PROGESTERONE - A CRITICAL ROLE IN THE PATHOGENESIS OF UTERINE MYOMAS

Uterine leiomyomas are monoclonal tumors. However, the factors involve d in their initiation and growth remain poorly understood. The neoplas tic transformation of myometrium to leiomyoma likely involves somatic mutations of normal myometrium and the complex interactions of sex ste roids and local growth factors. Traditionally, estrogen has been consi dered the major promoter of myoma growth. The purpose of this review i s to highlight the biochemical, histologic, and clinical evidence that supports an equally important role for progesterone in the growth of uterine myomas. Biochemical studies suggest that progesterone, progest ins, and the progesterone receptor modulate myoma mitotic activity. Se veral clinical trials demonstrate that progestins inhibit and/or rever se the ability of hypoestrogenism induced by a gonadotropin-releasing hormone agonist to shrink uterine myomas, suggesting a critical role f or progesterone in growth of myomas. A new hypothesis to explain the p athogenesis of myomas is presented.