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Environmental Science & Technology Dec 2023Organic pollutant exposure may alter sex steroid hormone levels in both animals and humans, but studies on mixture effects have been lacking and mainly limited to...
Organic pollutant exposure may alter sex steroid hormone levels in both animals and humans, but studies on mixture effects have been lacking and mainly limited to persistent organic pollutants, with few hormones being investigated. Moreover, measurements from a single blood or urine sample may not be able to reflect long-term status. Using hair analysis, here, we evaluated the relationship between multiclass organic pollutants and sex steroid hormones in 196 healthy Chinese women aged 25-45 years. Associations with nine sex steroid hormones, including progesterone, androstenedione (AD), testosterone (T), estrone (E1), and 17β-estradiol (E2), and eight related hormone ratios were explored on 54 pollutants from polychlorinated biphenyl (PCB), pesticide, and bisphenol families using stability-based Lasso regression analysis. Our results showed that each hormone was associated with a mixture of at least 10 examined pollutants. In particular, hair E2 concentration was associated with 19 pollutants, including γ-hexachlorocyclohexane, propoxur, permethrin, fipronil, mecoprop, prochloraz, and carbendazim. There were also associations between pollutants and hormone ratios, with pentachlorophenol, dimethylthiophosphate, 3-phenoxybenzoic acid, and flusilazole being related to both E1/AD and E2/T ratios. Our results suggest that exposure to background levels of pesticides PCB180 and bisphenol S may affect sex steroid hormone homeostasis among women of reproductive age.
Topics: Animals; Humans; Female; Environmental Pollutants; Environmental Exposure; Gonadal Steroid Hormones; Polychlorinated Biphenyls; Testosterone; Pesticides
PubMed: 37934613
DOI: 10.1021/acs.est.3c06095 -
Reproductive Sciences (Thousand Oaks,... Jun 2024Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere...
Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.
Topics: Humans; Polycystic Ovary Syndrome; Female; Obesity; Adult; Telomere Shortening; Body Mass Index; Young Adult; Insulin Resistance; Telomere; Leukocytes; Biomarkers
PubMed: 38393627
DOI: 10.1007/s43032-024-01485-z -
Andrology May 2024Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association...
BACKGROUND
Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men.
MATERIALS AND METHODS
This cross-sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography-tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity.
RESULTS
After adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high-sensitivity C-reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high-sensitivity C-reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist-to-hip ratio), 12.92% (defined by waist-to-height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity.
CONCLUSION
Inflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases.
Topics: Humans; Male; Androstenedione; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Obesity; Testosterone; Body Mass Index; Inflammation; China
PubMed: 37823215
DOI: 10.1111/andr.13544 -
Scandinavian Journal of Medicine &... Oct 2023Ketone bodies, such as 3-hydroxybutyrate (3-OHB), have been frequently used by endurance athletes, such as cyclists, to enhance performance and recovery and are...
Ketone bodies, such as 3-hydroxybutyrate (3-OHB), have been frequently used by endurance athletes, such as cyclists, to enhance performance and recovery and are recognized for their health benefits and therapeutic effects for decades. Testosterone is a potent regulator of red blood cell production. Evidence suggests that ketone bodies can increase the production of erythropoietin, which stimulates red blood cell production. Therefore, we investigated whether an acute increase in 3-OHB levels affects testosterone levels in healthy young men. We studied six healthy, young male participants who fasted overnight and were tested twice: (i) after drinking 37.5 g of Na-D/L-3-OHB dissolved in 500 mL of distilled water (KET), and (ii) after drinking 500 mL of placebo saline water (0.9% NaCl) (CTR). During the KET trial, 3-OHB levels increased to approximately 2.5 mM. Testosterone levels decreased significantly by 20% during KET compared to 3% during CTR. A simultaneous increase in luteinizing hormone was observed in KET. We observed no changes in other adrenal androgens, such as androstenedione and 11-keto androgens. In conclusion, an acute increase in 3-OHB levels decreases testosterone levels. Concomitantly, an increase in luteinizing hormone was observed. This suggests that 3-OHB may counteract some of the beneficial effects of endurance training. Further studies, involving larger sample sizes and performance outcomes, are required to fully understand this phenomenon.
Topics: Humans; Male; Testosterone; Androgens; Ketone Bodies; Luteinizing Hormone; Eating
PubMed: 37377131
DOI: 10.1111/sms.14441 -
Journal of Endocrinological... Feb 2024The aim of our study was to compare the incidence of idiopathic central precocious puberty (CPP) in our highly specialized Endocrinological Center before and after the...
PURPOSE
The aim of our study was to compare the incidence of idiopathic central precocious puberty (CPP) in our highly specialized Endocrinological Center before and after the onset of COVID-19 lockdown; we also aimed to identify any potential difference between girls with CPP from the two different time periods.
METHODS
We retrospectively analyzed the auxological profile of 49 girls with idiopathic CPP: 30 with pre-lockdown onset and 19 with post-lockdown onset of the disease. We collected patients' characteristics (medical history, physical examination, baseline and dynamic hormonal assessment, bone age, pelvic ultrasound) and compared them between the two groups.
RESULTS
We registered an almost threefold increase in CPP incidence in the 2020-2021 period compared to the previous six years. In post-lockdown patients we found a trend for an earlier diagnosis in terms of both chronological age (p 0.0866) and days between the onset of first pubertal signs and diagnosis (p 0.0618). We also found that post-lockdown patients had a significantly lower hypothalamus-pituitary-gonadal axis activation (lower ∆LH% after GnRH test, p 0.0497), a significantly lower increase in bone age calculated at RUS with TW3 method (p 0.0438) and a significantly reduced ovarian activation in females (lower delta-4-androstenedione levels, p 0.0115). Interestingly, post-lockdown patients were born from mothers with an older age at menarche (p 0.0039).
CONCLUSIONS
Besides confirming a significant increase in new diagnoses of CPP in the post-lockdown period, our findings among Post-lockdown girls also suggest a less progressive form of CPP and a stronger environmental influence compared to genetic background in determining the timing of pubertal onset.
Topics: Female; Humans; Infant, Newborn; Puberty, Precocious; COVID-19; Retrospective Studies; Communicable Disease Control; Menarche; Gonadotropin-Releasing Hormone
PubMed: 37566202
DOI: 10.1007/s40618-023-02146-9 -
Reproductive Sciences (Thousand Oaks,... Mar 2024There is a lack of consensus on the optimal screening strategy for insulin resistance (IR), particularly in lean women with polycystic ovary syndrome (PCOS). Therefore,...
There is a lack of consensus on the optimal screening strategy for insulin resistance (IR), particularly in lean women with polycystic ovary syndrome (PCOS). Therefore, we conducted a cross-sectional study in 80 women with PCOS (28 lean/52 obese) and 80 age- and body mass index (BMI)-matched controls. Using a 5-point 75-g oral glucose tolerance test (OGTT) (0, 30, 60, 90, 120 min), we examined glucose and insulin excursions, IR, insulin sensitivity, beta-cell function (ßF), and the effect of androgens on IR. Lean and obese women with PCOS had similar glucose but higher insulin (except fasting in lean women) and insulin AUC as compared to their respective controls (p < 0.05). Lean women with PCOS were equally insulin-resistant but more hyperinsulinemic than the obese controls (p < 0.05). Although ßF ([1st phase: 481.71 ± 263.53 vs. 430.56 ± 232.37], [2nd phase: 815.16 ± 447.12 vs. 752.66 ± 428.95]) was comparable in lean and obese women with PCOS, lean women had better insulin sensitivity (112.78 ± 66.26 vs. 75.49 ± 55.6) (p < 0.05). Dehydroepiandrosterone sulfate (DHEAS) and androstenedione decreased with increasing BMI in lean women, and this correlated with deteriorating insulin sensitivity and exaggerated hyperinsulinemia. In obese women with PCOS, sex hormone-binding globulin (SHBG) correlated negatively with BMI and hyperinsulinemia, and positively with insulin sensitivity. This data suggests that estimating only fasting insulin may miss IR in lean women with PCOS; hence, additional time points in OGTT will add value to screening for IR. DHEAS and androstenedione may have a beneficial effect on insulin sensitivity and may be used to screen IR in lean women, while SHBG can be used as a predictive marker for IR in obese women with PCOS.
Topics: Female; Humans; Insulin Resistance; Androgens; Polycystic Ovary Syndrome; Androstenedione; Cross-Sectional Studies; Blood Glucose; Insulin; Obesity; Glucose; Body Mass Index
PubMed: 37848646
DOI: 10.1007/s43032-023-01374-x -
Journal of Clinical Medicine Dec 2023Minipuberty is a period of increased reproductive axis activity in infancy, which seems to be implicated in the postnatal development of male genital organs. Impaired...
Minipuberty is a period of increased reproductive axis activity in infancy, which seems to be implicated in the postnatal development of male genital organs. Impaired thyroid function during pregnancy is associated with an increased risk of prenatal, perinatal, and postnatal complications. The aim of this study was to investigate whether the presence of hypothyroidism during pregnancy modulates the course of male minipuberty. We compared three matched groups of male infants: sons of women with hypothyroidism uncontrolled or poorly controlled during pregnancy (group A), male offspring of women treated over the entire pregnancy with adequate doses of levothyroxine (group B), and sons born to women with no evidence of thyroid disease (group C). Salivary levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, progesterone, and 17-hydroxyprogesterone, as well as urine concentrations of FSH and LH, were assessed once a month in the first 6 months of life, and once every two months between months 6 and 12. Gonadotropin and testosterone levels during the first 6 months of life were lower in group A than in groups B and C. Differences in testosterone and gonadotropin levels were accompanied by similar differences in penile length and testicular volume. Concentrations of the remaining hormones did not differ between the study groups. The obtained results suggest that untreated or undertreated maternal thyroid hypofunction in pregnancy has an inhibitory effect on postnatal activation of the hypothalamic-pituitary-testicular axis and genital organ development in their male offspring.
PubMed: 38137718
DOI: 10.3390/jcm12247649 -
Epigenetics Dec 2023Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their...
Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby values. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.
Topics: Male; Humans; DNA Methylation; Epigenome; Gonadal Steroid Hormones; Estradiol; Dehydroepiandrosterone
PubMed: 36994855
DOI: 10.1080/15592294.2023.2196759 -
Cancer Jun 2024The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.
BACKGROUND
The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.
METHODS
Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984).
RESULTS
Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively).
CONCLUSIONS
Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.
PubMed: 38824654
DOI: 10.1002/cncr.35391 -
Journal of Chromatography. A Nov 2023Steroid hormones have been reported to be associated with endocrine system diseases. This paper proposes a novel procedure of deep eutectic solvent (DES)-assisted...
Development and validation of a deep eutectic solvent-assisted liquid-liquid extraction method for simultaneous quantification of six steroid hormones in serum by liquid chromatography-tandem mass spectrometry.
Steroid hormones have been reported to be associated with endocrine system diseases. This paper proposes a novel procedure of deep eutectic solvent (DES)-assisted liquid-liquid extraction (LLE) to extract six steroid hormones (including cortisone, cortisol, androstenedione, testosterone, 17-hydroxyprogesterone, and progesterone) from serum coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of five types of L-proline, choline chloride, and citric acid-based DESs were tailored; the DES from L-proline and ethylene glycol at a molar ratio of 1:4 with 20 % acetonitrile was selected as the best-fit assisted solvent for the six steroid hormones compared with other DESs. The parameters for extraction by selected DES were optimized using Box-Behnken design (BBD), and the optimal extraction conditions are 200 µL of acetonitrile, 100 µL of the sample, and 80 µL of DES. Under optimum conditions, the method has good linear calibration ranges (between 0.07 ng mL and 600 ng mL), correlation coefficients of determination (r>0.99), and low limits of quantification (between 0.02 and 0.60 ng mL). The extraction recoveries were in the range of 81.84-114.43 %, and the intra-day and inter-day relative standard deviations (RSDs) were less than 10 %.In general, the DES-LC-MS/MS method is a simple and environmentally-friendly method, which can be complementary to the presently available methods for determining steroid hormones in serum.
Topics: Chromatography, Liquid; Deep Eutectic Solvents; Tandem Mass Spectrometry; Limit of Detection; Steroids; Liquid-Liquid Extraction; Hydrocortisone; Acetonitriles; Proline; Chromatography, High Pressure Liquid
PubMed: 37806044
DOI: 10.1016/j.chroma.2023.464413