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International Journal of Environmental... Mar 2024Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It increases the risk of type 2 diabetes, cardiovascular... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It increases the risk of type 2 diabetes, cardiovascular disease, endometrial cancer, infertility, gestational diabetes, preeclampsia, and preterm birth. Accurately identifying predictors of these health risks is crucial. Electronic health records (EHRs) offer an affordable approach, however, the validity and reliability of EHRs for PCOS diagnosis are unclear. A scoping review of the literature on the prevalence and reliability of the diagnosis of PCOS using EHRs was performed. An analysis of the feasibility of obtaining diagnostic variables from a PCOS patient database was also carried out. Eight studies met the criteria. The prevalence of PCOS ranged from 0.27% to 5.8%. Reliability varied, with one study reporting a sensitivity of 50% and a specificity of 29%. Another study found a 74.4% agreement between international classification of disease (ICD) codes and clinical criteria. The database analysis found only 13.7%, 8%, and 7.5% of women had all the necessary variables for an objective diagnosis of PCOS using the Rotterdam, National Institutes of Health (NIH), and Androgen Excess and PCOS Society (AEPCOS) criteria, respectively. Using EHRs results in an underestimation of PCOS prevalence compared to other diagnostic criteria, and many women identified may not meet the complete diagnostic criteria. These findings have implications for future research studies on PCOS prevalence and related health risks.
Topics: Female; Humans; Diabetes Mellitus, Type 2; Electronic Health Records; Polycystic Ovary Syndrome; Premature Birth; Prevalence; Reproducibility of Results
PubMed: 38541353
DOI: 10.3390/ijerph21030354 -
Biomedicines Feb 2024Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of... (Review)
Review
Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of the hair growth cycle. This review focuses on the hormonal background of hair loss, including pathophysiology, underlying endocrine disorders, and possible treatment options for alopecia. In particular, the role of androgens, including dihydrotestosterone (DHT), testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), has been studied in the context of androgenetic alopecia. Androgen excess may cause miniaturization of hair follicles (HFs) in the scalp. Moreover, hair loss may occur in the case of estrogen deficiency, appearing naturally during menopause. Also, thyroid hormones and thyroid dysfunctions are linked with the most common types of alopecia, including telogen effluvium (TE), alopecia areata (AA), and androgenetic alopecia. Particular emphasis is placed on the role of the hypothalamic-pituitary-adrenal axis hormones (corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol) in stress-induced alopecia. This article also briefly discusses hormonal therapies, including 5-alpha-reductase inhibitors (finasteride, dutasteride), spironolactone, bicalutamide, estrogens, and others.
PubMed: 38540126
DOI: 10.3390/biomedicines12030513 -
Cellular and Molecular Life Sciences :... Mar 2024The prostate is a vital accessory gonad in the mammalian male reproductive system. With the ever-increasing proportion of the population over 60 years of age worldwide,...
The prostate is a vital accessory gonad in the mammalian male reproductive system. With the ever-increasing proportion of the population over 60 years of age worldwide, the incidence of prostate diseases, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), is on the rise and is gradually becoming a significant medical problem globally. The notch signaling pathway is essential in regulating prostate early development. However, the potential regulatory mechanism of Notch signaling in prostatic enlargement and hyperplasia remains unclear. In this study, we proved that overactivation of Notch1 signaling in mouse prostatic epithelial cells (OEx) led to prostatic enlargement via enhancing proliferation and inhibiting apoptosis of prostatic epithelial cells. Further study showed that N1ICD/RBPJ directly up-regulated the androgen receptor (AR) and enhanced prostatic sensitivity to androgens. Hyper-proliferation was not found in orchidectomized OEx mice without androgen supply but was observed after Dihydrotestosterone (DHT) supplementation. Our data showed that the number of mitochondrion in prostatic epithelial cells of OEx mice was increased, but the mitochondrial function was impaired, and the essential activity of the mitochondrial respiratory electron transport chain was significantly weakened. Disordered mitochondrial number and metabolic function further resulted in excessive accumulation of reactive oxygen species (ROS). Importantly, anti-oxidant N-Acetyl-L-Cysteine (NAC) therapy could alleviate prostatic hyperplasia caused by the over-activation of Notch1 signaling. Furthermore, we observed the incremental Notch signaling activity in progenitor-like club cells in the scRNA-seq data set of human BPH patients. Moreover, the increased number of TROP2 progenitors and Club cells was also confirmed in our OEx mice. In conclusion, our study revealed that over-activated Notch1 signaling induces prostatic enlargement by increasing androgen receptor sensitivity, disrupting cellular mitochondrial metabolism, increasing ROS, and a higher number of progenitor cells, all of which can be effectively rescued by NAC treatment.
Topics: Animals; Humans; Male; Mice; Androgens; Mammals; Mitochondria; Prostate; Prostatic Hyperplasia; Reactive Oxygen Species; Receptors, Androgen; Signal Transduction
PubMed: 38538986
DOI: 10.1007/s00018-024-05143-0 -
Cureus Feb 2024Polycystic ovary syndrome (PCOS) presents complex challenges in diagnosis and treatment due to its multifactorial nature. This case study focuses on a 31-year-old woman...
Polycystic ovary syndrome (PCOS) presents complex challenges in diagnosis and treatment due to its multifactorial nature. This case study focuses on a 31-year-old woman exhibiting symptoms of weight gain, irregular menstruation cycles, and hirsutism, leading to a diagnosis of PCOS. Conventional diagnostic criteria and ultrasound confirmation of multiple ovarian cysts supported the diagnosis. By integrating Ayurvedic principles alongside Western medical techniques, this study sought to address imbalances in the Kapha and Pitta doshas, fundamental energies according to Ayurveda, believed to contribute to PCOS symptoms. Clinical findings emphasized the role of Pitta dosha imbalance in inflammation, hormonal irregularities, and excessive body heat, while Kapha dosha imbalance manifested in fluid retention, weight gain, and increased mucus production. A holistic treatment approach was devised, aiming to restore doshic balance while addressing hormonal and metabolic dysregulation. The treatment protocol comprised lifestyle modifications, advocating for a regular exercise regimen focusing on activities enhancing insulin sensitivity and promoting weight loss. Swimming, yoga, and brisk walking were recommended to achieve these goals. Dietary interventions tailored to balance Kapha and Pitta doshas were prescribed, emphasizing nourishing, warming foods low in carbohydrates to prevent weight gain and boost metabolism. Anti-inflammatory foods, such as turmeric and ginger, were incorporated to mitigate inflammation. The integration of Ayurvedic principles alongside Western medicine offered a comprehensive approach to PCOS management, addressing both the root causes and symptoms of the condition. This personalized treatment strategy aimed not only to alleviate immediate symptoms but also to promote long-term health and well-being by restoring doshic equilibrium and optimizing hormonal and metabolic functions. In conclusion, this case study highlights the potential efficacy of combining Ayurvedic and Western medical approaches in the management of PCOS, offering a tailored and holistic treatment paradigm for patients seeking comprehensive care.
PubMed: 38500914
DOI: 10.7759/cureus.54342 -
Scientific Reports Mar 2024Gestational hyperandrogenism is a risk factor for adverse maternal and offspring outcomes with effects likely mediated in part via disruptions in maternal lipid...
Gestational testosterone excess early to mid-pregnancy disrupts maternal lipid homeostasis and activates biosynthesis of phosphoinositides and phosphatidylethanolamines in sheep.
Gestational hyperandrogenism is a risk factor for adverse maternal and offspring outcomes with effects likely mediated in part via disruptions in maternal lipid homeostasis. Using a translationally relevant sheep model of gestational testosterone (T) excess that manifests maternal hyperinsulinemia, intrauterine growth restriction (IUGR), and adverse offspring cardiometabolic outcomes, we tested if gestational T excess disrupts maternal lipidome. Dimensionality reduction models following shotgun lipidomics of gestational day 127.1 ± 5.3 (term 147 days) plasma revealed clear differences between control and T-treated sheep. Lipid signatures of gestational T-treated sheep included higher phosphoinositides (PI 36:2, 39:4) and lower acylcarnitines (CAR 16:0, 18:0, 18:1), phosphatidylcholines (PC 38:4, 40:5) and fatty acids (linoleic, arachidonic, Oleic). Gestational T excess activated phosphatidylethanolamines (PE) and PI biosynthesis. The reduction in key fatty acids may underlie IUGR and activated PI for the maternal hyperinsulinemia evidenced in this model. Maternal circulatory lipids contributing to adverse cardiometabolic outcomes are modifiable by dietary interventions.
Topics: Pregnancy; Female; Sheep; Animals; Phosphatidylethanolamines; Hyperandrogenism; Phosphatidylinositols; Testosterone; Fatty Acids; Homeostasis; Hyperinsulinism; Cardiovascular Diseases
PubMed: 38486090
DOI: 10.1038/s41598-024-56886-6 -
Zoological Research Mar 2024Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone...
Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, -/- zebrafish ( ) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in -/- fish compared to +/+ male fish, including stearoyl-CoA desaturase ( ) and fatty acid synthase ( ). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in +/+ male fish but not in -/- fish. Both androgen receptor ( )-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( ), , and expression. Mechanistically, the rescue effect of testosterone on -/- fish in terms of phenotypes was abolished when was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.
Topics: Male; Animals; Androgens; Lipogenesis; Zebrafish; Testosterone; Lipids; Signal Transduction; Chromatin
PubMed: 38485505
DOI: 10.24272/j.issn.2095-8137.2023.324 -
Annals of Pediatric Endocrinology &... Feb 2024Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was...
PURPOSE
Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk.
METHODS
This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively.
RESULTS
A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9α-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the salt-wasting type of 21-OHD.
CONCLUSION
This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9α-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis.
PubMed: 38461806
DOI: 10.6065/apem.2346014.007 -
Journal of the West African College of... 2023Leydig cell tumors are rare but are the most common nongerm cell gonadal tumors. They are mostly benign but malignant variants have been reported. Leydig cells...
Leydig cell tumors are rare but are the most common nongerm cell gonadal tumors. They are mostly benign but malignant variants have been reported. Leydig cells constitute the main androgen-synthesizing compartment in adult males but are also capable of estrogen production. This can manifest with clinical features of excessive hormone elaboration. We report a case of a 39-year-old man with abnormal bilateral breast development, reduced libido, and weak erection of 3 years' duration. He never noticed any testicular swelling before presentation. Examination revealed well-developed breasts bilaterally and a mass in the lower pole of the left testis. Scrotal ultrasound confirmed a hypoechoic tumor measuring 2 × 3 cm in the lower pole of the left testis and hormonal evaluation revealed a markedly elevated estradiol level. A diagnosis of estrogen-secreting testicular tumor was made. He had a testis-sparing excision of the scrotal lesion as well as liposuction and excision of glandular tissues of the breasts. He had an uneventful postoperative recovery and was discharged a day after surgery. Histology of excised testicular lesion revealed a benign Leydig cell tumor. Four months following surgery, there was an improvement in libido, erection, and sperm concentration of the patient. The patient was also very satisfied with the cosmetic outcome of the excision of the bilateral gynecomastia. We recommend self-examination of testicles as an important step for early diagnosis of testicular tumors.
PubMed: 38449551
DOI: 10.4103/jwas.jwas_54_23 -
Problemy Endokrinologii Feb 2024Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids...
Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.
Topics: Adolescent; Humans; Receptors, Glucocorticoid; Glucocorticoids; Adrenal Glands; Metabolism, Inborn Errors; Rare Diseases
PubMed: 38433539
DOI: 10.14341/probl13321 -
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