bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post‐menopausal ages
Authors: Evans S. F. , Davie M. W. J. 
Published: November 2003

OBJECTIVES We wished to appraise the effectiveness of hormone replacement therapy (HRT) in early (<67 years) and late (>67 years) post‐menopausal women referred to a metabolic outpatient clinic for assessment of their bone status. Because older women often experience side‐effects with conventional HRT, a low dose preparation (Estraderm 25) was also compared with conventional HRT (Estraderm 50).DESIGN AND SETTING Since all patients were symptomatic, the investigation was open and not placebo controlled. Patients were offered HRT and told about the two dosages. If they wished to use HRT, allocation of dosage was made randomly unless there were reasons to use a specific dose.PATIENTS One hundred and ninety‐six women were studied over 1 or 2 years with 80 reaching 3 years of treatment. Patients were divided into those under 67 years and those over 67 years at the start of treatment. Each group was further divided into those taking Estraderm 25 and those taking Estraderm 50 with norethisterone if appropriate.MEASUREMENTS Bone mineral density (BMD) was measured (DXA, Hologic) at the lumbar spine and femoral neck at 0 year (196 patients), at 1 year (169 patients), at 2 years (139 patients) and at 3 years (80 patients). Patients losing bone were expressed as those whose 3 year BMD was lower than initial or as those whose BMD at 3 years had fallen by more than twice the coefficient of variation for that site (non‐responders).RESULTS In lumbar spine, BMD increased maximally in the first year in all groups and the gain was maintained after 3 years. The change was similar whether patients were divided by age or dosage. For those on Estraderm 25, mean change after 3 years was 8.1 ± 6.8% and on Estraderm 50, 9.0 ± 8.3% (combined 8.7 ± 7.8%). Only 3.9% of patients were non‐responders at the lumbar spine after 3 years. At femoral neck, changes were significant at 3 years only in the Estraderm 25 >67 years and Estraderm 50 <67 years groups and averaged 2.3 ± 5.4% for all patients. At the femoral neck, 10.4% of patients were non‐responders after 3 years. Percentage change of BMD over 3 years at lumbar spine correlated with that at the femoral neck (r = 0.56). Percentage change of BMD at lumbar spine over 3 years correlated with menopausal age (r = 0.295). No relation was found between dosage of Estraderm/kg body weight and response of BMD at either site.CONCLUSIONS Transdermal oestrogen is effective at preventing bone loss in the spine at all post‐menopausal ages and is capable of doing this in low dosage. Prevention of bone loss at the femoral neck is less certain and the average change in BMD over 3 years was significantly lower (P < 0.001) than in the lumbar spine. Use of Estraderm 50 is not associated with a greater response of bone mass and there was no evidence of an increasing BMD response as oestradiol dosage/kg body weight increased.
Oropharyngeal regulation of water balance in polydipsic schizophrenics
Authors: Goldman Morris B. , Robertson Gary L. , Hedeker Donald 
Published: November 2003

OBJECTIVE Disordered water balance causes substantial morbidity in a subset of schizophrenics and is the consequence of unexplained defects in the regulation of fluid intake and antidiuretic function. We aimed to determine whether oropharyngeal regulation of water balance is altered in these patients.DESIGN A 2‐hour infusion of 3% saline, followed 35 minute later by an oral water load (10 ml/kg over 3 minutes).PATIENTS Age and sex‐matched polydipsic schizophrenics with (n = 5) and without (n = 8) hyponatraemia; non‐polydipsic schizophrenics (n = 6); and normal controls (n = 13).MEASUREMENTS Plasma osmolality, sodium, AVP, and reported desire for water (expressed in cups), determined prior to, and for 30 minutes following, the water load.RESULTS Plasma osmolality and sodium were consistently lower in the hyponatraemics (P<0.01). Significant changes did not occur until 20 and 25 minutes, respectively, after oral water loading, and were similar across the four groups. AVP levels were consistently lower in the two polydipsic groups (P<0.001), fell within 5 minutes after drinking and then levelled off. Neither the acute fall nor the overall pattern of the responses differed across groups. Subjective desire for water also decreased within 5 minutes of drinking, and also to a similar extent, in the four groups. Subsequent levels remained suppressed in the non‐polydipsic groups, but rebounded toward baseline in the two polydipsic groups. Thus the overall patterns differed (P<0.05). At the end of the study, ad lib intake correlated significantly with reported desire for water (r = 0.51, P<0.002).CONCLUSIONS The oropharyngeal regulation of water intake is disrupted in polydipsic schizophrenics with and without hyponatraemia. In contrast, the oropharyngeal regulation of AVP secretion appears preserved in the hyponatraemic subset. Previously observed elevations in plasma AVP in this subset are thus unlikely to be related to defects in oropharyngeal regulation.
Medroxyprogesterone acetate enhances the spinal bone mineral density response to oestrogen in late post‐menopausal women
Authors: Grey Andrew , Cundy Tim , Evans Margaret , Reid Ian 
Published: November 2003

OBJECTIVES The relative contributions of administered oestrogen and progestin to protection of the post‐menopausal skeleton remain unclear. We have compared the effect on spinal bone mineral density of continuous combined oestrogen/medroxyprogesterone therapy with that of unopposed oestrogen in late post‐menopausal women.DESIGN Observational study.SUBJECTS Seventy‐three osteoporotic post‐menopausal women attending the Auckland Hospital Bone Clinic. Twenty‐three hysterectomized women were treated with unopposed oestrogen (0.625 mg oral conjugated oestrogens daily), and 50 non‐hysterectomized women were treated with continuous combined oestrogen/medroxyprogesterone therapy (5 mg medroxyprogesterone acetate and 0.625 mg oral conjugated oestrogens daily).MEASUREMENTS Baseline and one‐year measurements of lumbar spine bone mineral density were performed using dual‐energy X‐ray absorptiometry.RESULTS After one year of therapy, spinal bone mineral density increased by 6.6% (95% confidence interval 5.6–7.6, P < 0.001 vs baseline) in the combined oestrogen/medroxyprogesterone therapy group, compared to 4.0% (CI 2.4–5.7, P < 0.001 vs baseline) in the unopposed oestrogen group (difference between means 2.6% (CI 0.8–4.4, P < 0.01).CONCLUSION In osteoporotic post‐menopausal women, one year of continuous combined oestrogen/medroxyprogesterone therapy is associated with a 65% greater increment in spinal bone mineral density than is observed in response to unopposed oestrogen. The prescription of combined oestrogen/progestin therapy should be considered in osteoporotic post‐menopausal women who have undergone hysterectomy, in order to maximize the skeletal protection provided by hormone replacement therapy.
Circulating levels of growth hormone, insulin‐like growth factor‐I and growth hormone binding protein in normal women of advanced reproductive age
Authors: Klein Nancy A. , Battaglia David E. , Miller Paul B. , Soules Michael R. 
Published: November 2003

OBJECTIVE Women experience an age‐related decline in fertility despite regular ovulatory cycles and normal production of ovarian steroids. Growth hormone and IGF‐I are both reported to decline with age, and there is evidence that both hormones promote intraovarian actions of gonadotrophins. The purpose of this study was to characterize circulating levels of GH and IGF‐I in normal, older reproductive age women with ovulatory cycles.DESIGN Prospective, controlled.PATIENTS Twenty‐eight regularly cycling older (n = 16) and younger (n = 12) women were recruited for daily blood sampling throughout a menstrual cycle.MEASUREMENTS Serum obtained from daily blood sampling was analysed for LH, FSH, oestradiol (E2) and progesterone (P). Serum obtained from frequent sampling during the admission was analysed for pulsatile GH secretion. IGF‐I and GH binding protein (GHBP) were also measured in subsets of the two age groups.RESULTS All subjects exhibited normal patterns of LH, FSH, E2 and P consistent with ovulatory cycles. There were no differences between the two age groups in integrated 24‐hour GH secretion or in GH pulse amplitude or frequency. There were no differences in GH secretion between the early follicular and midluteal phases when data were combined for the two subject groups. Plasma concentrations of IGF‐I were significantly lower throughout the cycle in the older women. There were no significant differences in levels of GHBP across the cycle or between the two age groups.CONCLUSIONS IGF‐I decreases with age in women without identifiable changes in the amount or pattern of GH secretion or in circulating GHBP concentrations. Decreased IGF‐I production may be related to decreased ovarian gonadotrophin sensitivity in older reproductive age women.
Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries
Authors: Robinson S. , Henderson A. D. , Gelding S. V. , Kiddy D. , Niththyananthan R. , Bush A. , Richmond W. , Johnston D. G. , Franks S. 
Published: November 2003

OBJECTIVE Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history.DESIGN A cross‐sectional study of insulin sensitivity and lipids in a cohort of PCO subjects compared to weight and ethnic group matched controls.PATIENTS AND METHODS We have therefore investigated glucose tolerance, plasma lipids and lipoproteins in 19 lean (LP) and 55 obese (OP) patients with PCO and compared the results with those in 22 lean (LC) and 15 obese (OC) control women. Insulin sensitivity was measured in the same subjects with a short insulin (0.05 U/kg i.v. insulin) tolerance test (LP, n = 18; OP, n = 20; LC, n = 19; OC, n = 11).RESULTS Results are expressed as mean ± SEM or median (interquartile range). Fasting plasma glucose levels were similar in the four groups but the plasma glucose area was higher after oral glucose (75 g) in both the lean and obese PCOS groups than in their controls (LC 32.4 ± 0.7 vs LP 35.2 ± 1.2, P < 0.01; OC 34.7 ± l.8 vs OP 37.8 ± 1.5 mmol/l/3 h, P < 0.01). Insulin sensitivity was significantly reduced in obese PCOS women (LC 196 ± 9 vs LP 179 ± 9, NS; OC 168 ± 12 vs OP 133 ± 9 mmol/l/min, P < 0.01). Total serum cholesterol levels were similar in the four groups but HDL2‐cholesterol was reduced in both obese and lean PCOS (LC 0.42 (0.38–0.62), LP 0.31 (0.26–0.44), P < 0.05; OC 0.34 (0.21–0.47), OP 0.21 (0.12–0.32) mmol/l, P < 0.01). Total HDL‐cholesterol was decreased significantly only in the obese PCOS group. Body mass index correlated significantly and negatively with total HDL‐cholesterol and with HDL2‐cholesterol levels both within the PCOS group and the control women. Using multiple regression insulin insensitivity contributes significantly beyond BMI to the low HDL‐cholesterol in women with polycystic ovaries.CONCLUSION Polycystic ovary syndrome is associated with biochemical risk factors for premature vascular disease, which cannot be explained by obesity alone.
Growth hormone secretion in normal prepubertal children: importance of relations between endogenous secretion, pulsatility and body mass
Authors: Martín‐Hernández T. , Gálvez M. Díaz , Cuadro A. Torres , Herrera‐Justiniano E. 
Published: November 2003

OBJECTIVE Although a negative relation between GH secretion and body mass has been described, few studies have been carried out in prepubertal subjects of normal weight and height. The aim of the present study was to examine the relations between GH secretion, pulsatility and body mass throughout the wide range of weights in normal prepubertal children.METHODS We determined integrated GH concentrations during the day (IC‐GHD), night (IC‐GHN), and 24 hours (IC‐GH24) in 46 prepubertal children (26 males, 20 females) of normal height and growth velocity and with a Z‐score (BMI‐SD) between +2 and −2 SD. In addition, in 28 of these patients randomized by their BMI‐SD, the secretory profile was studied by the Pulsar program: area under curve (AUC), peak number (NP), high spontaneous peak of secretory profile (HSP), and area of pulses (AP) which were considered large (L) or small (S) if their amplitude was greater or less than 4 μg/l (8 mU/l).RESULTS BMI‐SD correlated negatively with IC‐GH (IC‐GHD, r = −0.48, P < 0.01; IC‐GHN, r = −0.45, P < 0.001; IC‐GH24, r = −0.58, P < 0.001) and with Pulsar parameters (AUC‐24, r = −0.73, P < 0.0001; HSP, r = −0.65, P < 0.0001). The NP correlated negatively with BMI‐SD (r = −0.51, P < 0.005) at the expense of NLP (r = −0.54, P < 0.003) without being significantly correlated with NSP. This inverse correlation between BMI‐SD and NLP was greater during daytime (NLDP, r = −0.60, P < 0.001) and was not significant at night. NSP did not correlate with BMI‐SD. A similar relation was observed with respect to pulse area (ALP, r = −0.38, P < 0.05; ALDP, r = −0.46, P < 0.02;) and was not significant for ALP during the night or for ASP in any period.CONCLUSIONS We suggest that it should be necessary to relate GH secretion to body mass in prepubertal children before defining their secretion as normal or pathological.
Polycystic ovaries in pre and post‐menopausal women
Authors: Birdsall Mary Ann , Farquhar Cynthia Margaret 
Published: November 2003

OBJECTIVE Polycystic ovaries have been diagnosed in more than 20% of premenopausal women using ultrasound. The aim of this study was to determine whether polycystic ovaries exist in post‐menopausal women.DESIGN Two groups of women were studied; group 1 consisted of 18 post‐menopausal volunteers and group 2 comprised 142 women, 94 of whom were post‐menopausal who had recently undergone coronary angiography.MEASUREMENTS Transabdominal and transvaginal ultrasound scans were performed and measurements made of uterine area, endometrial thickness and ovarian volume. The morphological appearance of the ovaries was also noted. Fasting blood samples were taken. Medical and menstrual questionnaires were completed.RESULTS Polycystic ovaries were found in 8/18 (44%) of group 1 and 60/142 (42%) in group 2. Polycystic ovaries were detected in 35/94 (37%) of the post‐menopausal women in group 2. Post‐menopausal women with polycystic ovaries had larger ovaries containing more follicles compared with post‐menopausal women with normal ovaries. Post‐menopausal women with polycystic ovaries had higher serum concentrations of testosterone and triglycerides than had post‐menopausal women with normal ovaries.CONCLUSIONS Polycystic ovaries can be detected in post‐menopausal women and have some of the same endocrine abnormalities which are evident in premenopausal women with polycystic ovaries, that is, raised serum concentrations of testosterone and triglycerides.
Hypergastrinaemia in Cushing’s syndrome: pituitary origin or glucocorticoid‐induced?
Authors: López‐Guzmán A. , Salvador J. , Frutos R. , Díez J. J. , Iglesias P. , Sastre J. , Gómez‐Pan A. 
Published: November 2003

OBJECTIVES Several reports have shown an increase in serum gastrin levels in patients with Cushing’s syndrome (CS). However, the actual origin of this hypergastrinaemia is not known. Two hypotheses have been proposed: concomitant ACTH and gastrin secretion by corticotrophic pituitary adenomas or hypergastrinaemia induced by hypercortisolism.DESIGN AND PATIENTS We performed simultaneous, bilateral inferior petrosal sinus (IPS) sampling in nine patients with Cushing’s disease (CD), proven by histological studies. In all of them, blood samples were taken from both IPS and a peripheral vein to measure plasma ACTH and serum gastrin. In addition, we measured peripheral serum gastrin levels after an overnight fast in 10 patients with CS (seven with pituitary tumours and three with adrenal tumours) before and after surgical treatment.RESULTS Petrosal‐peripheral and interpetrosal gradients of ACTH were higher than 2.0 and 1.4, respectively, confirming the pituitary origin of ACTH. Mean serum gastrin levels were 149.1 ± 53.6 ng/l in peripheral vein, 183.4 ± 71.7 ng/l in dominant IPS and 181.4 ± 68.9 ng/l in non‐dominant IPS. No significant differences in gastrin concentrations in these locations were found. Mean preoperative gastrin level in patients with CD was 194.6 ± 47.9 ng/l, whereas in patients with adrenal tumours it was 247.3 ± 125.9 ng/l. After surgical treatment, the gastrin levels decreased to 62.1 ± 13.2 ng/l (P  < 0.05) and 90.3 ± 50.3 ng/l (NS), respectively.CONCLUSIONS These results suggest that hypergastrinaemia is a common finding in patients with Cushing’s syndrome. The lack of significant petrosal‐peripheral gradient in individuals with Cushing’s disease and the reduction in gastrin level following adrenal tumour resection argues against the hypothesis of a predominantly pituitary source of gastrin, suggesting a glucocorticoid related mechanism as an explanation for the hypergastrinaemia.
The maternal hypothalamic–pituitary–adrenal axis in the third trimester of human pregnancy
Authors: Magiakou Maria‐Alexandra , Mastorakos George , Rabin Douglas , Margioris Andrew N. , Dubbert Bellinda , Calogero Aldo E. , Tsigos Constantine , Munson Peter J. , Chrousos George P. 
Published: November 2003

OBJECTIVE The third trimester of pregnancy is characterized by a mildly hyperactive hypothalamic–pituitary–adrenal (HPA) axis, possibly driven by elevated circulating levels of corticotrophin releasing hormone (CRH) of placental origin. In‐vitro studies have demonstrated that glucocorticoids and oestrogen stimulate while progesterone inhibits the expression of CRH mRNA and/or protein, suggesting that several potential interactions between the placenta and the HPA axis may exist.DESIGN AND PATIENTS To investigate the detailed pattern of circulating immunoreactive (ir) CRH, ACTH, cortisol, oestradiol and progesterone during the third trimester of pregnancy, plasma samples were drawn serially every 30 minutes from 22 healthy pregnant women (age 32.0 ± 1.1 years, mean ± SE) between the 34th and 36th week of gestation. Ten women had plasma samples drawn between 0800 h and 2000 h (daytime group), and 12 between 2000 h and 0800 h (night‐time group). The hormone concentrations obtained were analysed for pulsatility by the Detect program, for detection of circadian rhythmicity by comparison between the first and second 6‐hour periods within each group by Student's t‐test, and for time‐dependent correlations by cross‐correlation analysis.RESULTS All five hormones were secreted in a pulsatile fashion. There was no apparent circadian rhythm of CRH or oes tradiol secretion, whereas there was a clear circadian rhythm in plasma ACTH, cortisol and progesterone secretion, with the latter in reverse phase (P<0.05). No significant correlations were observed between CRH and ACTH, whereas, as expected, ACTH and cortisol concentrations were strongly correlated with each other over time (r=0.32 and 0.70 at lag time 30 minutes for the daytime and night‐time groups, respectively), with ACTH leading cortisol. A weak positive correlation was observed between CRH and cortisol concentrations for the night‐time group at lag time 0 minute, suggesting that the latter may have a positive effect on the former in vivoCONCLUSIONS These data suggest that placental CRH, although pulsatile, drives quantitatively the maternal HPA axis in the third trimester of pregnancy in a non‐circadian, non‐pulsatile fashion. The maternal HPA axis is probably driven in a circadian and pulsatile fashion by another major ACTH secretagogue, most likely AVP of parvocellular paraventricular nucleus origin.
Comparison of methods to estimate body fat in growth hormone deficient adults
Authors: Bosaeus Ingvar , Johannsson Gudmundur , Rosén Thord , Hallgren Per , Tölli Jukka , Sjöström Lars , Bengtsson Bengt‐Åke 
Published: November 2003

OBJECTIVE All of the presently used methods for in‐vivo determination of body composition have inherent methodological errors and depend on various assumptions. We have therefore compared several different methods used to measure body fat in adult GH deficiency during GH treatment.DESIGN Comparison of body composition data from a two‐phase trial with an initial placebo‐controlled, double‐blind 6‐month period, followed by open treatment with GH until all patients had received GH for 12 months.PATIENTS Twenty‐five patients with known GH deficiency entered the study. Baseline examinations were complete in 23 patients, and 22 patients (16 males, 6 females) completed all examinations after treatment.MEASUREMENTS Body fat calculated from total body potassium (TBK) by whole‐body 40K counting, total body water (TBW) by tritium dilution, total body nitrogen (TBN) by neutron activation, and bioelectric impedance (BIA) measurements were compared to body fat determinations by dual‐energy X‐ray absorptiometry (DEXA) in two‐compartment and multicompartment body composition models.RESULTS At baseline, DEXA fat mass agreed well at group level with measurements based on TBW or TBK alone, in a four‐compartment model based on TBK and TBW, and a multicompartment model based on bone mineral (by DEXA), TBN and TBW. Body fat by BIA agreed less well. After 12 months of GH treatment, body fat decreased by all methods used. This decrease was smaller by DEXA than by the other methods. The four‐compartment model based on TBK and TBW, and TBW alone, showed the best agreement with changes in DEXA fat.CONCLUSION All methods showed a decrease of body fat with GH treatment, but variation between methods was considerable.