Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations

Abstract

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 burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-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, 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.

Keywords: Hypogonadism; Male aging; Practice guideline; Sexual dysfunction; Testosterone.

Fig. 1

Male hypothalamic-pituitary-gonadal (HPG) axis: homeostatic & environmental inputs: endocrine & paracrine actions of testosterone. KNDy, kisspeptin, neurokinin B, and dynorphin; NKB, neurokinin B; GC, glucocorticosteroid; GnRH, gonadotropin-releasing hormone; E2, oestradiol; FSH, follicle-stimulating hormone; LH, luteinizing hormone; Lc, Leydig cell; Sc, Sertoli cell.

Fig. 2

An approach to low testosterone levels in primary care. HIV, human immunodeficiency virus; BMI, body mass index; Hb/Hct, hemoglobin/hematocrit; TT, total testosterone; SHBG, sex hormone binding globulin; FSH, follicle-stimulating hormone; LH, luteinizing hormone; T4, thyroxine; T3, triiodothyronine; TSH, thyroid stimulating hormone; TIBC, total iron binding capacity; TRT, testosterone replacement therapy; MRI, magnetic resonance imaging. ^aConsider your local laboratory reference range as measurements can be variable from laboratory to another, in shift workers measure within 3 hours of waking; ^bwww.issam.ch/freetesto.htm.