Estrone Levels Research Articles

Elevated Steroid Hormone Levels in Active Chronic Central Serous Chorioretinopathy.

Chronic central serous chorioretinopathy (cCSC) is characterized by fluid accumulation between photoreceptors and the retinal pigment epithelium of which the cause is unknown. Associations with steroid use, stress, pregnancy, and the male sex suggest a role for the steroid hormone system in the disease. Here, we performed a comprehensive analysis of the steroid hormone system in active cCSC. Serum hormone levels of 17 steroid hormones were measured in 46 male Caucasian patients with active cCSC and 46 male Caucasian age-matched controls using the AbsoluteIDQ stero17 kit. Elevated levels of androsterone, estrone, etiocholanolone, and androstenedione were observed in cCSC patients compared with controls. Median hormone levels in cCSC patients versus controls, respectively, were as follows: androsterone, 0.84 ng/mL (interquartile range [IQR] = 0.61-1.06) versus 0.69 ng/mL (IQR = 0.48-0.96, P = 0.031); estrone, 0.12 ng/mL (IQR = 0.10-0.15) versus 0.10 ng/mL (IQR = 0.08-0.11; P = 0.0048); etiocholanolone, 0.19 ng/mL (IQR = 0.15-0.29) versus 0.13 ng/mL (IQR = 0.099-0.20, P = 0.0061). Mean levels of androstenedione were 3.10 ng/ml (SD = 1.03) versus 2.55 ng/mL (SD = 0.95), in cCSC patients versus controls, respectively. Additionally, Spearman's correlations between aldosterone and 11-deoxycortisol, androsterone, DHEA, DHEAS, and E1 differed between cCSC patients and controls, as well as between andosterone and E1, and between DHT and 17OHP. We present a comprehensive overview of the status of the steroid hormone system in active cCSC. Levels of four hormones were elevated in cCSC patients compared with controls, and the relationships between steroid hormones was altered, indicating that the balance in the steroid hormone system is altered in cCSC patients.

Foetal oestrogens and autism

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

Circulating sclerostin levels in relation to nutritional status, sex hormones and selected bone turnover biochemical markers levels in peri- and postmenopausal women

Hormonal changes during the peri- and postmenopausal age, especially decreasing estradiol levels as the result of the expired ovarian function, are an established link of the pathogenesis of postmenopausal osteoporosis. The objective of the study was to examine the association between the circulating sclerostin levels and nutritional status, sex hormones and selected bone markers turnover levels in peri- and postmenopausal women. The study enrolled 84 stable-body mass women (31 perimenopausal and 54 postmenopausal). Anthropometric measurements and serum estrone, testosterone, androstenedione, DHEA-S, osteocalcin, β-CTx, 25-OHVitamin D and sclerostin levels were obtained. There were not any differences between body mass, BMI, body fat and waist circumference between the study groups. The serum androstenedione and DHEA-S levels were similar in both study groups. However, estrone and total testosterone levels were observed to be notably higher in the perimenopausal group, unlike in the postmenopausal group (124.1 pg/mL vs. 98.3 pg/mL, p < 0.01 and 0.3 pg/mL vs. 0.22 pg/mL, p < 0.01, respectively). Higher plasma osteocalcin and β-CTx levels were shown in the postmenopausal rather than in the perimenopausal group (19.8 ng/mL vs. 16.8 ng/mL, p < 0.001 and 0.35 ng/mL vs. 0.29 ng/mL, p < 0.05, respectively). Plasma sclerostin and 25-OH-Vitamin D levels were similar. There was not any correlation between plasma sclerostin levels and the other studied parameters. In the multivariate regression analyses, sclerostin levels were proportional to the androstenedione ones (b = 0.06; p < 0.05) but inversely related to the log10(testosterone) levels (b = -0.18; p < 0.05). Circulating sclerostin levels are similar in peri- and postmenopausal women and are related to the androstenedione and testosterone levels regardless of the nutritional status.

Evolution of steroid concentrations in saliva from immature to pubertal gilts for the identification of biomarkers of gilts receptivity to boar effect

Estrus synchronization is necessary for management of gilt reproduction in pig farms. It is usually achieved by using synthetic progestagens, but there is increasing demand for non-hormonal alternative tools with the prospect of sustainability of livestock production. Moreover, in organic farms, synthetic hormones are not allowed. Before reaching puberty, gilts exhibit a “waiting period” during which external stimulations, such as boar exposure, could trigger and synchronize the first ovulation. However, practical non-invasive tools for detection of the “waiting period” in pig farms are lacking. During this period, estrone levels in urine are high, but urine sampling is difficult in group-housed females. Our objective was to identify among steroids potential biomarkers of this “waiting period” through saliva monitoring from immature to pubertal gilts using gas chromatography coupled to tandem mass spectrometry.Starting between 144 and 147 days of age, six Large White gilts were submitted to ultrasound puberty diagnosis 3 times a week until first ovulation. Urine and saliva samples were collected to analyze weekly estrone and steroidome respectively, until puberty. Urinary estrone concentration significantly increased 2 weeks before first ovulation occurring between 182 and 192 days of age. The period with increasing estrone levels was considered as the “waiting period”. Steroidome analysis allowed identifying and quantifying 28 steroids in 500 µl of gilts saliva. Significant decrease of dehydroepiandrosterone and significant increase of 5α-dihydroprogesterone and 17β-estradiol were detected 2 weeks before puberty, suggesting that these steroids could be potential biomarkers of the “waiting period”.These results show that painless sampling of saliva could be a non-invasive welfare-friendly tool for the identification of the physiological hormonal status of the gilts and possibly the optimal time for application of the boar effect, a solution to synchronize puberty without exogenous hormones.

Short-term exposure to 12‰ brackish water has significant effects on the endocrine physiology of juvenile American alligator (Alligator mississippiensis)

American alligators (Alligator mississippiensis) mainly inhabit freshwater habitats but can be exposed to a wide range of salinities during storm surges, droughts or from alterations in freshwater flows. Although some salinization events last weeks, others only last a few days. This study assessed changes in the endocrine function of the renin-angiotensin-aldosterone system (RAAS) and steroid hormone production (steroidogenesis) in juvenile alligators exposed to brackish water (12‰) for 7 days. We quantified plasma levels of angiotensin II and the corticosteroids (aldosterone, corticosterone and 11-deoxycortisol). Various progestogens, androgens, and estrogens were further assessed. The protein expression for the RAAS enzymes, renin and angiotensin converting enzyme (ACE), was quantified immunohistochemically in kidney and lung tissue, respectively, and histology was performed on kidney, lung and gonad tissues. Finally, blood biochemistry parameters such as electrolyte levels and diagnostic indicators for dehydration, renal, and hepatic function were measured. Corticosterone, 11-deoxycortisol, Na+, Cl−, total protein, albumin, uric acid, and cholesterol levels were all significantly elevated in alligators exposed to brackish water compared with alligators in freshwater. The levels of 17β-estradiol and estrone were significantly lowered while histology showed alterations in gonad tissue in the brackish water exposed group. In contrast, while there were no effects of exposure on aldosterone levels, angiotensin II was significantly reduced in brackish water exposed alligators. These results correlated with significantly decreased expressions for both renin and ACE in kidney and lung tissue. Overall, this study showed that short-term exposure of alligators to 12‰ brackish water has significant endocrine effects on juvenile alligators.

Особенности течения миомы матки в постменопаузальный период

The objective: to study the clinical manifestations of uterine fibroids in the postmenopausal period. Materials and methods. 85 patients with uterine myoma in the postmenopausal period were examined. The average age of patients was 58±1.0 (47–80) years. Criteria of inclusion are all patients with uterine myoma of up to 12 weeks of gestation of various localization in the postmenopausal period .In all patients, the clinical and anamnestic manifestations of uterine fibroids were studied. The state of the hypothalamic-pituitary-ovarian system, the determination of the level of the CA 125 tumor. Results. In 47 (55.3%) patients, various clinical manifestations of uterine fibroids were noted: in 37 (78.7%) patients there was pain of varying intensity, in 22 (46.8%) of patients was bloody discharge, in 17 (36.2%) dysuric phenomena, 10 (21.3%) patients had bleeding and 10 (21.3%) patients had defecation disorders. In 34 (72.3%) patients, the presence of menopausal syndrome of varying severity was noted. At the same time, the frequency of mild menopausal syndrome was 23.4% (n=11), moderate climacteric syndrome was 21.3% (n=10), and the frequency of severe degree was 27.7% (n=13). In patients with uterine myoma in the postmenopausal period, there was a significant increase in Prl, DHEA-S, E1 and a significant decrease in the LH / FSH ratio, E2, and Ttot (P&lt;0.05). The changes in the level of the CA125 tumor marker were insignificant and did not represent diagnostic value. Conclusion. Data analysis of the results of this study demonstrated that the main factors affecting the growth and development of uterine fibroids in postmenopause are the presence of hyperprolactinemia, hyperandrogenism of adrenal genesis and hyperestrogenia due to an increase in estrone level, which leads to an imbalance of apoptosis and proliferation mechanisms. Key words: uterine myoma, postmenopausal period, bleeding, hyperandrogenism, hypoestrogenism, climacteric syndrome.

Relationship between early follicular serum estrone level and other hormonal or ultrasonographic parameters in women with polycystic ovary syndrome

The aim of this study was to investigate the relationship between serum estrone (E1) level and other cardinal features in women with polycystic ovary syndrome (PCOS). 133 Korean women aged 18–35 years who were newly diagnosed with PCOS at a university hospital were included in the present study. Blood samples were collected from all participants during the early follicular phase to determine the serum E1 level and other biochemical hormonal parameters. The total antral follicle count (TFC) and the total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasound. A significant correlation was found between serum E1 and luteinizing hormone (LH) levels in women with PCOS. In addition, statistically significant correlations were observed between serum E1 level and other hormonal parameters, including testosterone, free testosterone, dehydroepiandrosterone sulfate, and 17α-hydroxyprogesterone. With respect to the ultrasound features, serum E1 levels were significantly correlated with TFC and TOV. All results did not change after adjusting for body mass index (BMI). In conclusion, serum E1 level is significantly correlated with serum LH and androgen levels, and it may be a useful marker for representing the status of the ovarian volume in women with PCOS.

Association of Gastrointestinal Microbial Profiles and Estrogen Metabolism in Patients With Preterm Birth [21A

INTRODUCTION: Researchers have explored various causes for preterm birth (PTB); yet, the effects of maternal gastrointestinal microbiome on estrogen metabolism and its influence on pregnancy remains unknown. The aim of this study is to analyze the effects of maternal gastrointestinal microbiome on estrogen metabolism during pregnancy by correlating the estrogen metabolite bioactivity with preterm birth. METHODS: Study participants (IRB#14-185) were recruited at Southern Illinois University School of Medicine, Department of Ob/Gyn. Twenty-four patients identified as being at risk for a repeat, PTB were recruited. Biological samples (urine and fecal samples) were collected during each trimester and a postpartum timepoint. Fecal samples were frozen and processed for DNA isolation. Microbial analyses were performed by miSeq amplicon sequencing using the V4 region of the bacterial 16S rRNA gene. Identification of 15 estrogen metabolites (2-, 4- and 16-hydroxylation pathways) in urine samples was performed using tandem mass spectrophotometry analysis. Data was evaluated using analysis of variance (ANOVA) and then by repeat measure design. RESULTS: Of the 24 patients, 18 delivered at term and 6 delivered preterm (25%). Gastrointestinal microbial profiles were altered in women with subsequent PTB. Additionally, decreased urinary levels of estrone, 17-epiestriol and 17-estradiol were found as early as the first trimester in subjects who delivered prematurely. CONCLUSION: This study highlights the interaction of the gastrointestinal microbiome on estrogen metabolism, possibly through hormone conjugation. Unbalanced levels of estrogen during pregnancy may predispose women to PTB. This investigation may elucidate novel screening tools to identify patients at risk for PTB and enable early clinical intervention.

Altered umbilical sex steroids in preterm infants born small for gestational age

Background: Boys born small for gestational age (SGA) are at increased risk of testicular dysgenesis syndrome, and girls born SGA face the risk of polycystic ovary syndrome later in life. Our aim was to study whether neonates born SGA have an altered profile of steroid hormones at birth.Materials and methods: A total of 168 singletons (99 boys, 69 girls) born at 32.0–36.9 gestational weeks were recruited to a population-based, university hospital, single-center study. Of these, 31 infants (17 boys, 14 girls) were born SGA. The concentrations of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, cortisone, and cortisol were analyzed in umbilical cord serum with mass spectrometry.Results: Girls born SGA had higher levels of androstenedione than girls born appropriate for gestational age (AGA) (4.0 versus 2.6 nmol/L, p = .002). Boys born SGA had lower levels of estrone than boys born AGA (33 822 versus 62 471 pmol/L, p = .038). Infants born SGA had lower levels of cortisone than infants born AGA, both in girls (340 versus 579 nmol/L, p = .010) and in boys (308 versus 521 nmol/L, p = .045). Furthermore, boys born SGA had a higher cortisol/cortisone ratio than boys born AGA (0.41 versus 0.25, p = .028). Gestational age correlated with DHEAS (boys r = 0.48, p = .000, girls r = 0.35, p = .013), and cortisol (boys r = 0.48, p = .000, girls r = 0.29, p = .039).Conclusions: In moderate-to-late preterm infants born SGA, we observed a different steroid hormone profile in cord serum. Girls born SGA show increased levels of androstenedione and boys born SGA show decreased levels of estrone in cord serum, which could be related to placental aromatase deficiency in intrauterine growth restriction.

OR15-4 Long-Term Follow-Up of a Female with a Mutation in the Estrogen Receptor Alpha (ESR1) Gene

We previously reported the first female with a mutation in the ESR1 gene encoding estrogen receptor-α (ER-α), which dramatically reduced estrogen signaling in vitro. She presented at 179/12 years with absent breast development, markedly elevated serum estradiol and estrone levels, modestly high gonadotropins, and multicystic ovaries by ultrasound. The natural history of estrogen insensitivity in women is unknown. The purpose of this report is to present: 1) the neuroendocrine phenotype; 2) studies to identify a ligand to stimulate the mutant receptor; and 3) the effect of targeted treatment. We now provide long-term clinical follow up and a detailed hormonal analysis of the patient at age 234/12 years. On no treatment, serum FSH and LH were drawn every 10 minutes for 8 hours, and estradiol and estrone levels were measured every hour during the study. Various compounds that are potential for treatment were used in transient transfection assays to determine if estrogen signaling could be induced. A personalized medicine approach was tailored to our patient, in which she received increasing doses of diethylstilbestrol (DES) with the primary endpoints being increased vaginal discharge and breast development. Follow up exams, labs, pelvic ultrasounds, DXA, and bone age X-rays were completed at various intervals up to age 234/12 years. The Bioethics Board approved this treatment. During the frequent sampling study, E2 was 604 pg/mL, E1 was 596 pg/mL, FSH was 10.0+/-0.1 IU/L (mean+/-SE), and LH was 6.7+/-0.2 IU/L. There were 3 pulses in 8 hr with an LH pulse amplitude of 2.3+/-0.5 IU/L. Although DES was shown to successfully transactivate the mutant ESR1in vitro, both in HEK293 cells and in her lymphoblastoid cells, the patient had no clinical response. After 2.5 years of treatment with increasing doses of DES, there was no vaginal discharge and breasts remained at Tanner 1. At 234/12 years, LH, FSH and E2 were unchanged. A vaginal maturation index showed a predominance of parabasal cells consistent with a lack of estrogen effect. Ultrasound showed bilateral ovarian cysts. At chronologic age 234/12 years, her bone age was 17 years and the epiphysis remained open in the ulnar bone. DXA revealed a Z-score of -2.9 at the femoral neck and -4.5 at the lumbar spine. Our findings in this severely estrogen insensitive female indicate elevated gonadotropins with normal amplitude and low frequency LH pulse dynamics in the presence of markedly increased estrogens. Treatment with DES, which stimulated estrogen signaling in vitro, did not induce secondary sexual characteristics in our patient. She remains hypoestrogenic despite the presence of ovarian cysts with a hypoestrogenic vaginal smear, absent breast development, and low bone mineral mass. Future studies will be directed towards further identification of other potential signaling mechanisms and activators of this mutant receptor.

SAT-288 Successful Virilization of a PAIS Patient with a Missense Mutation In The Ligand-binding Domain Of The Androgen Receptor with Combined High-dose Testosterone and Aromatase Inhibitor

The main complain of patients with partial androgen insensitivity patients (PAIS) is undervirilization signs and the small penile length. Supplemental androgen therapy has enhanced virilization in only a few patients with PAIS. Aromatase inhibitors as anastrozole and letrozole are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450 reducing estrogen and estrone levels and increasing LH and FSH levels and consequently testosterone levels. We hypothesized that the combination of high-dose testosterone with anastrozole can maintain a sustained elevated testosterone levels and also deviated testosterone metabolization from estrogen to DHT, therefore increasing penile length. Case Report This experimental treatment was proposed and both patient and parents willing to participate. Patient was firstly evaluated at 7 yrs of age. The hemizygous c.2599G>C; p.V867L AR in the ligand-binding domain (LBD) was found in both affected siblings. He was previously submitted to three unsuccessful genital masculinizing surgeries and bilateral orchidopexia. The external genitalia presented a microphalus (penile length of 2 cm, -4.5 SDS), perineal hypospadias and bilateral topic testis. He received testosterone cypionate (50 mg IM injections monthly, for 3 times at age of 7 and 200 mg IM injections monthly, for 4 times at age of 8); topic DHT gel (5-10 g/daily for three months at age of 7 yrs). At age of 12.3 yrs, the genital masculinization surgeries were completed, penile length was 3.5 cm (-2.6 SDS), testicular size of 2.6x1.5 cm and pubic hair Tanner II stage. LH and FSH levels were (9.4 and 3.2 IU/L respectively), testosterone (304 ng/dL), DHT (26 ng/dL) and estradiol (<17 pg/mL). The effect of 200 mg of testosterone cypionate weekly associated to 1 mg of anastrozole daily was evaluated. After 6 months of treatment, he presented enlargement of penile length (7.0 cm, -1 SDS), and testicular size (3.0x2.0 cm) and Tanner IV of pubic hair. Gynecomastia was absent. The hormonal profile showed: decreased values of LH and FSH (0.8 and 1.1 IU/L respectively), and estradiol (<17 pg/mL) levels, and increased testosterone and DHT levels (1753 and 167 ng/dL, respectively). Bone age did not advance during treatment. Conclusion This is the first documentation of successful virilization in a PAIS boy with androgen insensitivity due to a hemizygous missense mutation in AR with a combination of high-dose testosterone and aromatase inhibitor.

Endothelial Estrogen Receptor α/β Protein Ratio is Associated with Circulating Estrogen Levels in Healthy Women

OBJECTIVEVascular aging, featuring endothelial dysfunction, precedes an increased risk of cardiovascular disease (CVD). The menopause transition (i.e., perimenopause) is characterized by changes in ovarian hormone and vascular health. We previously reported a decline in endothelial function that was correlated with lower estradiol (E2) and estrone levels. Biological effects of E2 on endothelial function are mediated via estrogen receptors (ER). We determined whether ER α and β activation (i.e. nuclear translocation) and the ER α/β ratio in endothelial cell (EC)s differed by menopause stages and whether they were associated with reduced endothelial function across menopause stages.METHODSEC samples were harvested from 67 healthy, fasted women (aged 30–70 years) classified as premenopausal (Pre; regular menstrual cycles; n=15, 33±6yrs; mean±SD), early perimenopausal (EPeri; &gt; 2 cycles with cycle length changes of ≥7 days; n=15, 49±3yrs), late perimenopausal (LPeri; ≥2 but &lt;12 months of amenorrhea; n=17, 49±4yrs), or postmenopausal (Post; n=20, 56±5yrs). ECs were analyzed for whole cell and nuclear ER α and β protein content by immunofluorescence. Endothelial‐dependent vasodilation was measured by brachial artery flow‐mediated dilation (FMD) using ultrasound.RESULTSERα nuclear/cell protein ratio (a surrogate marker of nuclear translocation) was lower (p&lt;0.01) in EPeri compared to other menopause stages; ERβ nuclear/cell protein ratio showed a similar trend (p=0.07). ER α/β protein ratio in whole cell showed no difference across stages, but was correlated with serum E2 (r=0.30, p=0.08) and estrone (r=0.38, p=0.03) across menopause stages. FMD was not correlated with any ER protein data.CONCLUSIONThe menopause transition, specifically the early perimenopausal period, may be a vulnerable period for the decline of endothelial ER α and β activation; however, we failed to show any correlation between endothelial function and ER protein content. Whether the decline in endothelial ER function/activity contributes to vascular dysfunction warrants further study.Support or Funding InformationNIH R01AG049762, R01AG027678, R56HL114073, P30DK048520, P50HD073063, NCATS Colorado CTSA UL1TR001082, and Eastern Colorado VA GRECCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Pubertal Maturation and Chronologic Age on Sex Steroids in Peripubertal Girls.

There is a 4- to 5-year variation in age of breast maturation in girls. To examine longitudinal changes in sex hormone values relative to chronologic age and time relative to breast maturation. Longitudinal observational study into which girls were recruited at 6 to 7 years of age and followed up every 6 months. Maturation status, chronologic age, race, and fasting blood specimen data were obtained. Hormones were analyzed at 6-month intervals between 2 years before and 1 year after breast maturation, using HPLC tandem mass spectroscopy. Estradiol and estrone levels correlated with chronologic age (R = 0.350 and 0.444, respectively); time was correlated relative to breast maturation (R = 0.222 and 0.323, respectively; all correlations, P < 0.0001). In generalized estimating equation (GEE) models, chronologic age and time relative to pubertal onset were significantly associated with serum estradiol, with similar results for estrone. Local estimated scatterplot smoothing for estradiol and estrone, by chronologic age, demonstrated differences between black and white girls, especially between 8.5 and 11 years of age, but not by race in time relative to breast maturation. Testosterone level was correlated to chronologic age (R = 0.362) and time relative to breast maturation (R = 0.259); in the GEE model, only chronologic age was significant. Chronologic age as well as time relative to onset of puberty provided unique information regarding estradiol and estrone concentrations in peripubertal girls. Serum estrogen concentrations should be evaluated with reference to chronologic age and race.

Effects of exercise on circulating levels of sex hormones in overweight and obese postmenopausal women: A systematic review

Summary Objective This study aimed to examine the evidence regarding the regulatory role of exercise in circulating levels of sex hormones in overweight and obese postmenopausal women. News Exercise has shown to be an effective non-pharmacological tool in obesity and breast cancer prevention. Sex hormones have been proposed as a potential link by which exercise may modulate obesity and breast cancer after menopause, however, the response of sex hormones as a metabolic pathway responsible for the connection between both pathologies are not entirely understood. An extensive search was performed using PubMed, Medline, Scopus and SPORTDiscus databases for the period from inception of each database to May 2018. A total of 778 studies were found in the search. Of these, 9 met the inclusion criteria and were further analyzed. Despite the different exercise protocols performed, most studies found a decrease in circulating levels of estrone and estradiol, and an increase in sex hormone-binding globulin (SHBG). However, when the effect of exercise on these sex hormones was compared to an unexercised control group, conflicting results were obtained. A reduction in body mass was reported in those studies in which exercise caused a significant effect on estrone, estradiol and SHBG compared to a control group. Conclusion These results suggest that exercise-induced weight loss and the type of exercise performed may to be critical factors in the modification of the circulation expression of some sex hormones. Further studies are required to elucidate the most effective exercise dose to restore sex hormones homeostasis as potential obesity-breast cancer nexus in the postmenopausal woman.

Variation of urinary follicle-stimulating hormone level after menopause : From the results of Japan Nurses' Health Study.

The change in follicle-stimulating hormone (FSH) during the menopausal transition and associations of FSH with various diseases have been assessed by using blood samples. We examined cross-sectionally the variation of FSH levels, associations of estrone and estradiol with FSH, and associations of BMI with these hormones by using urinary samples from peri- and postmenopausal women in Japan. Of 4472 participants in the Urinary Isoflavone Concentration Survey of the Japan Nurses' Health Study, we analyzed urinary levels of estrone, estradiol and FSH in 547 women aged from 45 to 54 years. Urinary FSH levels varied widely in postmenopausal women and the pattern of change in urinary FSH levels seems to be similar to that in blood FSH levels in previous studies. There were no significant differences in age, body mass index (BMI), estradiol, estrone and estradiol/estrone ratio among three groups according to the tertile of FSH. In postmenopausal women, there were significant associations of BMI with levels of estrone and estradiol, but there was no significant association of BMI with FSH. Studies using urinary samples will allow us to establish a study project as a large-scale population-based study to determine associations between FSH and various diseases after menopause. J. Med. Invest. 66 : 297-302, August, 2019.

MONITORING OF PROGESTERONE AND ESTRONE FECAL METABOLITES THROUGHOUT GESTATION IN EWES

Abstract The aim of this study was to monitor the progesterone and fecal estrone metabolites throughout gestation in ewes correlating with the serum levels of these steroid hormones. Therefore, fecal and serum samples were collected from 5 weeks before mating and gestation until two weeks postparturition. Serum levels of progesterone and estrone and their fecal metabolites were measured by enzyme immunoassay. Serum and fecal hormonal patterns showed a significant correlation for both hormones (R = 0.8572, P &lt; 0.001 for progesterone and R = 0.5893, P &lt; 0.001 for estrone). The fecal progesterone metabolite levels showed significant increasing values among the three thirds of pregnancies, consistent with the serum levels and with the literature. Additionally, the prepartum peak of estrone in the fecal matrix was identified but without observation in the serum matrix due to the blood collection interval used. Therefore, this study demonstrated the viability of progesterone and estrone monitoring throughout gestation using fecal samples, making noninvasive longitudinal endocrine monitoring throughout gestation possible in this species.

Salivary and urinary metabolome analysis for pre-puberty-related biomarkers identification in porcine

Estrus synchronization is important for optimal management of gilt reproduction in pig farms. Hormonal treatments, such as synthetic progestogens, are used on a routine basis, but there is a growing demand for non-hormonal alternative breeding tools. Before puberty, gilts exhibit a ‘waiting period,’ related to the ovarian development and gonadotrophin secretions, during which external stimulations, such as boar exposure, could induce and synchronize first ovulation. Practical non-invasive tools for identification of this period in farms are lacking. During this period, urinary oestrone levels are high, but urine sampling is difficult in group-housed females. The aim of this work was to search for specific biomarkers of the ‘waiting period’ in saliva and urine. In total, nine 144- to 147-day-old Large White gilts were subjected to trans-abdominal ultrasonography three times a week for 5 weeks until puberty detection (week –5 to week –1 before puberty). Urine and saliva samples were collected for oestrone assay to detect the ‘waiting period’ and for metabolome analysis using 1H-nuclear magnetic resonance spectroscopy to detect potential biomarkers of the ‘waiting period.’ Gilts were slaughtered 7 days after puberty detection for puberty confirmation. Results were consistent with ultrasonography data for six gilts. Urine and saliva samples from these six gilts were analyzed. Urinary estrone concentration significantly increased 2 weeks before puberty detection. Metabolome analysis of urine samples allowed the identification of 78 spectral bins, among them, 42 low-molecular-weight metabolites were identified. Metabolome analysis of salivary samples allowed the identification of 59 spectral bins, among them, 23 low-molecular-weight metabolites were detected and 17 were identified. No potential biomarker was identified in urinary samples. In saliva, butyrate and 2HOvalerate, 5.79 ppm (putatively uridine), formate, malonate and propionate could be biomarker candidates to ascertain the pre-puberty period in gilt reproduction. These results confirm that non-invasive salivary samples could allow the identification of the physiological status of the gilts and presumably the optimal time for application of the boar effect. This could contribute to synchronize puberty onset and hence to develop non-hormonal breeding tools.

Sex hormone levels by presence and severity of cirrhosis in women with chronic hepatitis C virus infection.

Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive-aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post-menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child-Turcotte-Pugh (CTP) class. Results: There were n=18 cirrhotic and n=21 noncirrhotic women with a median age of 57years (interquartile range [IQR] 53-62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0pg/mL, P=0.05) and oestrone levels (32.0 vs 8.0ng/mL, P<0.001), and lower sex hormone binding globulin (SHBG) (69.2 vs 155.6nmol/L, P=0.001), and FSH levels (4.9 vs 89.6 mIU/mL, P<0.001). Among cirrhotic women, there was a progressive decline in FSH and SHBG and concurrent rise in oestrone levels from CTP class A to C (test of trend, P values ≤0.02). Cirrhosis is associated with lower FSH and SHBG levels in cirrhotic compared to noncirrhotic women with HCV infection. In cirrhotic women, these levels demonstrate steady decline by disease severity. Given known associations of low SHBG and FSH with cardio-metabolic disease, the clinical implications of hormonal changes by cirrhosis severity in HCV-infected women warrants investigation.

Prolactin-Induced Protein is a novel biomarker for Keratoconus

PurposeThe purpose of the study was to investigate the role of Prolactin-Induced Protein (PIP) as a predictive biomarker for Keratoconus (KC). ParticipantsThis study included one hundred and forty-seven patients with KC (105 male, 42 female), and sixty healthy controls (27 male, 33 female). MethodsTears, plasma and saliva samples were collected from all participants. In both KC and healthy groups all collected samples were divided into four age subgroups (15-24y), (25-34y), (35-44y) and (45y and up). Samples were analyzed using western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy for distinguishing between KC and healthy eyes. Main outcome measuresDifference in PIP protein levels between patients with KC and healthy controls. ResultsResults showed significant downregulation of PIP expression in all three biological fluids on KC patients when compared to healthy controls, independent of age, sex and severity. Since PIP is a hormonal-regulated protein, we also investigated the expression of major sex hormones. We detected significant upregulation in salivary and plasma Dehydroepiandrosterone sulfate (DHEA-S) levels and significant downregulation of estrone and estriol levels, in KC patients compared to healthy controls, independent of sex, age, and KC severity stage. ROC was used to determine the overall predictive accuracy of this protein in KC. Data showed an area under the curve (AUC) for PIP in tears of 0.937 (95%CI: 0.902–0.971), in plasma of 0.928 (95%CI: 0.890–0.968) and in saliva of 0.929 (95%CI: 0.890–0.968). ConclusionsConclusively, our results show that PIP levels are reduced in all three human biological fluids tested, and may independently or in combination with current imaging techniques aid in screening and diagnosis of KC. Our data revealed that PIP levels can potentially differentiate between disease and healthy cases, and PIP levels are stable in relation to KC severity, sex and age. Moreover, alterations in sex hormone levels in correlation with reduced PIP levels in KC provide an intriguing insight in the underlying KC pathophysiology and highlights the role of PIP as a KC biomarker.

Hormone Levels in Pregnancy and Subsequent Risk of Maternal Breast and Ovarian Cancer: A Systematic Review.

Some maternal hormone levels in pregnancy are associated with a higher risk of breast and ovarian cancer. This study systematically assessed the association between blood hormone levels measured in pregnancy and future risk of these cancers. Two reviewers independently conducted a literature search of MEDLINE and EMBASE databases from January 1970 to August 2017. Studies were included that measured one or more serum hormone levels in pregnancy and later assessed for cancer. Cancer outcomes were considered by cancer type, each in relation to a specific maternal hormone. Eleven studies were included, comprising a total of 57 967 women. The interval between pregnancy and cancer onset varied from 4.1 to 20.5 years. Elevated serum chorionic gonadotropin (two of four studies) and alpha fetoprotein (two of three studies) were each associated with a lower risk of maternal breast cancer, whereas elevated estrone levels suggested a higher risk (one of three studies). Elevated testosterone (one of one study) and androstenedione (one of one study) were each associated with a significantly greater risk of sex-cord stromal ovarian tumours. Higher serum 17-hydroxyprogesterone was associated with an increased risk of sex-cord stromal (one of one study) and epithelial (one of one study) ovarian cancer. Observational studies suggest some degree of association between serum hormones measured in pregnancy and a woman's future risk of breast and ovarian cancer. More data are needed to determine sufficiently whether certain blood hormone levels measured in pregnancy are predictive of future cancer risk.