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Andrology Nov 2020The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed... (Review)
Review
BACKGROUND
The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal and intramuscular (IM).
OBJECTIVES
The aim of this narrative review was to describe and compare all available and approved testosterone preparations according to pharmacology, PKs and adverse effects.
MATERIALS AND METHODS
We have performed an extensive PubMed review of the literature on TRT in clinical practice. Contraindications and monitoring of TRT were analyzed by comparing available guidelines released in the last five years. We provide a review of advantages and disadvantages of different modalities of TRT and how to monitor treatment to minimize the risks.
RESULTS
TRT is associated with multiple benefits highly relevant to the patient. However, the recommendations given in different guidelines on TRT are based on data from a limited number of randomized controlled trials (RCTs), as well as non-randomized clinical studies and observational studies. This is the case for the safety of a long-term TRT in late-onset hypogonadism (LOH). No evidence is provided indeed on the effects of TRT on endpoints such as deterioration of heart failure suggesting a cautious approach to T replacement in older men with a history of heart failure.
CONCLUSION
Clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of LOH in order to provide the safest and most beneficial results.
Topics: Clinical Decision-Making; Dosage Forms; Drug Administration Routes; Drug Compounding; Eunuchism; Hormone Replacement Therapy; Humans; Male; Risk Assessment; Risk Factors; Testosterone; Treatment Outcome
PubMed: 32068334
DOI: 10.1111/andr.12774 -
Biomolecules Oct 2018Enhancing and protecting testosterone production is one target for many scientists because of its crucial role as a primary sex hormone in males. Several in vivo trials... (Review)
Review
Enhancing and protecting testosterone production is one target for many scientists because of its crucial role as a primary sex hormone in males. Several in vivo trials have utilized different dietary supplements and medicinal plants to enhance testosterone production in males. Since 1991, various in-vivo, as well as basic research studies, have discovered a link between ginger () and testosterone. However, such a link has not yet been collectively reviewed. This review systematically discusses and summarizes the effect of ginger and ginger extracts on testosterone. To achieve this contribution, we searched the PubMed, Scopus, and Web of Science databases for English language articles (full texts or abstracts) from November 1991 through August 2018 using the keywords "ginger" and "" versus "testosterone". Additionally, the references from related published articles were also reviewed, only if relevant. In conclusion, the mainstream of research that links ginger to testosterone demonstrated that ginger supplementation, particularly in oxidative stress conditions, enhances testosterone production in males. The mechanisms by which this occurs mainly by enhancing luteinizing hormone (LH) production, increasing the level of cholesterol in the testes, reducing oxidative stress and lipid peroxidation in the testes, enhancing the activity of the antioxidant enzymes, normalizing blood glucose, increasing blood flow in the testes, increasing testicular weight, and recycling testosterone receptors. However, the effect of ginger on testosterone is not yet confirmed in humans. Therefore, clinical studies in this context of research are imperative.
Topics: Animals; Zingiber officinale; Humans; Plant Extracts; Testosterone
PubMed: 30360442
DOI: 10.3390/biom8040119 -
Nature Reviews. Disease Primers May 2019The hypothalamic-pituitary-gonadal axis is of relevance in many processes related to the development, maturation and ageing of the male. Through this axis, a cascade of... (Review)
Review
The hypothalamic-pituitary-gonadal axis is of relevance in many processes related to the development, maturation and ageing of the male. Through this axis, a cascade of coordinated activities is carried out leading to sustained testicular endocrine function, with gonadal testosterone production, as well as exocrine function, with spermatogenesis. Conditions impairing the hypothalamic-pituitary-gonadal axis during paediatric or pubertal life may result in delayed puberty. Late-onset hypogonadism is a clinical condition in the ageing male combining low concentrations of circulating testosterone and specific symptoms associated with impaired hormone production. Testosterone therapy for congenital forms of hypogonadism must be lifelong, whereas testosterone treatment of late-onset hypogonadism remains a matter of debate because of unclear indications for replacement, uncertain efficacy and potential risks. This Primer focuses on a reappraisal of the physiological role of testosterone, with emphasis on the critical interpretation of the hypogonadal conditions throughout the lifespan of the male individual, with the exception of hypogonadal states resulting from congenital disorders of sex development.
Topics: Adult; Age Factors; Child; Humans; Hypogonadism; Male; Testosterone
PubMed: 31147553
DOI: 10.1038/s41572-019-0087-y -
Endocrine Reviews Oct 2018Elite athletic competitions have separate male and female events due to men's physical advantages in strength, speed, and endurance so that a protected female category... (Review)
Review
Elite athletic competitions have separate male and female events due to men's physical advantages in strength, speed, and endurance so that a protected female category with objective entry criteria is required. Prior to puberty, there is no sex difference in circulating testosterone concentrations or athletic performance, but from puberty onward a clear sex difference in athletic performance emerges as circulating testosterone concentrations rise in men because testes produce 30 times more testosterone than before puberty with circulating testosterone exceeding 15-fold that of women at any age. There is a wide sex difference in circulating testosterone concentrations and a reproducible dose-response relationship between circulating testosterone and muscle mass and strength as well as circulating hemoglobin in both men and women. These dichotomies largely account for the sex differences in muscle mass and strength and circulating hemoglobin levels that result in at least an 8% to 12% ergogenic advantage in men. Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases. Based on the nonoverlapping, bimodal distribution of circulating testosterone concentration (measured by liquid chromatography-mass spectrometry)-and making an allowance for women with mild hyperandrogenism, notably women with polycystic ovary syndrome (who are overrepresented in elite athletics)-the appropriate eligibility criterion for female athletic events should be a circulating testosterone of <5.0 nmol/L. This would include all women other than those with untreated hyperandrogenic disorders of sexual development and noncompliant male-to-female transgender as well as testosterone-treated female-to-male transgender or androgen dopers.
Topics: Athletes; Athletic Performance; Female; Humans; Male; Sex Characteristics; Testosterone
PubMed: 30010735
DOI: 10.1210/er.2018-00020 -
Cold Spring Harbor Perspectives in... Jan 2018Osteoporosis is a significant public health problem, and a major cause of the disease is estrogen deficiency following menopause in women. In addition, considerable... (Review)
Review
Osteoporosis is a significant public health problem, and a major cause of the disease is estrogen deficiency following menopause in women. In addition, considerable evidence now shows that estrogen is also a major regulator of bone metabolism in men. Since the original description of the effects of estrogen deficiency on bone by Fuller Albright more than 70 years ago, there has been enormous progress in understanding the mechanisms of estrogen and testosterone action on bone using human and mouse models. Although we understand more about the effects of estrogen on bone as compared with testosterone, both sex steroids do play important roles, perhaps in a somewhat compartment-specific (i.e., cancellous vs. cortical bone) manner. This review summarizes our current knowledge of sex steroid action on bone based on human and mouse studies, identifies both agreements and potential discrepancies between these studies, and suggests directions for future research in this important area.
Topics: Animals; Bone Density; Bone and Bones; Disease Models, Animal; Estrogens; Female; Humans; Male; Mice; Observational Studies as Topic; Osteoporosis; Testosterone
PubMed: 28710257
DOI: 10.1101/cshperspect.a031211 -
The Journal of Clinical Endocrinology... Oct 2019This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International...
This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women's Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynecologists.
Topics: Androgens; Female; Humans; Off-Label Use; Postmenopause; Premenopause; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Testosterone
PubMed: 31498871
DOI: 10.1210/jc.2019-01603 -
Andrology Nov 2020Testosterone plays a pivotal role in maintaining balance within the multi-dimensional psychological network of mood, behaviour, self-perception and perceived quality of... (Review)
Review
Testosterone plays a pivotal role in maintaining balance within the multi-dimensional psychological network of mood, behaviour, self-perception and perceived quality of life in men of any age. Apart from classical forms of hypogonadism, low testosterone concentrations can also be seen in older men, described as an age- and comorbidity-driven functional hypogonadism and might relate to depressive symptoms exhibiting a wide array of clinical pictures ranging from dysthymia and fatigue over inertia, listlessness to hopelessness and suicidal thoughts. Also, various traits of anxiety, from unfocussed fear to phobic anxiousness and open panic syndromes, are influenced by testosterone. Correspondingly, anxiolysis is likely to be modulated by testosterone via stress resilience, threat vigilance and reward processing. The steroid modulates pro-active and re-active dimensions of aggression, which has to be seen within the context of gaining or maintaining status. This may also include other strategies impacting the social position: heroic or parochial altruism and non-aggressive paths of assertiveness, such as posture and social vigilance. Independent rather than relationship-associated self-construal and self-esteem influence risk-taking traits under the modulation of testosterone. In addition, the genetic setting of the androgen receptor modulates the role of testosterone in aspects regarding mood and personality. Dimensions of sexuality are rather important in this context, but are not target of this article and covered in another part of this special edition. Overall, the quality of life in older hypogonadal men can be positively influenced by testosterone substitution, as has been demonstrated in large placebo-controlled trials.
Topics: Affect; Age of Onset; Animals; Behavior; Biomarkers; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Mental Health; Quality of Life; Receptors, Androgen; Testosterone; Testosterone Congeners
PubMed: 32657051
DOI: 10.1111/andr.12867 -
Endocrine Reviews Aug 2017In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution,... (Review)
Review
In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.
Topics: Humans; Serum Albumin, Human; Sex Hormone-Binding Globulin; Testosterone; Transcortin
PubMed: 28673039
DOI: 10.1210/er.2017-00025 -
Medicina (Kaunas, Lithuania) Aug 2022: Male hypogonadism is a clinical disorder characterized by reduced serum testosterone in men. Although treatment using herbal medicines, including has been... (Review)
Review
: Male hypogonadism is a clinical disorder characterized by reduced serum testosterone in men. Although treatment using herbal medicines, including has been investigated, the benefits remain unclear. This study aims to investigate the efficacy of as a sole intervention to increase testosterone levels in males. : We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the PRISMA guidelines. Relevant articles were retrieved from the databases PubMed, Scopus, Web of Science, Cochrane, Ovid/Embase, and Google Scholar. After literature screening, a total of nine studies was included in the systematic review. Five RCTs were included in the meta-analysis. A significant improvement in total testosterone levels after treatment was mostly reported in both healthy volunteers and hypogonadal men. The random model effect revealed a significant increase (SMD = 1.352, 95% CI 0.565 to 2.138, = 0.001) in the total testosterone levels in men receiving supplementation, which was confirmed in the hypogonadism subgroup. : This systematic review and meta-analysis of the literature supports the possible use of supplementation for enhancing testosterone production. Although more research is required before its use in clinical practice, this may represent a safe and promising therapeutic option, particularly in hypogonadal men.
Topics: Eurycoma; Humans; Hypogonadism; Male; Plant Extracts; Plants, Medicinal; Testosterone
PubMed: 36013514
DOI: 10.3390/medicina58081047 -
Endocrine Reviews Jun 2018The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled, double-blind trials in 788 men with a mean age of 72 years to determine the...
The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled, double-blind trials in 788 men with a mean age of 72 years to determine the efficacy of increasing the testosterone levels of older men with low testosterone. Testosterone treatment increased the median testosterone level from unequivocally low at baseline to midnormal for young men after 3 months and maintained that level until month 12. In the Sexual Function Trial, testosterone increased sexual activity, sexual desire, and erectile function. In the Physical Function Trial, testosterone did not increase the distance walked in 6 minutes in men whose walk speed was slow; however, in all TTrial participants, testosterone did increase the distance walked. In the Vitality Trial, testosterone did not increase energy but slightly improved mood and depressive symptoms. In the Cognitive Function Trial, testosterone did not improve cognitive function. In the Anemia Trial, testosterone increased hemoglobin in both men who had anemia of a known cause and in men with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral density and the estimated strength of the spine and hip. In the Cardiovascular Trial, testosterone increased the coronary artery noncalcified plaque volume as assessed using computed tomographic angiography. Although testosterone was not associated with more cardiovascular or prostate adverse events than placebo, a trial of a much larger number of men for a much longer period would be necessary to determine whether testosterone increases cardiovascular or prostate risk.
Topics: Aged; Aging; Androgens; Controlled Clinical Trials as Topic; Hormone Replacement Therapy; Humans; Male; Outcome Assessment, Health Care; Testosterone
PubMed: 29522088
DOI: 10.1210/er.2017-00234