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Life (Basel, Switzerland) Mar 2024Hyperandrogenism is a condition in which the levels of androgen hormones in the blood are significantly increased and could be of an adrenal or ovarian origin. The... (Review)
Review
Hyperandrogenism is a condition in which the levels of androgen hormones in the blood are significantly increased and could be of an adrenal or ovarian origin. The adrenal androgens, normally secreted by the zona reticularis, are steroid hormones with weak androgen activity. The causes of hyperandrogenism are diverse and could be endogenous and exogenous. Androgen excess affecting different tissues and organs results in clinical features such as acne, hirsutism, virilization, and reproductive dysfunction such as oligomenorrhoea/amenorrhoea. Although androgen excess is rarely associated with adrenal tumours, it is important as it could be predictive of malignancy. A careful evaluation of the androgen pattern, also in patients with clear signs of hyperandrogenism, could be useful. Laboratory evaluation should focus on measuring total testosterone levels, followed by the estimation of other androgens such as dehydroepiandrosterone and androstenedione, and using visualisation procedures in the further management. The treatment of adrenal hyperandrogenism is eminently surgical, in consideration of the frequent malignant origin. The aim of this review is to elaborate and summarize the prevalence and clinical management of hyperandrogenism of an adrenal origin by describing the physiological mechanisms of adrenal androgen steroidogenesis, the clinical manifestations of hyperandrogenism with a special reference to hyperandrogenism in adrenal adenomas and carcinomas, and the diagnostic methods that will lead us to establishing the correct diagnosis and different treatment options to manage this condition according to the clinical presentation of the patient.
PubMed: 38541685
DOI: 10.3390/life14030360 -
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 -
Abdominal Radiology (New York) Jun 2024Hirsutism is a relatively common disorder which affects approximately 5% to 15% of women. It is defined by excessive growth of terminal hair in women, which primarily... (Review)
Review
Hirsutism is a relatively common disorder which affects approximately 5% to 15% of women. It is defined by excessive growth of terminal hair in women, which primarily affects areas dependent on androgens, such as the face, abdomen, buttocks, and thighs. Hirsutism can be caused by a variety of etiologies, which are most often not lifethreatening. However, in some cases, hirsutism can be an indicator of more serious underlying pathology, such as a neoplasm, which may require further elucidation with imaging. Within the abdomen and pelvis, adrenal and ovarian pathologies are the primary consideration. The goal of this manuscript is to review the etiologies and imaging features of various intra-abdominal and intra-pelvic causes of hirsutism.
Topics: Humans; Female; Hirsutism; Diagnosis, Differential; Adrenal Gland Diseases
PubMed: 38499827
DOI: 10.1007/s00261-024-04189-9 -
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 -
Journal of Endocrinological... Jul 2024Polycystic ovary syndrome (PCOS) is the most common feminine endocrine disorder, characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common feminine endocrine disorder, characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. The negative impact of symptoms on the quality of life (QoL) of patients is still not clear.
PURPOSE
The present review aimed at studying the impact of the symptoms, the psychological symptoms, and brain alterations in women with PCOS.
METHODS
A systematic search was undertaken for studies that assessed the impact of PCOS symptoms on QoL, psychological symptoms, and brain alterations in PCOS patients.
RESULTS
Most of the information about QoL came from psychometric studies, which used culture-based questionnaires. Alterations of sleep quality, body image, and mood disorders can negatively affect the QoL of the patients. Sexual satisfaction and desire were affected by PCOS. Brain imaging studies showed functional alterations that are associated with impairments of visuospatial working memory, episodic and verbal memory, attention, and executive function.
CONCLUSIONS
Several factors can negatively influence the quality of life of the patients, and they are directly related to hyperandrogenism and the risk of infertility. In particular, obesity, hirsutism, acne, and the fear of infertility can have a direct impact on self-esteem and sexual function. Metabolic and psychiatric comorbidities, such as mood, anxiety, and eating disorders, can affect the well-being of the patients. Moreover, specific cognitive alterations, such as impairments in attention and memory, can limit PCOS patients in a series of aspects of daily life.
Topics: Humans; Polycystic Ovary Syndrome; Quality of Life; Female; Brain
PubMed: 38485896
DOI: 10.1007/s40618-024-02329-y -
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