Clinical research library

Secular decline in male serum testosterone across five countries, 1972–2019

This pooled analysis combined 118,593 male testosterone observations from the USA, Denmark, Finland, Israel and Brazil spanning 1972–2019. It was presented at the 2026 annual meeting of the European Society of Human Reproduction and Embryology and reported the largest cross-country estimate of the secular decline discussed on this site.

Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age

Pastuszak and colleagues reviewed pharmacokinetic profiles of approved testosterone formulations and set them against the endogenous diurnal curve in young men and in older men. The point of the paper is the shape of the curve, not a ranking of products.

Testosterone treatment to prevent or revert type 2 diabetes

T4DM was a two-year, randomised, double-blind trial of 1,007 overweight or obese men with impaired glucose tolerance or newly diagnosed type 2 diabetes. Both groups joined a lifestyle programme; one also received testosterone undecanoate.

Remission of type 2 diabetes following long-term testosterone therapy

Haider et al. followed 356 men with type 2 diabetes and total testosterone below 350 ng/dL (12.1 nmol/L) in a real-world registry for as long as 11 years. 178 of them received long-acting testosterone therapy prescribed by their physician; the remainder formed the untreated comparison group. Treated men had significant, progressive and sustained reductions in fasting glucose, HbA1c and fasting insulin across the treatment period. As an observational registry, it shows association, not proof that treatment caused the change.

Main conclusion

"Testosterone therapy is potentially a novel additional therapy for men with type 2 diabetes and hypogonadism."

Decline in serum testosterone levels among adolescent and young adult men in the USA

Using the American NHANES health database, Lokeshwar et al. asked whether the well-documented population decline has now reached adolescents and young adults. 4,045 men aged 15–39 were analysed across survey cycles from 1999 to 2016.

Insulin resistance and inflammation in hypogonadotropic hypogonadism

In this placebo-controlled trial, men with type 2 diabetes and hypogonadotropic hypogonadism received testosterone or placebo for six months. Insulin sensitivity was measured directly with a euglycaemic clamp rather than inferred from symptoms.

Hypogonadal symptoms in young men are associated with a serum total testosterone threshold of 400 ng/dL

Scovell et al. asked at which serum level young men actually begin to feel hypogonadal, rather than at which level a laboratory reports an abnormal value. The answer sat considerably higher than most European reference ranges: symptoms were associated with a total testosterone threshold of 400 ng/dL (14 nmol/L). Crucially, the symptoms that predicted low testosterone best were not sexual but energetic and cognitive — the everyday complaints usually attributed to stress, workload or simply getting older.

Main conclusion

"Lack of energy appears to be the most important symptom that predicts a total testosterone level of 400 ng/dL (14 nmol/L) or below."

The benefits and risks of testosterone replacement therapy: a review

Traish et al. reviewed long-term observational evidence on testosterone therapy in men with testosterone deficiency, focusing on metabolic health, body composition, sexual function and quality of life.

A cohort effect on serum testosterone levels in Finnish men

Finnish researchers analysed serum from three population surveys carried out in 1972, 1977 and 2002, covering 3,271 men aged 25–74. Because different birth cohorts could be compared at the same age, the design shows whether each generation starts from a lower baseline than the one before it.

Reference ranges for testosterone in men generated using LC–MS/MS in healthy non-obese young men (Framingham Heart Study)

This is a widely cited reference-range study. Bhasin et al. measured total testosterone by liquid chromatography–tandem mass spectrometry in healthy, non-obese men aged 19–40 in the Framingham Heart Study, then tested the resulting cut-off in three other cohorts.

Identification of late-onset hypogonadism in middle-aged and elderly men

The European Male Ageing Study evaluated more than 3,000 men across eight European centres to identify which symptoms consistently accompany low testosterone. Its central contribution was a symptom-plus-biochemistry definition of late-onset hypogonadism.

A population-level decline in serum testosterone levels in American men

This longitudinal analysis compared testosterone measurements from successive sampling periods in the Massachusetts Male Aging Study. It was designed to distinguish ordinary age-related decline from a broader birth-cohort effect in the male population.

Secular decline in male testosterone and SHBG serum levels in Danish population surveys

Researchers at Rigshospitalet in Copenhagen analysed 5,350 male serum samples from four Danish population surveys between 1982 and 2001. It is the Danish counterpart to the American and Finnish cohort studies, and it examines Leydig cell function alongside the known trends in semen quality.

Association of specific symptoms and metabolic risks with serum testosterone in older men

Zitzmann, Faber and Nieschlag at the Institute of Reproductive Medicine in Münster examined how specific symptoms and metabolic risks map onto serum testosterone in ageing men. They widen the threshold further than Scovell: the first symptoms appeared around 15 nmol/L, but the authors note there was no clear-cut boundary — some men experience symptoms earlier than others. Their cluster analysis is the reason low testosterone should not be read as one syndrome: it presents as three largely independent pictures.

Main conclusion

"Prevalence of psychosomatic symptoms and metabolic risk factors accumulated with decreasing androgen levels. For example, prevalence of loss of libido or vigour increased below testosterone concentrations of 15 nmol/L (P < 0.001), whereas depression and diabetes type 2 (also in non-obese men) were significantly more present in men with testosterone concentrations below 10 nmol/L."

Longitudinal effects of aging on serum total and free testosterone levels in healthy men

Harman et al. measured testosterone and SHBG in stored serum from 890 men followed for decades in the Baltimore Longitudinal Study of Aging. Because the same men were sampled repeatedly, the study could separate true ageing from illness, medication and other age-related factors — and it is the classic description of how free, bioavailable testosterone falls faster than total testosterone as SHBG climbs.

Testosterone dose–response relationships in healthy young men

Bhasin et al. suppressed endogenous production and assigned healthy men to graded weekly testosterone doses. The controlled design helped isolate how circulating testosterone relates to lean mass, fat mass, strength and physical power.