Transvaginal progesterone: evidence for a new functional 'portal system' flowing from the vagina to the uterus

The results of many recent experimental and clinical studies support the hy pothesis that progesterone administered vaginally is distributed selectivel y to the uterus where tissue concentrations and effects exceed expectations . This phenomenon has multiple clinical implications in several fields of g ynaecological endocrinology, notably in assisted reproductive treatments an d new forms of hormone replacement therapy. Yet, the actual mechanisms by w hich vaginal administration of progesterone can induce higher concentration s in the uterus, despite low concentrations in the systemic circulation, re main obscure and most puzzling to many gynaecologists, This review aims to muster ideas and propose different mechanisms to explain the observed pheno menon. In particular, we will summarize data that support the various putat ive modes of transport including, direct diffusion through tissue, intracer vical aspiration, absorption into the venous or lymphatic circulatory syste ms and countercurrent vascular exchange with diffusion from utero-vaginal v eins/lymph vessels to arteries. All these mechanisms may concur to various extents to the uterine specificity of vaginal progesterone.