Testosterone

Testosterone is a C19 steroid synthesised from cholesterol, in men almost entirely by testicular Leydig cells under LH control and in women far more sparingly by ovary and adrenal. It acts on the nuclear androgen receptor but also serves as a prohormone: 5-alpha-reductase makes dihydrotestosterone, a more potent androgen behind much of the prostate and skin effect, while aromatase makes estradiol, which mediates much of the effect on bone and on pituitary feedback.

Secretion is pulsatile with a diurnal peak in the early morning, so diagnostic samples are drawn fasting before mid-morning and an afternoon result can read misleadingly low. Guidelines diagnose deficiency on two such samples against a harmonised total testosterone threshold near 264 to 300 nanograms per decilitre. Liquid chromatography with tandem mass spectrometry is the reference method; immunoassays are tolerable in the adult male mid-range but unreliable at the low concentrations seen in women and children.

Measurement and treatment are frequently conflated. Levels track acute illness, sleep loss, obesity and opioid use, so a low value is a finding to explain, not a diagnosis. The TRAVERSE trial, reported in 2023, tested replacement in over five thousand hypogonadal men at cardiovascular risk and found no excess of major adverse cardiac events, while flagging more pulmonary embolism, atrial fibrillation and acute kidney injury.

The error running through consumer testosterone marketing is treating the number as the target. A high-normal level produced by exogenous androgen is not the same thing as one produced endogenously: gonadotropins are suppressed, intratesticular concentrations fall, fertility is impaired and the axis must recover afterwards. Reference intervals also vary by assay and by the population used to build them, so a result flagged low by one laboratory can sit inside another's range.