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BMJ Case Reports Jun 2021Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years....
Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years. Hormone-secreting ACCs represent most cases; of these, only a small minority presents with virilisation alone. Early diagnosis is key to increase the chances of a better outcome. Here, we report a case of a 41-year-old woman who presented with menstrual irregularities, hirsutism and virilising symptoms, associated with abdominal discomfort and constitutional symptoms. On physical examination, there was a palpable mass in the right upper quadrant. Laboratory workup revealed elevated serum androgens. The imaging study showed a 163×110×122 cm right adrenal mass with features consistent with ACC and suggested potential hepatic invasion. Our patient underwent surgical resection, and the histopathological findings confirmed the diagnosis. She was referred to a specialised centre for follow-up and adjuvant therapy.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Adult; Androgens; Female; Humans; Liver; Virilism
PubMed: 34083198
DOI: 10.1136/bcr-2021-242895 -
Drugs Jan 2019Unplanned pregnancies are an ongoing global burden, posing health and economic risks for women, children, and families. Advances in male contraception have been... (Review)
Review
Unplanned pregnancies are an ongoing global burden, posing health and economic risks for women, children, and families. Advances in male contraception have been historically stymied by concerning failure rates, problematic side effects, and perceived market limitations. However, increased interest in reliable and reversible options for male contraception have resulted in resurgent efforts to introduce novel contraceptives for men. Hormonal male contraception relies on exogenous androgens and progestogens that suppress gonadotropin production, thereby suppressing testicular testosterone and sperm production. In many men, effective suppression of spermatogenesis can be achieved by androgen-progestin combination therapy. Small-scale contraceptive efficacy studies in couples have demonstrated effectiveness and reversibility with male hormonal methods, but side effects related to mood, sexual desire and cholesterol remain concerning. A number of novel androgens have reached clinical testing as potential contraceptive agents; many of these have both androgenic and progestogenic action in a single, modified steroid, thereby holding promise as single-agent contraceptives. Currently, these novel steroids hold promise as both a "male pill" and long-acting injections. Among non-hormonal methods, studies of reversible vaso-occlusive methods (polymers that block transport of sperm through the vas deferens) are ongoing, but reliable reversibility and long-term safety in men have not been established. Proteins involved in sperm maturation and motility are attractive targets, but to date both specificity and biologic redundancy have been challenges for drug development. In this review, we aim to summarize landmark studies on male contraception, highlight the most recent advances and future development in this important field of public health and medicine.
Topics: Androgens; Contraception; Contraceptive Agents, Male; Female; Gonadotropins; Humans; Male; Progestins; Spermatogenesis; Testosterone
PubMed: 30588563
DOI: 10.1007/s40265-018-1038-8 -
The consequence and mechanism of dietary flavonoids on androgen profiles and disorders amelioration.Critical Reviews in Food Science and... 2023Androgen is a kind of steroid hormone that plays a vital role in reproductive system and homeostasis of the body. Disrupted androgen balance serves as the causal... (Review)
Review
Androgen is a kind of steroid hormone that plays a vital role in reproductive system and homeostasis of the body. Disrupted androgen balance serves as the causal contributor to a series of physiological disorders and even diseases. Flavonoids, as an extremely frequent family of natural polyphenols, exist widely in plants and foods and have received great attention when considering their inevitable consumption and estrogen-like effects. Mounting evidence illustrates that flavonoids have a propensity to interfere with androgen synthesis and metabolism, and also have a designated improvement effect on androgen disorders. Therefore, flavonoids were divided into six subclasses based on the structural feature in this paper, and the literature about their effects on androgens published in the past ten years was summarized. It could be concluded that flavonoids have the potential to regulate androgen levels and biological effects, mainly by interfering with the hypothalamic-pituitary-gonadal axis, androgen synthesis and metabolism, androgen binding with its receptors and membrane receptors, and antioxidant effects. The faced challenges about androgen regulation by flavonoids masterly include target mechanism exploration, individual heterogeneity, food matrixes interaction, and lack of clinical study. This review also provides a scientific basis for nutritional intervention using flavonoids to improve androgen disorder symptoms.
Topics: Androgens; Estrogens; Polyphenols; Flavonoids
PubMed: 35796699
DOI: 10.1080/10408398.2022.2090893 -
Physiological Research Sep 2020The adrenal glands produce significant amounts of steroid hormones and their metabolites, with various levels of androgenic activities. Until recently, the androgenic... (Review)
Review
The adrenal glands produce significant amounts of steroid hormones and their metabolites, with various levels of androgenic activities. Until recently, the androgenic potency of these adrenal-derived compounds were not well known, but some recent studies have shown that the production of 11-oxo- and 11beta-hydroxy-derived testosterone and dihydrotestosterone evidently have high androgenic activity. This fact has clinical importance, for instance, in various types of congenital adrenal hyperplasia with androgenization or polycystic ovarian syndrome, and laboratory determinations of these substances could help to better evaluate the total androgen pressure in patients with these disorders. Another area of concern is the treatment of prostate cancer with androgen deprivation, which loses effectiveness after a certain time. The concurrent blocking of the secretion of adrenal C(19)-steroids, whether using corticoids or adrenostatics, could increase the effectiveness of androgen-deprivation therapy.
Topics: Adrenal Hyperplasia, Congenital; Androgen Antagonists; Androgens; Animals; Humans; Male; Molecular Targeted Therapy; Prostatic Neoplasms; Testosterone
PubMed: 33094617
DOI: 10.33549/physiolres.934516 -
Deutsche Medizinische Wochenschrift... Oct 2017
Review
Topics: Adrenogenital Syndrome; Diagnosis, Differential; Evidence-Based Medicine; Female; Feminization; Glucocorticoids; Hormone Replacement Therapy; Humans; Male; Treatment Outcome; Virilism
PubMed: 29017204
DOI: 10.1055/s-0042-117270 -
Frontiers in Endocrinology 2020The prevalence of cardiovascular mortality is higher in men than in age-matched premenopausal women. Gender differences are linked to circulating sex-related steroid... (Review)
Review
The prevalence of cardiovascular mortality is higher in men than in age-matched premenopausal women. Gender differences are linked to circulating sex-related steroid hormone levels and their cardio-specific actions, which are critical factors involved in the prevalence and features of age-associated cardiovascular disease. In women, estrogens have been described as cardioprotective agents, while in men, testosterone is the main sex steroid hormone. The effects of testosterone as a metabolic regulator and cardioprotective agent in aging men are poorly understood. With advancing age, testosterone levels gradually decrease in men, an effect associated with increasing fat mass, decrease in lean body mass, dyslipidemia, insulin resistance and adjustment in energy substrate metabolism. Aging is associated with a decline in metabolism, characterized by modifications in cardiac function, excitation-contraction coupling, and lower efficacy to generate energy. Testosterone deficiency -as found in elderly men- rapidly becomes an epidemic condition, associated with prominent cardiometabolic disorders. Therefore, it is highly probable that senior men showing low testosterone levels will display symptoms of androgen deficiency, presenting an unfavorable metabolic profile and increased cardiovascular risk. Moreover, recent reports establish that testosterone replacement improves cardiomyocyte bioenergetics, increases glucose metabolism and reduces insulin resistance in elderly men. Thus, testosterone-related metabolic signaling and gene expression may constitute relevant therapeutic target for preventing, or treating, age- and gender-related cardiometabolic diseases in men. Here, we will discuss the impact of current evidence showing how cardiac metabolism is regulated by androgen levels in aging men.
Topics: Aged; Aging; Androgens; Cardiovascular Diseases; Humans; Male
PubMed: 32499759
DOI: 10.3389/fendo.2020.00316 -
Molecular and Cellular Endocrinology Apr 2018Androgens are synthesised in both the ovary and adrenals in women and play an important role in the regulation of female fertility, as well as in the aetiology of... (Review)
Review
Androgens are synthesised in both the ovary and adrenals in women and play an important role in the regulation of female fertility, as well as in the aetiology of disorders such as polycystic ovarian syndrome, endometriosis and endometrial cancer. The endometrium is an androgen target tissue and the impact of AR-mediated effects has been studied using human endometrial tissue samples and rodent models. In this review we highlight recent evidence that endometrial androgen biosynthesis and intracrine action is important in preparation of a tissue microenvironment that can support implantation and establishment of pregnancy. The impact of androgens on endometrial cell proliferation, in repair of the endometrial wound at the time of menstruation and in endometrial disorders is discussed. Future directions for research focused on AR function as a therapeutic target are considered.
Topics: Androgens; Animals; Cell Proliferation; Endometrium; Female; Humans; Menstrual Cycle; Receptors, Androgen; Wound Healing
PubMed: 28919297
DOI: 10.1016/j.mce.2017.09.022 -
The Journal of Steroid Biochemistry and... Sep 2014Androgens play an important role in regulation of body fat distribution in humans. They exert direct effects on adipocyte differentiation in a depot-specific manner, via... (Review)
Review
Androgens play an important role in regulation of body fat distribution in humans. They exert direct effects on adipocyte differentiation in a depot-specific manner, via the androgen receptor (AR), leading to modulation of adipocyte size and fat compartment expansion. Androgens also impact directly on key adipocyte functions including insulin signalling, lipid metabolism, fatty acid uptake and adipokine production. Androgen excess and deficiency have implications for metabolic health in both males and females, and these metabolic effects may be mediated through adipose tissue via effects on fat distribution, adipocyte function and lipolysis. Research into the field of androgen metabolism in human and animal adipose tissue has produced inconsistent results; it is important to take into account the sex-, depot- and organism-specific effects of androgens in fat. In general, studies point towards a stimulatory effect on lipolysis, with impairment of adipocyte differentiation, insulin signalling and adipokine generation. Observed effects are frequently gender-specific. Adipose tissue is an important organ of pre-receptor androgen metabolism, through which local androgen availability is rigorously controlled. Adipose androgen exposure is tightly controlled by isoenzymes of AKR1C, 5α-reductase and others, but regulation of the balance between generation and irreversible inactivation remains poorly understood. In particular, AKR1C2 and AKR1C3 are crucial in the regulation of local androgen bioavailability within adipose tissue. These isoforms control the balance between activation of androstenedione (A) to testosterone (T) by the 17β-hydroxysteroid dehydrogenase activity (17β-HSD) of AKR1C3, or inactivation of 5α-dihydrotestosterone (DHT) to 5α-androstane-3α,17β-diol by the 3α-hydroxysteroid dehydrogenase (3α-HSD) activity of AKR1C2. Most studies suggest that androgen inactivation is the predominant reaction in fat, particularly in the abdominal subcutaneous (SC) depot. Modulation of local adipose androgen availability may afford future therapeutic options to improve metabolic phenotype in disorders of androgen excess and deficiency.
Topics: Adipose Tissue; Androgens; Animals; Female; Humans; Male
PubMed: 24787657
DOI: 10.1016/j.jsbmb.2014.04.008 -
Reproductive Toxicology (Elmsford, N.Y.) Oct 2018A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US... (Review)
Review
A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US EPA's chemicals screened for endocrine activity, and the library of chemicals run in US EPA 's ToxCast in vitro assays. For 134 chemicals that met pre-defined criteria, experimental results were extracted into a database used to characterize uncertainty in results and evaluate the concordance of the Hershberger assay with other in vivo rodent studies that measure androgen-responsive endpoints. Of 25 chemicals tested in >1 Hershberger study, 28% had disagreements between studies (i.e. ≥1 positive and ≥1 negative study), and of the 65 chemicals tested in Hershberger studies and other in vivo studies with androgen-responsive endpoints, 43% indicated disagreements, though in some cases these may be explained by differences in study designs or physiology of the animal model. Ultimately, 49 chemicals were identified with reproducible androgen pathway responses confirmed in ≥2 in vivo rodent studies that could be considered reference chemicals useful for validating alternative methods.
Topics: Androgen Antagonists; Androgens; Animals; Biological Assay; Humans
PubMed: 30205136
DOI: 10.1016/j.reprotox.2018.08.016 -
Der Hautarzt; Zeitschrift Fur... Oct 2020Hyperandrogenism or hyperandrogenemia are medical conditions characterized by excessive levels of androgens in the periphery or systemically. Clinical manifestations of... (Review)
Review
Hyperandrogenism or hyperandrogenemia are medical conditions characterized by excessive levels of androgens in the periphery or systemically. Clinical manifestations of hyperandrogenism include hirsutism, seborrhea, acne, androgenetic alopecia, and virilization. Hirsutism, defined as excessive growth of terminal hair in women in a male-like pattern, is the most commonly used clinical diagnostic criterion of hyperandrogenism and is determined by using a standardized scoring system of hair growth. Acne and alopecia are further common androgenic skin changes and might be observed without hirsutism in some women. Clitoris hypertrophy, increase of muscle mass, irregular menstrual cycle, and metabolic syndrome can also accompany this condition. Among others polycystic ovary syndrome (PCOS), Cushing disease, and late-onset adrenogenital syndrome belong to the most frequent causes of hyperandrogenemia. Virilization is a relatively uncommon feature of hyperandrogenemia and its presence often suggests an androgen-producing tumor. Management of symptoms include the use of antiandrogens such as cyproterone acetate, spironolactone, and flutamide. A thorough history, a focused clinical examination and an interdisciplinary approach together with gynecologists and endocrinologists are extremely helpful in the diagnostic evaluation and therapy of patients with suspected hyperandrogenism.
Topics: Acne Vulgaris; Alopecia; Androgens; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome
PubMed: 32857168
DOI: 10.1007/s00105-020-04677-1