-
Journal of Multidisciplinary Healthcare 2023The use of anabolic androgenic steroids (AAS) for strength training and muscle building is a widespread practice among athletes and young individuals. Athletes and... (Review)
Review
The use of anabolic androgenic steroids (AAS) for strength training and muscle building is a widespread practice among athletes and young individuals. Athletes and bodybuilders are using these substances for various purposes, such as enhancing muscle mass, strengthening their bodies, and enhancing their performances. AAS exert a wide range of physiological effects that result in the activation of central signaling, resulting in adverse effects. Moreover, excessive use of AAS which can be categorized as AAS abuse; is linked to biological and psychological pathologies, which can lead to mortality. Complications arising from steroid abuse involve both cellular and physiological complications. Cellular complications arise when activation of signaling proteins like mTOR, Akt, etc. leads to alteration in protein synthesis pathways, cell cycle, oxidative stress, and apoptosis, contributing to damage at the cellular level. Physiological complications are evident with cardiovascular pathologies, including an altered lipid profile, cardiac hypertrophy, hypogonadism after discontinuation of AAS, and modulation of GABA receptors in the brain, all contributed by the androgen receptor signaling. Clinical complications budding from these altered physiological processes lead to clinical effects like testicular dysfunction, acne, gynecomastia, and neuropsychiatric disorders. Despite potential therapeutic benefits, AAS use is prohibited by the World Anti-Doping Agency (WADA) due to concerns over adverse health effects. This review highlights the molecular mechanisms, physiological processes, and clinical complications arising from the excessive use of AAS among athletes.
PubMed: 38170017
DOI: 10.2147/JMDH.S439384 -
Journal of the Endocrine Society Dec 2023Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with obesity, insulin resistance, and dyslipidemia. Hyperandrogenism is a major...
CONTEXT
Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with obesity, insulin resistance, and dyslipidemia. Hyperandrogenism is a major characteristic of PCOS. Increased androgen exposure is believed to deregulate metabolic processes in various tissues as part of the PCOS pathogenesis, predominantly through the androgen receptor (AR). Notably, various metabolic features in PCOS are similar to those observed after excess glucocorticoid exposure.
OBJECTIVE
We hypothesized that glucocorticoid receptor (GR) signaling is involved in the metabolic symptoms of PCOS.
METHODS
In a PCOS model of chronic dihydrotestosterone (DHT) exposure in female mice, we investigated whether GR signaling machinery was (de)regulated, and if treatment with a selective GR antagonist alleviated the metabolic symptoms.
RESULTS
We observed an upregulation of GR messenger RNA expression in the liver after DHT exposure. In white adipose tissues and liver we found that DHT upregulated , which encodes for the enzyme that converts inactive into active glucocorticoids. We found that preventive but not therapeutic administration of a GR antagonist alleviated DHT-induced hyperglycemia and restored glucose tolerance. We did not observe strong effects of GR antagonism in DHT-exposed mice on other features like total fat mass and lipid accumulation in various tissues.
CONCLUSION
We conclude that GR activation may play a role in glucose metabolism in DHT-exposed mice.
PubMed: 38169733
DOI: 10.1210/jendso/bvad162 -
PloS One 2024Deficient water, sanitation, and hygiene (WASH) significantly account for a high burden of disease across the globe. Lebanon, an Eastern Mediterranean...
Deficient water, sanitation, and hygiene (WASH) significantly account for a high burden of disease across the globe. Lebanon, an Eastern Mediterranean lower-middle-income country with a polluted environment, a fragmented healthcare system, and an ongoing severe economic crisis, faces serious challenges in sustaining safe water supplies, especially in vulnerable communities, while also hosting the world highest refugee population per capita. This study aimed to examine the mutagenicity, and the estrogenic and androgenic activities of water supplies, across both a Palestinian refugee camp and a Syrian informal settlement. Water samples were collected from two targeted camps in Dbayeh and Choueifat, North and South of the Capital City Beirut, respectively, between the months of September and October 2022. Microbial and physicochemical properties of samples were determined, including fecal contamination, total dissolved solids, and various minerals and salts. Organic pollutants were extracted using pre-packed solid phase extraction (SPE) columns, and then mutagenicity of extracts was examined using the Ames test in two Salmonella typhi bacterial strains. The estrogenic and androgenic activities of extracts were assessed using the yeast estrogen and androgen screen tests assays (YES/YAS). Results show excessive levels of total coliforms and total dissolved solids (TDS) in samples from both sites. In addition, the water supply from the Dbayeh Palestinian refugee camp is mutagenic, while the water supply from the Choueifat Syrian informal settlement shows anti-androgen activity. Our findings provide valuable WASH baseline data in two major vulnerable communities in Lebanon, and highlight the importance of a water toxicity testing approach concomitant with a water safety plan, based on a holistic strategy that covers all stages of the water supply chain.
Topics: Humans; Lebanon; Refugee Camps; Syria; Arabs; Water Supply; Refugees
PubMed: 38165866
DOI: 10.1371/journal.pone.0294679 -
Frontiers in Endocrinology 2023Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no cure for PCOS, and current treatments primarily alleviate its symptoms due to a poor understanding of its etiology. Compelling evidence suggests that hyperandrogenism is not just a primary feature of PCOS. Instead, it may be a causative factor for this condition. Thus, figuring out the mechanisms of androgen synthesis, conversion, and metabolism is relatively important. Traditionally, studies of androgen excess have largely focused on classical androgen, but in recent years, adrenal-derived 11-oxygenated androgen has also garnered interest. Herein, this Review aims to investigate the origins of androgen excess, androgen synthesis, how androgen receptor (AR) signaling mediates adverse PCOS traits, and the role of 11-oxygenated androgen in the pathophysiology of PCOS. In addition, it provides therapeutic strategies targeting hyperandrogenism in PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Androgens; Phenotype
PubMed: 38152131
DOI: 10.3389/fendo.2023.1273542 -
Ginekologia Polska 2024Polycystic ovary syndrome (PCOS) is a widely prevalent condition that affects approximately 5-10% of women of reproductive age. Although first described in the 18th... (Review)
Review
Polycystic ovary syndrome (PCOS) is a widely prevalent condition that affects approximately 5-10% of women of reproductive age. Although first described in the 18th century, a detailed account of the disease was not provided until Stein and Leventhal's 1935 report. Due to the varied symptomatology of PCOS, treatment must be tailored and often involves using multiple drugs for optimal pharmacotherapy. Berberine, an alkaloid with a longstanding history of use, has gained popularity as a potential treatment option for PCOS. Previous studies have demonstrated that berberine can improve hormonal imbalances by reducing testosterone and FAI, increasing SHBG, and mitigating the clinical symptoms of androgen excess, including hirsutism and acne. Moreover, berberine enhances the therapeutic effects of other drugs commonly used in PCOS, such as metformin and oral contraceptive pills. It is generally well-tolerated with a favourable safety profile. However, further research is warranted to establish conclusive evidence regarding berberine's mechanistic underpinnings, therapeutic potential, and long-term safety as a PCOS treatment modality.
Topics: Humans; Polycystic Ovary Syndrome; Berberine; Female; Metformin; Testosterone; Hypoglycemic Agents
PubMed: 38108460
DOI: 10.5603/gpl.95138 -
Journal of Medicine and Life Sep 2023Male hypogonadism and erectile dysfunction in different populations are associated with excess body weight. A key aspect in most studies is the metabolism of sexual...
Male hypogonadism and erectile dysfunction in different populations are associated with excess body weight. A key aspect in most studies is the metabolism of sexual hormones, primarily testosterone. At the same time, the binding protein sex hormone binding globulin (SHBG) can play a large role, as it determines the ratio of total and bioavailable testosterone in blood, i.e. both the hormone content and level of its production. Recent research has identified common mutations that affect SHBG levels, such as the rs727428 polymorphic locus, which is associated with alterations in histone protein function, affecting the regulation of ribonucleic acid (RNA) protein SHBG synthesis. Similar relationships have been observed for prevalent mutations, including rs5934505 and rs10822184, in diverse populations. This study involved 300 individuals of Kazakh nationality from the Eastern Kazakhstan region, examining three polymorphic variants of the SHBG gene (rs727428, rs5934505, and rs10822184). The participants were categorized into three groups: individuals with hypogonadism and obesity (group 1, n=85), those with excess body weight but no hypogonadism (group 2, n=70), and individuals with neither excess body weight nor hypogonadism (group 3, n=145). The frequency of mutant gene alleles impacting GPS (SHBG) synthesis in the Kazakh population was notably high, comparable to European and South-East Asian populations. However, the association between excess body weight and these mutations exhibited varying patterns. Hypogonadism was linked to decreased GPS levels, strongly correlating with total testosterone but not bioavailable testosterone. The retention of sexual functions in overweight men was not always directly related to BMI levels and GPS concentrations.
Topics: Male; Humans; Overweight; Hypogonadism; Testosterone; Obesity; Erectile Dysfunction
PubMed: 38107722
DOI: 10.25122/jml-2022-0203 -
Journal of Clinical Research in... Mar 20243’-Phosphoadenosine 5’-phosphosulfate synthase 2 (PAPSS2) deficiency is a rare disorder due to biallelic pathogenic variants in the gene. This disorder was first... (Review)
Review
3’-Phosphoadenosine 5’-phosphosulfate synthase 2 (PAPSS2) deficiency is a rare disorder due to biallelic pathogenic variants in the gene. This disorder was first described in 1998 by Ahmad et al. and Faiyaz ul Haque et al. To date, 79 patients with PAPSS2 deficiency have been reported. The main reported features of these patients are related to bone abnormalities and clinical/biochemical androgen excess. Disproportionate short stature and symptoms associated with spondylar skeletal dysplasia are the most common clinical features that require clinical attention. Androgen excess has been described much less commonly. This review summarizes the currently published clinical, molecular, and biochemical features of patients with PAPSS2 deficiency.
Topics: Humans; Androgens; Phenotype; Dwarfism
PubMed: 38084048
DOI: 10.4274/jcrpe.galenos.2023.2023-12-10 -
International Journal of Molecular... Nov 2023In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In... (Review)
Review
In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and β-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases.
Topics: Animals; Humans; Female; Androgens; Insulin Resistance; Obesity; Metabolic Diseases; Animals, Laboratory; Polycystic Ovary Syndrome
PubMed: 38068890
DOI: 10.3390/ijms242316567 -
AACE Clinical Case Reports 2023Leydig cell tumors are a rare androgen-secreting ovarian tumor. We present a patient with virilization symptoms secondary to a Leydig cell tumor, with nonrevealing...
BACKGROUND/OBJECTIVE
Leydig cell tumors are a rare androgen-secreting ovarian tumor. We present a patient with virilization symptoms secondary to a Leydig cell tumor, with nonrevealing imaging studies, that was localized using ovarian vein sampling (OVS).
CASE REPORT
A 56-year-old postmenopausal woman was referred by her gynecologist to the endocrinology clinic for voice-deepening, clitoral enlargement, scalp hair loss, and excessive body hair growth. Her total testosterone was 11.5 (0.3-1.3 nmol/L), bioavailable testosterone was 7.19 (0.1-0.6 nmol/L), and dehydroepiandrosterone sulfate was 4.0 (0.8-4.9 μmol/L). Transvaginal ultrasound and abdominal magnetic resonance imaging showed no adrenal or ovarian masses bilaterally. On adrenal vein sampling (AVS) and OVS, total testosterone from the left gonadal vein was 780.0 (0.3-1.3 nmol/L) and right gonadal vein was 18.6 (0.3-1.3 nmol/L), with a left-to-right ovarian testosterone ratio of 41.94. A bilateral salpingo-oophorectomy was performed, and a 1.0 cm Leydig cell tumor in the left ovary was noted on histopathology. One month after surgery, her total and bioavailable testosterone were <0.4 (0.3-1.3 nmol/L and 0.1-0.6 nmol/L, respectively). At 6 months, she had normalization of her voice to baseline, decreased clitoral size, decreased hair growth on her back, and improvement in her male-pattern baldness.
DISCUSSION
OVS and AVS are useful diagnostic investigation tools in cases of virilization, in which imaging is nonrevealing. Our case supports previously suggested left-to-right ovarian vein testosterone ratio of ≥15 being associated with a left-sided tumor.
CONCLUSION
Few cases have been published on the interpretation of AVS and OVS in the setting of virilization. Previously suggested ratios for lateralization were valid for this patient.
PubMed: 38045790
DOI: 10.1016/j.aace.2023.07.003 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =...Hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndrome is a special and rare subtype of polycystic ovarian syndrome. It can lead to hyperandrogenism... (Review)
Review
Hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndrome is a special and rare subtype of polycystic ovarian syndrome. It can lead to hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) accompanied by acne, hirutism, irregular menstruation, and other androgen excess symptoms. A case of pediatric HAIR-AN syndrome with severe AN was admitted to the Department of Endocrinology, China-Japan Friendship Hospital. The patient's clinical manifestations, laboratory data, imaging features, and gene sequencing were analyzed, and the patient was diagnosed with pediatric HAIR-AN syndrome. Obesity, IR, hyperglycemia, menstrual disorder, and AN were significantly improved after treating with metformin and liraglutide. HAIR-AN syndrome occurs in various forms. When the patient appears unexplained acanthosis nigricans and menstrual disorders, the disease should be considered possible. Early diagnosis and symptomatic supportive treatment can improve the quality of life.
Topics: Female; Child; Humans; Hyperandrogenism; Acanthosis Nigricans; Liraglutide; Metformin; Quality of Life; Insulin Resistance; Polycystic Ovary Syndrome; Metabolic Syndrome
PubMed: 38044655
DOI: 10.11817/j.issn.1672-7347.2023.230100