Clinical practice update on testosterone therapy for male hypogonadism: Contrasting perspectives to optimize care

Abstract

US Endocrine Society (ES) published a clinical practice guideline on testosterone therapy in men with hypogonadism, and Endocrine Society of Australia (ESA) a position statement on management of male hypogonadism. Both emphasize the importance of diagnosing men who are androgen deficient due to organic (classical or pathological) hypogonadism arising from disorders of the hypothalamus, pituitary or testes, who assuredly benefit from testosterone therapy. Both recognize that men with an intact gonadal axis may have low testosterone concentrations, for instance older men or men with obesity or other medical comorbidities. ES guidelines classify such symptomatic men as having organic (advanced age) or functional (obesity, medical comorbidities) hypogonadism, giving an option for testosterone therapy as a shared decision between clinicians and individual patients. ESA did not recommend testosterone therapy in these men. ES offers a reference range for total testosterone established in young men, while ESA cites age‐standardized reference ranges. ES recommends using free testosterone as well as total testosterone to identify men with hypogonadism in conditions where sex hormone‐binding globulin (SHBG) is altered, or when total testosterone is borderline. ESA recommends confirmatory biochemical testing with total testosterone, recognizing that this may be lower than expected if SHBG concentrations are low. Both emphasize the importance of identifying pre‐existing prostate and cardiovascular disease prior to initiating testosterone therapy, with ES providing specific recommendations for PSA measurement, deferring testosterone therapy after major cardiovascular events and indications for pituitary imaging. These contrasting approaches highlight gaps in the evidence base where individualized patient management is required.

NONO and tumorigenesis: More than splicing

“…The relationship between NONO and AR shows a positive correlation too, and NONO knock‐down can effectively reduce the expression of AR/AR‐V7 at the mRNA and protein levels . Hormone therapy is an important method to treat prostate cancers, and androgen deprivation therapy (ADT) is the main treatment for aggressive PCa . Unfortunately, like many other cancer types, resistance is a frequent event associated with PCa, such as castration‐resistant prostate cancer (CRPC) .…”

Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment

“…International guidelines (not specifically directed at men with Type 2 diabetes) on testosterone treatment in older men with low testosterone show some differences in recommendations. Australian guidelines recommend against treatment for indications other than organic hypogonadism, whereas American guidelines give an option in carefully selected older men, in the context of a shared decision between clinicians and men with low testosterone provided they are fully informed as to the benefits and risks . British guidelines state that symptomatic men with a confirmed testosterone of < 8 nmol/l ‘usually require testosterone treatment’, whereas those with as level between 8 and 12 nmol/l ‘might require a trial’ of treatment.…”

“…Based on some evidence, men can be reassured that the risk of sustained iatrogenic gonadal axis suppression if testosterone treatment is ceased after 12 months is likely low . Contraindications to testosterone treatment include planning fertility in the near term, a personal history of breast or prostate cancer, presence of a palpable prostate nodule or induration, prostate‐specific antigen > 4 ng/ml (without further urological evaluation), elevated haematocrit, untreated severe obstructive sleep apnoea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia . In men in whom low serum testosterone contributes to clinical manifestations, symptoms should generally improve within 3–6 months after initiation of testosterone treatment, provided that adequate circulating testosterone concentrations, targeted to the mid–normal range for healthy young men, are achieved and maintained .…”

“…However, with respect to improvements in other manifestations, such as sarcopaenia or osteoporosis, a longer duration of testosterone treatment may be required. During testosterone treatment, monitoring for adverse effects includes, within 3–6 and then 12 months after initiation, and subsequently at least annually, clinical assessment, haematocrit monitoring and individualized prostate health monitoring, as further outlined in the US Endocrine Society guidelines . Reassuringly, in the 12‐month Testosterone trials , which included carefully selected symptomatic men with a confirmed low testosterone and followed US Endocrine Society guidelines with respect to both contraindications to and monitoring during treatment, adverse events were similar between testosterone‐ and placebo‐treated men.…”

Androgen deficiency in older men

“…14 While Australian guidelines 1 recommend against testosterone treatment for older men without organic hypogonadism, US Endocrine Society guidelines 9 give an option for testosterone therapy as a shared decision between clinicians and carefully selected individual patients. 14 If treatment is considered, men with functional hypogonadism should be informed about the absence of high-level evidence regarding long-term benefits and risks. Clear, patient-specific goals should be identified, and treatment should be stopped if these goals are not achieved.…”