Does estrone become the predominant estrogen after menopause?

After menopause, the cessation of ovarian follicular activity causes estradiol levels to drop precipitously, leaving estrone as the predominant circulating estrogen.

Postmenopausal production and shifts

• Peripheral aromatization: Isotopic tracer and metabolic clearance studies confirm that over 95% of circulating estrone in postmenopausal women is derived from the peripheral aromatization of adrenal-derived androstenedione, principally within adipose tissue.
• Production drivers: Above-range estrone alongside optimal estradiol can indicate accelerated aromatization due to increased adiposity or first-pass hepatic metabolism of oral estrogen therapy.

Clearance and detoxification pathways

• Phase II conjugation: Systemic estrone clearance relies on hepatic sulfation (via sulfotransferases, SULTs) and glucuronidation (via UDP-glucuronosyltransferases, UGTs) for biliary and urinary excretion. Glucuronidation represents an irreversible excretory pathway, while sulfation creates a reversible storage reservoir.
• Downstream metabolism: Catechol metabolites (2-hydroxyestrone and 4-hydroxyestrone) are methylated by catechol-O-methyltransferase (COMT) to reduce redox and estrogenic toxicity. Impaired clearance may stem from hypothyroidism, liver disease, or cofactor deficiencies.
• Enterohepatic recirculation: Biliary-excreted estrone glucuronides can be deconjugated in the gut by microbial beta-glucuronidase, regenerating free estrone for reabsorption and delaying total clearance.

Bottom line

• Elevated postmenopausal estrone with optimal estradiol indicates either heightened peripheral aromatization (often driven by adipose mass or oral estrogen) or impaired elimination via hepatic Phase II conjugation, COMT methylation, or gut microbial deconjugation.