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Clinical Chemistry and Laboratory... Jun 2024Steroid hormone levels of patients may be monitored via dried blood spot (DBS) sampling at home. Stability of steroid hormones in DBS samples, however, needs to be...
OBJECTIVES
Steroid hormone levels of patients may be monitored via dried blood spot (DBS) sampling at home. Stability of steroid hormones in DBS samples, however, needs to be established.
METHODS
DBS samples from healthy volunteers were collected and stored at various temperatures. Steroid hormone concentrations in DBS were measured directly, at day 2, day 7 and day 14 following storage at 37 °C and after 7 days, 14 days, 3 months and 6 months following storage at -20 °C, 4 °C and room temperature (RT). Cortisol, cortisone, corticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were assessed using LC-MS/MS.
RESULTS
All steroids were stable (±15 %) up to 14 days when stored at 37 °C, except for cortisone (only stable until 2 days). All steroids were stable up to 6 months when stored at -20 °C, 4 °C and RT. However, there were some exceptions, for androstenedione at RT (only stable until 7 days), for 17-OHP when stored at -20 °C (only stable until 3 months), for cortisone at RT and 4 °C (only stable until 14 days), and cortisol at RT (only stable until 3 months).
CONCLUSIONS
Overall, we demonstrated stability of steroid hormone concentrations in DBS under various conditions which may be encountered during shipping to the diagnostic laboratory and during long-term storage before analysis.
PubMed: 38874994
DOI: 10.1515/cclm-2024-0142 -
Journal of the Endocrine Society Dec 2023Altered metabolic signatures on steroidogenesis may characterize individual subtypes of congenital adrenal hyperplasia (CAH), but conventional diagnostic approaches are...
CONTEXT
Altered metabolic signatures on steroidogenesis may characterize individual subtypes of congenital adrenal hyperplasia (CAH), but conventional diagnostic approaches are limited to differentiate subtypes.
OBJECTIVE
We explored metabolic characterizations and identified multiple diagnostic biomarkers specific to individual subtypes of CAH.
METHODS
Liquid chromatography-mass spectrometry-based profiling of 33 adrenal steroids was developed and applied to serum samples obtained from 67 CAH patients and 38 healthy volunteers.
RESULTS
Within- and between-run precisions were 95.4% to 108.3% and 94.1% to 110.0%, respectively, while all accuracies were <12% and the correlation coefficients () were > 0.910. Metabolic ratios corresponding to 21-hydroxylase characterized 21-hydroxylase deficiency (21-OHD; n = 63) from healthy controls (area under the curve = 1.0, < 1 × 10 for all) and other patients with CAH in addition to significantly increased serum 17α-hydroxyprogesterone ( < 1 × 10) and 21-deoxycortisol ( < 1 × 10) levels. Higher levels of mineralocorticoids, such as corticosterone (B) and 18-hydroxyB, were observed in 17α-hydroxylase deficiency (17α-OHD; N = 3), while metabolic ratio of dehydroepiandrosterone sulfate to pregnenolone sulfate was remarkably decreased against all subjects. A patient with 11β-hydroxylase deficiency (11β-OHD) demonstrated significantly elevated 11-deoxycortisol and its metabolite tetrahydroxy-11-deoxyF, with reduced metabolic ratios of 11β-hydroxytestosterone/testosterone and 11β-hydroxyandrostenedione/androstenedione. The steroid profiles resulted in significantly decreased cortisol metabolism in both 21-OHD and 17α-OHD but not in 11β-OHD.
CONCLUSION
The metabolic signatures with specific steroids and their corresponding metabolic ratios may reveal individual CAH subtypes. Further investigations with more substantial sample sizes should be explored to enhance the clinical validity.
PubMed: 38130465
DOI: 10.1210/jendso/bvad155 -
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 -
Biomedicines Feb 2024Polycystic ovary syndrome (PCOS) is a multisystem reproductive-metabolic disorder and the most common endocrine cause of infertility. The objective of our study was to...
The Comparative Effects of Myo-Inositol and Metformin Therapy on the Clinical and Biochemical Parameters of Women of Normal Weight Suffering from Polycystic Ovary Syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a multisystem reproductive-metabolic disorder and the most common endocrine cause of infertility. The objective of our study was to determine the influence of myo-inositol (MI) on insulin resistance (IR), menstrual cycle regularity, and hyperandrogenism in women suffering from PCOS with normal BMI and diagnosed IR.
METHODS
We performed a prospective randomized controlled trial (RCT) that included 60 participants with PCOS who had IR and a normal BMI. Two groups were formed. A group of thirty patients received MI, and thirty patients in the control group received metformin (MET).
RESULTS
A statistically significant reduction in the area under the curve (AUC) of insulin values during the oral glucose tolerance test (OGTT) was recorded in both examined groups after the applied therapy with MI and MET. The regularity of the menstrual cycle in both groups was improved in >90% of patients. A statistically significant decrease in androgenic hormones (testosterone, SHBG, free androgen index-FAI, androstenedione) was recorded in both groups and did not differ between the groups.
CONCLUSIONS
Both MI and MET can be considered very effective in the regulation of IR, menstrual cycle irregularities, and hyperandrogenism in women with PCOS.
PubMed: 38397951
DOI: 10.3390/biomedicines12020349 -
Journal of the Endocrine Society Jan 2024Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and...
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis.
METHODS
Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G.
RESULTS
Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans.
CONCLUSION
LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.
PubMed: 38213910
DOI: 10.1210/jendso/bvad169 -
EBioMedicine Jan 2024Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely...
BACKGROUND
Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored.
METHODS
We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments.
FINDINGS
We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1 CD25 CD62L CD127) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor.
INTERPRETATION
Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications.
FUNDING
Found in acknowledgements.
Topics: Humans; Cortodoxone; Progesterone; Androstenedione; Steroids; Phenotype
PubMed: 38134621
DOI: 10.1016/j.ebiom.2023.104935 -
Research Square Oct 2023Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk...
PURPOSE
Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways.
METHODS
This analysis included 1,208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders.
RESULTS
Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI: 1.03 to 1.44), androstenedione (RR: 1.20, 95% CI: 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI: 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI: 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI: 0.98 to 1.28), estrone (RR: 1.21, 95% CI: 0.99 to 1.48), total estradiol (RR: 1.19, 95% CI: 1.02 to 1.39) and free estradiol (RR: 1.22, 95% CI: 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR: 0.83, 95% CI: 0.66 to 1.05).
CONCLUSION
Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex hormone-driven nature of postmenopausal breast cancer.
PubMed: 37886482
DOI: 10.21203/rs.3.rs-3406466/v1 -
The Journal of Steroid Biochemistry and... Jul 2023The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes have reciprocal relationships with steroidogenesis regulation. However, the...
The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes have reciprocal relationships with steroidogenesis regulation. However, the relationship between testicular steroids and defective glucocorticoid production under chronic stress remains unclear. Metabolic changes of testicular steroids in bilateral adrenalectomized (bADX) 8-week-old C57BL/6 male mice were measured using gas chromatography-mass spectrometry. Twelve weeks after surgery, testis samples were obtained from the model mice, which were divided into tap-water (n = 12) and 1 % saline (n = 24) supplementation groups, and their testicular steroid levels were compared with those of sham controls (n = 11). An increased survival rate with lower testicular levels of tetrahydro-11-deoxycorticosterone was observed in the 1 % saline group compared to both the tap-water (p = 0.029) and sham (p = 0.062) groups. Testicular corticosterone levels were significantly decreased in both tap-water (4.22 ± 2.73 ng/g, p = 0.015) and 1 % saline (3.70 ± 1.69, p = 0.002) groups compared to those in sham controls (7.41 ± 7.39). Testicular testosterone levels tended to increase in both bADX groups compared to those in the sham controls. In addition, increased metabolic ratios of testosterone to androstenedione in tap-water (2.24 ± 0.44, p < 0.05) and 1 % saline (2.18 ± 0.60, p < 0.05) mice compared to sham controls (1.87 ± 0.55) suggested increased production of testicular testosterone. No significant differences in serum steroid levels were observed. Defective adrenal corticosterone secretion and increased testicular production in bADX models revealed an interactive mechanism underlying chronic stress. The present experimental evidence suggests the crosstalk between the HPA and HPG axes in homeostatic steroidogenesis.
Topics: Mice; Male; Animals; Testosterone; Testis; Adrenalectomy; Corticosterone; Mice, Inbred C57BL; Steroids
PubMed: 37244300
DOI: 10.1016/j.jsbmb.2023.106333 -
Biomedicine & Pharmacotherapy =... Jun 202417-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using...
DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.
17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.
Topics: Humans; Estradiol; Male; Biomarkers, Tumor; Androstenedione; Asbestos; Female; Middle Aged; Occupational Exposure; Aged; Mesothelioma, Malignant; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; Dehydroepiandrosterone; Case-Control Studies; Early Detection of Cancer
PubMed: 38692064
DOI: 10.1016/j.biopha.2024.116662