madman
Super Moderator
Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations
Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasing worldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to the burden of extra-gonadal comorbidities such as obesity, diabetes, and metabolic syndrome, but with an underlying intact hypothalamic-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy and safety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, the accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey before achieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have been published specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism and test their respective recommendations against current best evidence.
INTRODUCTION
Male hypogonadism (MH)—termed testosterone (T) deficiency syndrome by some investigators—is a clinical syndrome characterized by impaired testicular function, with reduced or absent spermatogenesis and T secretion. It is caused either by disease at the level of the hypothalamus or pituitary gland (central, secondary, or hypogonadotropic hypogonadism [HH]), wherein the testes lack gonadotropic stimulation by luteinizing hormone (LH) and follicle-stimulating hormone, or an intrinsic defect of the testes themselves (primary hypogonadism [PH]), wherein the function Leydig and Sertoli and germ cells are intrinsically impaired (Fig. 1) [1].
The prevalence of MH has been estimated at 6% to 12%, depending on the study population and the degree of diagnostic rigor [2,3]. If untreated, MH can lead to sexual dysfunction, anemia, osteoporosis and fracture, myopathy and frailty, tender gynecomastia, psychosocial impairments, and reduced quality of life. There is also a strong association of MH with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) [4], although the direction of causation is unclear [5].
DEFINING MH CLINICALLY AND BIOCHEMICALLY
WHO TO SCREEN FOR MH?
SERUM T CUTOFF TO SUPPORT THE DIAGNOSIS OF MH
APPROACH TO LOW-BORDERLINE SERUM T VALUE
INDICATIONS FOR TESTOSTERONE TREATMENT
AGING, OBESITY, AND OTHER COMORBIDITIES
CAUSES OF HH THAT SHOULD NOT BE MISSED?
TESTOSTERONE TREATMENT AND ANDROGEN-SENSITIVE CANCERS
TESTOSTERONE AND CV DISEASE
MONITORING TESTOSTERONE THERAPY
CONCLUSIONS
Current national and international guidelines relating to MH are remarkably heterogeneous in respect of diagnostic, treatment, and monitoring criteria. Indeed, several guidelines do not even refer to MH as such, but rather to “testosterone deficiency.” Specifically, for men having low serum T associated with low or “inappropriately normal” gonadotropins (a biochemical fingerprint that is shared by both HH and NGI) guidelines vary hugely in the degree to which further evaluation for underlying local or systemic co-morbidities is indicated in order to identify a proximate cause or overarching diagnosis.
There are also major variances as to whether “functional HH” (or NGI) associated with obesity and metabolic syndrome should be considered for testosterone therapy, whether as a first-line treatment, second-line after a lifestyle change, or not at all. Crucially, although testosterone ameliorates some surrogate markers of CV risk such as lean body mass and biochemical metabolic profiles and also improves bone density and hematocrit, it does not greatly improve sexual function, physical or mental vitality. Indeed, there are persisting concerns relating to CV disease that may relate to a counterbalancing risk arising from a greater propensity to arterial thrombosis with rising hematocrit.
At the same time, many men with organic MH, who would be expected to benefit from testosterone treatment, continue to remain undiagnosed and untreated due to deficient basic and postgraduate medical training in sexual medicine. Indeed, the voices and perspective of patients affected by MH have been conspicuously lacking in relation to the process of drafting guidance. We hope this review will allow clinicians to navigate the field of MH with greater confidence and, thereby, offer the most appropriate and safe advice and management subject to limitations of the existing evidence base.
Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasing worldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to the burden of extra-gonadal comorbidities such as obesity, diabetes, and metabolic syndrome, but with an underlying intact hypothalamic-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy and safety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, the accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey before achieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have been published specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism and test their respective recommendations against current best evidence.
INTRODUCTION
Male hypogonadism (MH)—termed testosterone (T) deficiency syndrome by some investigators—is a clinical syndrome characterized by impaired testicular function, with reduced or absent spermatogenesis and T secretion. It is caused either by disease at the level of the hypothalamus or pituitary gland (central, secondary, or hypogonadotropic hypogonadism [HH]), wherein the testes lack gonadotropic stimulation by luteinizing hormone (LH) and follicle-stimulating hormone, or an intrinsic defect of the testes themselves (primary hypogonadism [PH]), wherein the function Leydig and Sertoli and germ cells are intrinsically impaired (Fig. 1) [1].
The prevalence of MH has been estimated at 6% to 12%, depending on the study population and the degree of diagnostic rigor [2,3]. If untreated, MH can lead to sexual dysfunction, anemia, osteoporosis and fracture, myopathy and frailty, tender gynecomastia, psychosocial impairments, and reduced quality of life. There is also a strong association of MH with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) [4], although the direction of causation is unclear [5].
DEFINING MH CLINICALLY AND BIOCHEMICALLY
WHO TO SCREEN FOR MH?
SERUM T CUTOFF TO SUPPORT THE DIAGNOSIS OF MH
APPROACH TO LOW-BORDERLINE SERUM T VALUE
INDICATIONS FOR TESTOSTERONE TREATMENT
AGING, OBESITY, AND OTHER COMORBIDITIES
CAUSES OF HH THAT SHOULD NOT BE MISSED?
TESTOSTERONE TREATMENT AND ANDROGEN-SENSITIVE CANCERS
TESTOSTERONE AND CV DISEASE
MONITORING TESTOSTERONE THERAPY
CONCLUSIONS
Current national and international guidelines relating to MH are remarkably heterogeneous in respect of diagnostic, treatment, and monitoring criteria. Indeed, several guidelines do not even refer to MH as such, but rather to “testosterone deficiency.” Specifically, for men having low serum T associated with low or “inappropriately normal” gonadotropins (a biochemical fingerprint that is shared by both HH and NGI) guidelines vary hugely in the degree to which further evaluation for underlying local or systemic co-morbidities is indicated in order to identify a proximate cause or overarching diagnosis.
There are also major variances as to whether “functional HH” (or NGI) associated with obesity and metabolic syndrome should be considered for testosterone therapy, whether as a first-line treatment, second-line after a lifestyle change, or not at all. Crucially, although testosterone ameliorates some surrogate markers of CV risk such as lean body mass and biochemical metabolic profiles and also improves bone density and hematocrit, it does not greatly improve sexual function, physical or mental vitality. Indeed, there are persisting concerns relating to CV disease that may relate to a counterbalancing risk arising from a greater propensity to arterial thrombosis with rising hematocrit.
At the same time, many men with organic MH, who would be expected to benefit from testosterone treatment, continue to remain undiagnosed and untreated due to deficient basic and postgraduate medical training in sexual medicine. Indeed, the voices and perspective of patients affected by MH have been conspicuously lacking in relation to the process of drafting guidance. We hope this review will allow clinicians to navigate the field of MH with greater confidence and, thereby, offer the most appropriate and safe advice and management subject to limitations of the existing evidence base.
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