The relationship between cooking fuel use and sex hormone levels: A cross-sectional study and Mendelian randomization study.

PURPOSE: The aim of this study was to investigate the effect of solid fuel use on serum sex hormone levels. Furthermore, the effects of improved kitchen ventilation and duration of cooking time on the relationship between solid fuel use and serum sex hormone levels will be further explored. METHODS: In this cross-sectional study, 5386 individuals were recruited. Gender and menopausal status modified associations between solid fuel type and serum sex hormone levels was investigated through generalized linear models and further analyzed by improving kitchen ventilation and length of cooking time on the relationship between solid fuel use and serum sex hormone levels. To identify the causal association, mendelian randomization of two-sample was performed. RESULTS: In observational analyses, for ln-17-hydroxyprogesterone, ln-testosterone, and ln-androstenedione among premenopausal women, the estimated ß and 95 % CI of sex hormone levels for the effect of solid fuel users was -0.337 (-0.657, -0.017), -0.233 (-0.47, 0.005), and - 0.240 (-0.452, -0.028) respectively, and - 0.150 (-0.296, -0.004) in ln-progesterone among postmenopausal women. It was found that combining solid fuels with long cooking periods or no ventilation more effectively reduced testosterone and androstenedione in premenopausal women. We further found the adverse effects of using solid fuel on progesterone, testosterone, and androstenedione levels were enhanced with the increases of PM1, PM2.5, PM10, and NO2. Corresponding genetic, the causal risk effect of solid fuel were - 0.056 (-0.513, 0.4) and 0.026 (-3.495, 3.547) for testosterone levels and sex hormone binding globulin, respectively. CONCLUSION: Using gas or solid fuel was negatively related to sex hormone levels. A combination of using solid fuels, cooking for a long time, or cooking without ventilation had a stronger effect on sex hormone levels. However, genetic evidence did not support causality for the associations. WHAT IS ALREADY KNOWN ON THIS TOPIC?: The mechanisms underlying these associations household air pollution (HAP) from incomplete combustion of such fuels and occurrence of chronic diseases remained obscure. Recent years, extensive evidences from animal as well as human researches have suggested that progestogen and androgen hormones are involved in the development of diabetes, hypertension, and cardiovascular disease, which indicated that changes in serum progestogen and androgen hormones levels might play a role in these pathological mechanisms. However, limited evidence exists examining the effect of HAP from solid fuel use on serum sex hormone levels.

High sensitivity LC-MS methods for quantitation of hydroxy- and keto-androgens.

The quantitation of androgens is necessary to diagnose and monitor the development of diseases such as prostate cancer and polycystic ovary syndrome. Androgen measurements also support the laboratory-based study of androgen metabolism in cellular and animal models. The methods described in this chapter combine chemical derivatization of hydroxy- and keto-androgens with stable isotope dilution liquid chromatography mass spectrometry (SID-LC-MS). Chemical derivatization of hydroxy-androgens by picolinic acid and keto-androgens by Girard P enhances the ionization and detection sensitivity of androgens, while chromatographic separation and [13C]-labeled internal standards add specificity that allow for simultaneous quantitation of multiple androgens. This chapter describes the materials and protocols necessary for chemical derivatization, enzymatic synthesis of internal standards, and LC-MS detection of keto- and hydroxy-androgens.

Characteristics of steroid hormones in systemic lupus erythematosus revealed by GC/MS-based metabolic profiling.

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a remarkable predominance in female, suggesting that steroid hormones may be involved in the pathogenesis. However, steroid signature of SLE patients has not been fully explored. Methods: A metabolic profiling analysis based on gas chromatography/mass spectrometry (GC/MS) with high sensitivity and reproducibility was employed to comprehensively reveal SLE-specific steroid alterations. Results: More than 70 kinds of steroids in urine were detected by gas chromatography/mass spectrometry (GC/MS) to reveal SLE-specific steroid alterations. Principle component analysis demonstrated that the steroid profile was obviously distinguished between patients with SLE and controls. A lower level of total androgens was observed in patients, and nine androgens [dehydroepiandrosterone (DHEA), testosterone, Etio, androsterone, ßαß-Diol, Epi-An, Epi-DHT, 16α-OH-DHEA, and A-Diol] underwent significant decrease. Moreover, patients with SLE exhibited a slightly higher level of total estrogens than controls, and three estrogens (17-Epi-E3, 17α-E2, and E3) were remarkably increased. Furthermore, we identified the elevation of two sterols (Lan and Chol), and the reduction of one corticoid (11-DeoxyF) and two progestins (5α-DHP and 11ß-OH-Prog) in patients. Discussion: In this study, metabolic signature of urinary steroids associated with SLE was comprehensively defined by GC/MS for the first time, and steroid metabolism disorders were found in patients with SLE, especially the conversion of androgens to estrogens. Our findings will provide new insights for a deeper understanding of the mechanism of steroid hormones in the pathogenesis of SLE and will help to unravel the reason of sexual disparity in SLE.

Estrogenic, androgenic, and glucocorticoid activities and major causative compounds in river waters from three Asian countries.

Estrogen, androgen, and glucocorticoid receptors (ER, AR, and GR) agonist activities in river water samples from Chennai and Bangalore (India), Jakarta (Indonesia), and Hanoi (Vietnam) were evaluated using a panel of chemical-activated luciferase gene expression (CALUX) assays and were detected mainly in the dissolved phase. The ER agonist activity levels were 0.011-55 ng estradiol (E2)-equivalent/l, higher than the proposed effect-based trigger (EBT) value of 0.5 ng/l in most of the samples. The AR agonist activity levels were < 2.1-110 ng dihydrotestosterone (DHT)-equivalent/l, and all levels above the limit of quantification exceeded the EBT value of 3.4 ng/l. GR agonist activities were detected in only Bangalore and Hanoi samples at dexamethasone (Dex)-equivalent levels of < 16-150 ng/l and exceeded the EBT value of 100 ng/l in only two Bangalore samples. Major compounds contributing to the ER, AR, and GR agonist activities were identified for water samples from Bangalore and Hanoi, which had substantially higher activities in all assays, by using a combination of fractionation, CALUX measurement, and non-target and target chemical analysis. The results for pooled samples showed that the major ER agonists were the endogenous estrogens E2 and estriol, and the major GR agonists were the synthetic glucocorticoids Dex and clobetasol propionate. The only AR agonist identified in major androgenic water extract fractions was DHT, but several unidentified compounds with the same molecular formulae as endogenous androgens were also found.

Using follicular fluid metabolomics to investigate the association between air pollution and oocyte quality.

BACKGROUND AND AIM: Our objective was to use metabolomics in a toxicological-relevant target tissue to gain insight into the biological processes that may underlie the negative association between air pollution exposure and oocyte quality. METHODS: Our study included 125 women undergoing in vitro fertilization at an academic fertility center in Massachusetts, US (2005-2015). A follicular fluid sample was collected during oocyte retrieval and untargeted metabolic profiling was conducted using liquid chromatography with ultra-high-resolution mass spectrometry and two chromatography columns (C18 and HILIC). Daily exposure to nitrogen dioxide (NO2), ozone, fine particulate matter, and black carbon was estimated at the women's residence using spatiotemporal models and averaged over the period of ovarian stimulation (2-weeks). Multivariable linear regression models were used to evaluate the associations between the air pollutants, number of mature oocytes, and metabolic feature intensities. A meet-in-the-middle approach was used to identify overlapping features and metabolic pathways. RESULTS: Of the air pollutants, NO2 exposure had the largest number of overlapping metabolites (C18: 105; HILIC: 91) and biological pathways (C18: 3; HILIC: 6) with number of mature oocytes. Key pathways of overlap included vitamin D3 metabolism (both columns), bile acid biosynthesis (both columns), C21-steroid hormone metabolism (HILIC), androgen and estrogen metabolism (HILIC), vitamin A metabolism (HILIC), carnitine shuttle (HILIC), and prostaglandin formation (C18). Three overlapping metabolites were confirmed with level-1 or level-2 evidence. For example, hypoxanthine, a metabolite that protects against oxidant-induced cell injury, was positively associated with NO2 exposure and negatively associated with number of mature oocytes. Minimal overlap was observed between the other pollutants and the number of mature oocytes. CONCLUSIONS: Higher exposure to NO2 during ovarian stimulation was associated with many metabolites and biologic pathways involved in endogenous vitamin metabolism, hormone synthesis, and oxidative stress that may mediate the observed associations with lower oocyte quality.

Digit ratio (2D:4D) and maternal testosterone-to-estradiol ratio measured in early pregnancy.

The ratio of index to ring finger (2D:4D) has been hypothesised to indicate prenatal androgen exposure, yet evidence for its validity is lacking. We report the first pre-registered study to investigate mothers' early pregnancy sex hormone concentrations in relation to their children's digit ratios measured at 18-22-month follow-up. Although the testosterone (T) to estradiol (E) ratio correlated negatively with right hand digit ratio (R2D:4D) and directional asymmetry (right-minus-left) in digit ratio (D[R-L]), neither effect remained statistically significant once demographic and obstetric covariates were controlled for. Nevertheless, the multivariate level of analysis did reveal that T correlated positively with left hand digit ratio (L2D:4D) and negatively with D[R-L]. However, the first of these effects is in the opposite direction to that predicted by theory. Taken together, the results of our study suggest research with larger samples is required to determine whether digit ratios are valid proxies for maternal sex hormone exposure.

The relationship between prostatic microvessel density and different concentrations of oestrogen/androgen in Sprague-Dawley rats.

BACKGROUND: Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations. METHODS: Male SD rats aged 3-4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD. RESULTS: Compared with the control group, the MVD decreased significantly in the castration group (P < 0.05). When the exogenous E concentration was constant, in general, the MVD of rats in all the groups increased with increasing exogenous DHT concentration. Compared with the castration group, the MVD increased significantly in the E0.05 + DHT0.015 mg/kg, E0.05 + DHT0.05 mg/kg, E0.05 + DHT0.15 mg/kg, E0.05 + DHT0.5 mg/kg, and E0.05 + DHT1.5 mg/kg groups (P < 0.05). In addition, when the exogenous DHT concentration was constant, the MVD increased with increasing exogenous E concentration in all the groups. Among them, compared with the control and castration groups, the MVD increased significantly in the DHT0.15 + E0.015 mg/kg, DHT0.15 + E0.15 mg/kg, and DHT0.15 + E0.5 mg/kg groups (P < 0.05). CONCLUSIONS: Androgens play an important role in the regulation of prostatic MVD in SD rats, and a decrease in DHT concentration can induce a decrease in prostatic MVD. In contrast, prostatic MVD can be increased with increasing DHT concentration. In addition, prostatic MVD can be increased gradually with increasing oestrogen concentration.

Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-ß/Smad signaling pathway.

OBJECTIVE: The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis. METHODS: Different concentrations of dihydrotestosterone (DHT) or estradiol (E2) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague-Dawley (SD) rats over 28 consecutive days. Masson's trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT + E2 at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-ß1 (TGF-ß1), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT + 5 pM E2 were incubated with the TGF-ß/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB. RESULTS: Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p < 0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p < 0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E2 treatment group compared to the 0.15 mg/kg DHT group (p < 0.05, p < 0.01). Following treatment with 0.05 mg/kg E2, the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E2 group (p < 0.05, p < 0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-ß1 and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p < 0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-ß1, and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E2 concentration treatment compared to the 10 nM DHT group (p < 0.05, p < 0.01). Following treatment with 5 pM E2, the expression of collagen I, fibronectin, TGF-ß1, and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E2 group (p < 0.05, p < 0.01). Compared to the 10 nM DHT + 5 pM E2 group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-ß/Smad pathway inhibitor SD208 group (p < 0.05, p < 0.01). CONCLUSIONS: An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-ß/Smad signaling pathway.

Circulating and Intratumoral Adrenal Androgens Correlate with Response to Abiraterone in Men with Castration-Resistant Prostate Cancer.

PURPOSE: In metastatic castration-resistant prostate cancer (mCRPC) low serum androgens prior to starting abiraterone acetate (AA) is associated with more rapid progression. We evaluated the effect of AA on androgens in castration-resistant prostate cancer (CRPC) metastases and associations of intratumoral androgens with response. EXPERIMENTAL DESIGN: We performed a phase II study of AA plus prednisone in mCRPC. The primary outcome was tissue testosterone at 4 weeks. Exploratory outcomes were association of steroid levels and genomic alterations with response, and escalating AA to 2,000 mg at progression. RESULTS: Twenty-nine of 30 men were evaluable. Testosterone in metastatic biopsies became undetectable at 4 weeks (P < 0.001). Serum and tissue dehydroepiandrosterone sulfate (DHEAS) remained detectable in many patients and was not increased at progression. Serum and tissue DHEAS in the lowest quartile (pretreatment), serum DHEAS in the lowest quartile (4 weeks), and undetectable tissue DHEAS (on-therapy) associated with rapid progression (20 vs. 48 weeks, P = 0.0018; 20 vs. 52 weeks, P = 0.0003; 14 vs. 40 weeks, P = 0.0001; 20 vs. 56 weeks, P = 0.02, respectively). One of 16 men escalating to 2,000 mg had a 30% PSA decline; 13 developed radiographic progression by 12 weeks. Among patients with high serum DHEAS at baseline, wild-type (WT) PTEN status associated with longer response (61 vs. 33 weeks, P = 0.02). CONCLUSIONS: Low-circulating adrenal androgen levels are strongly associated with an androgen-poor tumor microenvironment and with poor response to AA. Patients with CRPC with higher serum DHEAS levels may benefit from dual androgen receptor (AR)-pathway inhibition, while those in the lowest quartile may require combinations with non-AR-directed therapy.

Quantification of androgens and their precursors in full-term human placenta.

INTRODUCTION: The two major androgens in humans are testosterone (T) and dihydrotestosterone (DHT). DHT is produced via the classical, backdoor, and alternative steroidogenic pathways. In addition, recent studies have identified C11-oxy C19 steroids as novel human androgens. Although the placenta is known to be involved in steroid metabolism, androgen levels in full-term placentas have poorly been investigated. SUBJECTS AND METHODS: Ten placentas of healthy full-term neonates (five males and five females) were examined. We quantified progesterone, androstenedione (A4), T, allopregnanolone, androsterone, and estradiol, as well as four C11-oxy androgens (11ß-hydroxyandrostenedione, 11ß-hydroxytestosterone, 11-ketoandrostenedione (11KA4), and 11-ketotestosterone (11KT)), using liquid chromatography-tandem mass spectrometry. RESULTS: In all samples, levels of the ten steroids were above the detection limit. Progesterone was by far most abundant, while levels of T and androsterone were relatively low. Levels of 11KT and 11KA4 were higher than those of T and A4, respectively. There were no differences in steroid levels between male and female samples. DISCUSSION: This study demonstrates that full-term placentas contain several steroids in the classical, backdoor, and alternative pathways. Placentas are likely to function as the supplier of progesterone to other steroidogenic tissues. More importantly, we found that placentas comprise relatively large amounts of 11KA4 and 11KT, which may be produced through steroid transfer from the adrenal gland or from the maternal circulation. These results indicate that the placenta participates in a feto-maternal multi-organ network for androgen biosynthesis.

Green bioanalytical sample preparation: fabric phase sorptive extraction.

Fabric phase sorptive extraction (FPSE) is a recently introduced sample preparation technique that has attracted substantial interest of the scientific community dealing with bioanalysis. This technique is based on a permeable and flexible substrate made of fabric, coated with a sol-gel organic-inorganic sorbent. Among the benefits of FPSE are its tunable selectivity, adjustable porosity, minimized sample preparation workflow, substantially reduced organic solvent consumption, rapid extraction kinetics and superior extraction efficiency, many of which are well-known criteria for Green Analytical Chemistry. As such, FPSE has established itself as a leading green sample preparation technology of 21st century. In this review, we discuss the principal steps for the development of an FPSE method, the main method optimization strategies, as well as the applications of FPSE in bioanalysis for the extraction of a wide range of analytes (e.g., estrogens, benzodiazepines, androgens and progestogens, penicillins, anti-inflammatory drugs, parabens etc.).

Relationship of preoperative androgen levels and metabolic syndrome with quality of life and erectile function in patients who are to undergo radical prostatectomy.

This study aims to investigate whether clinical and biological preoperative characteristics of patients who were to undergo radical prostatectomy were associated with impairment in patient-reported quality of life (QoL) and erectile dysfunction immediately before intervention. We evaluated patient-reported outcomes among 1019 patients (out of 1343) of the AndroCan study, willing to score the Aging Male Symptom (AMS) and the International Index of Erectile Function 5-item (IIEF-5) auto-questionnaires. Univariate linear regression and robust multiple regression were used to ascertain the relationship between demographic, clinical, and hormonal parameters and global AMS or IIEF-5 scores. As a result, most patients (85.1') of the Androcan cohort agreed to complete questionnaires. Significantly higher IIEF-5 global scores were found in non-Caucasian and obese patients, with larger waist circumference, metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, high blood sugar, concomitant medications, and hypogonadism, while the AMS global score was significantly higher in patients with larger waist circumference, metabolic syndrome, high blood pressure, raised glycemia, and concomitant medication. The IIEF-5 global score was correlated to age, dehydroepiandrosterone (DHEA), fat mass percentage, and androstenediol (D5). The AMS global score was significantly correlated to DHEA, D5, and DHEA sulfate. Finally, the multivariate models showed that QoL and erectile function were significantly affected, before surgery, by symptoms and signs that are usually considered as pertaining to the metabolic syndrome, while sexual hormones are essentially correlated to erectile dysfunction.

The value of serum-free androgen index in the diagnosis of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: It is found that there is a significant difference in serum-free androgen index (FAI) between patients with polycystic ovary syndrome (PCOS) and healthy people, and the selection of appropriate cutoff value has a certain diagnostic value for PCOS. However, the current research conclusions on the diagnostic value of FAI for PCOS are not consistent. The purpose of this study is to explore the diagnostic value of FAI in PCOS, in order to provide reference for clinicians to select appropriate diagnostic indicators in the future. METHODS: Cochrane Library, Medline, Excerpta Medica Database, China National Knowledge Infrastructure, and China Wanfang database were searched until July 2020. A comprehensive collection of FAI studies on the diagnosis of PCOS was conducted. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were analyzed by Stata15.0 software, and the receiver operating characteristic (ROC) curves of the subjects were drawn. RESULTS: A total of seven high-quality clinical studies were included. The results of meta-analysis showed that the pooled sensitivity = 0.76 (95% confidence interval [CI]: 0.69 ~ 0.82), specificity = 0.82 (95%CI: 0.69 ~ 0.90), +LR = 4.12 (95%CI: 2.12 ~ 4.03), -LR = 0.29 (95%CI: 0.22 ~ 0.38), DOR = 14.08 (95%CI: 7.13 ~ 27.83), and the area under ROC was 0.84. CONCLUSION: FAI has a moderate diagnostic value for PCOS. It may be possible to add new experimental designs to find the best cut-off value for FAI diagnosis to improve the diagnostic efficacy.

Occurrence and distribution of natural and synthetic progestins, androgens, and estrogens in soils from agricultural production areas in China.

The occurrence of biologically potent sex hormones in agricultural soils is of growing concern due to their ability to disrupt the endocrine systems of aquatic organisms after being transported to surface waters via runoff. This study, therefore, examined the large-scale occurrence of 34 natural and synthetic sex hormones (13 progestins, 16 androgens, and 5 estrogens) in soils from 7 provinces and 1 municipality in China. The target sex hormones were detected in 99.3% of the soil samples, indicating their widespread occurrence in most agricultural areas. Additionally, seven synthetic progestins were detected in soils for the first time. The total concentration of the 34 sex hormones (Σsex hormones) in the sampled soils ranged from below the method detection limit to 23.7 ng/g (mean of 4.72 ± 4.07 ng/g), with androgens and progestins being the most dominant hormone groups. Significant correlations were observed among the concentrations of Σestrogens, Σandrogens, and Σprogestins (r = 0.117-0.433, p < 0.001), suggesting similar sources of sex hormones. The mean concentration of Σsex hormones varied considerably across the selected provinces/municipality. Notably, the annual slaughter of poultry and swine (R2 = 0.75-0.88), female population (R2 = 0.57-0.58), and soil organic carbon content (R2 = 0.20-0.55) in each province were significantly correlated with the concentrations or mean concentrations of Σsex hormones, Σestrogens, or Σprogestins. This finding implies that these parameters contributed to the occurrence and distribution of sex hormones in the studied soils. Finally, risk quotients for some sex hormones exceeded 0.01, indicating medium or high risks to agroecosystems. This study highlights the importance of designing an optimal manure fertilization strategy in order to mitigate the risks posed by sex hormones in agroecosystems.

The effect of polycystic ovary syndrome without hyperandrogenism on pregnancy-related outcomes: a retrospective cohort study.

OBJECTIVE: To evaluate the effect of polycystic ovary syndrome (PCOS) without hyperandrogenism on pregnancy-related outcomes. DESIGN: A retrospective cohort study. SETTING: Reproductive Medicine Centre of Tongji Hospital. POPULATION: Women without hyperandrogenism undergoing their first single blastocyst transfers in frozen-thawed cycles were divided into a PCOS group and a non-PCOS group according to the Rotterdam criteria. METHODS: The pregnancy-related outcomes of women with and without PCOS were compared. Propensity score matching and multiple logistic regression models were used to eliminate essential impacts on pregnancy-related outcomes. MAIN OUTCOME MEASURES: Pregnancy-related outcomes included pregnancy loss and abnormal perinatal outcomes. RESULTS: A total of 4083 women without hyperandrogenism met the study criteria, among whom 557 met the diagnostic criteria for PCOS. Women with PCOS had higher rates of clinical pregnancy (P = 0.035) and cumulative live births (P = 0.023). However, there were no significant differences in the rates of biochemical pregnancy, twins and pregnancy loss between the two groups. Among women with singleton pregnancies, the incidences of preterm birth, hypertensive disorders of pregnancy, gestational diabetes, placenta praevia, fetal malformation, macrosomia and low birthweight did not differ significantly between the two groups. The results remained unchanged even after adjustments were made for propensity score matching and multiple logistic regression analyses. CONCLUSION: Women with PCOS without hyperandrogenism may achieve higher rates of clinical pregnancy and cumulative live birth than those without PCOS, without increases in their rates of biochemical pregnancy, pregnancy loss or other abnormal perinatal outcomes. TWEETABLE ABSTRACT: PCOS without hyperandrogenism was not associated with abnormal pregnancy-related outcomes.

Reproductive hormone measurement from minimally invasive sample types: Methodological considerations and anthropological importance.

Energetic investment in human reproduction has long been recognized as costly, influencing developmental, physiological, and behavioral patterns in males and females. These effects are largely coordinated through the actions of reproductive hormones (eg, testosterone, estradiol, and progesterone). Here, the utility and limitations of minimally invasive sampling techniques are explored, providing a novel perspective on how reproductive hormone measurements can enhance reproductive endocrinology research. Salivary steroid measures are most commonly used, although several dried blood spot and urine assays are also available, and researchers continue to explore the efficacy of other sample types. These relatively simple measures have facilitated the collection of multiple samples from a single participant, allowing researchers to more accurately track the diurnal and cyclical variation exhibited by many reproductive hormones. Ultimately, the ability to collect fine-grained participant data allows biological anthropologists to better test questions central to human reproductive ecology, life history theory, and public health. For example, fieldwork using these techniques suggests that testosterone profile variation across populations is influenced by energetic constraints and reproductive status. Moreover, hormone concentrations shape the development of sex characteristics, with implications for evolutionary questions related to sexual selection. Hormone levels also can be used to identify a range of medical concerns (eg, suppressed hormone production levels linked with psychosocial stress). These findings highlight how minimally invasive collection techniques can be applied to test diverse evolutionary hypotheses and identify important health concerns. Still, more work is needed to standardize collection and laboratory analysis procedures, thereby enabling more direct data comparisons between researchers.

An in vitro assay approach to investigate the potential impact of different doping agents on the steroid profile.

The steroid profile, that is, the urinary concentrations and concentration ratios of selected steroids, is used in sports drug testing to detect the misuse of endogenous steroids such as testosterone. Since several years, not only population-based thresholds are applied but also the steroid profile is monitored via the Athlete Biological Passport whereby the individual reference ranges derived from multiple test results of the same athlete are compared to population-based thresholds. In order to maintain a high probative force of the passport, samples collected or analyzed under suboptimal conditions should not be included in the longitudinal review. This applies to biologically affected or degraded samples and to samples excluded owing to the presence of other substances potentially (or evidently) altering the steroid profile. Nineteen different doping agents comprising anabolic steroids, selective androgen receptor modulators, selective estrogen receptor modulators, ibutamoren, and tibolone were investigated for their effect on the steroid profile using an androgen receptor activation test, an androgen receptor binding assay, an aromatase assay, and a steroidogenesis assay. The in vitro tests were coupled with well-established liquid chromatography/mass spectrometry-based analytical approaches and for a subset of steroidal analytes by gas chromatography/mass spectrometry. The variety of tests employed should produce a comprehensive data set to better understand how a compound under investigation may impact the steroid profile. Although our data set may allow an estimate of whether or not a substance will have an impact on the overall steroid metabolism, predicting which parameter in particular may be influenced remains difficult.

Androgen levels in the fetal cord blood of children born to women with polycystic ovary syndrome: a meta-analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. It is reported that intrauterine exposure to hyperandrogenism may induce the development of PCOS and associated complications in later life. To analyze the intrauterine androgen levels in infants born to PCOS mothers, we evaluated the androgen levels in fetal cord blood through a meta-analysis of observational studies. MATERIAL AND METHODS: The following online databases were systematically searched: PubMed, EMBASE, Cochrane library databases and Web of Science up to December 2019. Human studies compared cord blood androgen levels, including testosterone (T) and androstenedione (ADION), in fetal cord blood of mothers with and without PCOS. Statistical analysis was performed in Review Manager, Version 5.3, with the inverse variance method based on a random-effects model. RESULTS: A total of 7 articles were scrutinized and a total of 570 samples including 268 female and 222 male infants were qualified for review. In the mass spectrograph (MS) subgroup, PCOS mothers showed no signs of increased T concentration in umbilical cord blood at birth (4 studies; hazard ratio [HR] = - 0.05; 95% confidence interval [CI] = [- 0.33,0.24]; I2 = 7%; P = 0.75; fixed-effects model). ADION level tends to be lower in daughters' cord blood of PCOS mothers (3 studies; HR = -0.59; 95%CI = [- 1.00, - 0.19]; I2 = 0%; P = 0.004; fixed-effects model). CONCLUSIONS: Fetal cord blood T level is not related to PCOS, while ADION levels tend to be lower in the cord blood of daughters born to mothers with PCOS.

Non-targeted detection and differentiation of agonists versus antagonists, directly in bioprofiles of everyday products.

Xenoestrogens exert antiandrogenic effects on the human androgen receptor. In the analytical field, such antagonists block the detection of testosterone and falsify results obtained by sum parameter assays. Currently, such agonistic versus antagonistic effects are not differentiated in complex mixtures. Oppositely acting hormonal effects present in products of everyday use can only be differentiated after tedious fractionation and isolation of the individual compounds along with subjection of each fraction/compound to the status quo bioassay testing. However, such long-lasting procedures are not suited for routine. Hence, we developed a fast bioanalytical tool that figures out agonists versus antagonists directly in complex mixtures. Exemplarily, 8 cosmetics and 15 thermal papers were analyzed. The determined antagonistic potentials of active compounds found were comparable to the ones of known antagonists (in reference shown for bisphenol A, 4-n-nonylphenol and four parabens). Relevant biological/chromatographic parameters such as cell viability, culture conditions, dose response curves, limits of biological detection/quantification and working range (shown for testosterone, dihydrotestosterone, nandrolone and trenbolone) were investigated to obtain the best sensitivity of the biological detection. The developed and validated method was newly termed reversed phase high-performance thin-layer chromatography planar yeast ant-/agonistic androgen screen (RP-HPTLC-pYAAS bioassay). Results were also compared with the RP-HPTLC-Aliivibrio fischeri bioassay (applied on RP plates for the first time). As proof-of-concept, the transfer to another bioassay (RP-HPTLC-pYES) was successfully demonstrated, analogously termed RP-HPTLC-pYAES bioassay detecting anti-/estrogens (exemplarily shown for evaluation of 4 pharmaceuticals used in breast cancer treatment). The new imaging concept provides (1) detection and differentiation of individual agonistic versus antagonistic effects in the bioprofiles, (2) bioanalytical quantification of their activity potential by scanning densitometry and (3) characterization of unknown bioactive compound zones by hyphenation to high-resolution mass spectrometry. Depending on the hormonal bioassay, 15 samples were analyzed in parallel within 5 h or 6 h (calculated as 20 or 24 min per sample). For the first time, piezoelectric spraying of the yeast cells was successfully demonstrated for the planar yeast-based bioassays.

Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.

BACKGROUND AND OBJECTIVE: Our patient cohort revealed that obesity is strongly associated with steroid-5α reductase type 2 (SRD5A2) promoter methylation and reduced protein expression. The underlying mechanism of prostatic growth in this population is poorly understood. Here we addressed the question of how obesity, inflammation, and steroid hormones affect the development of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: We used preadipocytes, macrophages, primary human prostatic stromal cells, prostate tissues from high-fat diet-induced obese mice, and 35 prostate specimens that were collected from patients who underwent transurethral resection of the prostate (TURP). RNA was isolated and quantified with RT-PCR. Genome DNA was extracted and SRD5A2 promoter methylation was determined. Sex hormones were determined by high-performance liquid chromatography-tandem mass spectrometry. Protein was extracted and determined by ELISA test. RESULTS: In prostatic tissues with obesity, the levels of inflammatory mediators were elevated. SRD5A2 promoter methylation was promoted, but SRD5A2 expression was inhibited. Inflammatory mediators and saturated fatty acid synergistically regulated aromatase activity. Obesity promoted an androgenic to estrogenic switch in the prostate. CONCLUSIONS: Our findings suggest that obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland, which may serve as an effective strategy for alternative therapies for management of lower urinary tract symptoms associated with BPH in select individuals.