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Article ; Online: Major cardiovascular disease risk in men with testosterone deficiency (hypogonadism): appraisal of short, medium and long-term testosterone therapy - a narrative review.

Traish, Abdulmaged M

2023 Volume 11, Issue 4, Page(s) 384–394

Abstract: Introduction: Low testosterone (T) levels are associated with obesity, metabolic syndrome, type 2 diabetes mellitus and altered lipid profiles, thus contributing to increased cardiovascular disease risk. Hence T deficiency has a detrimental effect on ... ...

Abstract	Introduction: Low testosterone (T) levels are associated with obesity, metabolic syndrome, type 2 diabetes mellitus and altered lipid profiles, thus contributing to increased cardiovascular disease risk. Hence T deficiency has a detrimental effect on men's vascular health, quality of life and increased mortality. Objectives: This review aims to present summary of data in the contemporary clinical literature pertaining to the benefits of T therapy in clinical studies with varying durations on vascular health in men with T deficiency. Methods: A Medline search using PubMed and EMBASE was performed using the following key words: "testosterone deficiency," "testosterone therapy," major cardiovascular adverse events", "cardiovascular disease". Relevant studies were extracted, evaluated, and analyzed. We evaluated findings from clinical trials, observational studies and systematic reviews and meta-analyses to develop a comprehensive account of the critical role of T in maintaining vascular health. Results: Considerable evidence beginning with studies published in 1940s concomitant with findings from the utmost recent clinical studies suggests a clinical value of T therapy in maintaining vascular health and reducing cardiovascular mortality. The current scientific and clinical evidence demonstrates strong relationship between low circulating T levels and risk of cardiovascular disease and T therapy is deemed safe in men with hypogonadism when given in the physiological range with no apparent harm. Conclusion: What emerges from the current clinical literature is that, irrespective of the length of study durations, testosterone therapy provides significant health benefits and reduces risk of cardiovascular disease. More important is that data from many observational and registry studies, demonstrated that longer durations of testosterone therapy were associated with greater health benefits and reduced cardiovascular risk. T therapy in men with T deficiency reduces the incidence of major adverse cardiovascular events attributed to improving overall metabolic function.
MeSH term(s)	Male ; Humans ; Testosterone ; Cardiovascular Diseases/etiology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Quality of Life ; Hypogonadism/complications ; Hypogonadism/drug therapy
Chemical Substances	Testosterone (3XMK78S47O)
Language	English
Publishing date	2023-08-16
Publishing country	Netherlands
Document type	Review ; Journal Article
ZDB-ID	2722257-3
ISSN	2050-0521 ; 2050-0513
ISSN (online)	2050-0521
ISSN	2050-0513
DOI	10.1093/sxmrev/qead031
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Article ; Online: Sex steroids and COVID-19 mortality in women.

Traish, Abdulmaged M

Trends in endocrinology and metabolism: TEM

2021 Volume 32, Issue 8, Page(s) 533–536

Abstract: More men died of coronavirus disease 2019 (COVID-19) than women, suggesting estrogens may protect women. However, COVID-19 deaths among men and women were inconsistent among countries throughout the world. Genetics, epigenetics, and inborn errors of ... ...

Abstract	More men died of coronavirus disease 2019 (COVID-19) than women, suggesting estrogens may protect women. However, COVID-19 deaths among men and women were inconsistent among countries throughout the world. Genetics, epigenetics, and inborn errors of immunity may account for the disparity in mortality among men and women with COVID-19 more than sex steroid hormones.
MeSH term(s)	COVID-19 ; Female ; Gonadal Steroid Hormones ; Humans ; Male ; SARS-CoV-2 ; Sex Factors ; Steroids
Chemical Substances	Gonadal Steroid Hormones ; Steroids
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2021.04.006
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Article: Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm.

Traish, Abdulmaged M

The world journal of men's health

2020 Volume 38, Issue 3, Page(s) 323–337

Abstract: 5α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, ...

Abstract	5α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, the physiological role of 5α-DHT in human physiology, remains questionable and, at best, poorly appreciated. Recent emerging literature supports a role for 5α-DHT in the physiological function of liver, pancreatic β-cell function and survival, ocular function and prevention of dry eye disease and kidney physiological function. Thus, inhibition of 5α-reductases with finasteride or dutasteride to reduce 5α-DHT biosynthesis in the course of treatment of benign prostatic hyperplasia (BPH) or male pattern hair loss, known as androgenetic alopecia (AGA) my induces a novel form of tissue specific androgen deficiency and contributes to a host of pathophysiological conditions, that are yet to be fully recognized. Here, we advance the concept that blockade of 5α-reductases by finasteride or dutasteride in a mechanism-based, irreversible, inhabitation of 5α-DHT biosynthesis results in a novel state of androgen deficiency, independent of circulating testosterone levels. Finasteride and dutasteride are frequently prescribed for long-term treatment of lower urinary tract symptoms in men with BPH and in men with AGA. This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. We suggest that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease.
Language	English
Publishing date	2020-03-20
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2719786-4
ISSN	2287-4690 ; 2287-4208
ISSN (online)	2287-4690
ISSN	2287-4208
DOI	10.5534/wjmh.200012
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Post-finasteride syndrome: a surmountable challenge for clinicians.

Traish, Abdulmaged M

Fertility and sterility

2020 Volume 113, Issue 1, Page(s) 21–50

Abstract: Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic ... ...

Abstract	Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.
MeSH term(s)	5-alpha Reductase Inhibitors/adverse effects ; Alopecia/drug therapy ; Alopecia/physiopathology ; Clinical Trials as Topic/methods ; Finasteride/adverse effects ; Humans ; Male ; Observational Studies as Topic/methods ; Prostatic Hyperplasia/drug therapy ; Prostatic Hyperplasia/physiopathology ; Sexual Dysfunction, Physiological/chemically induced ; Sexual Dysfunction, Physiological/diagnosis ; Sexual Dysfunction, Physiological/physiopathology ; Syndrome ; Withholding Treatment/trends
Chemical Substances	5-alpha Reductase Inhibitors ; Finasteride (57GNO57U7G)
Language	English
Publishing date	2020-02-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80133-1
ISSN	1556-5653 ; 0015-0282
ISSN (online)	1556-5653
ISSN	0015-0282
DOI	10.1016/j.fertnstert.2019.11.030
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Article ; Online: Health Risks Associated with Long-Term Finasteride and Dutasteride Use

Abdulmaged M. Traish

The World Journal of Men's Health, Vol 38, Iss 3, Pp 323-

It’s Time to Sound the Alarm

2020 Volume 337

Abstract	5α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, the physiological role of 5α-DHT in human physiology, remains questionable and, at best, poorly appreciated. Recent emerging literature supports a role for 5α-DHT in the physiological function of liver, pancreatic b-cell function and survival, ocular function and prevention of dry eye disease and kidney physiological function. Thus, inhibition of 5α-reductases with finasteride or dutasteride to reduce 5α-DHT biosynthesis in the course of treatment of benign prostatic hyperplasia (BPH) or male pattern hair loss, known as androgenetic alopecia (AGA) my induces a novel form of tissue specific androgen deficiency and contributes to a host of pathophysiological conditions, that are yet to be fully recognized. Here, we advance the concept that blockade of 5α-reductases by finasteride or dutasteride in a mechanism-based, irreversible, inhabitation of 5α-DHT biosynthesis results in a novel state of androgen deficiency, independent of circulating testosterone levels. Finasteride and dutasteride are frequently prescribed for long-term treatment of lower urinary tract symptoms in men with BPH and in men with AGA. This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. We suggest that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease.
Keywords	diabetes mellitus ; dry eye syndromes ; hypogonadism ; kidney diseases ; non-alcoholic fatty liver disease ; 5-alpha reductase inhibitors ; Medicine ; R ; Diseases of the genitourinary system. Urology ; RC870-923
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Korean Society for Sexual Medicine and Andrology
Document type	Article ; Online
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Article ; Online: Letter to the editor: Questioning the evidence behind the Saturation Model for testosterone replacement therapy in prostate cancer.

Morgentaler, Abraham / Traish, Abdulmaged M

Investigative and clinical urology

2020 Volume 61, Issue 4, Page(s) 452–454

MeSH term(s)	Androgens ; Hormone Replacement Therapy/adverse effects ; Humans ; Male ; Prostatic Neoplasms/drug therapy ; Testosterone
Chemical Substances	Androgens ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2020-06-29
Publishing country	Korea (South)
Document type	Letter ; Comment
ZDB-ID	2923014-7
ISSN	2466-054X ; 2466-0493
ISSN (online)	2466-054X
ISSN	2466-0493
DOI	10.4111/icu.2020.61.4.452
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Article: Negative Impact of Testosterone Deficiency and 5α-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men.

Traish, Abdulmaged M

Advances in experimental medicine and biology

2017 Volume 1043, Page(s) 473–526

Abstract: Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent ... ...

Abstract	Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent metabolite 5α-dihydrotestosterone (5α-DHT) or via aromatization into estradiol (E
MeSH term(s)	5-alpha Reductase Inhibitors/adverse effects ; Energy Metabolism/drug effects ; Health Status ; Hormone Replacement Therapy/adverse effects ; Humans ; Hypogonadism/blood ; Hypogonadism/chemically induced ; Hypogonadism/drug therapy ; Hypogonadism/physiopathology ; Male ; Quality of Life ; Risk Factors ; Sex Factors ; Sexual Behavior/drug effects ; Sexual Dysfunction, Physiological/chemically induced ; Sexual Dysfunction, Physiological/physiopathology ; Sexual Dysfunction, Physiological/psychology ; Sexual Dysfunctions, Psychological/chemically induced ; Sexual Dysfunctions, Psychological/physiopathology ; Sexual Dysfunctions, Psychological/psychology ; Testosterone/adverse effects ; Testosterone/blood ; Testosterone/deficiency
Chemical Substances	5-alpha Reductase Inhibitors ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-70178-3_22
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Article ; Online: Benefits and Health Implications of Testosterone Therapy in Men With Testosterone Deficiency.

Traish, Abdulmaged M

Sexual medicine reviews

2017 Volume 6, Issue 1, Page(s) 86–105

Abstract: ... Traish AM. Benefits and Health Implications of Testosterone Therapy in Men With Testosterone Deficiency ...

Abstract	Introduction: Testosterone (T) deficiency (TD; hypogonadism) has deleterious effects on men's health; negatively affects glycometabolic and cardiometabolic functions, body composition, and bone mineral density; contributes to anemia and sexual dysfunction; and lowers quality of life. T therapy (TTh) has been used for the past 8 decades to treat TD, with positive effects on signs and symptoms of TD. Aim: To summarize the health benefits of TTh in men with TD. Methods: A comprehensive literature search was carried out using PubMed, articles relevant to TTh were accessed and evaluated, and a comprehensive summary was synthesized. Main outcome measures: Improvements in signs and symptoms of TD reported in observational studies, registries, clinical trials, and meta-analyses were reviewed and summarized. Results: A large body of evidence provides significant valuable information pertaining to the therapeutic value of TTh in men with TD. TTh in men with TD provides real health benefits for bone mineral density, anemia, sexual function, glycometabolic and cardiometabolic function, and improvements in body composition, anthropometric parameters, and quality of life. Conclusion: TTh in the physiologic range for men with TD is a safe and effective therapeutic modality and imparts great benefits on men's health and quality of life. Traish AM. Benefits and Health Implications of Testosterone Therapy in Men With Testosterone Deficiency. Sex Med Rev 2018;6:86-105.
MeSH term(s)	Androgens/therapeutic use ; Clinical Protocols ; Evidence-Based Medicine ; Hormone Replacement Therapy ; Humans ; Hypogonadism/drug therapy ; Hypogonadism/physiopathology ; Male ; Quality of Life ; Sexual Dysfunction, Physiological/drug therapy ; Testosterone/deficiency ; Testosterone/therapeutic use
Chemical Substances	Androgens ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2017-11-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2722257-3
ISSN	2050-0521 ; 2050-0513
ISSN (online)	2050-0521
ISSN	2050-0513
DOI	10.1016/j.sxmr.2017.10.001
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Article ; Online: Testosterone therapy in men with testosterone deficiency: are the benefits and cardiovascular risks real or imagined?

Traish, Abdulmaged M

American journal of physiology. Regulatory, integrative and comparative physiology

2016 Volume 311, Issue 3, Page(s) R566–73

Abstract: In the adult male, testosterone (T) deficiency (TD) also known as male hypogonadism, is a well-established medical condition, which has been recognized for more than a century. T therapy in men with TD was introduced as early as 1940s and was reported to ...

Abstract	In the adult male, testosterone (T) deficiency (TD) also known as male hypogonadism, is a well-established medical condition, which has been recognized for more than a century. T therapy in men with TD was introduced as early as 1940s and was reported to improve overall health with no concomitant serious adverse effects. A wealth of recent studies demonstrated that T therapy in men with TD is associated with increased lean body mass, reduced fat mass and waist circumference, improvement in glycemic control, and reduced obesity. T therapy is also associated with improvements in lipid profiles, amelioration of metabolic syndrome (Met S) components, reduced inflammatory biomarkers, reduced systolic and diastolic blood pressure, and improvements in sexual function. More importantly, T therapy is associated with amelioration of diabetes and reduced mortality. However, few studies, marred with serious methodological and analytical flaws reported between 2010 and 2014, suggested that T therapy is associated with increased cardiovascular (CV) risk. As summarized in this review, a thorough and critical analysis of these studies showed that the risks purported are unsubstantiated and such studies lacked credible scientific and clinical evidence. Moreover, recent observational, registry studies, clinical trials, and meta-analyses, all revealed no increase in CV risks in men receiving T therapy. In this review, the benefits of T therapy in adult men with TD and the lack of credible evidence suggesting that T therapy is linked to increased CV risks are discussed. It should be noted that the literature is replete with studies demonstrating beneficial effects of T therapy on CV and overall health.
MeSH term(s)	Aged ; Aged, 80 and over ; Cardiovascular Diseases/mortality ; Causality ; Comorbidity ; Hormone Replacement Therapy/mortality ; Humans ; Hypogonadism/drug therapy ; Hypogonadism/mortality ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Survival Rate ; Testosterone/deficiency ; Testosterone/therapeutic use ; Treatment Outcome
Chemical Substances	Testosterone (3XMK78S47O)
Language	English
Publishing date	2016-08-03
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00174.2016
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Article ; Online: A Critique of the AUA Guidelines on Testosterone Deficiency.

Morgentaler, Abraham / Traish, Abdulmaged M / Khera, Mohit

The journal of sexual medicine

2019 Volume 17, Issue 4, Page(s) 561–564

MeSH term(s)	Societies, Medical ; Testosterone ; Urology
Chemical Substances	Testosterone (3XMK78S47O)
Language	English
Publishing date	2019-12-04
Publishing country	Netherlands
Document type	Journal Article ; Comment
ZDB-ID	2251959-2
ISSN	1743-6109 ; 1743-6095
ISSN (online)	1743-6109
ISSN	1743-6095
DOI	10.1016/j.jsxm.2019.10.019
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