hormone (FSH) and the prognosis in women with invasive breast cancer.Methods. Serum levels of FSH were measured in 182 premenopausal and 581 peri- or postmenopausal women with invasive breast cancer. They were followed for a mean time of 84 months. The study endpoint was death from breast cancer (182 events). Analyses were stratified on menopausal status.Results. None of the stimates showed a statistically significant result. In both pre- and postmenopausal women there was a nominally higher probability of survival with a higher FSH level. Point estimates in multivariate analysis incorporating age, tumour diameter, axillary lymph status, estrogen and progesteron receptor content and year of treatment indicated a stronger association with FSH levels in premenopausal than postmenopausal women (relative hazard 0.63 or 0.85, respectively in the highest compared with the lowest quartile).Conclusion. We did not find any statistically significant association between preoperative serum level of FSH and prognosis. Today, FSH is not a clinical target for intervention or a clinically useful prognostic factor and the results of clinical studies up to date can only be used for motivation of further experimental laboratory research. (C) 2004 Elsevier Ltd. All rights reserved.

OBJECTIVES:To evaluate the possible effect of androgen status on sexuality and mental wellbeing in patients with primary Sjögren's syndrome (pSS). METHODS:Serum levels of dehydroepiandrosterone sulphate (DHEA-S), testosterone (T), androstenedione, sex hormone binding globulin (SHBG), and the SHBG/T ratio were measured in 21 women with pSS. Sexual life was assessed by a Swedish version of the McCoy scale, which covers sexual experience and responsiveness during the past 30 days. A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine quality of life and psychological symptoms in patients with pSS. RESULTS:Positive correlations were found between DHEA-S serum levels and the total McCoy score (r(s)=0.62; p<0.01), as well as the subscales of this score reflecting arousal (0.59; p<0.05), desire (r(s)=0.52; p<0.05), and satisfaction (r(s)=0.66; p<0.01). Serum DHEA-S concentrations were also related to the total PGWB score (r(s)=0.60; p<0.01) and subscales of this score: depression (r(s)=0.62; p<0.01), wellbeing (r(s)=0.64; p<0.01), general health (r(s)=0.67; p<0.01), and self control (r(s)=0.67; p<0.01). Total McCoy and PGWB scores and their subscales were not related to the serum levels of testosterone and androstenedione or the T/SHBG ratio. CONCLUSIONS:Circulating levels of the weak androgen DHEA-S are positively related to the quality of sexual life and mental wellbeing in women with pSS.

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.

A remarkable 80-fold difference in median growth hormone (GH) values in young adult men and women was recently found in a study of sera taken in ambulatory state in the morning, after overnight fasting. In this study, the effect of ageing on morning ambulatory GH levels was investigated in 254 apparently healthy men, 21-75 years of age, and 40 women, 21-85 years. Furthermore, the effect of oestradiol on morning GH values was studied in 19 postmenopausal women, 51-79 years, treated with subcutaneous implants of 17beta-oestradiol (E2). The sera were analysed for GH, sex hormone-binding globulin (SHBG), E2, and in the men, also for testosterone (T). The morning GH levels increased (p<0.0001) with age in a group of 195 men of 41-75 years. After adjustment for age, an inverse correlation (p <0.05) was found between the levels of GH and free androgen index (T/SHBG) and a direct correlation between GH and SHBG. These relationships were more pronounced before the age of 60 than after. In the women, the GH levels decreased (p<0.01) with age and the gender difference of median values was reduced from 102-fold at younger age, 21-39 years, to 12-fold in elderly individuals, 60-75 years. In the E2-treated postmenopausal women, the morning GH values were similar to those of an untreated control group, indicating that the decrease with age in the morning GH levels in women is not a result of lower oestrogen levels alone. The gender difference in median ambulatory morning GH values decreased from 102-fold at a mean age of 25 years to 12-fold at a mean age of 68 years owing to opposite changes with age in men and women: an increase in men and a decrease in women.

Serum erythropoietin levels (s-[epo]), haemoglobin concentration ([Hb]), haematocrit (hct), and ferritin concentration ([fer]) were measured in seven healthy male volunteers (20-23 years) exposed continuously to hypoxia (PO(2) 14 kPa) for 10 days. Serum erythropoietin concentration increased significantly from 9.5 +/- 3.51 to 33.6 +/- 11.64 U L(-1) (P < 0.05) after 2 days of hypoxia. Thereafter, s-[epo] decreased. However, after 10 days s-[epo] was 18.7 +/- 5.83 U L(-1) which was still increased above the pre-hypoxia level (P < 0.05). Serum haemoglobin concentration and hct increased over the 10 days of hypoxia, [Hb] from 152 +/- 8.9 to 168 +/- 9.2 gL(-1) (P < 0.001), and hct from 43 +/- 2.4 to 49 +/- 2.6% (P < 0.001). Ferritin concentration decreased significantly during the hypoxic exposure from 82 +/- 46.9 to 44 +/- 31.7 mmol L(-1) after 10 days (P < 0.01). In conclusion, the initial increase of s-[epo] under controlled normobaric hypoxia was marked, 353%, and levelled off after 5-10 days at 62-97% above normoxia level. There was also a significant increase in [Hb] and hct and a decrease in [fer] after 10 days of exposure to normobaric hypoxia.

Fifteen healthy males, aged 20-30 years, participated in a double-blind cross-over study on the effect of the beta-2 stimulator salbutamol on erythropoietin concentration and hemoglobin concentration. The treatment period comprised inhalation of salbutamol, 0.8 mg four times daily for 2 weeks. Serum-erythropoietin was essentially unaltered after treatment with salbutamol, 9.5 +/- 4.94 IU. l-1 (mean +/- SD), as compared to both control situation, 9.2 +/- 4.50 IU. l-1(mean +/- SD), and placebo treatment (9.7 +/- 4.07 IU. l-1) (mean+/-SD). The same pattern, no significant changes between control situation and treatment with salbutamol or placebo, also applied to hemoglobin concentration. In conclusion, it is not possible to increase erythropoietin concentration, and thereby erythropoiesis, by inhalation of high doses of the International Olympic Committee (IOC)-approved beta-2 stimulator salbutamol for 2 weeks in healthy young males.

The ordinary doping control urine samples of 36 anonymous participants (cross‐country skiers, biathlon athletes, and curling athletes) of the 1998 Nagano Olympic Games were analyzed for erythropoietin and erythropoietin isoforms. The urine erythropoietin concentration (IU/l) was determined with a competitive radioimmunoassay method and the isoforms were studied by electrophoresis and given as milli albumin mobility units (mAMU). Erythropoietin was detectable in 23 out of 36 specimens (64%). The biathlon and curling athletes had similar urine concentration of erythropoietin. The group of 16 cross‐country skiers had significantly (P < 0.05) increased urine concentration of erythropoietin as compared to curling athletes and four of them had urine erythropoietin concentrations between 3.6 and 5.1 IU/l. The electrophoretic mobility of erythropoietin was determined in all eight samples with urine concentration of erythropoietin of more than 2 (range 2.1–5.1) IU/l. No single urine specimen with a median erythropoietin electrophoretic mobility below the cut‐off level of 670 mAMU (indicative of doping with recombinant erythropoietin) was registered. Erythropoietin in urine was detected in 71% and the isoforms of Epo characterized in 29% of the anonymous Olympic endurance athletes. The urine concentration of erythropoietin in the biathlon and curling athletes were similar to those of non‐athletes. The group of cross‐country skiers had higher levels of erythropoietin in urine. These higher levels of urine erythropoietin in cross‐country skiers are partly due to more concentrated urine specimens.

Aims There are clinical observations that operation during the luteal phase of the menstrual cycle (with high oestradiol levels) may positively influence prognosis in breast cancer. However, few studies have information on plasma levels of hormones pre-operatively. Methods We studied 774 women treated for breast cancer where plasma levels of oestradiol had been measured 1–2 days pre-operatively. Date and cause of death were ascertained from the files of the Swedish Cancer Register and 5434 person-years were observed. The endpoint was death with breast cancer as the underlying cause (n=41 and n=158 in the pre- and post-menopausal group, respectively). Results In life-table analyses, only pre-menopausal patients with oestradiol 500 pmol/l and above had a tendency (not statistically significant) for better survival. Multivariate Cox models with oestradiol modelled in continuous form yielded relative hazards (RH) close to unity in all women and in strata according to menopausal status. Conclusions When oestradiol was analysed in categorized form, only women with the highest levels had a tendency for improved prognosis (RH around 0.7; not statistically significant). Moreover, this pattern was not apparent for pre-menopausal women. Our findings contradict the notion that the pre-operative oestradiol level is independently associated with breast cancer prognosis.

OBJECTIVE:To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN:Combined cross-sectional and prospective study. SETTING:ICU in a university hospital. PATIENTS:Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION:Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

OBJECTIVE:Effects of short-term administration of growth hormone (GH) with respect to gender and oral contraceptives (OCs) were investigated in healthy young adults.DESIGN:Open, prospective 2-week study.SETTING:Clinical research centre, university hospital.SUBJECTS:Three groups of healthy young adults were included: six men, six women with normal menstrual cycles, and six women taking OCs.INTERVENTIONS:The subjects were given recombinant human GH subcutaneously for 2 weeks: 1 U m-2 body surface daily during the first week, and 3 U m-2 daily during the second week.MAIN OUTCOME MEASURES:Serum samples were drawn in the morning after overnight fasting on days 0, 3, 7, 10 and 14, and were analysed for GH, insulin-like growth factor 1 (IGF-1), insulin, testosterone, sex hormone-binding globulin (SHBG), lipids and markers of bone metabolism. Second-void morning urine was analysed for deoxypyridinoline (Dpyr).RESULTS:During administration of GH, serum IGF-1 increased in the men and in the women without OCs (86 and 52%, respectively). In the OC women, IGF-1 did not change significantly. Serum insulin increased in all three groups, with the largest change (122%) in the men and the smallest (47%) in the OC women. Blood glucose was unchanged. Total cholesterol, low-density lipoprotein (LDL) cholesterol and the LDL/high-density lipoprotein cholesterol ratio were reduced in the men only. Biochemical markers of bone resorption (serum procollagen type I, urinary Dpyr) increased in the men, and markers of bone formation (serum osteocalcin and telopeptide of collagen type I) increased in the men as well as in the women not taking OCs. The testosterone/SHBG ratio increased in the men on account of a reduction in SHBG.CONCLUSION:The response to short-term administration of GH differed in the three groups, with the largest effect in the men and the smallest in the OC women. The inhibitory influence of contraceptives underlines the role of sex steroids in modulating the susceptibility to GH.

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.

The prevalence of polycystic ovaries, according to ultrasonography, and associated clinical, endocrine, and metabolic features were investigated in women with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5 yr before the investigation and 36 controls with uncomplicated pregnancies, selected for similar age, parity, and date of delivery, were investigated. The women with previous GDM showed a higher prevalence of polycystic ovaries [14 of 34 (41%) vs. 1 of 36 (3%); P < 0.0001], hirsutism (P < 0.01), irregular menstrual cycles (P < 0.01), and a higher body mass index (BMI; P < 0.001) than the controls. Five women (15%) with previous GDM had developed manifest diabetes (excluded in comparisons of metabolic variables). After dividing the women with previous GDM into subgroups according to ovarian appearance, the 2 subgroups showed similar glucose tolerance and prevalence of diabetes, whereas the women with polycystic ovaries were younger (mean +/- SD, 33.3 +/- 1.4 vs. 38.2 +/- 1.1; P < 0.01), had higher truncal-abdominal/femoral fat ratio according to skin folds (P < 0.05), had higher concentrations of androstenedione (P < 0.01) and testosterone (P < 0.01), and had a higher LH/FSH ratio (P < 0.01), lower levels of GH (P < 0.01), higher levels of triglycerides (P < 0.05) and cholesterol (P < 0.05) in very low density lipoprotein, all independent of age and BMI, and had a higher prevalence of pregnancy-induced hypertension (50% vs. 15%; P < 0.05) during the index pregnancy compared with the women with normal ovaries. The group of women with GDM showed a lower early insulin release after glucose (i.v. glucose tolerance test) for their degree of insulin resistance (euglycemic hyperinsulinemic clamp) compared with controls (P < 0.05). In the two subgroups, insulin sensitivity was lower in the polycystic ovaries group, independent of BMI (P < 0.05), than in the group with normal ovaries. In conclusion, ultrasonographic, clinical and endocrine signs of polycystic ovary syndrome were much increased in women with a history of GDM. Compared with the women with normal ovaries and previous GDM, those with polycystic ovaries formed a distinct subgroup that may be more prone to develop various features of the insulin resistance syndrome. Both groups showed a similarly disturbed balance between beta-cell activity and insulin sensitivity, but in women with polycystic ovaries, insulin resistance may be the dominant component.

Characteristics probably associated with the fetal hormonal milieu have recently been shown to increase (birth size indicators, prematurity, neonatal jaundice) or decrease (pregnancy toxaemia) breast cancer risk in the female offspring. However, it is unknown whether differences in pregnancy hormone levels may contribute to the marked geographical variation in breast cancer incidence. We have compared, in a highly standardized manner, pregnancy hormone levels in a population with high incidence and one with low incidence of breast cancer. Three hundred and four pregnant Caucasian women in Boston and 334 pregnant Chinese women in Shanghai were enrolled from March 1994 to October 1995. Levels of oestradiol, oestriol, prolactin, progesterone, human growth hormone, albumin and sex hormone-binding globulin were measured in maternal blood at weeks 16 and 27 of gestation and compared between the two study sites using non-parametric Wilcoxon's rank-sum test. Demographical, anthropometrical and pregnancy characteristics were ascertained through interview, and relevant variables concerning delivery and the newborn were abstracted from medical records and paediatric charts. During the first visit, median serum levels of all studied hormones were statistically significant, and in most instances substantially, higher among Chinese women, who have a low incidence of breast cancer, compared with American women, who have a high incidence of breast cancer. An analogous pattern was evident during the second visit, although the relative differences tended to be smaller. Further research is needed to identify lifestyle or other exogenous determinants of pregnancy hormone levels, as well as possible mechanisms by which they may influence carcinogenic processes in the breast and possibly other organs.

Effects on erythropoiesis and blood pressure as well as physical performance and mental effects were studied in 15 healthy subjects during intermittent exposure to normobaric hypoxia corresponding to either 2000 m (6 persons) or 2700 m (9 persons) above sea level; another group (5 persons) also served as controls at normoxia. The concept “live hightrain low” was used for 10 d consecutively and the exposure to hypoxia was 12 h/d. Blood pO2 and oxygen saturation were significantly decreased during the 10 d at hypoxia. [Hb] and Hct decreased significantly after 2 d in hypoxia and then returned to pre‐study levels. Erythropoietin was significantly elevated in both hypoxia groups during the initial 3–5 d. Reticulocytes were significantly increased during 7 d of hypoxia. Submaximal and maximal oxygen uptake, blood pressure at rest and during exercise and the profile of mood states (POMS test) did not change during the study. In conclusion, intermittent normobaric hypoxia for 10 d resulted in a significant stimulation of erythropoiesis. Staying at normobaric hypoxia may serve as a complement to an ordinary altitude level sojourn.