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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 -
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 -
Seminars in Cell & Developmental Biology Jan 2022Signaling by androgens through androgen receptor (AR) is essential to complete spermatogenesis in the testis. Similarly, loss of the main estrogen receptor, estrogen... (Review)
Review
Signaling by androgens through androgen receptor (AR) is essential to complete spermatogenesis in the testis. Similarly, loss of the main estrogen receptor, estrogen receptor 1 (ESR1; also known as ERα), results in male infertility, due in part to indirect deleterious effects on the seminiferous epithelium and spermatogenesis. Effects of steroid hormones are induced primarily through genomic changes induced by hormone-mediated activation of their intracellular receptors and subsequent effects on nuclear gene transcription. However, androgens and estrogens also signal through rapid nonclassical pathways involving actions initiated at the cell membrane. Here we review the data that nonclassical androgen and estrogen signaling pathways support processes essential for male fertility in the testis and reproductive tract. The recent development of transgenic mice lacking nonclassical AR or ESR1 signaling but retaining genomic nuclear signaling has provided a powerful tool to elucidate the function of nonclassical signaling in the overall response to androgens and estrogens. Results from these mice have emphasized that nonclassical signaling is essential for full responses to these hormones, and absence of either nonclassical or classical AR or ESR1 pathways produces abnormalities in spermatogenesis and the male reproductive tract. Although additional work is required to fully understand how classical and nonclassical receptor signaling synergize to produce full steroid hormone responses, here we summarize the known physiological functions of the classical and nonclassical androgen and estrogen signaling pathways in the testis and reproductive tract.
Topics: Androgens; Animals; Estrogens; Male; Mice; Mice, Transgenic; Spermatogenesis
PubMed: 34119408
DOI: 10.1016/j.semcdb.2021.05.032 -
Differentiation; Research in Biological... 2020The common view on penile development is that it is androgen-dependent, based first and foremost on the fact that the genital tubercle forms a penis in males and a... (Review)
Review
The common view on penile development is that it is androgen-dependent, based first and foremost on the fact that the genital tubercle forms a penis in males and a clitoris in females. However, critical examination of the complex processes involved in human penile development reveals that many individual steps in development of the genital tubercle are common to both males and females, and thus can be interpreted as androgen-independent. For certain developmental events this conclusion is bolstered by observations in androgen-insensitive patients and androgen receptor mutant mice. Events in genital tubercle development that are common to human males and females include: formation of (a) the genital tubercle, (b) the urethral plate, (c) the urethral groove, (d) the glans, (e) the prepuce and (f) the corporal body. For humans 6 of 13 individual developmental steps in penile development were interpreted as androgen-independent. For mice 5 of 11 individual developmental steps were found to be androgen-independent, which were verified through analysis of androgen-insensitive mutants. Observations from development of external genitalia of other species (moles and spotted hyena) provide further examples of androgen-independent events in penile development. These observations support the counter-intuitive idea that penile development involves both androgen-independent and androgen-dependent processes.
Topics: Androgens; Animals; Humans; Male; Organogenesis; Penis; Receptors, Androgen
PubMed: 31783219
DOI: 10.1016/j.diff.2019.07.005 -
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 -
Best Practice & Research. Clinical... Sep 2022Male hypogonadism is associated with reduced quality of life and the development of co-morbidities including obesity, diabetes mellitus, and dyslipidaemia. The mainstay... (Review)
Review
Male hypogonadism is associated with reduced quality of life and the development of co-morbidities including obesity, diabetes mellitus, and dyslipidaemia. The mainstay of treatment for male hypogonadism is testosterone replacement therapy (TRT). However, TRT has recognised side effects including impaired spermatogenesis and there are concerns regarding its use in men with concurrent cardiovascular disease. Thus, there has been an impetus to develop novel androgen therapies for treating male hypogonadism to mitigate the side effects of TRT. This review will discuss the benefits and adverse effects of TRT, and novel therapies including nasal testosterone, aromatase inhibitors, selective oestrogen receptor modulators, and selective androgen receptor modulators.
Topics: Androgen Receptor Antagonists; Androgens; Aromatase Inhibitors; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Quality of Life; Receptors, Androgen; Selective Estrogen Receptor Modulators; Testosterone
PubMed: 35981955
DOI: 10.1016/j.beem.2022.101686 -
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 -
Current Opinion in Endocrinology,... Dec 2022To explore the recent updates in the diagnosis, management, and clinical implications of androgenic alopecia among patients diagnosed with polycystic ovarian syndrome... (Review)
Review
PURPOSE OF REVIEW
To explore the recent updates in the diagnosis, management, and clinical implications of androgenic alopecia among patients diagnosed with polycystic ovarian syndrome (PCOS).
RECENT FINDINGS
PCOS diagnosis continues to be the most common cause of infertility among reproductively aged women, serving as the most common endocrinopathy among this population. Female pattern hair loss (FPHL) has been seen to be associated and more common among patients with PCOS, however, there are limited studies examining the impact of FPHL among PCOS patients. Although hyperandrogenism is associated with FPHL, the pathophysiology continues to be unclear as FPHL can be present with normal biochemical androgen markers. Treatment can be complex, as common treatments to promote hair growth can exacerbate undesired hirsutism, which can be overcome by cosmetic treatments. New second-line treatment options such as low level laser therapy and platelet rich plasma have been emerging, with limited data supporting efficacy.
SUMMARY
PCOS is a complex endocrinological disorder that has significant gynecologic, cutaneous, and metabolic implications that require multidisciplinary collaboration and care. Reproductive goals should be thoroughly discussed prior to starting any treatment, as PCOS is the most common cause of infertility among reproductively-aged women.
Topics: Female; Humans; Aged; Hirsutism; Polycystic Ovary Syndrome; Androgens; Hyperandrogenism; Alopecia; Infertility
PubMed: 36226726
DOI: 10.1097/MED.0000000000000777 -
The Canadian Journal of Cardiology Dec 2022Androgens, including testosterone and its more potent metabolite dihydrotestosterone, exert multiple actions in the body. Physiologically, they play a critical role in... (Review)
Review
Androgens, including testosterone and its more potent metabolite dihydrotestosterone, exert multiple actions in the body. Physiologically, they play a critical role in male sex development. In addition, they influence vascular function, including arterial vasodilation and mediation of myogenic tone. Androgens are produced from 9 weeks' gestation in the human fetal testis, as well as in small amounts by the adrenal glands. Serum concentrations vary according to age and sex. The vasculature is a target for direct actions of androgens, which bind to various sex hormone receptors expressed in endothelial and vascular smooth muscle cells. Androgens exert both vasoprotective and vasoinjurious effects, depending on multiple factors including sex-specific effects of androgens, heterogeneity of the vascular endothelium, differential expression of androgen and sex hormone receptors in endothelial and vascular smooth muscle cells, and the chronicity of androgen administration. Long-term administration of androgens induces vasoconstriction and influences endothelial permeability, whereas acute administration may have opposite effects. At the cellular level, androgens stimulate endothelial cell production of nitric oxide and inhibit proinflammatory signalling pathways, inducing vasorelaxation and vasoprotection. However, androgens also activate endothelial production of vasoconstrictors and stimulate recruitment of endothelial progenitor cells. In humans, both androgen deficiency and androgen excess are associated with increased cardiovascular morbidity and mortality. This review discusses how androgens modulate vascular sex differences across the lifespan by considering the actions and production of androgens in both sexes and describes how cardiovascular risk is altered as levels of androgens change with aging.
Topics: Female; Humans; Male; Androgens; Endothelial Progenitor Cells; Endothelium, Vascular; Gonadal Steroid Hormones; Receptors, Androgen; Sex Characteristics
PubMed: 36156286
DOI: 10.1016/j.cjca.2022.09.018