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estrone sulfate e1s e1so4 3-sulfate oestrone natural endogenous steroid estrogen ester conjugate medication menopausal hormone therapy relative binding affinity estrogen-associated diseases breast cancer benign disease endometrial ovarian prostate colorectal steroid hormone 3d hormonal replacement function action endocrine endocrinology level prohormone analogue precursor intermediate metabolite metabolism biosynthesis mechanism biosynthetic intermediate biogenesis synthesis derivative bioprecursor metabolic contractor