Special Issue "Testosterone and Men’s Health: From Evidence to Clinical Practice"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (28 February 2019).

Special Issue Editors

Prof. Dr. Du Geon Moon
E-Mail Website
Guest Editor
Department of Urology, Korea University Guro Hospital, #80, Guro-dong, Guro-ku, Seoul 152-703, Korea
Interests: sexual function in men and women; men’s health and TRT; nocturia; laser in prostate and endoscopic surgery; regenerative medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Hyun Jun Park
E-Mail Website
Guest Editor
Department of Urology, Pusan National University College of Medicine, Pusan, Korea
Interests: male sexual health and dysfunction; male infertility; hormonal regulation of male reproduction and hypogonadism; prostate diseases and male voiding dysfunctions; healthy aging and anti-aging treatments
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since the personal expert opinion of Dr. Morales in 1996, ‘Clinical practice guidelines for screening and monitoring male patients receiving testosterone supplementation therapy’ in the treatment of ED, great amount of new informations has been accumulated for the management of androgen deficiency, traditionally, most testosterone replacement has been applied for primary hypogonadism. Recently, TRT (Testosterone Replacement Therapy) has been increased from the development of safe, effective non-alkylated preparations and increased life expectancy with secondary hypogonadism of LOH (Late Onset Hypogonadism). From the first official recommendations of ISSAM 2002, the official recommendations on the diagnosis, treatment and monitoring of hypogonadism in men has evolved due to there being more evidence. ISSAM released updates in 2004, 2008 and 2014 in conjunction with ISA (International Society for Andrology), EAU (European Association of Urology), EAA (European Association of Andrology) and ASA (American Society for Andrology).

The diagnosis of late-onset testosterone deficiency is based on the presence of symptoms or signs and persistent low serum testosterone levels. However, we still do not have accurate measurement of serum testosterone level and no diagnostic questionnaire. Furthermore, safety concerns of TRT regarding the prostate and cardiovascular system are problematic. The benefits and risks of testosterone therapy must be clearly discussed with the patient and assessment of prostate and other risk factors considered before commencing testosterone treatment. Response to testosterone treatment should be assessed. If there is no improvement of symptoms and signs, treatment should be withdrawn and the patient investigated for other possible causes of the clinical presentations.

Clinically, urologists are at the center of TRT due to the closer association of sexual symptoms with testosterone and concern of prostate safety after TRT. We should recognize the differences between endocrinological and uroandrological points of view, and be more interested in the systemic manifestation of TRT for better clinical practice in the era of men’s health.

The following topics will be discussed in our special issue:

Testosterone and Insulin Resistance, Diabetes
Testosterone and Brain, Cognitive Function
Testosterone and Physical Performance
Testosterone and Bone Metabolism
Testosterone and Lipid Metabolism
Optimal Indication of Testosterone Replacement Therapy?
How to Select Optimal Regimen for Testosterone Replacement Therapy?
Emerging Evidences in Long Standing Controversies about Testosterone Replacement Therapy
(I) Cardiovascular Issues
(II) Prostate Issues
What is the Goal of TRT: Testosterone Level or Symptom?
Evolving Concept of TRT Guideline

Prof. Dr. Du Geon Moon
Prof. Dr. Hyun Jun Park
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Testosterone replacement
  • Hypogonadism
  • Late onset hypogonadism
  • Prostate
  • Cardiovascular disease
  • Diagnosis
  • Treatment

Published Papers (7 papers)

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Editorial

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Editorial
Evolution of Guidelines for Testosterone Replacement Therapy
J. Clin. Med. 2019, 8(3), 410; https://doi.org/10.3390/jcm8030410 - 25 Mar 2019
Cited by 18 | Viewed by 2646
Abstract
Testosterone is an essential hormone required for the developmental growth and maintenance of the male phenotype during the whole life. With the increasing male life expectancy worldwide and development of adequate testosterone preparations, the prescription of testosterone has increased tremendously. Testosterone replacement should [...] Read more.
Testosterone is an essential hormone required for the developmental growth and maintenance of the male phenotype during the whole life. With the increasing male life expectancy worldwide and development of adequate testosterone preparations, the prescription of testosterone has increased tremendously. Testosterone replacement should be based on low serum testosterone and related clinical symptoms. In the last two decades, with the accumulation of data, official recommendations have evolved in terms of definition, diagnosis, treatment, and follow-up. In practice, it is better for physicians to follow the Institutional Official Recommendations or Clinical Practice Guideline for an adequate diagnosis and treatment of testosterone deficiency. Currently, four official recommendations are available for diagnosis and treatment of patients with testosterone deficiency. The inconsistencies in the guidelines merely create confusion among the physicians instead of providing clear information. Furthermore, there is no definite method to assess serum testosterone and clinical symptoms. In the era of active testosterone replacement therapy (TRT), physicians’ practice patterns should be consistent with the clinical practice guidelines to avoid the misuse of testosterone. In this review, the author introduces the evolution of clinical guidelines to provide a comprehensive understanding of the differences and controversies with respect to TRT. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
Editorial
The Ideal Goal of Testosterone Replacement Therapy: Maintaining Testosterone Levels or Managing Symptoms?
J. Clin. Med. 2019, 8(3), 362; https://doi.org/10.3390/jcm8030362 - 14 Mar 2019
Cited by 1 | Viewed by 1048
Abstract
Typically, the goal of testosterone replacement therapy (TRT) is to restore blood testosterone to normal levels [...] Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)

Research

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Article
Predictive Factors of Efficacy Maintenance after Testosterone Treatment Cessation
J. Clin. Med. 2019, 8(2), 151; https://doi.org/10.3390/jcm8020151 - 29 Jan 2019
Cited by 1 | Viewed by 1235
Abstract
There is no conclusive evidence as to whether patients with testosterone deficiency (TD) who benefit from testosterone treatment (TRT) must continue the treatment for the rest of their lives. In some patients, the effect of TRT does not maintained after stopping TRT and, [...] Read more.
There is no conclusive evidence as to whether patients with testosterone deficiency (TD) who benefit from testosterone treatment (TRT) must continue the treatment for the rest of their lives. In some patients, the effect of TRT does not maintained after stopping TRT and, some patients show no significant TD symptoms, with normal testosterone levels after TRT cessation. Therefore, we investigated the predictive factors of response maintenance after TRT cessation. A total of 151 men with TD who responded to TRT were followed up for six months after TRT discontinuation. Ninety-two patients (Group I) failed to show response maintenance; 59 patients (Group II) had a maintained response. The groups did not differ in baseline characteristics or the type of TRT (oral, gel, short/long-acting injectables). However, TRT duration was significantly longer (10.7 vs. 5.2 months), and peak total testosterone (TT) level was significantly higher (713.7 vs. 546.1 ng/dL), in Group II than in Group I. More patients regularly exercised in Group II than in Group I (45.8% vs. 9.8%, p < 0.001). A multivariate logistic regression analysis revealed that exercise (B = 2.325, odds ratio = 10.231, p < 0.001) and TRT duration (B = 0.153, Exp(B) = 1.166, p < 0.001) were independent predictive factors of response maintenance. In men with TD who respond to TRT, longer treatment periods can improve the response durability after TRT cessation, regardless of the type of TRT. Additionally, regular exercise can increase the probability of maintaining the response after TRT cessation. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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Article
Evidence for a Common Genetic Origin of Classic and Milder Adult-Onset Forms of Isolated Hypogonadotropic Hypogonadism
J. Clin. Med. 2019, 8(1), 126; https://doi.org/10.3390/jcm8010126 - 21 Jan 2019
Cited by 22 | Viewed by 2097
Abstract
Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism (IHH) in males, whereas classic IHH is a rare congenital condition with a strong genetic background. Since we recently uncovered a frequent familiarity for classic IHH among patients [...] Read more.
Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism (IHH) in males, whereas classic IHH is a rare congenital condition with a strong genetic background. Since we recently uncovered a frequent familiarity for classic IHH among patients with mild adult-onset hypogonadism (AO-IHH), here we performed a genetic characterization by next generation sequencing of 160 males with classic or “functional” forms. The prevalence of rare variants in 28 candidate genes was significantly higher than in controls in all IHH patients, independently of the age of IHH onset, degree of hypogonadism or presence of obesity. In fact, it did not differ among patients with classic or milder forms of IHH, however particular genes appear to be more specifically associated with one or the other category of IHH. ROC curves showed that Total Testosterone <6.05 nmol/L and an age of onset <41 years are sensitive cutoffs to identify patients with significantly higher chances of harboring rare IHH gene variants. In conclusion, rare IHH genes variants can frequently predispose to AO-IHH with acquired mild hormonal deficiencies. The identification of a genetic predisposition can improve the familial and individual management of AO-IHH and explain the heritability of congenital IHH. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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Review

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Review
The Optimal Indication for Testosterone Replacement Therapy in Late Onset Hypogonadism
J. Clin. Med. 2019, 8(2), 209; https://doi.org/10.3390/jcm8020209 - 07 Feb 2019
Cited by 9 | Viewed by 1949
Abstract
The use of testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH) is increasing every year; however, the literature shows that many men are using testosterone (T) without a clear indication. Previous studies have estimated that up to 25% of men who receive TRT [...] Read more.
The use of testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH) is increasing every year; however, the literature shows that many men are using testosterone (T) without a clear indication. Previous studies have estimated that up to 25% of men who receive TRT do not have their T tested prior to initiation of the therapy. Given the growing concern and need for proper TRT, clinicians need evidence-based information that informs them on the optimal indication for TRT in LOH patients. The diagnosis of LOH requires the presence of characteristic signs and symptoms, in combination with decreased serum total testosterone (TT). Based on the recent guidelines by the International Society for the Study of Aging Male (ISSAM), the European Association of Urology (EAU), the European Society of Endocrinology (ESE), the European Academy of Andrology (EAA), and the American Association of Urology (AUA), a TT of 250–350 ng/dL is the proper threshold value to define low T. The optimal indication for TRT in LOH is the presence of signs and symptoms of hypogonadism, and low T without contraindications for TRT. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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Review
Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events
J. Clin. Med. 2019, 8(1), 11; https://doi.org/10.3390/jcm8010011 - 21 Dec 2018
Cited by 11 | Viewed by 2407
Abstract
In our sequential studies of 67 and 21 patients, testosterone therapy (TT) interacted with thrombophilia–hypofibrinolysis, leading to venous thromboembolism (VTE). Compared to 111 VTE controls not taking TT (VTE-no TT), the 67 and 21 cases were more likely (p < 0.05 for [...] Read more.
In our sequential studies of 67 and 21 patients, testosterone therapy (TT) interacted with thrombophilia–hypofibrinolysis, leading to venous thromboembolism (VTE). Compared to 111 VTE controls not taking TT (VTE-no TT), the 67 and 21 cases were more likely (p < 0.05 for all) to have Factor V Leiden (FVL) heterogeneity (24% and 33% vs. 12%), the lupus anticoagulant (14% and 33% vs. 4%), and high lipoprotein(a) (33% vs. 13%, n = 21). After a first VTE and continuing TT, 11 thrombophilic cases had a second VTE despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third VTE. The greatest density of thrombotic events was at three months after starting TT, with a rapid decline by 10 months. From <1 to 8 months after starting TT, 65% of VTE occurred, which may reflect TT-induced depletion of susceptible thrombophilic patients, leaving a winnowed residual group with fewer VTE events despite the continuation of TT. Before starting TT, we suggest screening for FVL, lipoprotein(a), and the lupus anticoagulant to identify patients at increased VTE risk, with an adverse risk-to-benefit ratio for TT. We suggest that TT should not be started in patients with known thrombophilia–hypofibrinolysis, and should not be continued after a first VTE. When TT is given to patients with thrombophilia–hypofibrinolysis, VTE may occur and then recur despite adequate anticoagulation. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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Review
Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence
J. Clin. Med. 2018, 7(12), 549; https://doi.org/10.3390/jcm7120549 - 14 Dec 2018
Cited by 44 | Viewed by 3296
Abstract
The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, [...] Read more.
The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, including the following key words: “testosterone”, “androgens”, “inflammatory cytokines”, “inflammatory biomarkers” with focus on clinical studies as well as basic scientific studies in human and animal models. Significant benefits of testosterone therapy in ameliorating or attenuating the symptoms of several chronic inflammatory diseases were reported. Because anti–tumor necrosis factor therapy is the mainstay for the treatment of moderate-to-severe inflammatory bowel disease; including Crohn’s disease and ulcerative colitis, and because testosterone therapy in hypogonadal men with chronic inflammatory conditions reduce tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6, we suggest that testosterone therapy attenuates the inflammatory process and reduces the burden of disease by mechanisms inhibiting inflammatory cytokine expression and function. Mechanistically, androgens regulate the expression and function of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and CRP (C-reactive protein). Here, we suggest that testosterone regulates multiple and overlapping cellular and molecular pathways involving a host of immune cells and biochemical factors that converge to contribute to attenuation of the inflammatory process. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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