-
1.
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
-
-
Free full text
-
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.
-
2.
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.
-
3.
Covid-19 in Man: A Very Dangerous Affair.
Lisco, G, Giagulli, VA, De Pergola, G, De Tullio, A, Guastamacchia, E, Triggiani, V
Endocrine, metabolic & immune disorders drug targets. 2021;(9):1544-1554
Abstract
The novel pandemic of Coronavirus disease 2019 (COVID-19) has become a public health issue since March 2020, with more than 30 million people found to be infected worldwide. Men may be considered to be at a higher risk of poor prognosis or death once the infection occurred. Concerns surfaced regarding the risk of a possible testicular injury due to SARS-CoV-2 infection. Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On the one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, a younger man with normal testicular function compared to a woman of similar age is prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that the SARS-CoV-2 genome is not normally found in gonads and gametes. Therefore, transmission through sex could be excluded as a possible way to spread the COVID-19. Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection, even if it occurred asymptomatically. Still, no long-term evidence is currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.
-
4.
Effect of fenugreek extract supplement on testosterone levels in male: A meta-analysis of clinical trials.
Mansoori, A, Hosseini, S, Zilaee, M, Hormoznejad, R, Fathi, M
Phytotherapy research : PTR. 2020;(7):1550-1555
Abstract
Different types of glycosides extract of fenugreek have shown androgenic and anabolic effect in male. The aim of the study was to evaluate the effect of fenugreek extract on total testosterone levels in male. Medline via PubMed, Scopus databases, Cochrane Library, Web of Science, and Google Scholar were searched up to November 2018 for randomized clinical trials comparing intake of fenugreek extract with control group. Data on change in serum total testosterone were pooled using random-effects models. A total of four trials were included. Fenugreek extract has a significant effect on total serum testosterone. Results from clinical trials suggest that fenugreek extract supplement has an effect on serum total testosterone levels in male.
-
5.
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.
-
6.
Sex Differences in Adipose Tissue Function.
Gavin, KM, Bessesen, DH
Endocrinology and metabolism clinics of North America. 2020;(2):215-228
-
-
Free full text
-
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.
-
7.
The causes of adverse changes of testosterone levels in men.
Wrzosek, M, Woźniak, J, Włodarek, D
Expert review of endocrinology & metabolism. 2020;(5):355-362
Abstract
INTRODUCTION As men age, progressive testosterone deficiency syndrome becomes an increasingly common problem. However, the decreased testosterone levels are not only the result of advanced age. AREAS COVERED PubMed search of published data on testosterone, nutritional deficiency, stress, sleep, and obesity. Many factors impact the male HPG axis (the hypothalamic-pituitary-adrenal), including body weight, calorific and nutritional value of a diet, the amount and quality of sleep, as well as the level of stress. In the case of persons of healthy weight, a below-average calorific value of a diet may decrease the levels of testosterone in men. On the other hand, the same caloric deficiency in obese persons may result in a neutral or positive impact on testosterone levels. EXPERT OPINION Many factors, including external, environmental and internal factors, influence testosterone levels. Undoubtedly, nutritional deficiency, and particularly of such nutrients as zinc, magnesium, vitamin D, together with low polyphenols intake, affects the HPG axis. The levels of mental and oxidative stress can also adversely impact the axis. Hence, a diagnosis of the cause of disturbance in testosterone levels depends on many factors and requires a broad range of research, as well as a change of patients' lifestyle.
-
8.
Reviewing the Evidence on Vitamin D Supplementation in the Management of Testosterone Status and Its Effects on Male Reproductive System (Testis and Prostate): Mechanistically Dazzling but Clinically Disappointing.
Santos, HO, Howell, S, Nichols, K, Teixeira, FJ
Clinical therapeutics. 2020;(6):e101-e114
Abstract
PURPOSE Vitamin D supplementation has been suggested to increase testosterone levels. The primary purpose of this literature review was to critically assess the physiologic effects of vitamin D supplementation on serum testosterone concentrations in men and the secondary purpose was to evaluate the feasibility of vitamin D status toward urologic health (testis and prostate). METHODS A structured literature review was performed using the Cochrane, MEDLINE, and Web of Science databases. The literature search encompassed studies published between 2011 and 2019. FINDINGS Observational studies suggest an association between higher testosterone and serum vitamin D concentrations. Conversely, most randomized clinical trials that investigated the effect of vitamin D administration on testosterone levels have failed to detect any significant effect. Physiologically, vitamin D is engaging in spermatogenesis, but it remains unclear whether vitamin D is a determinant of fertility. With prostate support, the management of vitamin D status has been associated with a decreased prevalence of benign prostatic hyperplasia and symptoms (ie, lower urinary tract symptoms). However, with prostate cancer, there is a paucity of evidence pertaining to vitamin D supplementation. IMPLICATIONS Mechanistically, vitamin D exhibits essential roles in the testis and prostate; otherwise, there is no apparent evidence to support the use of vitamin D supplementation to increase testosterone levels and to improve clinical outcomes related to the male reproductive system.
-
9.
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.
-
10.
Sarcopenia.
Keller, K
Wiener medizinische Wochenschrift (1946). 2019;(7-8):157-172
Abstract
Sarcopenia is a very common, but frequently overlooked and undertreated geriatric syndrome comprising pronounced muscle mass and strength/performance loss. Estimated prevalence is between 5 and 40% in the general population, accompanied by an exponential incline with increasing age. Sarcopenia is connected to atrophy and loss of muscle fibers and motor units, affecting primarily the fast-twitch muscle fibers und their motor units. Fast-twitch muscle fibers seem to be more prone to failure of function and loss over time. Main causes for the development of sarcopenia are hormonal changes (reduced release of testosterone, estrogen, and growth hormone), nutritional deficiencies, chronic inflammation, and particularly a decrease in physical activity due to sedentary lifestyle with advancing age. Treatment options for sarcopenia comprise an active lifestyle with physical activity and exercise training, modifications of nutritional intake, and pharmacological therapies. Strength training and an adequate nutritional intake form the basis of successful sarcopenia treatment.