Serum Estradiol Concentrations Research Articles

Knockdown of lncRNA Meg3 delays the onset of puberty in female rats

This study investigated how lncRNA Meg3 affects the onset of puberty in female rats. We determined Meg3 expression in the hypothalamus-pituitary-ovary axis of female rats at the infancy, prepubertal, pubertal, and adult life stages, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). We also assessed the effects of Meg3 knockdown on the expression levels of puberty-related genes and Wnt/β-catenin proteins in the hypothalamus, time of puberty onset, levels of reproductive genes and hormones, and ovarian morphology in female rats. Meg3 expression in the ovary varied significantly between prepuberty and puberty (P < 0.01). Meg3 knockdown decreased the expression of Gnrh, and Kiss1 mRNA (P < 0.05) and increased the expression of Wnt (P < 0.01) and β-catenin proteins (P < 0.05) in the hypothalamic cells. Onset of puberty in Meg3 knockdown rats was delayed compared to the control group (P < 0.05). Meg3 knockdown decreased Gnrh mRNA levels (P < 0.05) and increased Rfrp-3 mRNA levels (P < 0.05) in the hypothalamus. The serum concentrations of progesterone (P4) and estradiol (E2) of Meg3 knockdown rats were lower than those in the control animals (P < 0.05). Higher longitudinal diameter and ovary weight were found in Meg3 knockdown rats (P < 0.05). These findings suggest that Meg3 regulates the expression of Gnrh, Kiss-1 mRNA and Wnt/β-catenin proteins in the hypothalamic cells, and Gnrh, Rfrp-3 mRNA of the hypothalamus and the serum concentration of P4 and E2, and its knockdown delays the onset of puberty in female rats.

Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea

Background Neurokinin B (NKB) belongs to the tachykinin family of proteins who’s regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. Aim To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. Materials and methods A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. Results Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. Conclusions Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA.

Ex Vivo Colonic Tissue Susceptibility to HIV-1 in Cisgender Men and Women.

The biology of HIV-1 acquisition through unprotected receptive anal intercourse is understudied. Considering that sex hormones are implicated in intestinal physiology, pathology, and HIV acquisition and pathogenesis, we explored links between sex hormones, ex vivo HIV-1BaL infection of colonic mucosa, and candidate biomarkers of susceptibility to HIV-1 (CD4+ T cell frequencies and immune mediators) in cisgender women and men. No consistent significant associations between sex hormone concentrations and ex vivo tissue infection with HIV-1BaL were detected. In men, serum estradiol (E2) concentrations were positively associated with tissue proinflammatory mediators (IL17A, GM-CSF, IFNγ, TNFα, and MIG/CXCL9) and serum testosterone concentrations were negatively associated with frequencies of activated CD4+ T cells (CD4+CCR5+, CD4+HLA-DR+, and CD4+CD38+HLA-DR+). In women, the only significant interactions were positive associations between progesterone (P4)/E2 ratios and tissue ILRA concentrations and between P4/E2 ratios and frequencies of tissue CD4+α4β7high+ T cells. The study did not reveal relationships between biological sex or phase of the menstrual cycle and ex vivo tissue HIV-1BaL infection and tissue immune mediators. A comparison of CD4+ T cell frequencies between study groups revealed a higher frequency of tissue CD4+α4β7high+ T cells in women versus men. In contrast, higher frequencies of tissue CD4+CD103+ T cells were detected in men versus women in the follicular phase of the menstrual cycle. Overall, the study identified associations between systemic sex hormone concentrations, biological sex, and tissue candidate biomarkers of susceptibility to HIV-1. The significance of these results for tissue susceptibility to HIV-1 and early HIV-1 pathogenesis warrants further investigation.

Effects of electroacupuncture on pregnancy outcome in poor ovarian response patients of kidney essence deficiency and undergoing in vitro fertilization-embryo transfer

To observe the effects of electroacupuncture (EA) on ovarian reaction, egg and embryo quality, as well as pregnancy rate in poor ovarian response (POR) patients of kidney essence deficiency and undergoing in vitro fertilization-embryo transfer (IVF-ET). Ninety-six patients who met the inclusion criteria were randomly divided into an EA group and a control group, with 48 cases in each group. Before IVF-ET, the patients in the EA group received EA, once daily, 2 or 3 treatments a week for 12 weeks. Before and after the treatment, traditional Chinese medicine (TCM) syndrome score and clinical pregnancy rate were assessed in two groups. The concentrations of serum follicle-stimulating hormone (FSH), luteinsing hormone, estradiol, progesterone and anti-mullerian hormone were detected by chemiluminescence; the contents of serum insulin-like growth factor-1, serum inhibin B (INHB) and Kisspeptin in follicular fluid were determined by enzyme linked immunosorbent assay (ELISA); the antral follicle counting (AFC) was detected by color Doppler ultrasonography; and the egg and embryo conditions were observed under microscope. Fourteen days after embryo transfer, the positive rate of serum hemchoriconic gonadotropin (HCG) and clinical pregnancy rate were calculated. After the treatment, the TCM syndrome score and level of serum FSH were reduced (P<0.05); the INHB in serum and AFC were increased (P<0.05) when compared with those before the treatment in the EA group. After the treatment, in comparison with the control group, the TCM syndrome score and level of serum FSH were lower (P<0.05); and the contents of serum INHB, AFC, the numbers of MⅡ eggs and high-quality embryos, as well as serum HCG positive rate were all increased (P<0.05) in the EA group. EA can relieve the clinical symptoms of TCM in POR patients of kidney essence deficiency and undergoing IVF-ET, increase the ovarian reserve, reduce the serum FSH level, and improve the content of serum INHB, and the quality of eggs and embryos. This therapy tends to improve the clinical pregnancy rate and clinical pregnancy outcome.

Serum leptin, estradiol and testasterone concentrations in normal healthy fertile women with different weights

Background: Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese, leptin affects not only nutritional homeostasis but also reproductive events. A prospective study was done to investigate serum leptin ,estradiol and testosterone levels in 100 fertile healthy women with regular cycle aged(18-45) years with different weights and to see the influence of obesity on these parameters , the correlation of leptin with body mass index ,waist hip ratio , estradiol and testosterone level was determined. Methods fasting blood samples were obtained for the measurement of all studied parameters. serum concentrations of leptin was measured using ( ELISA) , estradiol and testosterone concentrations measured by ( ELFA ) technique (enzyme linked fluorescent assay)by mividus, the body-mass index was defined as the weight in kilo-grams divided by the square of the height in meters. Results: according to the body mass index (BMI), the women were divided in to 3 groups: Group (1) normal weight(30 women) with BMI≤24.9 kgm2 , group( 2) Overweight(30 women) with BMI=25-29.9 kgm2 , group ( 3) obese (40 women) with BMI≥ 30 kgm2. The mean value ±SD of the weight in normal weight group was (53±5)kg , of overweight group was(65.8 ± 4.7) and of obese group was(91.6±16) so there was a highly significant difference between the 3 groups (p-value=0.000) , the Mean ± SD of waisthip ratio in normal, over weight and obese groups were (0.79 ± 0.06, 0.81 ± 0.03 and 0.84 ± 0.05) respectively and there was significant difference between the 3 groups(p-value=0.04), the leptin mean ± SD of normal ,overweight and obese groups were(12.4±6.7, 18.2±5.8 and 24.4±16.4) respectively, and p-value =0.000. Estradiol mean±SD of normal ,overweight and obese groups were (46.2±30.2 ,54.6±25 and79.9 ±52.7)respectively ,p-value =0.03,Testosterone mean±SD of normal, overweight and obese groups were (0.14±0.06, 0.16±0.07 and 0.2±0.09)respectively, p-value =0.00. Conclusions. Leptin correlate significantly with BMI, WH ratio and estradiol level, the women with higher BMI(obese) has higher level of leptin, estradiol and testosterone so the leptin clearly appears to be linked to the reproductive system .

Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial.

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.

Endometrial safety of low-dose vaginal estrogens.

It is estimated that up to 50% to 90% of postmenopausal women may experience genitourinary syndrome of menopause (GSM), which may have a detrimental impact on quality of life. One of the most effective modes of treatment of GSM is low-dose vaginal estrogens. Numerous studies have addressed the safety of these estrogens using endometrial biopsy and/or endometrial thickness on ultrasound. Based on these studies, the consensus is that low-dose vaginal estrogens do not substantially increase the risk of endometrial hyperplasia or cancer; however, the data are severely limited by short duration of follow-up. Although long-term trials are warranted, they are difficult to carry out, costly, and will not yield data for years. More immediate information regarding endometrial safety may be obtained from studies measuring endometrial tissue and serum concentrations of estradiol, estrone, and relevant equine estrogens after administration of different estrogen formulations and doses. This would allow us to understand better the metabolism of estrogens by the vagina and endometrium, and how much estrogen is reaching the endometrium. Here, we discuss metabolism, receptor binding, and signaling of estrogens in vaginal and endometrial tissue, and summarize the existing studies on the endometrial impact of low-dose vaginal estrogen treatment in postmenopausal women.

Does Intense Endurance Workout Have an Impact on Serum Levels of Sex Hormones in Males?

The benefits of physical activity and sports are widely known and proved to be crucial for overall health and well-being. In this research, the authors decided to measure the impact of endurance training in a professional male rowing team on the serum concentration levels of testosterone, estradiol, sex hormone binding globulin (SHBG) and nitric oxide (NO) and apolipoprotein A1 (Apo-A1). Proper levels of the serum concentration are necessary in order to maintain physical effectiveness. Authors analyzed the data and reviewed the former conterminous articles to find the possible mechanisms leading to changes of serum concentration of certain hormones and molecules. The direct effect of physical activity was a decrease in testosterone serum concentration (from 7.12 ± 0.4 to 6.59 ± 0.35 (ng/mL)), sex hormone binding globulin serum concentration (from 39.50 ± 2.48 to 34.27 ± 2.33 (nmol/L)), nitric oxide serum concentration (from 440.21 ± 88.64 to 432 ± 91.89 (ng/mL)), increase in estradiol serum concentration (from 78.2 ± 11.21 to 83.01 ± 13.21 (pg/mL)) and no significant increase in Apo-A1 serum concentration (from 2.63 ± 0.2 to 2.69 ± 0.21 (mg/mL)). Low testosterone concentration in OTS may be a consequence of increased conversion to estradiol, because gonadotropic stimulation is maintained. Apo-A1 serum concentration was measured due to a strong connection with testosterone level and its possible impact of decreasing cardiovascular risk.

Associations between exposure to a mixture of phenols and sex steroid hormones among pre- and postmenopausal women: evidence from NHANES 2015-2016.

Environmental phenols are well known as emerging endocrine-disrupting chemicals; however, their impacts on sex hormone homeostasis among pre- and postmenopausal women remain unknown. Our objective was to evaluate independent and combined relationships between phenol levels in urine and sex steroid hormones among 323 premenopausal women and 263 postmenopausal women from National Health and Nutrition Examination Survey (NHANES) 2015-2016. A total of 10 phenol concentrations in urine were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum concentrations of estradiol and total testosterone were measured by LC-MS/MS and serum sex hormone-binding globulin (SHBG) concentrations were measured using an immunofluorometric assay. Multivariable linear regression models were conducted to explore associations of individual phenol concentration in urine with natural logarithm-transformed serum hormone levels. Bayesian kernel machine regression (BKMR) model was conducted to evaluate phenol mixtures exposure in association with sex hormones among pre- and postmenopausal women, respectively. Considering both single-chemical models and multiple-chemical models, each doubling of urinary BPS concentration was significantly inversely related to serum SHBG concentration in premenopausal women (percent change: -6.70%, 95% confidence interval, CI: -11.12%, -2.73%; P = 0.002). Moreover, every doubling of urinary BP-3 concentration was significantly positively associated with SHBG level in serum (percent change: 3.53%, 95%CI: 0.70%, 5.70%; P = 0.008). Regarding postmenopausal women, inverse associations between urinary BPS levels and serum estradiol concentrations were observed (percent change: -8.62%, 95% CI: -15.33%, -2.06%; P = 0.012). The results revealed that BPS and BP-3 exposure may adversely disrupt sex hormone homeostasis at the current exposure levels among women in the USA. The findings and their underlying mechanisms are warranted to be confirmed and comprehensively interpreted in further epidemiological and experimental studies.

Phase 2, double-blind, randomized, placebo-controlled study of the safety and efficacy of elagolix in women with polycystic ovary syndrome

Evaluate the efficacy and safety of elagolix, a GnRH antagonist, to treat polycystic ovarian syndrome (PCOS). A phase 2, multicenter, double-blind, randomized, placebo-controlled trial. Outpatient and academic medical centers. One hundred fourteen women with PCOS (aged 18-35 years, body mass index 18.5-38 kg/m2). Patients were randomized 2:2:2:2:2:3 to elagolix (25 mg twice daily, 50 mg once daily, 75 mg twice daily, 150 mg once daily, and 300 mg twice daily) or placebo. The primary endpoint was menstrual cycle normalization (defined as 2 menstrual cycles 21-35 days in length during the 4-month treatment period). The secondary endpoint was change from baseline to week 1 in the area under the luteinizing hormone (LH) serum concentration-time curve (AUC). Additional endpoints included change from baseline in serum hormone levels. No significant improvement in restoring normal menstrual cycles was observed in treated subjects; 3 of 114 patients met the primary endpoint. Six patients experienced progesterone elevations indicative of ovulation. The LH levels decreased from baseline to week 16, and LH AUC was significantly reduced from baseline to week 1 in all elagolix treatment groups (P<.1 vs placebo). Follicle-stimulating hormone (FSH) levels generally remained stable through week 16, with no significant differences in FSH AUCs. Serum estradiol and testosterone concentrations were consistently reduced from baseline in all elagolix dose groups compared with placebo. Adverse event rates were similar across treatment groups. Elagolix treatment did not normalize the ovulatory cycle in patients with PCOS. NCT03951077.

Smooth endoplasmic reticulum cluster presence does not affect embryo ploidy.

We examined the impacts of the smooth endoplasmic reticulum cluster (sERC) presence on embryonic development and blastocyst ploidy. Patients who underwent oocyte retrieval from January 2019 to November 2021 were included in the study. We classified the oocytes into three groups: normal oocytes in the sERC ( -) cycle, normal oocytes in the sERC ( +) cycle, and sERC ( +) oocytes. Next, the levels of serum estradiol, progesterone, anti-Mullerian hormone, follicle-stimulating hormone, and human menopausal gonadotropin were compared between the groups. Moreover, fertilization, degeneration, and abnormal fertilization rates were compared between groups. To investigate developmental outcomes, the blastocyst and good-quality blastocyst rates after intracytoplasmic sperm injection were compared. The quality of the transferred blastocysts was evaluated at follow-up. Additionally, embryos were submitted for next-generation sequencing analysis to examine the effect of sERC presence on ploidy. The sERC ( +) group had significantly higher serum estradiol, serum progesterone, and serum anti-Mullerian hormone concentrations compared to those in the sERC ( -) group (P < 0.01). The abnormal fertilization rate was higher in the sERC ( +) cycle-sERC ( +) oocyte group (16.1%; 37/230) than in the sERC ( +) cycle-normal oocyte (6.2%; 63/971) and sERC ( -) cycle-normal oocyte groups (7.1%; 174/2467) (P < 0.01). After embryo transfer, nine women gave birth, and no confirmed congenital anomalies were observed. There was no significant difference in ploidy between the sERC ( +) and sERC ( -) groups. The occurrence rates of embryos with euploidy were similar between the sERC ( +) and sERC ( -) groups.

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause.

Phthalates, ubiquitous endocrine-disrupting chemicals, may affect ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1189 multiracial/multiethnic women aged 45 to 56 years without hormone therapy from the Study of Women's Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999 to 2000 and 2002 to 2003, resulting in a total of 2111 observations. Linear mixed-effect models were used to calculate percentage differences (%D) and 95% CIs in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed statistically significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%; 95% CI, -3.66 to -0.47) and MnBP with testosterone (%D: -1.99%; 95% CI, -3.82 to -0.13), after adjusting for multiple comparisons with false discovery rates less than 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%; 95% CI, -24.10 to -3.14), MEHHP (%D: -15.58%; 95% CI, -24.59 to -5.50), and MEOHP (%D: -13.50%; 95% CI, -22.93 to -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.

Embryo Cryopreservation in a Patient with Sickle Cell Disease Utilizing Letrozole and Enoxaparin: A Case Report

To describe a patient with sickle cell disease, a prothrombotic disorder, who underwent successful embryo cryopreservation for the purposes of fertility preservation prior to hematopoietic stem cell transplant. To report a successful case of gonadotropin stimulation and embryo cryopreservation using the aromatase inhibitor letrozole to maintain low serum estradiol to minimize thrombotic risk in a patient with sickle cell disease (SCD) and history of retinal artery thrombosis planning hematopoietic stem cell transplant (HSCT). The patient was given letrozole (5 mg daily) as well as prophylactic enoxaparin while undergoing gonadotropin stimulation with an antagonist protocol to preserve fertility prior to HSCT. After the oocyte retrieval, letrozole was continued for one additional week. The patient's peak serum estradiol concentration was 172 pg/mL during gonadotropin stimulation. Ten mature oocytes were retrieved and a total of 10 blastocysts were cryopreserved. The patient required pain medication and intravenous fluids after oocyte retrieval due to pain but had significant improvement at the scheduled post-operative day one follow-up. No embolic events occurred during stimulation or 6 months thereafter. The utilization of definitive treatment for SCD with stem cell transplant is increasing. We successfully used letrozole to maintain low serum estradiol during gonadotropin stimulation along with prophylactic enoxaparin in a patient with SCD to minimize her risk of thrombosis. This approach will allow patients planning definitive treatment with stem cell transplant the opportunity to preserve their fertility safely.

At-home urine estrone-3-glucuronide quantification predicts oocyte retrieval outcomes comparably with serum estradiol

To investigate the feasibility of monitoring urine estrone-3-glucuronide (E3G) with an at-home device during gonadotropin stimulation for invitro fertilization and oocyte cryopreservation. Prospective, observational cohort study. Private fertility clinic. Thirty patients undergoing stimulation with a gonadotropin-releasing hormone antagonist protocol for invitro fertilization or oocyte cryopreservation. Daily collection of the first urine in the morning during stimulation and analysis performed at home by each patient with the Mira Fertility Tracker. Primary outcomes were correlation of urine E3G and serum estradiol (E2) concentrations on the day of trigger to the number of total and metaphase 2 oocytes (MII). Secondary outcomes of interest were the correlation of matched E3G and E2 measurements and the daily trends of E3G and E2 during stimulation. Both urine E3G and serum E2 concentrations on the day of trigger significantly correlated with retrieval outcomes to a similar extent, with E3G demonstrating slightly higher correlation to the number of MII oocytes than that demonstrated by E2 (r = 0.485 vs. 0.391, respectively). The Pearson correlation coefficient for matched E3G and E2 levels was 0.761. The correlation coefficients of determination for daily trends of E3G and E2 during stimulation were 0.7066 and 0.6102, respectively. Measured on the day of trigger, urine E3G monitoring during gonadotropin stimulation was comparable with serum E2 for predicting oocyte retrieval outcomes. Matched daily samples confirmed good correlation of urine E3G and serum E2. The option of at-home estrogen monitoring with devices such as Mira offers an alternative to traditional serum monitoring that may improve patient experience. NCT05493202.

A case of primary ovarian failure with Nijmegen Breakage a chromosomal instability syndrome

Abstract Introduction Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive chromosomal instability syndrome, characterized by dysmorphic facial features, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, combined immune deficiency, radiosensitivity, increased risk for cancer, as well as premature ovarian failure. Nibrin gene mutation is responsible for the pathogenesis of the disease. The mechanism of gonadal failure in NBS is thought to be meiotic arrest in gametocytes. Clinical Case A 23-year-old female was admitted to the Marmara University endocrinology outpatient clinic because of secondary amenorrhea. Her first menarche occurred spontaneously at the age of 13, but she has never bled again afterwards. In physical examination, blood pressure was 109/68 mmHg, pulse was 80/min, and temperature was 36°C. Her height was 163 cm, and weight was 67 kg, BMI: 25.6 kg/m2. Midfacial prominent appearance, micrognathia, microcephaly was observed. Breast was assessed for II stage in Tanner scale. Ferriman–Gallwey score was 5. Psychomotor development was natural, cognitive dysfunction was not observed. Her three siblings and aunt had a history of infertility, also her parents were third degree consanguineous. The patient stated that she had recurrent sinopulmonary infections and used several antibiotics since childhood. However, there was no hospitalization due to infection by now. Her two older sisters died due to cancer when they were 10 and 21 years old. The patient had primary ovarian insufficiency according to elevated serum gonadotropins concentration and low serum estradiol concentration (Table 1). The uterus was 50 mm in size, its contours were smooth, and the echo of myometrium was diffusely homogeneous. Bilateral ovaries were not observed in the suprapubic pelvic US examination. Karyotype analysis was performed that was found 46, XX. When considering her family history, facial dysmorphic appearance, and findings of primary ovarian failure, genetic analysis revealed NM_001024688.2 c.625C&amp;gt;T(p.Q209*) homozygous mutation. The patient was started on hormone replacement therapy (estrogen 2 mg once daily, dydrogesterone 10 mg once daily) after the diagnosis. Genetic counseling, immunodeficiency and malignancy screenings were performed. Interestingly, despite the history of recurrent infection, total Ig levels and vaccine responses were normal. Although no malignancy was observed in our case, it is noteworthy that two older sisters died due to cancer. It was recommended to continue the annual screenings. Conclusion Family history should be thoroughly questioned in patients presenting with hypogonadism. NBS should be kept in mind as a rare cause in the presence of a typical phenotypic appearance, recurrent infections, and a family history of infertility and malignancy.

Estrus Behaviour and Estrus Intensity Score in Relation to Hormonal Profile in Kankrej Cows at an Organized Farm

The present investigation was undertaken to study the estrus behaviour in Kankrej cattle at an organized farm during 3 different seasons. In each of three seasons, seven (07) Kankrej heifers and seven (07) Kankrej cows showing estrus were considered. In Kankrej cattle, majority of the animals showed acceptance of teaser bull (100%), estrual mucus discharge (88.10%), homosexuality (78.57%), excitement, and edema erythema and wetness of vulva (76.19% each), frequent micturition (59.52%) and bellowing (16.67%). None of the Kankrej cattle went partial or complete off-feed during estrus phase. Overall it was revealed that the estrus signs were manifested more during summer season than monsoon and winter, which shows the heat tolerance capability of the Kankrej cows in the area. Nearly three forth (73.81%) of the total Kankrej cows exhibited normal and above normal estrus intensity score, whereas one forth (26.19%) animals showed weak estrus intensity score. The difference between Kankrej cows and heifers for overall intensity score was found non-significant (p&gt;0.05). The serum estradiol concentrations in Kankrej heifers and cows were significantly higher on the day of estrus than the corresponding levels on 11th day of estrus with inverse trend of serum progesterone in all three seasons. On the day of estrus the mean estradiol level in Kankrej heifers and progesterone levels in cows were higher in summer than winter and monsoon.

Analytical Performance Evaluation for Estradiol using Liquid Chromatography–Tandem Mass Spectrometry

BackgroundThere is an increased need for the sensitive and accurate measurement of estradiol levels in patients with estradiol-related endocrine disorders. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a reliable and accurate method for measuring steroid hormone levels. Here, we aimed to establish an LC-MS/MS-based method to quantify estradiol levels without sample derivatization and evaluated its analytical performance. MethodsSciex Triple Quad 6500 + LC-MS/MS was used for estradiol analysis. We evaluated its analytical performance, including linearity, precision, the lower limit of detection and quantification (LoD and LoQ, respectively), accuracy, and carryover. The estradiol results determined by LC-MS/MS were compared with those obtained using a chemiluminescent microparticle immunoassay. ResultsThe LC-MS/MS output was linear for serum estradiol concentrations in the range of 0.2–10311.6 pmol/L. The intra-laboratory precision (coefficient of variation) was 3.0–10.1 %. The LoD and LoQ were 2.8 and 7.5 pmol/L, respectively. The overall accuracy was within 15 % of bias, and the carryover was within the acceptable range (<1.0 %). The results of the estradiol analysis determined by LC-MS/MS were comparable to those obtained by the chemiluminescent microparticle immunoassay (r2 = 0.9843), although there was a negative bias of − 17.82 (95 % confidence interval, −27.21 to − 8.44). ConclusionsA highly sensitive, derivatization-free LC-MS/MS method was successfully developed in this study. This may be beneficial for estradiol measurements in patients with estradiol-related endocrine disorders.

Effect of supplementation of polyunsaturated fatty acid-rich linseed grain on steroid hormones and reproduction in Goats

The effect of polyunsaturated fatty acid (PUFA)- rich linseed grain supplementation was assessed on steroid hormones and reproduction in goats. Twenty-four acyclic and clinically healthy non-descript goats were divided into 4 equal groups. Gr A(control) was supplemented with concentrate without linseed grain while Gr B, C and D were supplemented with concentrate containing 10, 15 and 20% of linseed grain respectively. Goats were supplemented during prebreeding period for 30 days. Blood samples were collected for estimation of serum estradiol and progesterone during pre-breeding and post-oestrus periods. Serum estradiol concentration (pg/ml) was significantly (P<0.05) higher in Gr B (58.79±3.62), C (70.34±5.95) and D (49.48±5.02) compared to control Gr A (38.51±4.03) on 30 days of pre-breeding period. It was significantly (P<0.05) lower in Gr B (9.61±1.45) compared to A (15.61±2.65), C (12.61±1.35) and D (12.61±2.65) on 7 days of post-oestrus period. Serum progesterone levels were comparable among the groups on 30 days of pre- breeding and on 7 days of post- oestrus period. Blood glucose level was comparable on 21 days of supplementation in pre-breeding and 0 day of postoestrus period. Conception (83.33%) and kidding (83.33%) rates were higher in Gr B compared to control Gr A (50.00 and 33.33%). The study suggested that supplementation of PUFA-rich linseed grain in concentrate @ 15% decreased the serum estradiol and increased the serum progesterone during post-oestrus period and improved the conception and kidding rates in goats.

Функционирование АВСВ1-белка при беременности

Objective. To study the functioning of ABCB1 protein in pregnancy, namely, to evaluate its amount in the organs that play a significant role in pharmacokinetics and its functional activity at the whole organism level. Materials and methods. The study was performed on 52 female rabbits divided into two groups. Serum concentrations of progesterone, estradiol, testosterone, and prolactin were determined in animals before the experiment and on days 7, 14, 21, and 28 of pregnancy by the radioimmunoassay method. In group 1, the amount of ABCB1 protein was assessed in the jejunum, liver, kidneys, and cerebral cortex at the indicated gestational ages by enzyme immunoassay. In group 2, the functional activity of ABCB1 protein was studied during the same periods by evaluating the pharmacokinetics of its marker substrate fexofenadine. Results. Elevated serum concentrations of progesterone were detected at all gestational ages. There was an increase in the amount of ABCB1 protein compared to non-pregnant animals in the jejunum on days 7, 14, 21, and 28, in the liver – on day 7 with a tendency to increase on day 14, in kidneys and large cerebral cortex – on day 28. Pharmacokinetic parameters of fexofenadine did not differ significantly from those of intact animals, except for elevated T1/2 values on day 14. The results indicate an increase in the amount of ABCB1 protein in the studied organs, which is leveled by a decrease in its activity, which is probably due to the effect of progesterone. Conclusion. The functioning of ABCB1 protein does not change throughout the gestational period; therefore, pharmacotherapy with ABCB1 protein substrates during pregnancy does not require dose adjustments. Key words: ABCB1 protein (P-glycoprotein, Pgp), activity, amount, pharmacotherapy during pregnancy, function

Association between reproductive factors in women and risk of brain ageing and dementia

AbstractBackgroundWomen have a higher prevalence of dementia than men. We determined the association between female reproductive factors and risk of cognitive outcomes, including incident dementia, in a community‐based sample of cognitively healthy individuals.MethodLifetime reproductive factors including age of menarche, age of menopause, reproductive lifespan (age of menopause minus age of menarche), number of live births, post‐menopausal hormone replacement therapy use, and serum estradiol and estrone concentrations were measured in 796 dementia‐free women [mean age 68.4 (SD 5.7) yr] from the Framingham Heart Study Offspring cohort at examination cycle seven (1998‐2001). We related reproductive factors to subsequent risk of incident dementia. Structural MRI brain measures and neurocognitive test performance were included as secondary outcomes.ResultDuring a median 10 [Q1‐Q3, 8.04‐10.0] year follow‐up, 138 participants developed dementia. On Cox proportional‐hazards analysis adjusting for age and education, a longer reproductive lifespan was associated with a reduced risk of incident dementia (HR 0.94, 95% CI 0.91‐0.98, p = 0.004) while earlier age of menopause of ≤49 vs 50‐51 years was associated with an increased dementia risk (HR 2.56, 95% CI 1.12‐5.88, p = 0.027). Earlier menopause (≤49 versus 50‐51 years) was cross‐sectionally associated with lower hippocampal volume (β±SE, ‐0.123±0.057, p = 0.03). Compared to no live births, 1‐2 live births (5.85±2.03, p = 0.004) and ≥3 live births (5.17±2.06, p = 0.01) were associated with greater total cerebral brain volume. Use of post‐menopausal HRT (0.15±0.055, p = 0.007) and elevated serum estradiol (0.058±0.027, p = 0.03) and estrone concentrations (0.078±0.029, p = 0.006) were cross‐sectionally associated with improved abstract reasoning (Similarities test). Compared to no live births, 1‐2 live births (0.20±0.08, p = 0.018) and ≥3 live births (0.25±0.08, p = 0.003) were also associated with superior visuospatial performance.ConclusionGreater exposure to estrogen throughout a woman’s reproductive life was associated with a lower risk of incident dementia and cross‐sectionally associated with larger brain volumes and enhanced cognitive performance. Our results suggest positive cognitive benefits of greater lifetime estrogen exposure and highlight the potential role of estrogen exposure in modifying the risk of dementia.