Serum Estradiol Concentrations Research Articles

Effect of prostaglandin alone and in combination with trace minerals on the follicular and luteal dynamics, estrus response and pregnancy in sub-estrus buffaloes (Bubalus bubalis).

Sub-estrus is a condition when buffaloes do not display behavioural estrus signs, despite being in estrus and causes a delay in conception and increases the service period. The present study describes the effect of synthetic prostaglandin (PGF2α) alone and in combination with trace minerals on the follicular and corpus luteum (CL) dynamics, serum estradiol (E2) and progesterone (P4) concentration correlating estrus response and pregnancy outcome in sub-estrus buffaloes during the breeding season. A total of 50 sub-estrus buffaloes, identified through ultrasonography (USG) examination, were randomly allocated into three groups, viz. T1 (Synthetic PGF2α, Inj. Cloprostenol 500 μg, i.m, n = 17), T2 (Synthetic PGF2α + Trace mineral supplementation, Inj. Stimvet 1 mL/100 kg body weight, i.m., n = 17) and control (untreated; n = 16). Following treatment, 100% of sub-estrus buffaloes were induced estrus in the T1 and T2 groups, while only 18.75% were induced in the control. The CL diameter and serum P4 concentration were significantly lower at post-treatment, whereas the pre-ovulatory follicle (POF) size and serum E2 concentration were significantly higher in the T1 and T2 groups as compared to the control (p < .05). The buffaloes of the T2 group had a greater proportion of moderate intensities estrus than those of T1. Moreover, the proportion of buffaloes conceived in the T1 and T2 were 41.2% and 52.95%, respectively. The larger POF diameter and higher serum E2 concentration were associated with intense intensity estrus and higher conception rate (66.7%) in sub-estrus buffaloes. Similarly, CL regression rate, POF size and serum E2 concentration were relatively higher in the buffaloes conceived as compared to those not conceived. It is concluded that synthetic PGF2α in combination with trace minerals induces moderate to intense intensities estrus in a greater proportion of sub-estrus buffaloes and increases the conception rate during the breeding season. Moreover, behavioural estrus attributes correlating follicle and luteal morphometry, serum E2 and P4 concentration could be used to optimise the breeding time for augmenting the conception rate in sub-estrus buffaloes.

Impact of preovulatory follicle maturity on oocyte metabolism and embryo development

Abstract Improved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte’s metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites (P &amp;lt; 0.05). Blastocysts from oocytes matured in greater versus lesser maturity follicular fluid had a more moderate rate of development (P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater versus lesser maturity follicular fluid.

Pu-erh tea theabrownin improves the ovarian function and gut microbiota in laying hens

Studies have reported that theabrownin can moderate the lipid metabolism and intestinal microbiota, thereby affecting the health of humans and model animals, however the research on laying hens is scarce. The present study aimed to investigate the effects of dietary theabrownin supplementation on lipid metabolism, microbial composition and ovarian function in laying hens. A total of 80 laying hens (25 wk of age) were fed with normal diet (CON) and normal diet +100 mg/kg theabrownin (PT group) for 12 wk. The results showed that the addition of theabrownin enhanced villus height of duodenum and decreased crypt depth of jejunum (P < 0.05). At the same time, compared with CON, the concentration of IL-6 and the mRNA expression of IL-1β and IL-6 were decreased significantly in PT group (P < 0.05). Dietary theabrownin reduced the concentration of total cholesterol and glycerol, while decreased lipid droplet optical density in liver (P < 0.05). Compared with CON group, the mRNA expression of PPARγ, HMG-CoAS, ACC were down-regulated and the mRNA expression of CYP8B1 was up-regulated in PT group (P < 0.05). The ACE, Chao1 and Observed_species indexes in cecum microbiota were increased by PT group intervention (P < 0.05). Dietary PT supplementation enhanced the relative abundance of Firmicutes (phylum), Lactobacillus (genus) and the Firmicutes to Bacteroidetes ratio, and reduced the relative abundance of Bacteroidetes (phylum) in cecum (P < 0.05). The organic acids and its derivatives were up-regulated by theabrownin intervention in serum metabolites (P < 0.05). Dietary theabrownin supplementation resulted in higher mRNA expression of Bcl-2 and SIRT1 in ovary and increased the concentration of estradiol in serum (P < 0.05). These discovering indicated that dietary theabrownin supplementation enhanced the intestinal function and influenced serum metabolism by improving intestinal morphology, microbiota community structure and reducing the concentration and expression of inflammatory cytokines in intestine. Dietary theabrownin reduced hepatic lipid deposition and it also decreased the cell apoptosis rate to improve ovarian function and egg weight which were associated with the SIRT1 pathway.

Effect of Curcuma longa maceration treatment on ovarian follicular development, serum oestradiol, uterine growth and vascularisation in female albino rats

Abstract Introduction Curcuma longa is a well-known medicinal plant with various health benefits. This study was designed to evaluate the administration of Indonesian C. longa maceration for its effect on promoting growth and development of the ovary and uterus before mating in female albino rats. Material and Methods A total of 15 female Sprague Dawley rats in their dioestrous phase were assigned into three different groups: the Control group (mineral water); the Cur-Low group (mineral water with 1% C. longa maceration) and the Cur-High group (mineral water with 5% C. longa maceration). The treatments were given for 20 days. Serum concentrations of follicle-stimulating hormone, oestradiol and progesterone were determined. After the sacrifice of the rats, ovary and uterine relative weight, uterine cornua diameter and length, uterine gland diameter (by histology), the number of primary, secondary, tertiary, and Graafian follicles, the number of corpora lutea and vascular endothelial growth factor (VEGF) expression in the ovary were measured. Uterine vascularisation was also evaluated. Results Administration of C. longa maceration significantly improved the relative weights of the uterus and ovary; uterine cornua diameter, length and vascularisation; uterine gland diameter; and expression of VEGF in the ovary. It also increased the number of tertiary follicles and corpora lutea, albeit not significantly. Follicle-stimulating hormone serum concentrations were lower in the administered rats. Conclusion Oestradiol and progesterone levels rose with C. longa maceration treatment. The maceration improved the reproductive organs of unmated rats and had potential to optimise the uterine environment for supporting pregnancy in order to produce high-quality offspring.

Effect of High Energy Diet Supplementation during Periparturient Period on Ovarian Steroids and Reproductive Performance in Vrindavani Cows

The objective of the study was to assess the effect of high energy diet supplementation during periparturient period on ovarian steroids and reproductive performance in vrindavani cows. Postpartum vrindavani cows (n= 20) of second to fourth parity with lactation yield of &gt; 10 L/day were divided in to two groups (n=10 cow/group). Group I (CON) cows were fed with basal diet to serve as control. Group II (TRT) cows were provided with 20% extra concentrates in the form of energy. 20% additional concentrate diet was supplemented from second week to eight week after calving. Blood samples were collected at weekly interval from 4 week before calving to8weeks after calving. Blood samples were collected to determine estradiol (E2) and progesterone (P4) in the serum using RIA. Postpartum reproductive performance was assessed in terms occurrence of first postpartum estrus, calving to conception interval, conception rate and number of service per conception. Serum estradiol and progesterone concentration increased significantly(P&lt;0.05) from 2 to 8 week postpartum in Group II as compared to Group I. Marked significant(P&lt;0.05)improvement in the postpartum reproductive performance in terms of early occurrence of first postpartum estrus(67.0Vs 53.0), reduced calving to conception interval(85.87 Vs74.4), service per conception (1.62 Vs 1.2), days from calving to first AI(88.5 Vs 65.73), higher first AI conception rate(40 Vs 80%)  and cumulative conception rate(88.52 Vs 65.73%)  in group II as compared to group I. In conclusion, additional high energy diet supplemented group showed significant increased ovarian steroid hormonal concentrations and marked improvement in the reproductive performance in Vrindavani cows.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BackgroundOlanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. MethodsRats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. ResultsIn adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. ConclusionsThese results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

Influence of sex hormones on the aggressive behavior during peck order establishment and stabilization in meat and egg type chickens

In the poultry industry, broiler and layer strains are genetically selected for different purposes (e.g., high meat-yield and high egg-production). Genetic selection for productivity can have unintended consequences on the behavioral repertoire of the birds, including aggression. Alongside the increasing societal concern regarding the welfare of animal in agriculture, the number of countries that are advocating the prohibition of using battery cages for laying hens has resulted in the transition and adoption of cage-free or free-range systems. Thus, both broiler and layer chickens are housed in large flocks rather than housed individually in cages. Housing birds in groups increases the opportunity for birds to engage in social behaviors, including aggression, that are used to establish social status. Aggressive interactions are associated with the risk of injury and the potential for a subordinate animal to have unmet needs (e.g., access to feed). The aim of this study was to characterize the relationships among aggressive behavior, neurobiology, and hormones during peck order establishment and social hierarchy stabilization of 2 divergently selected strains (meat- and egg-type chicken). Meat-type strains performed more male on male (P < 0.001), male on female (P < 0.0001), and female on female (P < 0.0001) non-reciprocal aggression behavior (NRA) than egg-type strains. Greater serum testosterone and estradiol concentrations in the weeks after the peck order establishment were observed in meat-type birds compared those in egg-type birds for both males and females (all P < 0.05). Greater (P < 0.05) cellular densities of androgen receptors, but not estrogen receptors, were observed in the hypothalamus of meat-type birds compared to egg-type birds. These findings suggest that greater sex hormone concentrations in the meat-type birds may be a consequence of genetic selection for rapid growth resulting in more sex hormones-induced aggressive behavior.

Second trimester maternal serum progesterone and estradiol concentrations with live and demised fetuses: Secondary analysis results from a randomized controlled trial

AbstractObjectiveTo provide data on maternal levels of estradiol and progesterone in the second trimester of pregnancy with a live foetus and those complicated by a spontaneous foetal demise.MethodsWithin a randomised trial to assess efficacy of mifepristone in termination following foetal demise from 14 to 28 weeks of gestation, we measured progesterone and estradiol levels in trial patients and in women undergoing termination with a live foetus. Women admitted to King Edward Memorial Hospital (Western Australia) from 2013 to 2016 were considered for eligibility and enroled. Scatter plots with 95% confidence intervals were generated for hormone levels by gestation. Generalised linear models were used to estimate mean values of estradiol and progesterone, accounting for maternal age, gestation and parity.ResultsOverall, women with a foetal demise had lower estradiol levels compared to women with a live foetus, (mean difference of 10 460 pmol/L). With a live foetus, higher levels of estradiol were observed with increasing gestations: with a mean of 17 010 pmol/L at 14 ≤ 17 weeks, 31 180 pmol/L at 23–28 weeks and similarly progesterone with a mean of 113 nmol/L at 14 ≤ 17 weeks and 183 nmol/L at 23–28 weeks. Progesterone levels in women with foetal demise were 37 nmol/L higher than women in the live foetus group. In all women, each unit increase in parity was associated with a decrease of 10nmol/l of progesterone (95% confidence interval: 4–16, p = 0.001).ConclusionsEstradiol and progesterone levels in the second trimester vary between pregnant women with a live and demised foetus.

Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study

BackgroundThe relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive. To examine the association of serum testosterone and estradiol concentrations with cognitive function in older men with or without vascular risk factors (VRFs).MethodsThis cross-sectional study consisted of 224 community-dwelling men aged 65–90 years in the Songjiang District of Shanghai, China. Serum testosterone and estradiol were measured by electrochemiluminescence immunoassay. The following five factors were defined as VRFs in this study: obesity, history of hypertension, diabetes, stroke, and coronary heart disease. Multivariable linear regression was used to examine the association of testosterone and estradiol with the Mini-Mental State Examination (MMSE) in participants with or without VRF. Restricted cubic spline (RCS) regression was performed to account for the nonlinearity of these associations.ResultsAn inverted “U” shaped non-linear relationship was found between testosterone concentration and MMSE score in men with one VRF (P overall =.003, non-linear P =.002). Estradiol showed an inverted “U” shaped non-linear relationship with MMSE score independent of VRFs (men without VRF, P overall =.049, non-linear P =.015; men with one VRF, overall P =.007, non-linear P =.003; men with two or more VRFs, overall P =.009, non-linear P =.005).ConclusionIn older men, an optimal level of sex steroid concentration may be beneficial to cognitive function and the VRFs should be considered when interpreting the relationship between sex steroid and cognitive function.

Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

Research on liposomal hydrogels loaded with "Liu Zi Tang" compound Chinese medicine for the treatment of primary ovarian insufficiency

IntroductionPrimary ovarian insufficiency (POI) is marked by reduced estrogen production and irregular ovulation, often resulting in lowered fertility or infertility. The traditional Chinese medicine "Liu Zi Tang" (LZT) has displayed promising outcomes in treating POI. Yet, conventional oral LZT administration poses challenges, including gastrointestinal irritation and the liver's first-pass effect. Thus, a novel drug delivery approach is imperative. MethodThis research incorporated the extracts of traditional Chinese medicine LZT into a novel liposome type, leading to the creation of LZT-glycerol plasmid/chitosan hydrogel (LZT-Gly-Lip/CS Gel) drug-carrier patches for achieving transdermal gradual-release drug delivery. The POI model was established in rats through intraperitoneal injection of vinylcyclohexene dioxide (VCD). A total of twenty-four 4-week-old female SD rats were distributed randomly among four groups: negative control (NC), vinylcyclohexene dioxide model (VCD), LZT/chitosan hydrogel treatment (VCD+LZT/CS Gel), and LZT glycerol liposome/chitosan hydrogel treatment (VCD+LZT-Gly-Lip/CS Gel). The therapeutic efficacy was evaluated by observing and analyzing the rats' body weight, diverse organ indices, serum hormone levels, and histopathological sections. ResultRats treated with LZT-Gly-Lip/CS Gel manifested significant enhancements in body weight (243.0 ± 11.0 g), serum estradiol concentration (64.362 ± 6.461 pg/mL), and uterus index (0.34 ± 0.05 %), demonstrating outcomes approaching normal levels (245.3 ± 12.0 g, 74.280 ± 8.903 pg/mL, 0.32 ± 0.10 %, respectively). DiscussionThese results confirm the effectiveness of LZT-Gly-Lip/CS Gel as a promising transdermal drug delivery system for addressing POI.

Association of intrauterine synechiae with pituitary gonadotrophin pulse patterns: A pilot study

Background Intrauterine synechiae (IS) is an acquired uterine condition that occurs when scar tissues (adhesions) form within the uterus and/or cervix, causing menstrual disturbance. However, approximately 50% of patients with IS are refractory to treatment. Therefore, other endocrine disturbances, such as gonadotropin disturbance, may affect treatment success. Study aim To analyze gonadotropin levels in women with and without IS. Methods Ten women with refractory IS experiencing amenorrhea since at least 6 months and nine with normal menstrual cycles (control group) were included in this study. Blood sample were collected every 10 minutes during a 4-h period. The serial ultrasound was performed in both groups for evaluating the cycle phase. Blood was collected when the follicles size was between 5–10 mm. Serum LH, FSH, progesterone and estradiol concentrations were measured. To detect LH and FSH pulses, the technique proposed by Santen and Bardin was adopted; therefore, one pulse was defined as a 20% increase in the concentrations as to the preceding point, followed by an important decrease. Results No differences were observed between the study groups at baseline. Estradiol levels were lower in the IS group than in the control group, but the difference was not statistically significant. During the first hour of monitoring, cumulative FSH pulsatile frequency of IS group was lower than one of control. Conclusion Our data suggest that the estradiol levels of IS participants are lower than those of women with normal menstrual cycle. The role of this finding in the physiology of uterine synechiae requires further investigation.

The differential sensitivity of the hypothalamic-hypophysial-ovarian axis to 5-hydroxytryptophan alters the secretion of estradiol.

Serotonin [5-hydroxytryptamine (5-HT)] modulates ovarian function. The precursor of 5-HT, 5-hydroxytryptophan (5-HTP), has been used to treat depression. However, the effects of 5-HTP on ovarian and reproductive physiology remain unknown. In this research, we analysed the impact of 5-HTP on the monoaminergic system and its interactions with the reproductive axis and ovarian estradiol secretion when administered by distinct routes. Female rats 30 days of age were injected with 5-HTP i.p. (100mg/kg), into the ovarian bursa (1.5µg/40µL) or into the median raphe nucleus (20µg/2.5µL) and were killed 60 or 120min after injection. As controls, we used rats of the same age injected with vehicle (0.9% NaCl). Monoamine, gonadotrophin and steroid ovarian hormone concentrations were measured. The injection of 5-HTP either i.p. or directly into the ovarian bursa increased the concentrations of 5-HT and the metabolite 5-hydroxyindole-3-acetic acid in the ovary. For both routes of administration, the serum concentration of estradiol increased. After i.p. injection of 5-HTP, the concentrations of luteinizing hormone were decreased and follicle-stimulating hormone increased after 120min. Micro-injection of 5-HTP into the median raphe nucleus increased the concentrations of 5-HT in the anterior hypothalamus and dopamine in the medial hypothalamus after 120min. Our results suggest that the administration of 5-HTP either i.p. or directly into the ovarian bursa enhances ovarian estradiol secretion.

Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial

An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.

Inducing luteolysis prior to atresia of the first follicular wave by altering the interval to prostaglandin F2ɑ administration after long-term progestin presynchronization

A series of experiments was designed to evaluate treatment schedules for control of the estrous cycle in which luteolysis is induced prior to atresia of the first follicular wave following a long-term progestin presynchronization treatment in beef heifers. The overarching hypothesis was that the proportion of heifers undergoing luteolysis and expressing estrus following PG administration would be affected by the duration of treatment with an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) and/or by the interval from CIDR removal to prostaglandin F2ɑ (PG; 500 μg cloprostenol) administration. In each experiment, heifers were blocked by reproductive tract score (RTS) and body weight (BW) and were assigned randomly within block to treatment. In Experiment 1, heifers (n = 91) were assigned to one of four treatments in a 2 x 2 factorial design: presynchronization via CIDR treatment for either 14 d or 18 d with administration of PG either 8 d or 9 d following CIDR removal. In Experiment 2, heifers (n = 63) were assigned to receive administration of PG either 9 d or 10 d following a 14 d CIDR presynchronization. In Experiment 3, heifers (n = 83) were assigned to receive administration of PG either 9 d or 16 d following a 14 d CIDR presynchronization. In Experiment 1, there was a tendency for a greater proportion of heifers to express estrus by 96 h after PG administration when PG administration occurred 9 d versus 8 d after CIDR removal (P = 0.07). Additionally, serum estradiol (E2) concentrations were greater at the time of PG administration when PG was administered 9 d versus 8 d after CIDR removal following an 18 d CIDR treatment (P = 0.006). In Experiment 2, pregnancy rate to AI (P/AI) was greater among heifers receiving PG administration 9 d versus 10 d after CIDR removal (P = 0.03). There was a tendency for largest follicle diameter (LFD) to be greater among non-estrous heifers receiving PG administration 10 d versus 9 d after CIDR removal when measured at timed AI (P < 0.08). In Experiment 3, there was a tendency for serum progesterone (P4) concentrations at the time of PG administration to be greater among heifers receiving PG administration 16 d versus 9 d after CIDR removal (P = 0.07). These results provide a preliminary evaluation of the feasibility of inducing luteolysis prior to atresia of the first follicular wave following long-term progestin presynchronization.

PSXIV-24 Inducing Luteolysis Before Atresia of the First Follicular Wave By Altering the Interval to Prostaglandin F2ɑ Administration After Long-Term Progestin Presynchronization

Abstract A series of experiments was designed to evaluate treatment schedules for control of the estrous cycle in which luteolysis is induced before atresia of the first follicular wave following a long-term progestin presynchronization treatment in beef heifers. The central hypothesis was that the proportion of heifers undergoing luteolysis and expressing estrus following PG administration would be affected by the duration of treatment with an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) and/or by the interval from CIDR removal to prostaglandin F2ɑ (PG; 500 µg cloprostenol) administration. In each experiment, heifers were blocked by reproductive tract score and body weight and assigned randomly within block to treatment. In Experiment 1, heifers (n = 91) were assigned to one of four treatments in a 2 x 2 factorial design: presynchronization via CIDR treatment for either 14 d or 18 d with administration of PG either 8 d or 9 d following CIDR removal. In Experiment 2, heifers (n = 63) were assigned to receive administration of PG either 9 d or 10 d following a 14 d CIDR presynchronization. In Experiment 3, heifers (n = 83) were assigned to receive administration of PG either 9 d or 16 d following a 14 d CIDR presynchronization. In Experiments 1 and 2, heifers were artificially insemination (AI) 8 to 12 h after expressing estrus, with timed AI performed 96 h after PG administration for heifers failing to express estrus. In Experiment 3, heifers expressing estrus by 66 h after PG administration were inseminated at that time and all remaining heifers were inseminated at 90 h. In Experiment 1, there was a tendency for a greater proportion of heifers to express estrus by 96 h after PG administration when PG administration occurred 9 d versus 8 d after CIDR removal (P = 0.07). Additionally, serum estradiol concentrations were greater at the time of PG administration when PG was administered 9 d versus 8 d after CIDR removal following an 18 d CIDR treatment (P = 0.006). In Experiment 2, pregnancy rate to AI (P/AI) was greater among heifers receiving PG administration 9 d versus 10 d after CIDR removal (P = 0.03). There was a tendency for largest follicle diameter measured at timed AI to be greater among non-estrous heifers receiving PG administration 10 d versus 9 d after CIDR removal (P &amp;lt; 0.08). In Experiment 3, there was a tendency for serum progesterone concentrations at the time of PG administration to be greater among heifers receiving PG administration 16 d versus 9 d after CIDR removal (P = 0.07). These results provide a preliminary evaluation of the feasibility of inducing luteolysis before atresia of the first follicular wave following long-term progestin presynchronization.

Determinants of Bone Mineral Density in Iranian Women with Polycystic Ovary Syndrome.

Whether the endocrine aberrations caused by polycystic ovary syndrome (PCOS) might influence bone density in women of reproductive age is controversial. The present study aimed to compare PCOS women to a control group matched in terms of age and body mass index (BMI) regarding bone indices and to clarify the potential relationship between their hormonal changes and bone density. This case-control study consisted of 61 PCOS patients, and 35 women with normal ovulatory function served as controls. Bone parameters, including bone mineral content (BMC) and bone mineral density (BMD) in addition to T- and Z-scores, were measured at the lumbar vertebrae, neck of the left femur, hip, and distal part of the radial bone, using dual-energy X-ray absorptiometry. Blood samples were taken to be tested for biochemical parameters and serum concentrations of insulin, osteocalcin, parathyroid hormone (PTH), vitamin D, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, dehydroepiandrosterone sulfate (DHEAS), and estradiol were measured. Insulin resistance was evaluated through the homeostatic model assessment of insulin resistance (HOMA-IR). The results revealed greater levels of HOMA-IR and total testosterone in PCOS women than in controls. Nevertheless, the two groups were comparable in terms of bone parameters. In the control group, BMI was the only determinant of bone density at most of the skeletal sites. Nonetheless, BMI and HOMA-IR were independently and positively associated with bone indices at the femoral neck (FN) and total hip in the PCOS group. Parathyroid hormone and vitamin D concentrations were not different in the two groups. However, phosphate levels were higher in PCOS patients (P = 0.025). Osteocalcin was inversely correlated to BMI, and both groups had a negative correlation between DHEAS and PTH. Serum phosphate was inversely and independently associated with estrogen in the PCOS group (r = -0.377, P = 0.004). Body mass index and HOMA-IR were independent and positive determinants of FN and total hip bone density in the PCOS subjects. Nonetheless, in the non-PCOS women, BMI was the only independent determinant of bone density at most of the skeletal sites. Additionally, osteocalcin was inversely correlated with BMI in both groups.

A model for predicting low progesterone levels on the day of embryo transfer in hormonally prepared vitrified-warmed embryo transfer cycles: A secondary analysis of a prospective cohort study.

To develop a model that predicts low progesterone (P) levels on the day of embryo transfer (ET) based on patient and cycle characteristics, including serum estradiol (E2 ) concentration after vaginal administration of micronized E2 for endometrial preparation. A prospective cohort of 193 patients scheduled for cryopreserved blastocyst transfer during an artificial endometrial preparation cycle, using micronized E2 vaginally for first 4 days (4 mg/day), followed by oral administration (6 mg/day). Blood sampling for E2 was performed prospectively on day-5 of vaginal administration and analysis was performed retrospectively. On sixth day of P treatment (daily 300 mg of vaginal micronized P tablets), P levels were measured on ET day. Primary outcome measure was serum P levels after vaginal E2 administration. Patients with low P levels on the day of ET (<7.8 ng/mL, 25th percentile) were heavier (p < 0.001) and exhibited lower day 5 serum E2 levels (p < 0.001) compared with patients with adequate P levels. Multivariate linear regression analysis revealed that weight (p = 0.003) and day 5 E2 levels (p < 0.001) were independently associated with the P levels. The sensitivity, specificity, and positive and negative predictive values (%) were 71.4, 55.6, 35.4, and 85.1 for weight ≥ 65 kg; 71.4, 61.8, 38.9, and 86.4 for day 5 E2  ≤ 1615 pg/mL; 59.2, 83.3, 54.7, and 85.7 for the combination of these two variables; and 82.9, 62.5, 54.7, and 87.0 for the sequential inclusion of these variables, respectively. Low day 5 E2 levels following vaginal administration and high weight are independently associated with low P levels on the day of ET. Predictive performance is enhanced when these variables are considered sequentially or in combination.

OR06-03 Intergenerational Exposure To Endocrine-disrupting Chemicals (Edcs) Affects Dopamine-mediated Behaviors In A Sex-Specific Manner In Rats

Abstract Disclosure: E.N. Hilz: None. C. Schnurer: None. S. Bhamidipati: None. L. Thompson: None. E. Morales-Ledesma: None. A.C. Gore: None. Polychlorinated biphenyls (PCBs) are a weakly estrogenic class of ubiquitous environmental EDCs that affect a range of sex-specific neuroendocrine and reproductive outcomes. Furthermore, these effects can extend intergenerationally via epigenetic changes carried down the germline. In humans, PCBs are associated with sexually dimorphic and hormone sensitive neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD) and mood disorders such as depression; however, little preclinical work has modeled these cognitive changes in rats and none has determined if they extend intergenerationally via endocrine-mediated changes to the brain dopamine system. In the current work, three generations of male and female Sprague-Dawley rats were exposed to the PCB mixture Aroclor 1221 (A1221) at different life stages: as adults; through perinatal exposure via mother's diet; or preconceptionally, as the germ cells within the exposed fetus. Adults of each generation underwent a battery of behavioral tasks to assess attentional phenotype, cognitive flexibility, and affect as measured by attentional set-shifting, conditioned orienting, and sucrose preference tests. These outcomes were correlated with both serum estradiol concentrations and dopamine cell quantity in the midbrain. Results revealed that A1221 treatment had sex- and generation-specific effects: in adult-exposed females, decreased conditioned orienting suggested a hyporesponsive attentional phenotype; in males, preconceptional exposure reduced cognitive flexibility via impaired attentional set-shifting. All rats showed a strong preference for sucrose solution; however, A1221 treatment decreased the total amount of sucrose solution consumed (indicating anhedonia) regardless of sex or timing of exposure. Dopamine cell numbers were inversely affected by A1221 between the sexes: decreased in females and increased in males, which correlates well with the cognitive changes observed. Relationships among estradiol concentration, cognitive changes, and dopamine cell quantity will be ascertained using a multilevel model that accounts for endocrine-mediated disruptions at the brain, body, and behavioral levels. These data show that the PCB mixture A1221 impairs different aspects of cognitive behavior between the sexes depending on timing of exposure, while having a broader effect of increased anhedonia, in a manner potentially mediated by hypo- or hyper-availability of midbrain dopamine and serum estradiol. Supported by RO1 ES029464. Presentation: Thursday, June 15, 2023