Estradiol and tamoxifen enhance invasion of endometrial stromal cells in a three-dimensional coculture model of adenomyosis

ObjectiveTo examine the effect of estradiol alone or with progesterone and tamoxifen on the depth of invasion of endometrial stromal cells from women with and without adenomyosis in a three-dimensional (3D) coculture model that includes myocytes.DesignCase-controlled, blinded comparison.SettingMedical school department.Patient(s)Premenopausal women with and without uterine adenomyosis.Intervention(s)Human endometrial stromal and myometrial cells grown in a 3D coculture with crossover between cells from uteri with and without adenomyosis; cocultures treated with tamoxifen, estradiol alone, or estradiol with progesterone.Main Outcome Measure(s)Depth of stromal cell invasion into a collagen matrix.Result(s)The depth of invasion for adenomyotic stromal cells was statistically significantly higher than for the control stromal cells, whether grown on plain collagen, on collagen containing control or adenomyotic muscle cells. The addition of estradiol or tamoxifen, but not the estradiol and progesterone combination, increased the depth of invasion of both adenomyotic stromal cells and control stromal cells in all cell combinations. When grown on plain collagen, the depth of invasion for control stromal cells and adenomyotic stromal cells increased by 126% and 93% with the use of tamoxifen, and by 71% and 50%, with the use of estradiol.Conclusion(s)Both estradiol and tamoxifen enhance stromal cell invasion, but the greater depth of invasion of adenomyotic stromal cells and the enhancing effect of adenomyotic muscle were maintained under all experimental conditions, suggesting an inherent predisposition in affected women.