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Expert Review of Endocrinology &... 2024Hyperandrogenism and hypoandrogenism are complex disorders involving multiple-organ systems. While androgen excess is a well-characterized condition, androgen deficiency... (Review)
Review
INTRODUCTION
Hyperandrogenism and hypoandrogenism are complex disorders involving multiple-organ systems. While androgen excess is a well-characterized condition, androgen deficiency still needs diagnostic criteria, as there are no specific cutoffs.
AREAS COVERED
We highlight the most recent findings on the role of androgens in female pathophysiology, investigating clinically relevant conditions of androgen insufficiency or excess throughout a woman's life, and their possible therapeutic management.
EXPERT OPINION
Combined oral contraceptives (COCs) should be considered as first-line therapy for the management of menstrual irregularity and/or clinical hyperandrogenism in adolescents with a clear diagnosis of polycystic ovary syndrome (PCOS). There are limited evidence-based data regarding specific types or doses of COCs for management of PCOS in women; however, the lowest effective estrogen dose should be considered for treatment. Despite evidence regarding safety, efficacy, and clinical use, testosterone therapy has not been approved for women by most regulatory agencies for treatment of hypoactive sexual desire disorder (HSDD). The long-term safety for treatments with testosterone is still to be evaluated, and this review highlights the need for more research in this area.
Topics: Adolescent; Female; Humans; Hyperandrogenism; Androgens; Polycystic Ovary Syndrome; Testosterone; Estrogens
PubMed: 37953607
DOI: 10.1080/17446651.2023.2279537 -
Biomedicines Jul 2023Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer... (Review)
Review
Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.
PubMed: 37509723
DOI: 10.3390/biomedicines11072084 -
Annales D'endocrinologie Apr 2024Excessive use of anabolic-androgenic steroids (AAS) in sport occurs among professional athletes but increasingly also in amateurs. Prevalence of steroid use has been on... (Review)
Review
Excessive use of anabolic-androgenic steroids (AAS) in sport occurs among professional athletes but increasingly also in amateurs. Prevalence of steroid use has been on the rise for a number of years. While the practice involves mostly men, it also occurs in women with an estimated prevalence of 1.6%. Since 2014, a 'steroid passport' has operated for sports people in competition that is based on longitudinal urinary and blood steroid levels, measured by liquid chromatography and mass spectrometry. Androgen excess stimulates muscle growth and improves muscle performance. However, their consumption carries numerous side effects, including myocardial hypertrophy; altered lipid metabolism and pro-thrombotic effects. The excess of AAS is associated with increased risk of atherosclerosis and cardiovascular events. Data for their effects in women is lacking. Perturbations of the menstrual cycle are common in female athletes, with spaniomenorrhea and even amenorrhea. This can be a consequence of gonadotropin insufficiency due to negative caloric balance, but may also be due to endogenous or exogenous hyperandrogenism. The use of AAS is probably underestimated as a public health issue, particularly in women, and thus presents a prevention challenge for healthcare professionals.
Topics: Male; Humans; Female; Androgens; Anabolic Agents; Doping in Sports; Steroids; Athletes
PubMed: 38040089
DOI: 10.1016/j.ando.2023.11.001 -
JCEM Case Reports Apr 2024We describe a case of an Asian-Indian female patient who presented to us with abnormal fat accumulations in the torso and upper arms following indiscriminate use of...
We describe a case of an Asian-Indian female patient who presented to us with abnormal fat accumulations in the torso and upper arms following indiscriminate use of corticosteroid and anabolic steroids for about 7 years. Despite prolonged steroid use, the patient did not display cushingoid phenotype or metabolic decompensation. Bone density, echocardiography, and ultrasonogram of the liver were also normal with no evidence of excess pericardial fat, hepatic steatosis, or peliosis hepatis. Concurrent use of anabolic androgen is thought to be protective against the ill effects of steroids, especially on the muscle and bone. This phenomenon has been observed in children and adolescents with Cushing syndrome where the adrenal androgen excess and increased physical activity have shown to reasonably reduce protein catabolism and help in preserving muscle and bone mass. The patient was withdrawn from the drugs and was put on replacement hydrocortisone that was gradually tapered over the next few weeks and planned for surgical correction. This case highlights the fact that medical providers should be aware that a combination of anabolic steroids and glucocorticoids are still used for weight-building purposes, and these patients may present with atypical signs/symptoms as a result of this combination of drugs.
PubMed: 38638337
DOI: 10.1210/jcemcr/luae067 -
Pharmaceutics Jul 2023Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and (CA: formerly ) hyperproliferation in pilosebaceous follicles....
Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and (CA: formerly ) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Stokes and , against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-α, IL-6, p-STAT-3, and p-NF-κB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5α-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.
PubMed: 37514071
DOI: 10.3390/pharmaceutics15071885 -
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 -
Nature Reviews. Neurology Dec 2023The understanding of idiopathic intracranial hypertension (IIH) has evolved over the past few years. Previously, IIH was considered a disease exclusively affecting the... (Review)
Review
The understanding of idiopathic intracranial hypertension (IIH) has evolved over the past few years. Previously, IIH was considered a disease exclusively affecting the neuro-ophthalmic axis, characterized by raised intracranial pressure, headache and papilloedema, and resulting in the risk of severe and permanent visual loss and life-changing disabling headaches. Recent advances have begun to redefine IIH as a probable metabolic disease involving a range of systemic manifestations. More than 95% of individuals affected by the disease are women of reproductive age with obesity. The incidence is rapidly rising and parallels the escalating worldwide obesity rates. Contemporary insights identify associations with insulin resistance, type 2 diabetes and a twofold increased risk of cardiovascular disease in excess of that driven by obesity alone. Adipose distribution in people with IIH, like that in other metabolic diseases, is preferentially centripetal and is associated with changes in intracranial pressure. Evidence now demonstrates adipose tissue dysfunction in people with IIH, involving transcriptional and metabolic priming for lipogenesis and weight gain. Hormonal perturbations are also observed, including a unique phenotype of androgen excess that promotes cerebrospinal fluid secretion. Knowledge of these additional disease features is driving research into novel therapeutic targets and altering the approach to multidisciplinary care.
Topics: Female; Humans; Male; Pseudotumor Cerebri; Diabetes Mellitus, Type 2; Obesity; Headache; Vision Disorders
PubMed: 37957260
DOI: 10.1038/s41582-023-00893-0 -
Journal of Ovarian Research Jul 2023Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular...
BACKGROUND
Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials.
METHODS
Female Sprague-Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining.
RESULTS
Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen.
CONCLUSION
Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis.
Topics: Humans; Rats; Female; Animals; Polycystic Ovary Syndrome; Reactive Oxygen Species; NLR Family, Pyrin Domain-Containing 3 Protein; Endoribonucleases; Fibronectins; Rats, Sprague-Dawley; Protein Serine-Threonine Kinases; Inflammation; Fibrosis; Dehydroepiandrosterone; Carrier Proteins; Cell Cycle Proteins
PubMed: 37525261
DOI: 10.1186/s13048-023-01242-x -
Endocrinology Sep 2023Hyperandrogenemia and polycystic ovary syndrome are a result of the imbalance of androgen levels in females. Androgen receptor (Ar) mediates the effect of androgen, and...
Hyperandrogenemia and polycystic ovary syndrome are a result of the imbalance of androgen levels in females. Androgen receptor (Ar) mediates the effect of androgen, and this study examines how neuronal Ar in the central nervous system mediates metabolism under normal and increased androgen conditions in female mice. The neuron-specific ARKO mouse (SynARKO) was created from female (Ar fl/wt; synapsin promoter driven Cre) and male (Ar fl/y) mice. A glucose tolerance test revealed impaired glucose tolerance that was partially alleviated in the SynARKO-dihydrotestosterone (DHT) mice compared with Con-DHT mice after 4 months of DHT treatment. Heat production and food intake was higher in Con-DHT mice than in Con-veh mice; these effects were not altered between SynARKO-veh and SynARKO-DHT mice, indicating that excess androgens may partially alter calorie intake and energy expenditure in females via the neuronal Ar. The pAkt/Akt activity was higher in the hypothalamus in Con-DHT mice than in Con-veh mice, and this effect was attenuated in SynARKO-DHT mice. Western blot studies show that markers of inflammation and microglia activation, such as NF-kB p-65 and IBA1, increased in the hypothalamus of Con-DHT mice compared with Con-veh. These studies suggest that neuronal Ar mediates the metabolic impacts of androgen excess in females.
PubMed: 37738624
DOI: 10.1210/endocr/bqad141