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1.
The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?
Chiodo, C, Morelli, C, Cavaliere, F, Sisci, D, Lanzino, M
International journal of molecular sciences. 2021;(1)
Abstract
Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.
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2.
Vitamin D and Polycystic Ovary Syndrome: a Narrative Review.
Mu, Y, Cheng, D, Yin, TL, Yang, J
Reproductive sciences (Thousand Oaks, Calif.). 2021;(8):2110-2117
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of reproductive age women and contributes to metabolic dysfunctions including insulin resistance (IR) and dyslipidemia. Vitamin D is a steroid hormone, which is involved in calcium metabolism and bone structure and has a potential role in the prevention of many illnesses, including cancers, autoimmune disorders, hypertension, diabetes, and obesity. Recently, it has been reported that vitamin D deficiency was a common complication of PCOS and vitamin D status was associated with reproductive ability, metabolic alterations, and mental health of PCOS patients. This review summarizes the advances between vitamin D status and the pathophysiological process of PCOS. Vitamin D level was negatively associated with serum androgen level. Vitamin D treatment could reduce serum androgen and anti-MüllerianHormone (AMH) levels, and decrease endometrial thickness, which resulted in improvement of menstrual cycle and folliculogenesis of PCOS patients. Moreover, vitamin D concentrations were negatively correlated with parameters of IR and body fat mass. Vitamin D supplementation has beneficial effects on IR and lipid metabolism. In addition, a positive of vitamin D on mental health of PCOS patients was proposed. Understanding the relationship between vitamin D status and the symptoms of PCOS patients is of great clinical significance to treat and prevent the progression of PCOS.
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3.
The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.
Bertoldo, E, Adami, G, Rossini, M, Giollo, A, Orsolini, G, Viapiana, O, Gatti, D, Fassio, A
Frontiers in endocrinology. 2021;:620920
Abstract
The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.
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4.
Using Exercise and Nutrition to Alter Fat and Lean Mass in Men with Prostate Cancer Receiving Androgen Deprivation Therapy: A Narrative Review.
Wilson, RL, Taaffe, DR, Newton, RU, Hart, NH, Lyons-Wall, P, Galvão, DA
Nutrients. 2021;(5)
Abstract
Fat mass (FM) gain and lean mass (LM) loss are common side effects for patients with prostate cancer receiving androgen deprivation therapy (ADT). Excess FM has been associated with an increased risk of developing obesity-related comorbidities, exacerbating prostate cancer progression, and all-cause and cancer-specific mortality. LM is the predominant contributor to resting metabolic rate, with any loss impacting long-term weight management as well as physical function. Therefore, reducing FM and preserving LM may improve patient-reported outcomes, risk of disease progression, and ameliorate comorbidity development. In ADT-treated patients, exercise and nutrition programs can lead to improvements in quality of life and physical function; however, effects on body composition have been variable. The aim of this review was to provide a descriptive overview and critical appraisal of exercise and nutrition-based interventions in prostate cancer patients on ADT and their effect on FM and LM. Our findings are that FM gain and LM loss are side effects of ADT that could be reduced, prevented, or even reversed with the implementation of a combined exercise and nutrition program. However, the most effective combination of specific exercise and nutrition prescriptions are yet to be determined, and thus should be a focus for future studies.
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5.
Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer.
Abd Wahab, NA, Lajis, NH, Abas, F, Othman, I, Naidu, R
Nutrients. 2020;(3)
Abstract
Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
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6.
Kidney disease associated with androgenic-anabolic steroids and vitamin supplements abuse: Be aware!
Parente Filho, SLA, Gomes, PEAC, Forte, GA, Lima, LLL, Silva Júnior, GBD, Meneses, GC, Martins, AMC, Daher, EF
Nefrologia. 2020;(1):26-31
Abstract
The excessive chase for beauty standards and the rise of muscle dysmorphia have ultimately led to an increase in androgenic-anabolic steroids (AAS) and intramuscular injections of vitamins A, D and E (ADE) abuse, which is associated with several adverse effects and has become a public health issue. This review of literature discusses kidney injury associated with the use of AAS and ADE, highlighting the mechanisms of acute and chronic renal lesion, such as direct renal toxicity, glomerular hyperfiltration and hypercalcemia. Future perspectives regarding evaluation and early diagnosis of kidney injury in these patients are also discussed.
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7.
The role of adrenal derived androgens in castration resistant prostate cancer.
Barnard, M, Mostaghel, EA, Auchus, RJ, Storbeck, KH
The Journal of steroid biochemistry and molecular biology. 2020;:105506
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Abstract
Castration resistant prostate cancer (CRPC) remains androgen dependant despite castrate levels of circulating testosterone following androgen deprivation therapy, the first line of treatment for advanced metstatic prostate cancer. CRPC is characterized by alterations in the expression levels of steroidgenic enzymes that enable the tumour to derive potent androgens from circulating adrenal androgen precursors. Intratumoral androgen biosynthesis leads to the localized production of both canonical androgens such as 5α-dihydrotestosterone (DHT) as well as less well characterized 11-oxygenated androgens, which until recently have been overlooked in the context of CRPC. In this review we discuss the contribution of both canonical and 11-oxygenated androgen precursors to the intratumoral androgen pool in CRPC. We present evidence that CRPC remains androgen dependent and discuss the alterations in steroidogenic enzyme expression and how these affect the various pathways to intratumoral androgen biosynthesis. Finally we summarize the current treatment strategies for targeting adrenal derived androgen biosynthesis.
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8.
Androgen Therapy in Women.
Vegunta, S, Kling, JM, Kapoor, E
Journal of women's health (2002). 2020;(1):57-64
Abstract
Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. Testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD). However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause. In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms "HSDD," "DHEA in women," "testosterone in women," and "androgens in women," and reviewed most references from all relevant articles. Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known. A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.
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9.
Altered expression of cytochrome P450 enzymes involved in metabolism of androgens and vitamin D in the prostate as a risk factor for prostate cancer.
Maksymchuk, OV, Kashuba, VI
Pharmacological reports : PR. 2020;(5):1161-1172
Abstract
Prostate cancer is the most common malignant disease among men. The signaling pathways, regulated by the androgen and vitamin D receptors, play a key role in prostate cancer. The intracellular level of androgens and vitamin D determines not only receptor functionality, but also the efficacy of cellular processes regulated by them (cell proliferation, apoptosis, differentiation etc.). It is known that several androgen-metabolizing P450s (CYP3A4/5/43 and CYP2B6) and P450 enzymes (CYP2R1, CYP27A1, CYP27B1, CYP24A1, CYP3A4, CYP2J2), which are necessary for vitamin D metabolism, are expressed in the prostate. It was shown that alterations in an expression pattern of the certain cytochrome P450s might lead to the development of castration-resistant cancer (CYP3A4, CYP2J2, CYP24A1), and to chemo-resistance (CYP3A4, CYP3A5, CYP2B6) and early mortality (CYP2B6, CYP27A1, CYP24A1). Moreover, steroidogenic CYPs (CYP17A1, CYP11A1) are not expressed in normal prostate tissue. Alterations in their expression levels in steroidogenic tissues are closely associated with carcinogenesis, and, most importantly, with the development of aggressive forms of prostate cancer. Hence, it is important, to study how expression of CYPs in the prostate might be regulated, to understand the mechanisms of disease development and to improve the effectiveness of therapy. Several CYPs (CYP3A43, CYP2B6, CYP27A1, CYP24A1) can be considered as prognostic and diagnostic markers of prostate cancer. To propose personalized treatment, individual differences in CYP expression should be taken into account.
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10.
Understanding the Role of Androgen Action in Female Adipose Tissue.
Schiffer, L, Arlt, W, O'Reilly, MW
Frontiers of hormone research. 2019;:33-49
Abstract
Adipose tissue is an important target of androgen action in humans. Androgens exert important effects on adipose tissue biology, including fat mass expansion and distribution, insulin signalling and lipid metabolism. In conditions of female androgen excess such as polycystic ovary syndrome (PCOS), androgens exert metabolically deleterious effects on adipose tissue function in a depot-specific manner. Androgen excess in women is metabolically deleterious, and adverse metabolic effects may be mediated by effects on preadipocyte differentiation and adipocyte hypertrophy. Circulating androgen burden correlates with adiposity in women, and drives visceral fat mass accumulation. Adipose tissue is also an important organ of pre-receptor androgen metabolism, and is host to a complex network of androgen activating and inactivating enzymes. Adipose androgen generation is increased in subcutaneous (SC) adipose tissue in women with PCOS, and intra-adipose concentrations of potent androgens may exceed those measured in peripheral circulation. Increased expression of the key androgen-activating enzyme aldo-ketoreductase type 1C3 in PCOS SC adipose tissue leads to high concentrations of testosterone and dihydrotestosterone. Enhanced local androgen generation may further contribute to the adverse metabolic profile of women with PCOS by exerting lipotoxic effects on local adipose biology.