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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 -
Best Practice & Research. Clinical... Jul 2022Androgens are essential sex steroid hormones for both sexes. Testosterone (T) is the predominant androgen in males, while in adult females, T concentrations are about... (Review)
Review
Androgens are essential sex steroid hormones for both sexes. Testosterone (T) is the predominant androgen in males, while in adult females, T concentrations are about 15-fold lower and androgen precursors are converted to estrogens. T is produced primarily in testicular Leydig cells in men, while in women precursors are biosynthesised in the adrenal cortex and ovaries and converted into T in the periphery. The biosynthesis of T occurs via a series of enzymatic reactions in steroidogenic organs. Notably, the more potent androgen, dihydrotestosterone, may be synthesized from T in the classic pathway, however, alternate metabolic pathways also exist. The classic action of androgens on target organs is mediated through the androgen receptor, which regulates nuclear receptor gene transcription. However, the androgen-androgen receptor complex may also interact directly with membrane proteins or signaling molecules to exert more rapid effects. This review summarizes the current knowledge of androgen biosynthesis, mechanisms of action and endocrine effects in human biology, and relates these effects to respective human congenital and acquired disorders.
Topics: Androgens; Estrogens; Female; Humans; Male; Receptors, Androgen; Testis; Testosterone
PubMed: 35595638
DOI: 10.1016/j.beem.2022.101665 -
Endocrinology and Metabolism Clinics of... Mar 2022All approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations, and relieve symptoms in most... (Review)
Review
All approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations, and relieve symptoms in most hypogonadal men. Selection of the method depends on the patient's preference with advice from the physician. Dose adjustment is possible with most delivery methods but may not be necessary in all hypogonadal men. The use of hepatotoxic androgens must be avoided. Testosterone treatment induces reversible suppression of spermatogenesis; if fertility is desired in the near future, human chronic gonadotropin, selective estrogen receptor modulator, estrogen antagonist, or an aromatase inhibitor that stimulates endogenous testosterone production may be used.
Topics: Androgens; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Spermatogenesis; Testosterone
PubMed: 35216722
DOI: 10.1016/j.ecl.2021.11.005 -
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 -
Andrology Mar 2022Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamic-pituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism.
METHODS
The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects.
RESULTS
We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported.
CONCLUSION
Clomiphene citrate is an effective therapy for improving both biochemical as well as clinical symptoms of males suffering from hypogonadism. Clomiphene citrate has few reported side effects and good safety aspects.
Topics: Clomiphene; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Testosterone
PubMed: 34933414
DOI: 10.1111/andr.13146 -
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 -
International Journal of Molecular... Jul 2022Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often... (Review)
Review
Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often leads to impaired testicular function and male subfertility. Several mechanisms may indeed negatively affect the hypothalamic-pituitary-gonadal health, such as higher testosterone conversion to estradiol by aromatase activity in the adipose tissue, increased ROS production, and the release of several endocrine molecules affecting the hypothalamus-pituitary-testis axis by both direct and indirect mechanisms. In addition, androgen deficiency could further accelerate adipose tissue expansion and therefore exacerbate obesity, which in turn enhances hypogonadism, thus inducing a vicious cycle. Based on these considerations, we propose an overview on the relationship of adipose tissue dysfunction and male hypogonadism, highlighting the main biological pathways involved and the current therapeutic options to counteract this condition.
Topics: Adipose Tissue; Humans; Hypogonadism; Insulin Resistance; Male; Obesity; Testis; Testosterone
PubMed: 35897769
DOI: 10.3390/ijms23158194 -
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 -
Endocrinology Mar 2020Studies show that a subset of transgender men desire children; however, there is a paucity of literature on the effect of gender-affirming testosterone therapy on... (Review)
Review
Studies show that a subset of transgender men desire children; however, there is a paucity of literature on the effect of gender-affirming testosterone therapy on reproductive function. In this manuscript, we will review the process of gender-affirming hormone therapy for transgender men and what is known about ovarian and uterine consequences of testosterone exposure in transgender men; draw parallels with existing animal models of androgen exposure; summarize the existing literature on parenting experiences and desires in transgender people; discuss considerations for assisted reproductive technologies and fertility preservation; and identify gaps in the literature and opportunities for further research.
Topics: Androgens; Animals; Female; Genitalia, Female; Humans; Male; Models, Animal; Reproduction; Sex Reassignment Procedures; Testosterone; Transgender Persons
PubMed: 32105330
DOI: 10.1210/endocr/bqaa014