Androstenedione (Delta-4-Androstenedione)

When high

When HIGH (above approximately 8.5 nmol/L in adult males):

• Most common cause in athletes is exogenous DHEA or androstenedione (prohormone) supplementation -- reduce or stop the supplement and retest
• High androstenedione increases substrate for aromatisation to estrone and estradiol; can worsen estrogenic sides (oily skin, gynaecomastia risk, water retention)
• It also feeds the androgen pathway, so high levels can aggravate acne and hair loss in genetically predisposed individuals
• If elevated WITHOUT supplementation: investigate adrenal causes (17-hydroxyprogesterone, morning cortisol, ACTH, DHEA-S) to exclude late-onset congenital adrenal hyperplasia or, rarely, an androgen-secreting adrenal or testicular tumour

Pharmacological options:

• If estrogenic symptoms accompany high androstenedione on aromatising compounds, an aromatase inhibitor (anastrozole 0.25-0.5mg every 2-3 days, titrated to E2) reduces downstream conversion; do not crush E2 to zero
• Persistent unexplained elevation warrants endocrinology referral before any intervention; do not self-treat a suspected adrenal cause

When low

When LOW (below approximately 1.0 nmol/L in adult males):

• Expected on exogenous testosterone or AAS: HPG-axis suppression lowers endogenous precursors including androstenedione; not a concern while on cycle
• Off cycle or in PCT, a persistently low value suggests incomplete HPG-axis recovery or adrenal insufficiency
• Can also reflect ageing (precursor output declines with age) or chronic stress with cortisol dominance

During recovery / PCT:

• A rising androstenedione alongside recovering LH, FSH, and testosterone is a reassuring sign of returning endogenous production
• Some athletes use DHEA 25-50mg/day in PCT to support precursor supply; this raises androstenedione, testosterone, AND estradiol, so monitor E2
• If low with low DHEA-S and low cortisol, investigate adrenal function before assuming HPG cause

Clinical context:

• Androstenedione is produced by both the adrenal glands and the gonads, sitting one enzymatic step upstream of testosterone
• It converts to testosterone (via 17-beta-HSD) and to estrone (via aromatase), then to estradiol, so it influences both androgen and estrogen status
• Oral androstenedione supplementation reliably raises serum androstenedione and estradiol but does NOT meaningfully raise testosterone or improve training adaptations, while lowering HDL cholesterol: the evidence against 'andro' as a testosterone booster is strong
• Reference ranges are assay, age, and sex dependent; interpret against your own laboratory's quoted range