Irreversible Binding of Norethisterone to Human Serum Protein Induced by UV-B Light

In as much as oral contraceptive ingestion has been associated with photoallergic effects, the irreversible binding of 4-(14)C-norethisterone to proteins catalyzed by UV-B light (290-320 nm) was investigated. Irreversible binding to a human plasma protein mixture and to albumin of the radiolabeled progestogen was linear for 40min, when mixtures of protein and steroid were irradiated with UV-B light. Approximately 16 % of the radiolabel was irreversibly bound under the conditions of the assay. Irreversible binding also occurred, when proteins were added several hours after irradiation. Preliminary experiments in rats administered 4-(14)C-norethisterone also indicate the formation in skin and liver of irreversibly bound adducts under photoreactive conditions. Such reactions may in part be responsible for some of the side-effects associated with oral contraceptive use.