Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.

Male hypogonadism is defined by the guidelines as a clinical syndrome resulting from failure to produce physiological levels of testosterone and/or a normal number of spermatozoa.

• The guideline distinguishes between primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary dysfunction).
• The guidelines emphasize that diagnosis requires both biochemical evidence of testosterone deficiency and clinical symptoms consistent with hypogonadism.
• A multidisciplinary panel including endocrinology, primary care, clinical biochemistry, urology, and reproductive medicine contributed to the diagnostic criteria.

The guidelines recommend that testosterone deficiency be confirmed by measuring serum testosterone on at least two separate occasions using an early morning fasting sample.

• Total testosterone is the recommended first-line biochemical test.
• The guidelines acknowledge significant inter-laboratory variation and recommend use of assays with appropriate reference ranges.
• Calculated free testosterone is recommended when total testosterone is borderline or when SHBG may be abnormal (e.g., obesity, diabetes, liver disease).
• A threshold of total testosterone below 8–12 nmol/L is noted as the range where symptoms of deficiency typically manifest.

The guidelines recommend against testosterone replacement therapy in men with MH who are currently seeking fertility, and instead recommend referral to a specialist in reproductive medicine.

• Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and impairs spermatogenesis.
• Men with secondary hypogonadism seeking fertility may be treated with gonadotropin therapy to stimulate endogenous testosterone and spermatogenesis.
• The guideline highlights the importance of discussing fertility plans prior to initiating testosterone therapy.
• Sperm cryopreservation should be discussed with men who may want future fertility before starting testosterone replacement.

The guidelines state that testosterone replacement therapy is contraindicated in men with prostate cancer or breast cancer.

• Men with a history of prostate cancer should not routinely receive testosterone replacement therapy.
• Testosterone replacement may be considered in select men with low-risk prostate cancer after careful multidisciplinary discussion.
• The guidelines recommend prostate-specific antigen (PSA) monitoring and digital rectal examination before and during testosterone therapy.
• Breast cancer is listed as an absolute contraindication to testosterone therapy in men.

The guidelines identify polycythaemia as a clinically important adverse effect of testosterone replacement therapy requiring monitoring.

• Haematocrit should be measured at baseline and monitored at 3–6 months after initiation and then annually.
• Testosterone therapy should be withheld or the dose reduced if haematocrit exceeds 54%.
• The risk of polycythaemia is higher with injectable testosterone formulations compared with transdermal preparations.
• The guideline recommends venesection or switching to a lower-dose or transdermal formulation if polycythaemia develops.

The guidelines address the management of late-onset hypogonadism (LOH) and recommend caution in diagnosing and treating men with age-related testosterone decline in the presence of comorbidities.

• LOH is recognized as a distinct entity from classical hypogonadism, often associated with obesity, type 2 diabetes, and metabolic syndrome.
• The guidelines recommend that reversible causes of low testosterone (e.g., obesity, opioid use, intercurrent illness) be addressed before initiating testosterone replacement.
• Weight loss and lifestyle modification can normalize testosterone levels in obese men with LOH and should be the first-line intervention.
• The evidence base for testosterone therapy in LOH is noted as less robust than for classical hypogonadism, and treatment should be individualized.

The guidelines recommend a shared decision-making approach and patient perspective should be incorporated into management decisions for male hypogonadism.

• Patient-reported outcomes including sexual function, energy levels, mood, and quality of life should be assessed at baseline and during treatment.
• The guideline explicitly includes a patient perspective section to help clinicians best manage MH.
• Informed consent discussions should include benefits, risks, and alternatives to testosterone therapy.
• Patients should be counselled about the long-term commitment involved in testosterone replacement therapy and the potential need for lifelong treatment.

The guidelines provide recommendations on the available testosterone replacement formulations, noting that choice should be based on patient preference, pharmacokinetics, and clinical context.

• Available formulations include intramuscular injections (short-acting and long-acting), transdermal gels, patches, and oral/buccal preparations.
• Long-acting intramuscular testosterone undecanoate provides stable levels over approximately 10–14 weeks.
• Transdermal gels provide flexible dosing and are associated with lower risk of polycythaemia but carry a risk of transference to partners or children.
• Short-acting formulations may be preferred in older men or those with comorbidities where therapy may need to be rapidly withdrawn.

The guidelines were developed using a multidisciplinary approach commissioned by the Society for Endocrinology in response to existing uncertainties and single-discipline-driven guidelines.

• Expertise was drawn from endocrinology (medical and nursing), primary care, clinical biochemistry, urology, and reproductive medicine.
• The guideline acknowledges that prior guidelines have been driven predominantly by single disciplines.
• The goal was to provide all care providers with a unified, multidisciplinary framework for diagnosis and management.
• The guidelines also incorporate a patient perspective as a formal component of the guidance.