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Journal of the Endocrine Society Feb 2024Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone...
CONTEXT
Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone or together lead to earlier maturation.
OBJECTIVE
This work aimed to search for different growth trajectories using a clustering approach to analyze the effects of birth size and postnatal growth on adrenarchal and pubertal development.
METHODS
Altogether 351 children (48% girls) were examined prospectively at ages 6 to 9 and 9 to 11 years. Birth and early-growth data were collected retrospectively. Main outcome measures included clinical signs of adrenarche and puberty, and serum androgen concentrations (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone).
RESULTS
We detected 4 clusters with different birth sizes and postnatal growth trajectories: 1) children with average birth size and increased postnatal growth (AI), 2) children with small birth size and increased postnatal growth (SI), 3) children with average birth size and postnatal growth (AA), and 4) children with small birth size and average postnatal growth (SA). Thelarche at age 9 to 11 was most common and serum androgens at ages 6 to 9 and 9 to 11 years were highest in girls belonging to the AI and SI groups. Similar patterns in the onset of puberty and in androgen levels were not seen in the SA group.
CONCLUSION
Increased early growth and weight gain predict higher serum androgen concentrations and earlier onset of puberty in girls. Adrenarche and puberty do not appear to be shifted earlier in children with small birth size who do not have catch-up growth.
PubMed: 38425434
DOI: 10.1210/jendso/bvae026 -
JCEM Case Reports Mar 2024Nonclassic congenital adrenal hyperplasia (NCCAH) is characterized by mild cortisol deficiency, excess androgens and adrenocorticotropin (ACTH) production, and often...
Nonclassic congenital adrenal hyperplasia (NCCAH) is characterized by mild cortisol deficiency, excess androgens and adrenocorticotropin (ACTH) production, and often with various features of dysmetabolic syndrome. Elective bariatric surgery is one of the most effective long-term management strategies for severe obesity. Our case presents a 34-year-old woman with symptomatic NCCAH and class III obesity who status post Roux-en-Y gastric bypass (RYGB) had significant weight loss with metabolic resolution of NCCAH, and no longer required glucocorticoid (GC) therapy. At 11 months post operation and off GC therapy, she had a weight deficit of approximately 160 pounds (72.57 kg) with continued metabolic resolution of NCCAH markers including ACTH, 17-hydroxyprogesterone, and androstenedione. Presently, GC therapy remains one of the few available treatments for symptomatic NCCAH; however, long-term GC therapy has the potential for various complications and side effects. Our case presents elective bariatric surgery as a potential and unique treatment option for patients with NCCAH with associated class III obesity. The exact pathophysiologic basis for this effect and its potential role in long-term management of appropriate NCCAH patients requires further study.
PubMed: 38404690
DOI: 10.1210/jcemcr/luae018 -
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 -
Biomedicines Feb 2024Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and...
Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and neurokinin B (NKB) are produced by the placenta in high amounts, and they have been implicated in several pregnancy complications associated with placental dysfunction. However, their placental expression has not been studied in PCOS. We isolated mRNA after delivery from the placentae of 31 PCOS and 37 control women with term, uncomplicated, singleton pregnancies. The expression of KISS1, NKB, and neurokinin receptors 1, 2, and 3 was analyzed with real-time polymerase chain reaction, using β-actin as the reference gene. Maternal serum and umbilical cord levels of total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), androstenedione, dehydroepiandrosterone sulfate (DHEAS), Anti-Mullerian hormone (AMH), and estradiol were also assessed. placental mRNA expression was higher in PCOS women versus controls in pregnancies with female offspring. expression depended on fetal gender, being higher in pregnancies with male fetuses, regardless of PCOS. was positively correlated with umbilical cord FAI and AMH, and was positively correlated with cord testosterone and FAI; there was also a strong positive correlation between and expression. Women with PCOS had higher serum AMH and FAI and lower SHBG than controls. Our findings indicate that NKB might be involved in the PCOS-related placental dysfunction and warrant further investigation. Studies assessing the placental expression of should take fetal gender into consideration.
PubMed: 38397936
DOI: 10.3390/biomedicines12020334 -
Journal of the Endocrine Society Feb 2024Adrenocortical carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on...
Adrenocortical carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on identifying risk factors associated with ACC mortality. Our retrospective analysis included a cohort of 150 adult patients with ACC in all stage categories, treated between 1981 and 2022. Tumor hormonal hypersecretion was observed in 78.6% of the patients, and the median age of diagnosis was 40 years. The majority presented as European Network for the Study of Adrenal Tumors (ENSAT) III or IV (22.9% and 31.2%, respectively), and the overall mortality rate was 54.6%. Independent predictors of death were elevated secretion of cortisol (HR = 2.0), androstenedione (HR = 2.2), estradiol (HR = 2.8), 17-OH progesterone (HR = 2.0), and 11-deoxycortisol (HR = 5.1), higher Weiss (HR = 4.3), modified Weiss (HR = 4.4), and Helsinki scores (HR = 12.0), advanced ENSAT stage (HR = 27.1), larger tumor size (HR = 2.7), higher Ki-67 percentage (HR = 2.3), and incomplete surgical resection (HR = 2.5). Mitosis greater than 5/50 high-power field (HR = 5.6), atypical mitosis (HR = 2.3), confluent necrosis (HR = 15.4), venous invasion (HR = 2.8), and capsular invasion (HR = 2.4) were also identified as independent predictors of death. Knowing the risk factors for ACC's mortality may help determine the best treatment option.
PubMed: 38384443
DOI: 10.1210/jendso/bvad170 -
Journal of Ovarian Research Feb 2024To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with... (Randomized Controlled Trial)
Randomized Controlled Trial
Metformin versus metformin plus pioglitazone on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome: a single-center, open-labeled prospective randomized controlled trial.
OBJECTIVE
To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome (PCOS).
METHODS
Sixty normal-weight women with PCOS were recruited between January and September 2022 at the Shengjing Hospital of China Medical University. They were randomly assigned to the MET or PIOMET groups for 12 weeks of MET monotherapy or PIOMET therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and the oral glucose insulin-releasing test (OGIRT) were performed at baseline and after the 12-week treatment.
RESULTS
Thirty-six participants completed the trial. MET and PIOMET therapies improved menstrual cycles after the 4- and 12-week treatments; however, there was no statistical difference between the two groups. PIOMET therapy improved luteinizing hormone (LH), luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, and free androgen index (FAI) levels after the 4-week treatment, whereas MET monotherapy only improved total testosterone (TT) levels compared to baseline (P < 0.05). Both MET and PIOMET therapies improved TT and anti-Mullerian hormone (AMH) levels after the 12-week treatment (P < 0.05). In addition, only PIOMET therapy significantly improved sex hormone-binding globulin (SHBG), FAI, and androstenedione (AND) levels than the baseline (P < 0.05). PIOMET therapy improved SHBG and AMH levels more effectively than MET monotherapy (P < 0.05). Furthermore, PIOMET treatment was more effective in improving blood glucose levels at 120 and 180 min of OGIRT compared to MET monotherapy (P < 0.05).
CONCLUSIONS
In normal-weight women with PCOS, PIOMET treatment may have more benefits in improving SHBG, AMH, and postprandial glucose levels than MET monotherapy, and did not affect weight. However, the study findings need to be confirmed in PCOS study populations with larger sample sizes.
Topics: Female; Humans; Metformin; Polycystic Ovary Syndrome; Pioglitazone; Prospective Studies; Testosterone; Luteinizing Hormone; Follicle Stimulating Hormone; Anti-Mullerian Hormone; Metabolome; Glucose
PubMed: 38374053
DOI: 10.1186/s13048-024-01367-7 -
Cancer Causes & Control : CCC Jun 2024Sex-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 1208 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.
Topics: Humans; Female; Breast Neoplasms; Postmenopause; Middle Aged; Gonadal Steroid Hormones; Cohort Studies; Receptors, Estrogen; Risk Factors; Aged; Case-Control Studies; Sex Hormone-Binding Globulin
PubMed: 38363402
DOI: 10.1007/s10552-024-01856-6 -
ELife Feb 2024Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used...
BACKGROUND
Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.
METHODS
Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.
RESULTS
Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression.
CONCLUSIONS
Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.
FUNDING
This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).
Topics: Humans; Androstenedione; Bayes Theorem; Biomarkers; China; Cross-Sectional Studies; Glaucoma, Angle-Closure; Prospective Studies; Visual Fields
PubMed: 38358793
DOI: 10.7554/eLife.91407 -
Scientific Reports Feb 2024This study was conducted in two groups of girls with PCOS (polycystic ovary syndrome) categorized as slim (group N) and overweight-to-obese (group Ov/Ob). The study's...
This study was conducted in two groups of girls with PCOS (polycystic ovary syndrome) categorized as slim (group N) and overweight-to-obese (group Ov/Ob). The study's primary outcome was to assess the impact of a 12-week anti-inflammatory diet (AIDiet) intervention, without energy deficit, on daily diet quality improvement, evaluated according to the KIDMED index. The secondary outcome was improving inflammatory, redox, hormonal, and metabolic statuses. In the study, which was completed by 13 girls from the Ov/Ob group and 19 girls from the N group, a significant improvement in the mean KIDMED score was obtained. Moreover, the intervention significantly improves concentration of total antioxidant capacity (TAC), fasting insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) index, in the Ov/Ob group, while both groups experienced a reduction in the concentration of interleukin (IL)-1 and IL-6, tumour necrosis factor (TNF-α), and androstenedione. The AIDiet intervention effectively improved the quality of the subjects' diets, which was associated with the improvement of hormonal and immuno-metabolic markers. However, these changes in normal-weight patients were observed regardless of body weight reduction. ClinicalTrials.gov Identifier NCT04738409.
Topics: Female; Humans; Overweight; Polycystic Ovary Syndrome; Pilot Projects; Diet; Insulin; Insulin Resistance; Anti-Inflammatory Agents; Body Mass Index
PubMed: 38347150
DOI: 10.1038/s41598-024-54100-1 -
International Journal of Molecular... Jan 2024Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens...
Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens are synthesized from testosterone and androstenedione by the endoplasmic reticulum membrane-bound P450 aromatase/cytochrome P450 oxidoreductase complex (CYP19/CPR). Here, we report the characterization of novel mammalian CYP19 isoforms encoded by CYP19 gene copies. These CYP19 isoforms are all defined by a combination of mutations in the N-terminal transmembrane helix (E42K, D43N) and in helix C of the catalytic domain (P146T, F147Y). The mutant CYP19 isoforms show increased androgen conversion due to the KN transmembrane helix. In addition, the TY substitutions in helix C result in a substrate preference for androstenedione. Our structural models suggest that CYP19 mutants may interact differently with the membrane (affecting substrate uptake) and with CPR (affecting electron transfer), providing structural clues for the catalytic differences.
Topics: Animals; Female; Humans; Pregnancy; Amino Acids; Androstenedione; Aromatase; Estrogens; Mammals; Protein Isoforms; Protein Structure, Tertiary; Protein Structure, Secondary
PubMed: 38338720
DOI: 10.3390/ijms25031440