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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 -
Frontiers in Neuroendocrinology Jan 2014Compelling evidence exists for pervasive sex differences in pathological conditions, including anxiety and depressive disorders, with females more than twice as likely... (Review)
Review
Compelling evidence exists for pervasive sex differences in pathological conditions, including anxiety and depressive disorders, with females more than twice as likely to be afflicted. Gonadal hormones may be a major factor in this disparity, given that women are more likely to experience mood disturbances during times of hormonal flux, and testosterone may have protective benefits against anxiety and depression. In this review we focus on the effects of testosterone in males and females, revealed in both human and animal studies. We also present possible neurobiological mechanisms underlying testosterone's mostly protective benefits, including the brain regions, neural circuits, and cellular and molecular pathways involved. While the precise underlying mechanisms remain unclear, both activational and organizational effects of testosterone appear to contribute to these effects. Future clinical studies are necessary in order to better understand when and how testosterone therapy may be effective in both sexes.
Topics: Animals; Anxiety; Depression; Female; Humans; Male; Sex Characteristics; Signal Transduction; Testosterone
PubMed: 24076484
DOI: 10.1016/j.yfrne.2013.09.001 -
Hormones and Behavior Jan 2012Testosterone and other anabolic-androgenic steroids enhance athletic performance in men and women. As a result, exogenous androgen is banned from most competitive... (Review)
Review
Testosterone and other anabolic-androgenic steroids enhance athletic performance in men and women. As a result, exogenous androgen is banned from most competitive sports. However, due to variability in endogenous secretion, and similarities with exogenous testosterone, it has been challenging to establish allowable limits for testosterone in competition. Endogenous androgen production is dynamically regulated by both exercise and winning in competition. Furthermore, testosterone may promote athletic performance, not only through its long-term anabolic actions, but also through rapid effects on behavior. In women, excess production of endogenous testosterone due to inborn disorders of sexual development (DSD) may convey a competitive advantage. For many years, female competitors have been subject to tests of sexual genotype and phenotype known as gender verification. Although gender verification has not identified any normal man competing as a woman, this process has identified women athletes with DSD. As understanding of DSD has expanded in recent years, women with DSD are increasingly able to continue athletic competition.
Topics: Anabolic Agents; Athletic Performance; Doping in Sports; Epitestosterone; Female; Humans; Male; Sex Chromosome Aberrations; Sex Determination Analysis; Sex Differentiation; Testosterone
PubMed: 21983229
DOI: 10.1016/j.yhbeh.2011.09.010 -
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 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 -
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 -
The Journal of Clinical Endocrinology... Feb 2022Injections with intramuscular (IM) testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also...
CONTEXT
Injections with intramuscular (IM) testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous (SC) administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of SC testosterone therapy with both long- and ultralong-acting testosterone esters. In addition, we provide guidance for clinicians on how to counsel and manage their patients who opt for the SC route.
EVIDENCE ACQUISITION
Systematic review of available literature on SC testosterone administration including clinical trials, case series, and case reports. We also review the pharmacology of testosterone absorption after SC administration.
EVIDENCE SYNTHESIS
Available evidence, though limited, suggests that SC testosterone therapy in doses similar to those given via IM route results in comparable pharmacokinetics and mean serum testosterone levels. With appropriate training, patients should be able to safely self-administer testosterone esters SC with relative ease and less discomfort compared with the IM route.
CONCLUSION
Although studies directly comparing the safety of SC vs IM administration of testosterone esters are desirable, clinicians should consider discussing the SC route with their patients because it is easier to self-administer and has the potential to improve patient adherence.
Topics: Feasibility Studies; Female; Humans; Hypogonadism; Injections, Intramuscular; Injections, Subcutaneous; Male; Self Administration; Sex Reassignment Procedures; Testosterone; Transgender Persons
PubMed: 34698352
DOI: 10.1210/clinem/dgab772 -
ELife Oct 2020Testosterone products are prescribed to males for a variety of possible health benefits, but causal effects are unclear. Evidence from randomized trials are difficult to...
Testosterone products are prescribed to males for a variety of possible health benefits, but causal effects are unclear. Evidence from randomized trials are difficult to obtain, particularly regarding effects on long-term or rare outcomes. Mendelian randomization analyses were performed to infer phenome-wide effects of free testosterone on 461 outcomes in 161,268 males from the UK Biobank study. Lifelong increased free testosterone had beneficial effects on increased bone mineral density, and decreased body fat; adverse effects on decreased HDL, and increased risks of prostate cancer, androgenic alopecia, spinal stenosis, and hypertension; and context-dependent effects on increased hematocrit and decreased C-reactive protein. No benefit was observed for type 2 diabetes, cardiovascular or cognitive outcomes. Mendelian randomization suggests benefits of long-term increased testosterone should be considered against adverse effects, notably increased prostate cancer and hypertension. Well-powered randomized trials are needed to conclusively address risks and benefits of testosterone treatment on these outcomes.
Topics: Adult; Aged; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Phenotype; Risk Factors; Testosterone; United Kingdom
PubMed: 33063668
DOI: 10.7554/eLife.58914 -
Endocrine Journal Jul 2023Testosterone plays a key role in the maintenance of physical and mental functions in men. Age-related testosterone decline is closely associated with sarcopenia and...
Testosterone plays a key role in the maintenance of physical and mental functions in men. Age-related testosterone decline is closely associated with sarcopenia and muscle deterioration, while testosterone decline is linked with the etiology and prevention of diseases such as angina pectoris, arteriosclerosis, obesity, metabolic syndrome, and dementia. Late-onset hypogonadism (LOH) is defined as a disease characterized by age-related testosterone decline and associated clinical symptoms. Testosterone replacement therapy improves health-related QOL in patients with LOH.
Topics: Male; Humans; Testosterone; Men's Health; Quality of Life; Hypogonadism; Obesity; Hormone Replacement Therapy; Aging
PubMed: 37045775
DOI: 10.1507/endocrj.EJ22-0604 -
Urologic Oncology Aug 2020Often contraindicated because of the theoretical risk of progression based on the dogma of hormone dependent prostate cancer (CaP), testosterone replacement therapy...
Often contraindicated because of the theoretical risk of progression based on the dogma of hormone dependent prostate cancer (CaP), testosterone replacement therapy (TRT) is increasingly discussed and proposed for hypogonadal patients with localized CaP. To perform a systematic literature review to determine the relationship between TRT and the risk of CaP with a focus on the impact of TRT in the setting of previous or active localized CaP. As of October 15, 2019, systematic review was performed via Medline Embase and Cochrane databases in accordance with the PRISMA guidelines. All full text articles in English published from January 1994 to February 2018 were included. Articles were considered if they reported about the relationship between total testosterone or bioavailable testosterone and CaP. Emphasis was given to prospective studies, series with observational data and randomized controlled trials. Articles about the safety of the testosterone therapy were categorized by type of CaP management (active surveillance or curative treatment by radical prostatectomy, external radiotherapy or brachytherapy). Until more definitive data becomes available, clinicians wishing to treat their hypogonadal patients with localized CaP with TRT should inform them of the lack of evidence regarding the safety of long-term treatment for the risk of CaP progression. However, in patients without known CaP, the evidence seems sufficient to think that androgen therapy does not increase the risk of subsequent discovery of CaP.
Topics: Hormone Replacement Therapy; Humans; Male; Prostatic Neoplasms; Testosterone
PubMed: 32409202
DOI: 10.1016/j.urolonc.2020.04.008