Can zearalenone act as an estrogenic compound and interfere with male reproductive and endocrine function?

Zearalenone (ZEN), a dietary mycotoxin, has established estrogen-receptor activity and experimentally documented adverse effects on male endocrine and reproductive endpoints. For a 57-year-old man, the mechanistic hazard is credible, but the magnitude of risk at typical individual human exposure remains uncertain.

Estrogenic mechanism

• ZEN directly binds both ERα and ERβ with nanomolar affinity. In one comparison, relative binding was approximately 4.3% for ERα and 6.0% for ERβ versus estradiol.
• Receptor-transfection and reporter studies show functional ER-mediated transcriptional activity, most consistently full ERα agonism. ERβ effects can vary—agonist, antagonist, or mixed—depending on estradiol presence and cellular/promoter context.
• Metabolism may amplify estrogenic potential: α-zearalenol binds ERα/ERβ more strongly than ZEN and is reported to be about 60-fold more estrogenically potent.

Male reproductive and endocrine findings

• A meta-analysis of rodent studies found reduced serum testosterone, lower sperm concentration and motility, increased sperm abnormalities, and adverse testicular and Leydig-cell effects across prenatal, pubertal, and adult exposures.
• Biologically plausible pathways include disturbance of hypothalamic–pituitary–gonadal signaling, altered LH-related steroidogenesis (StAR, P450scc, 3β-HSD, P450c17, and Nur77), and testicular oxidative stress, apoptosis, and blood–testis-barrier injury.

Human relevance

• Biomonitoring in German and Swedish adults confirms widespread ZEN/metabolite exposure. Most estimated German intakes were below EFSA’s group tolerable daily intake of 0.25 μg/kg/day, although some exceeded it.
• Typical modeled European adult circulating ZEN/α-zearalenol concentrations are substantially below concentrations producing in-vitro estrogenic effects. Biomonitoring studies did not link exposure to testosterone, semen measures, fertility, or sexual function.

Bottom line

• ZEN is an ER-active estrogenic mycotoxin and can impair male reproductive/endocrine function in experimental models; direct evidence of such effects in adult men at real-world exposure levels is not established.