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Worse progression of COVID-19 in men: Is testosterone a key factor?
Giagulli, VA, Guastamacchia, E, Magrone, T, Jirillo, E, Lisco, G, De Pergola, G, Triggiani, V
Andrology. 2021;(1):53-64
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Abstract
BACKGROUND The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease 2019 (COVID-19) seems to have a worse clinical course among infected men compared with women, thus highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context. OBJECTIVE To overview on possible mechanisms by which serum T levels could affect the progression of COVID-19 in men. METHODS Authors searched PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, Google, and institutional websites for medical subject headings terms and free text words referred to "SARS-CoV-2," "COVID-19," "testosterone," "male hypogonadism," "gender" "immune system," "obesity," "thrombosis" until May 19th 2020. RESULTS T, co-regulating the expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS-CoV-2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. DISCUSSION AND CONCLUSION T in comparison to estrogen may predispose men to a widespread COVID-19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially elderly men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.
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Inositols: From Established Knowledge to Novel Approaches.
Dinicola, S, Unfer, V, Facchinetti, F, Soulage, CO, Greene, ND, Bizzarri, M, Laganà, AS, Chan, SY, Bevilacqua, A, Pkhaladze, L, et al
International journal of molecular sciences. 2021;(19)
Abstract
Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
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Sex Differences in Adipose Tissue Function.
Gavin, KM, Bessesen, DH
Endocrinology and metabolism clinics of North America. 2020;(2):215-228
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Abstract
Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number of products from adipose tissue are under the control of sex steroids, which act through a wide variety of mechanisms, both direct and indirect, to tailor metabolism to the unique needs of each sex. A fuller understanding of sex-based differences in adipose tissue function may help with tailored strategies for disease prevention and treatment and provide insights into fundamental differences in the processes that regulate nutrient homeostasis and body weight.
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Testosterone in Males as Enhanced by Onion (Allium Cepa L.).
Banihani, SA
Biomolecules. 2019;(2)
Abstract
Testosterone (17β-Hydroxyandrost-4-en-3-one) is the main sex hormone in males. Maintaining and enhancing testosterone level in men is an incessant target for many researchers. Examples of such research approaches is to utilize specific types of food or dietary supplements as a safe and easily reached means. Here, specifically, since 1967 until now, many research studies have revealed the effect of onion on testosterone; however, this link has yet to be collectively reviewed or summarized. To accomplish this contribution, we searched the Scopus, Web of Science, and PubMed databases for full articles or abstracts (published in English language) from April 1967 through December 2018 using the keywords "onion" versus "testosterone". In addition, a number of related published articles from the same databases were included to improve the integrity of the discussion, and hence the edge of the future directions. In summary, there is an evidence that onions enhance testosterone level in males. The mechanisms by which this occurs is mainly by increasing the production of luteinizing hormone, enhancing the antioxidant defense mechanism in the tests, neutralizing the damaging effects of the generated free radicals, ameliorating insulin resistance, promoting nitric oxide production, and altering the activity of adenosine 5'-monophosphate -activated protein kinase. However, this effect requires further approval in humans, mainly by conducting clinical trials.
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The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper.
Gillberg, C, Fernell, E, Kočovská, E, Minnis, H, Bourgeron, T, Thompson, L, Allely, CS
Autism research : official journal of the International Society for Autism Research. 2017;(6):1022-1044
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Abstract
Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the "autisms" [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as "steroid metabolism" and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. Autism Res 2017, 10: 1022-1044. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.
Grossmann, M, Matsumoto, AM
The Journal of clinical endocrinology and metabolism. 2017;(3):1067-1075
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Abstract
CONTEXT Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. EVIDENCE ACQUISITION Literature review from 1970 to October 2016. EVIDENCE SYNTHESIS Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. CONCLUSIONS There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.
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Pituitary insufficiency following traumatic thoracic injury in an adolescent male patient: A case report and literature review.
Gilis-Januszewska, A, Kluczyński, Ł, Wilusz, M, Pantofliński, J, Turek-Jabrocka, R, Pach, D, Hubalewska-Dydejczyk, A
Medicine. 2017;(44):e8406
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Abstract
RATIONALE Traumatic thoracic injuries in adolescents are rare but could be connected with traumatic brain injuries (TBI) and development of chronic hypopituitarism. Early recognition of these endocrine problems is a significant challenge to clinicians. We present difficulties in diagnosis of hypothalamic-pituitary insufficiency following traumatic thoracic injury in adolescence. We also review the literature of similar cases. PATIENT CONCERNS We present a case of a 24-years-old male. In 2007, at the age of 15 he underwent a severe traffic accident followed by thoracic injury with concussion, hemothorax and dissection of the aorta requiring aortic stent-graft implantation. DIAGNOSES During the post-traumatic period, transient polydipsia and polyuria symptoms were observed. The patient had no medical history of any serious disease before the accident, his growth and pubertal development was normal. After the accident the patient did not undergo any routine medical check-ups. In 2013 gonadal axis deficiency was diagnosed during investigation of libido problems. Following the diagnosis testosterone replacement therapy was initiated. INTERVENTIONS Further endocrinological investigation was carried out in 2016. The patient's main complaints were decreased mood and poor physical fitness. BMI was 27.34 kg/m, with a tendency to abdominal fat distribution. The patient's height is 160 cm, while Mid Parental Height (MPH) is 173.5 cm. Decreased bone density was found in DEXA examination. Serum growth hormone level (GH) was normal while insulin-like growth factor-1 (IGF-1) level was below normal. Insulin tolerance test (ITT) and low levels of IGF-1 confirmed somatotropic axis deficiency. Nuclear magnetic resonance (NMR) of the hypothalamo-pituitary region showed no abnormalities. PROP 1 and other common genetic mutations associated with GH deficits were excluded. Testosterone treatment was continued. The patient increased physical activity and implemented diet. OUTCOMES The patient has lost weight, improved physical activity performance and is feeling better. The procedure to start GH supplementation is now in process. LESSONS Based on our case and available literature we suggest that adolescent patients after traumatic brain injuries may require precise investigation and strict monitoring due to the possibility of unrecognized hypopituitarism.
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Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise.
Kraemer, WJ, Ratamess, NA, Nindl, BC
Journal of applied physiology (Bethesda, Md. : 1985). 2017;(3):549-558
Abstract
The complexity and redundancy of the endocrine pathways during recovery related to anabolic function in the body belie an oversimplistic approach to its study. The purpose of this review is to examine the role of resistance exercise (RE) on the recovery responses of three major anabolic hormones, testosterone, growth hormone(s), and insulin-like growth factor 1. Each hormone has a complexity related to differential pathways of action as well as interactions with binding proteins and receptor interactions. Testosterone is the primary anabolic hormone, and its concentration changes during the recovery period depending on the upregulation or downregulation of the androgen receptor. Multiple tissues beyond skeletal muscle are targeted under hormonal control and play critical roles in metabolism and physiological function. Growth hormone (GH) demonstrates differential increases in recovery with RE based on the type of GH being assayed and workout being used. IGF-1 shows variable increases in recovery with RE and is intimately linked to a host of binding proteins that are essential to its integrative actions and mediating targeting effects. The RE stress is related to recruitment of muscle tissue with the glandular release of hormones as signals to target tissues to support homeostatic mechanisms for metabolism and tissue repair during the recovery process. Anabolic hormones play a crucial role in the body's response to metabolism, repair, and adaptive capabilities especially in response to anabolic-type RE. Changes of these hormones following RE during recovery in the circulatory biocompartment of blood are reflective of the many mechanisms of action that are in play in the repair and recovery process.
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Effects of testosterone therapy on BMI, blood pressure, and laboratory profile of transgender men: a systematic review.
Velho, I, Fighera, TM, Ziegelmann, PK, Spritzer, PM
Andrology. 2017;(5):881-888
Abstract
Testosterone is the main hormonal agent used for cross-sex hormone therapy in female-to-male transgender persons. Our aim was to systematically review the literature concerning the effects of testosterone on body mass index (BMI), blood pressure, hematocrit, hemoglobin, lipid profile, and liver enzymes in transgender men. PUBMED and EMBASE were searched for studies published until March 2017. Studies were included if they reported interventions with any dose of testosterone and comparison of variables before and during treatment. Of 455 potentially eligible articles, 13 were reviewed. Study duration ranged from 6 to 60 months, sample size ranged from 12 to 97 patients, and the most common treatment was parenteral testosterone undecanoate 1000 mg/12 weeks. Slight but significant increases in BMI were reported (from 1.3 to 11.4%). Three out of seven studies assessing the impact of different testosterone formulations on blood pressure detected modest increases or clinically irrelevant changes in this variable. In another study, however, two patients developed hypertension, which was resolved after cessation of testosterone therapy. Decreases in HDL-cholesterol and increases in LDL-cholesterol were consistently observed. Eight studies observed a relationship between testosterone and increased hemoglobin (range: 4.9-12.5%) and hematocrit (range: 4.4-17.6%), but discontinuation of androgen therapy was not necessary. In one study, two patients developed erythrocytosis (hematocrit >52%) after 9 and 12 months of treatment. One study analyzing testosterone formulations observed smaller increases in hemoglobin and hematocrit with testosterone gel. Six studies assessing liver function showed slight or no changes. Overall, the quality of evidence was low, given the lack of randomized clinical/controlled trials and the small sample sizes. In conclusion, exogenous testosterone administration to transgender men was associated with modest increases in BMI, hemoglobin/hematocrit, and LDL-cholesterol, and with decreases in HDL-cholesterol. Long-term studies are needed to assess the long-term risks of testosterone therapy, particularly as they relate to cardiometabolic risks such as diabetes, dyslipidemia and the metabolic syndrome.
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Ketogenic diet and testosterone increase: Is the increased cholesterol intake responsible? To what extent and under what circumstances can there be benefits?
Santos, HO
Hormones (Athens, Greece). 2017;(3):150-160