What is the difference between Estrone and Estradiol?

Differences Between Estrone and Estradiol

Estradiol is the principal and most potent intracellular human estrogen, while estrone is a less potent metabolite of estradiol that becomes the predominant circulating estrogen in postmenopausal women.

Chemical Structure and Potency

• Estradiol contains two hydroxyl groups, making it more potent at estrogen receptors than estrone, which is one of its metabolites 1
• Estrone is produced primarily through conversion of androstenedione (secreted by the adrenal cortex) in peripheral tissues, becoming the most abundant circulating estrogen in postmenopausal women along with estrone sulfate 2
• Estradiol is the primary estrogen produced by ovarian follicles in premenopausal women, secreting 70-500 mcg daily depending on menstrual cycle phase 1

Physiological Effects

• Estradiol has stronger effects on the renin-angiotensin-aldosterone system (RAAS), with studies showing it increases angiotensinogen production more significantly than other estrogens 3
• Estrone has weaker estrogenic activity at estrogen receptors compared to estradiol, making it less potent in both beneficial and potentially harmful effects 4
• The ratio of estradiol to estrone varies with different administration routes - oral administration leads to higher estrone concentrations while transdermal/percutaneous routes produce higher estradiol levels 5

Metabolic Pathway

• Estradiol is converted reversibly to estrone, and both can be converted to estriol (the major urinary metabolite) 1
• Estrone can exist in sulfate-conjugated form (estrone sulfate), which serves as a circulating reservoir for formation of more active estrogens in postmenopausal women 2
• Estriol is produced from estrone and cannot be converted back to estradiol, making it a terminal metabolite in the estrogen pathway 3

Clinical Implications

• In endothelial colony-forming cells, estradiol and estrone demonstrate distinct concentration-dependent physiological effects - estradiol consistently increases proliferation, migration, and tube formation, while estrone shows biphasic effects 6
• When both hormones are present together, their ratio significantly impacts cellular function - high estrone-to-estradiol ratios decrease proliferative capacity, while high estradiol-to-estrone ratios increase it 6
• For women using aromatase inhibitors after breast cancer, estriol-containing preparations (derived from estrone) may be preferable over estradiol-containing ones since estriol cannot be converted back to estradiol 3, 7

Pharmacokinetic Differences

• Estradiol has a shorter half-life (approximately 1-12 hours) compared to some estrone metabolites, particularly estrone sulfate which can serve as a longer-term reservoir 5
• Oral administration of estrogens undergoes significant first-pass metabolism in the liver, converting much of the estradiol to estrone, resulting in higher estrone:estradiol ratios 8
• Transdermal or vaginal administration bypasses first-pass metabolism, leading to higher estradiol:estrone ratios compared to oral administration 8

Cardiovascular Effects

• Estradiol has more pronounced effects on vascular function, increasing stroke volume, heart rate, and contractility while reducing peripheral vascular resistance in postmenopausal women 3
• Estrone appears to have less impact on cardiovascular parameters but becomes increasingly important in postmenopausal women as estradiol levels decline 6
• The unique interaction between estrone and estradiol may contribute to cardiovascular disease risk observed in menopausal women and those undergoing hormone replacement therapy 6