Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

Saliva and plasma concentrations of norethisterone (NET) were determined by a radioimmunoassay in 5 healthy women and in one epileptic woman on phenytoin treatment during a 21-day cycle on an oral contraceptive containing 3 mg NET-acetate and 0.05 mg ethinyloestradiol. Plasma non-protein bound concentrations of NET were determined by equilibrium dialysis. Sex hormone binding globulin (SHBG) was measured in all samples. An excellent correlation was found between plasma total, plasma non-protein bound and saliva levels of NET. Plasma non-protein bound and saliva concentrations were in the same range throughout, indicating that saliva concentrations reflect the free fraction of NET in plasma. SHBG increased considerably in all women. A slight decrease in the ratio between total and non-protein bound concentrations was found with time, possibly reflecting a slight increase in protein binding with increasing SHBG. The woman on anticonvulsant therapy had plasma total, plasma unbound and saliva NET concentrations that were only 30 per cent of those of the healthy women. The relationship between the different fractions was similar to that found in the healthy women. The non-protein bound fraction of NET was 4–5 per cent of the total in all women studied.