Andropause (Late-Onset Hypogonadism)

“Andropause” is a misnomer. Unlike the menopause there is no abrupt, universal, inevitable loss of gonadal function in men; testosterone declines gradually and continuously throughout adulthood. The preferred term is late-onset hypogonadism (LOH).

Definition: hypogonadism is a combination of subnormal serum testosterone AND one or more attributable symptoms. It is primary (testicular) or secondary (pituitary/hypothalamic).

Physiology: free testosterone falls about 1% per year after age 30. In the European Male Ageing Study, between 40 and 79 years total testosterone fell 0.4% per year and free testosterone 1.3% per year — the free fraction falls faster because SHBG rises with age. Mechanisms: fewer Leydig cells, reduced Leydig cell response to LH, and reduced episodic and stimulated gonadotropin secretion.

Epidemiology: at least 30% of older men have subnormal testosterone, but true symptomatic LOH affects only about 2–3%. Only 5–35% of hypogonadal men are treated. Comorbidity — obesity, type 2 diabetes, chronic illness, opioids, glucocorticoids — contributes at least as much as age itself.

Symptoms: low libido is the most specific. Others: erectile dysfunction, loss of morning erections, reduced muscle mass and strength, increased body fat, reduced bone mineral density and osteoporosis, mild anaemia, breast discomfort and gynaecomastia, hot flushes, sleep disturbance, reduced vitality, poor concentration, depression and fatigue. Most of these overlap with normal ageing and with other diseases — the central diagnostic difficulty.

Screening tools: the ADAM questionnaire and the Aging Male Symptoms (AMS) scale are sensitive (97% and 83%) but poorly specific (30% and 39%), especially in the borderline range — useful to prompt testing, useless to confirm.

Diagnosis: two separate fasting early-morning (before 11 am) total testosterone measurements. If borderline, obese, or SHBG is abnormal, measure free testosterone by equilibrium dialysis or calculation. Then measure LH and FSH: raised = primary; low or inappropriately normal = secondary, which requires prolactin, iron studies, other pituitary hormones, and pituitary MRI if testosterone is very low or there are visual/headache symptoms.

Exclude reversible causes before treating: acute or chronic illness (non-gonadal illness suppresses testosterone), obesity, obstructive sleep apnoea, opioids, glucocorticoids, alcohol, uncontrolled diabetes. Weight loss and treating the illness may normalise testosterone without any hormone.

Treatment principle: testosterone is offered only to older men with a genuinely low testosterone AND clinically significant symptoms — never for an asymptomatic age-related decline. Aim for a lower target than in young men: about 300–400 ng/dL rather than 500–600 ng/dL, to minimise risk. Preparations: transdermal gel, intramuscular undecanoate or enanthate, buccal or nasal formulations; oral testosterone (other than undecanoate) is avoided because of hepatotoxicity, peliosis hepatis and hepatic tumours. Contraindications: prostate carcinoma (the major one), breast cancer, baseline haematocrit >48–50%, untreated severe sleep apnoea, decompensated heart failure, and any desire to father a child (testosterone suppresses spermatogenesis).

Monitoring and expectations: check testosterone, haematocrit (keep below 55%), PSA and digital rectal examination at baseline, at 3–6 and 12 months, then annually. Benefits are modest — improved libido, sexual activity, mood, bone mineral density, anaemia and body composition — but the T-Trials showed no benefit in vitality or walking distance. If symptoms do not improve, stop the testosterone and look for another cause. Latest Updates & Current Practice (2023–Present) — 3 Points TRAVERSE (Lincoff et al., NEJM 2023) — 5246 men aged 45–80 with symptomatic hypogonadism (two fasting testosterone levels <300 ng/dL) and pre-existing or high cardiovascular risk, randomised to 1.62% transdermal testosterone gel or placebo for a mean 22–27 months. Testosterone was non-inferior to placebo for major adverse cardiac events (7.0% vs 7.3%) and did not increase prostate cancer or prostate-related events — resolving the question the FDA had mandated in 2015. But the substudies matter as much: the fracture substudy (Snyder et al., NEJM 2024) found MORE clinical fractures on testosterone (3.50% vs 2.46%) — the opposite of expectation. There were also small excesses of atrial fibrillation, pulmonary embolism and acute kidney injury, alongside genuine benefits: a 22.5% reduction in progression from prediabetes to diabetes, and improvements in sexual desire and activity, depressive symptoms and anaemia. Practice implication: testosterone must NOT be used to treat osteoporosis in older men — use a bisphosphonate or denosumab instead. Counsel on falls prevention early in therapy, particularly in the frail, since increased vitality and activity may precede any skeletal benefit. EAU 2024 and the 2025 European Expert Panel (PaTeR) position statement have incorporated TRAVERSE, endorsing treatment for symptomatic hypogonadism provided these precautions and monitoring are followed.