Mechanisms of uterine specificity of vaginal progesterone

Endometrial transformations achieved by vaginal progesterone exceed those n ormally expected from the circulating concentrations obtained, this suggest s some degree of direct vagina to uterus transport. We speculate on the dif ferent mechanisms involved in uterine specificity of vaginal progesterone a nd report data of a preliminary randomized study comparing progesterone con centrations in serum and endometrial tissue obtained from hysterectomy spec imens after vaginal or i.m. administration. Eight post-menopausal women und ergoing transabdominal hysterectomy were randomized to receive either vagin al progesterone gel, 90 mg, or i.m. progesterone formulation, 50 mg, at 08. 00 and 20.00 on the day before surgery and at 06.00 on the day of surgery. Venous blood samples for progesterone measurement were drawn at 08.00 on th e day before surgery and during the surgery. Endometrial progesterone conce ntrations were markedly higher in women who received vaginal progesterone ( 1.38 +/- 0.66 and 0.38 +/- 0.19 ng/mg protein, for vaginal and i.m. groups respectively) (P < 0.02) despite lower serum concentrations (4.17 < 0.56 an d 32.32 +/- 11.06 ng/ml, for vaginal and i.m. groups respectively) (P < 0.0 01). The vaginal route induces endometrial progesterone concentrations that far exceed those expected from the serum progesterone concentrations achie ved.