Differences In Estradiol Concentrations Research Articles

Influence of preovulatory estradiol treatment on the maintenance of pregnancy in beef cattle receiving in vivo produced embryos

This experiment was designed to determine the role of preovulatory estradiol in pregnancy retention after embryo transfer (ET). Cows were synchronized with the 7-d CO-Synch + CIDR® protocol. On d0 (d-2 =CIDR® removal), cows were grouped by estrual status (estrual [Positive Control] and nonestrual), and nonestrual cows were administered Gonadotropin Releasing Hormone (GnRH) and randomly assigned to either no treatment (Negative Control) or Estradiol (0.1 mg estradiol 17-β IM). All cows received an embryo on d7. Pregnancy status was retrospectively classified on d56, 30, 24, and 19 by either ultrasonography, plasma pregnancy-associated glycoproteins analysis (PAGs), expression of interferon-stimulated genes, plasma progesterone (P4) concentrations, or a combination of the factors. There was no difference in estradiol concentrations on day 0 h 0 (P > 0.16). At day 0 h 2, Estradiol cows (15.7 ± 0.25 pg/mL) had elevated (P < 0.001) estradiol compared with Positive Controls (3.4 ± 0.26 pg/mL) or Negative Controls (4.3 ± 0.25 pg/mL). On d19, pregnancy rates did not differ (P = 0.14) among treatments. On d24, Positive Controls (47%) had greater (P < 0.01) pregnancy rates than Negative Controls (32%); Estradiol cows were intermediate (40%). There was no difference (P = 0.38) in pregnancy rates between Positive Control (41%) and Estradiol (36%) cows on d30, but Negative Control (27%) cows had (P = 0.01) or tended (P = 0.08) to have decreased pregnancy rates, respectively. Thus, preovulatory estradiol may elicit an effect on early uterine attachment or alter histotroph components, consequently improving pregnancy maintenance through d30.

Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders.

Does the gonadotropin (GN) starting dose and the addition of clomiphene citrate (CC) during the early follicular phase influence oocyte yield in poor responders undergoing ovarian stimulation for IVF treatment? The number of retrieved oocytes was similar regardless of the starting dose of GN (150 versus 450 IU) with or without the addition of CC (100 mg from Day 3 to 7 versus placebo). ART in poor responders is a challenge for patients and clinicians. So far, randomised controlled studies addressing interventions have shown that neither the GN dose nor the addition of oral medication has any significant effect on the clinical outcome of ART in poor responders. There is limited knowledge about the effect of GN starting dose in combination with CC during the early follicular phase of ovarian stimulation on ovarian response markers and ART outcome. This single-centre randomised double-blinded clinical trial was conducted from August 2013 until November 2017. Using the Bologna criteria, 220 of 2288 patients (9.6%) were identified as poor responders and 114 eligible participants underwent ovarian stimulation in a GnRH-antagonist protocol for ART. The participants were equally randomised to one of four treatment arms: Group A (n = 28) received 100 mg CC (Day 3-7) and a starting dose of 450 IU HMG, Group B (n = 29) received 100 mg CC and a starting dose of 150 IU HMG, Group C (n = 30) received placebo and a starting dose of 450 IU HMG and Group D (n = 27) received placebo and a starting dose of 150 IU HMG. Serum levels of FSH, LH, estradiol and progesterone were measured on Day 1 and 5 and on the day of ovulation induction. Available embryos were cultured up to the blastocyst stage and were always transferred in the same cycle. The primary outcome was the number of oocytes collected after ovarian stimulation. Other outcome measures were response to ovarian stimulation, embryo development and obstetrical outcome. All study participants (n = 114) fulfilled at least two of the Bologna criteria for poor responders. Median age of the study population was 38.5 years. There were 109 patients who underwent oocyte retrieval. The number of oocytes retrieved was similar among the groups (±SD; 95% confidence intervals); A: 2.85 (±0.48; 2.04-3.98), B: 4.32 (±0.59; 3.31-5.64); C: 3.33 (±0.52; 2.45-4.54); D: 3.22 (±0.51; 2.36-4.41); P overall = 0.246. However, ovarian stimulation with 150 IU plus CC resulted in a higher number of blastocysts compared to ovarian stimulation with 450 IU plus CC (±SD; 95% confidence intervals); A: 0.83 (±0.15; 0.58-1.2), B: 1.77 (±0.21; 1.42-2.22); P overall = 0.006. Mean FSH serum levels were lower in the groups with a starting dose of 150 IU. Adding CC did not affect mean serum FSH levels. There were no differences in estradiol concentrations among the groups. Endometrial thickness was lower in the groups receiving CC. The overall live birth rate (LBR) was 12.3%, and the cumulative LBR was 14.7%. The trial was powered to detect differences in neither the number of blastocysts nor the LBR, which would be the preferable primary outcome of interventional trials in ART. We found that ovarian stimulation with 150 IU gonadotrophin in combination with 100 mg CC produced more blastocysts. The effect of adding CC to GN on LBR in poor responders remains to be proven in randomised trials. High GN doses (450 IU) resulted in high FSH serum levels but increased neither the estradiol levels nor the number of retrieved oocytes, implying that granulosa cell function is not improved by high FSH serum levels. Lower starting doses of GN lead to a reduction of costs of medication. The small but significant difference in blastocyst formation and the lower FSH levels in the treatment groups receiving less GN may be an indication of better oocyte quality with higher developmental competence. The costs for the HMG used for ovarian stimulation were provided by IBSA Switzerland. The study was also supported by the Repronatal Foundation, Basel, Switzerland. The authors declare no conflict of interest. NCT01577472. 13 April 2012. August 2013.

Impact of Sex Hormones, Postmenopausal Hormone Therapy and Risk Factors on Development of Abdominal Aortic Aneurysm in Women: A Population-based Prospective Study in Norway: A Hunt Study

Introduction - Women develop abdominal aortic aneurysms (AAA) five to ten years later than men (1,2). The delay in AAA development may be secondary to a protection from estrogens (3,4). The aim of the present study was to evaluate the impact of risk factors associated with AAA development in women, including postmenopausal hormone therapy. This has previously been investigated in small cohorts with limited information. Methods - In a total cohort of 106,000 individuals from the Norwegian Nord-Trøndelag Health Study (HUNT), 20,024 postmenopausal women were identified, of which 201 developed AAAs during a median follow-up of 18 years (1995-2014, i.e. 295,554 person-years). The data is based on questionnaires, physical measurements, medical records and blood samples. A multivariable Cox regression model was constructed, where the final adjusted model included the following variables: smoking (current, past, never), body mass index, coronary heart disease, diabetes, hypertension and postmenopausal hormone therapy. Multiple imputation was performed for missing data (n=50 data sets). Serum estradiol concentrations were compared between women who later did or did not develop AAAs. Median time from blood sample collection to AAA diagnosis was seven years. Results - Mean age at AAA diagnosis was 77 (59 -100) years. 28% of the cohort reported ever use of postmenopausal hormone therapy. In the multivariable analysis, a notable Hazard ratio (HR) of 0.58 was observed for current use of hormone therapy, but the result was not statistically significant (95% CI 0.29-1.16, p=0.12). Women who reported current smoking had a more than ten-fold risk for developing AAA during follow-up (HR 10.9 (7.4-16.1)). Positive associations were also found for hypertension (HR 2.0 (1.4-3.0)) and coronary heart disease (HR 2.2 (1.6-3.2)). There was no substantial difference in estradiol concentrations between women with and without AAA (p=0.06). Conclusion - Postmenopausal hormone therapy is of less clinical importance compared to the strong associations observed between smoking, hypertension coronary heart disease and AAA development in women. These findings were supported by measured estradiol concentrations.

Female sex hormones and risk of incident abdominal aortic aneurysm in Norwegian women in the HUNT study

ObjectiveThe delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. MethodsThe present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. ResultsCurrent smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P = .075). ConclusionsThe effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease.

Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells.

UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality.

CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNP) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer.

Sex and regional differences in estradiol content in the prefrontal cortex, amygdala and hippocampus of adult male and female rats

In general, the behavioral and neural effects of estradiol administration to males and females differ. While much attention has been paid to the potential structural, cellular and sub-cellular mechanisms that may underlie such differences, as of yet there has been no examination of whether the differences observed may be related to differential uptake or storage of estradiol within the brain itself. We administered estradiol benzoate to gonadectomized male and female rats, and compared the concentration of estradiol in serum and brain tissue found in these rats to those of gonadectomized, oil-treated rats and intact rats of both sexes. Long-term gonadectomy (3 weeks) reduced estradiol concentration in the male and female hippocampus, but not in the male or female amygdala or in the female prefrontal cortex. Furthermore, exogenous treatment with estradiol increased estradiol content to levels above intact animals in the amygdala, prefrontal cortex and the male hippocampus. Levels of estradiol were undetectable in the prefrontal cortex of intact males, but were detectable in all other brain regions of intact rats. Here we demonstrate (1) that serum concentrations of estradiol are not necessarily reflective of brain tissue concentrations, (2) that within the brain, there are regional differences in the effects of gonadectomy and estradiol administration, and (3) that there is less evidence for local production of estradiol in males than females, particularly in the prefrontal cortex and perhaps the hippocampus. Thus there are regional differences in estradiol concentration in the prefrontal cortex, amygdala and hippocampus that are influenced by sex and hormone status.

Parity effects on maternal behaviour are not related to circulating oestradiol concentrations in two breeds of sheep

Primiparous females of many species, including the sheep, do not show as competent maternal behaviour as multiparous mothers. In this study we investigated whether circulating concentrations of oestradiol might be related to this response, since breed differences in oestradiol concentrations have been shown to correlate with maternal behaviours. Oestradiol concentrations were measured in plasma collected at 2-weekly intervals from primiparous and multiparous ewes of two breeds (Scottish Blackface and Suffolk) throughout gestation, and maternal behaviour was recorded at parturition. Circulating oestradiol concentrations, and the ratio of oestradiol to progesterone concentration (O:P ratio) were higher in late pregnancy in Blackface ewes, but there were no significant effects of ewe parity. However, there was a significant interaction between breed and parity as O:P ratio was lower in primiparous Suffolk ewes compared to multiparous. This relationship was not seen in Blackface ewes. Blackface ewes of both parities groomed their lambs more frequently and made more low-pitched vocalisations than Suffolk ewes. Primiparous ewes were more likely to move as the lamb attempted to suck, and to show withdrawal or aggression towards the lamb. Primiparous Suffolk ewes also made more high pitched bleats than other classes of ewe. The data support previous studies which show an effect of breed on circulating oestradiol and O:P ratio but suggest that parity effects on maternal behaviour may be mediated by sensitivity to circulating concentration of oestradiol rather than variations in the plasma concentrations of this hormone.

240 RELATIONSHIP BETWEEN PEAK NUMBER OF ANTRAL FOLLICLES AND FOLLICULAR WAVES, HORMONE CONCENTRATIONS, SUPEROVULATORY RESPONSE, AND EMBRYO QUALITY IN BEEF HEIFERS

Recent studies in dairy cattle demonstrate that the number of antral follicles during follicular waves is highly variable among animals, but highly repeatable within individuals, and the numbers of follicles during waves are inversely associated with serum FSH concentrations (Burns et al. 2005 Biol. Reprod. 73, 54-62). The aims of this study were to determine (1) serum FSH and estradiol concentrations during follicular waves in beef heifers categorized according to peak number of antral follicles per wave, and (2) the relationship between this categorization and superovulatory response. Estrous cycles of crossbred beef heifers (n = 90) were synchronized with two i.m. injections of PGF2� 11 days apart; animals were scanned daily for 5 days beginning 24 h after the second PG injection to determine the number of follicles during the first follicle wave in two or three consecutive estrous cycles. Heifers were grouped based on the peak number of follicles e 3 mm per wave in diameter (Low: d 15 follicles, n = 12; High: e 25 follicles, n = 11). Intermediate animals were excluded. Heifers were then re-synchronized and blood samples taken every 8 h up to Day 7 to characterize FSH and estradiol profiles. Subsequently, animals were superovulated (pFSH, Folltropin�; Bioniche Animal Health, Belleville, Ontario, Canada), inseminated, and flushed on Day 7; this procedure was repeated twice. All values for hormone concentrations were aligned relative to the peak FSH value. A mixed model, repeated-measures approach was used to determine if serum FSH and estradiol concentrations were different between groups. Differences in recovery rate (number of oocytes/embryos recovered compared to number of corpora lutea) and proportion of transferable embryos were analyzed using Chi-square analysis. The mean (�SE) peak postovulatory FSH concentration was lower (P d 0.03) for animals with high numbers of follicles. No differences in estradiol concentrations were observed. The mean superovulatory response (number of corpora lutea) was higher (P d 0.05) in the High group than in the low group (17.6 � 3.6 vs. 8.5 � 1.1). While there was no difference in the recovery rate of embryos (62 vs. 60%), significantly more (P d 0.05) oocytes/embryos (10.6 � 2.7 vs. 4.7 � 0.7) and transferable embryos (5.4 � 1.3 vs. 3.8 � 0.8) were recovered per animal in the High group. Of the embryos recovered, the proportion of transferable quality was higher for animals in the Low group (80 vs. 51%; P d 0.05). In conclusion, the number of antral follicles during a follicular wave in beef heifers is inversely related to peak postovulatory FSH concentration, but is unrelated to estradiol concentration. In addition, while the superovulatory response and number of transferable embryos were greater in animals with a high number of antral follicles, embryo quality, measured as the proportion of transferable embryos per donor, was reduced. We conclude that cattle with relatively high numbers of follicles per wave respond best to standard superovulation protocols. However, the reason the proportion of high quality embryos is reduced in cattle with high vs. low numbers of follicles per wave is unknown.

Enhanced oestradiol secretion briefly after embryo transfer in conception cycles from IVF

The hypothesis was tested that conception cycles (CC) resulting from IVF can be distinguished from non-conception cycles (NC) by differences in corpora lutea function that are detectable at the earliest stage of embryo implantation. Luteal oestradiol secretion was analysed retrospectively in 409 ovarian stimulation cycles of 296 patients from the day of embryo transfer until 14 days after embryo transfer (ET+14) in IVF/intracytoplasmic sperm injection (ICSI) cycles. Human chorionic gonadotrophin (HCG) was administered in 330 of 409 cycles in addition to vaginal progesterone in all cycles. Differences in serum oestradiol concentrations between CC and NC increased from day ET+1 onward and became statistically significant on days ET+4 through ET+14, with higher oestradiol concentrations in CC compared with NC. Even though exogenous HCG administration prevented the fall in luteal oestradiol concentrations after ET+4 both in CC and NC, increasing differences in oestradiol concentrations between CC and NC after embryo transfer were observed in both groups of HCG-supplemented and non-supplemented cycles. It is concluded that luteal oestradiol secretion is affected at the earliest stage of embryo implantation. The putative early signal to the corpus luteum associated with embryo attachment and early implantation appears to be superimposed onto the effect of exogenous luteal HCG administration and is clearly distinguishable as early as 4 days after embryo transfer in conception cycles.

Effects of food supplementation on litter size and oestradiol concentration during gestation and oestrous cycle of capybaras (Hydrochaeris hydrochaeris) in captivity

The present study analysed the response of adult female capybaras (Hydrochaeris hydrochaeris) to different dietary supplementation in relation to litter size per parturition and oestradiol secretion profile during pregnancy and the oestrous cycle. All four experimental groups received 'camerum' grass (Pennisetum purpureum) and water ad libitum and three of the groups were also fed a protein, lipid or protein and lipid supplement. Litter size per parturition did not show any significant difference among treatment groups, but was significantly higher (P < 0.05) than in the control group. There was no significant difference in oestradiol concentrations among treatments and the control group, during each phase of the oestrous cycle or during gestation. The average oestradiol concentrations in dioestrous, oestrous and metoestrous phases were not significantly different from each other, but were significantly lower (P < 0.05) than the average oestradiol concentration in the pro-oestrous phase. In addition, average oestradiol concentrations increased after the second gestation month, but were significantly higher (P < 0.05) only after the fourth gestation month, achieving maximum value by the end of gestation. Dietary supplementation had no significant effect on hormonal concentrations during the oestrous cycle and gestational period. However, an increase in litter size per parturition was observed among female capybaras that received dietary supplementation.

Association of uterine edema with follicle waves around the onset of the breeding season in pony mares

During spring transition, when estrus may be exhibited for prolonged periods, it is important for veterinarians and stud farm personnel to be able to predict whether a large follicle will ovulate or regress. It is thought that the presence of ultrasonically detectable uterine edema indicates that a follicle will ovulate, however, there is little evidence to support this. In the present study, 16 mares were regularly examined by transrectal ultrasonography to follow growth and regression of follicles from seasonal anestrus in February until second ovulation. Blood samples were collected daily for measurement of estradiol concentrations when a large ovarian follicle was present. Estrous-like uterine edema was detected during 7 of 11 (64%) anovulatory follicle waves, in 12 of 14 (86%) mares before their first ovulation, and in 100% of mares before their second ovulation. Uterine edema was first detected 43±6.7 days before first ovulation. Large anovulatory follicles tended to be present for longer periods of time than ovulatory follicles. Uterine edema was present for a significantly greater proportion of time in the presence of a large follicle at second ovulation than at first ovulation ( P<0.05) or for anovulatory follicles ( P<0.01). Peak plasma estradiol concentrations and mean plasma estradiol concentrations were significantly higher ( P<0.001) when a dominant preovulatory follicle was present compared with a dominant anovulatory follicle, but there was no difference in estradiol concentrations between first and second ovulations. It was apparent, therefore, that uterine edema was not a reliable indicator of follicular steroidogenic competence, or of whether the follicle would ovulate.

Follicle deviation and intrafollicular and systemic estradiol concentrations in mares.

By definition, follicle deviation begins on the day the two largest follicles of a wave begin to differ in growth rates. The relationships between follicle deviation and intrafollicular and systemic estradiol concentrations were studied in ponies, using a two-follicle model in which all but the two largest follicles were ablated. A 20-microliter sample of follicular fluid was obtained from each of the two follicles by transvaginal ultrasonography. In experiment 1, the two follicles were sampled when the larger follicle reached 15 mm. No differences (p > 0.05) in post-sampling follicle characteristics were found between control (n = 6) and sampled (n = 8) groups except that the growth rate was slower (p < 0.01) in the larger follicle between the day of sampling and the next day (0.7 +/- 0.7 mm per day) than in the controls (3.3 +/- 0.3 mm per day). The growth rates between 2 and 5 days after sampling were not different between groups. Follicular fluid estradiol-17beta concentrations were higher (p < 0.007) in the larger follicle (460 +/- 67 ng/ml; diameter, 16.4 +/- 0.4 mm) than in the smaller follicle (322 +/- 50 ng/ml; diameter, 14.6 +/- 0.6 mm). In experiment 2, the pair of follicles was sampled when the larger follicle reached 15 mm, 20 mm, or 25 mm (n = 5 per group). There were no significant differences among the three groups for day of deviation and diameters of larger and smaller follicles at deviation. The difference in diameter between the larger and smaller follicles was similar for the 15-mm (2.2 +/- 0.9 mm) and 20-mm (3.1 +/- 1.0 mm) groups, but the difference between follicles for the 25-mm group (7.9 +/- 1.2 mm) was greater (p < 0.004) than for the other two groups. In contrast, the differences in estradiol concentrations between the larger and smaller follicles increased (p < 0.0001) progressively for the 15-mm (13.0 +/- 86.8 ng/ml), 20-mm (722.0 +/- 173.8 ng/ml), and 25-mm (1873.5 +/- 310.3 ng/ml) groups. The first significant (p < 0.007) increase in systemic estradiol occurred between the day before and the day of the beginning of deviation. Detection of an increased difference in estradiol concentrations between the two follicles before the detection of a change in differences in diameter suggests, on a temporal basis, that estradiol is a candidate for involvement in the mechanism that leads to follicle-diameter deviation in mares.

Alterations in growth and body composition during puberty: III. Influence of maturation, gender, body composition, fat distribution, aerobic fitness, and energy expenditure on nocturnal growth hormone release.

We examined the relationships among gender, sexual maturation, four-compartment model estimates of body composition, body fat distribution (magnetic resonance imaging for abdominal visceral fat and anthropometrics), aerobic fitness, basal and total energy expenditure, and overnight GH release in an ultrasensitive chemiluminescence assay in healthy prepubertal and pubertal boys (n = 18 and 11, respectively) and girls (n = 12 and 18, respectively). Blood samples were withdrawn every 10 min from 1800-0600 h to determine the area under the serum GH-time curve (AUC), sum of the GH peak heights (sigma GH peak heights), and the mean nadir GH concentration. GH release was greater in the pubertal than prepubertal subjects due to an increase in sigma GH peak heights (43.8 +/- 3.6 vs. 24.1 +/- 3.5 ng.mL-1, P = 0.0002) and mean nadir (1.7 +/- 0.2 vs. 0.7 +/- 0.2 ng.mL-1, P = 0.0002), but not peak number (4.3 +/- 0.2 vs. 4.5 +/- 0.2). The girls had a greater sigma GH peak heights (39.0 +/- 3.5 vs. 28.8 +/- 3.6 ng.mL-1, P = 0.05) and mean nadir concentration (1.4 +/- 0.2 vs. 0.9 +/- 0.2 ng.mL-1, P = 0.05) than the boys. Significant inverse relationships existed between sigma GH peak heights (r = -0.35, P = 0.06) or mean nadir (r = -0.39, P = 0.04) and four-compartment percent body fat for all boys but not for all girls or when combining all subjects. For all girls, significant inverse relationships existed between sigma GH peak heights (r = -0.39, P = 0.03) or mean nadir (r = -0.37, P = 0.04) and waist/hip ratio. Similar inverse relationships in all boys or all subjects were not significant. Forward stepwise regression analysis determined that bone age (i.e. maturation, primary factor) and gender were the significant predictors of AUC, sigma GH peak heights, and mean nadir. The influence of maturation reflects rising sex steroid concentrations, and the gender differences appear to be because of differences in estradiol concentrations rather than to body composition or body fat distribution.

A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey.

The associations between serum concentrations of oestradiol, progesterone, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in premenopausal women were investigated in a prospective study of breast cancer on the island of Guernsey. Sixty-two women diagnosed with breast cancer an average of 8 years subsequent to blood collection were matched for day of menstrual cycle, age and year of blood collection with 182 control subjects. Cases had a 12% higher mean oestradiol concentration over the whole menstrual cycle (P = 0.17) with a large difference at mid-cycle (75% higher, P = 0.04). Differences between cases and control subjects in progesterone (luteal phase), testosterone and SHBG were small and not statistically significant: luteal phase progesterone 9% lower in cases, P = 0.64; testosterone 4% higher, P = 0.57; SHBG 8% higher, P = 0.24. The small difference in oestradiol concentration could be aetiologically important, but larger prospective studies are needed.