The distribution of endometrial leukocytes and their proliferation markersin trimegestone-treated postmenopausal women compared to the endometrium of the natural cycle: a dose-ranging study

The effect of trimegestone-based sequential hormone replacement therapy (HR T) on the distribution of endometrial leukocytes and Ki-67 expression was i nvestigated and the findings compared with the endometrium of the natural c ycle. Endometrial cells positive for CD45(+), CD56(+), CD3(+), Ki-67(+) and CD45(+)/Ki-67(+) antigens were immunohistochemically evaluated in samples from postmenopausal women who completed a randomized, double-blind, dose-ra nging study of oral trimegestone (0.05, 0.1, 0.25 and 0.5 mg per day) from days 15 to 28 with continuous micronized oestradiol 2 mg daily for six trea tment cycles. The control samples were luteinizing hormone (LH)-dated endom etrial biopsies. Cell counts were interpreted using linear discriminant ana lysis and unpaired t-test, The dose of trimegestone did not significantly a ffect the mean count of CD45(+), CD56(+), CD3(+), Ki-67(+) and CD45(+)/Ki-6 7(+) cells in the endometrial biopsies obtained from treated women. Endomet rial sections from women who bled on the day of the biopsy contained higher numbers of CD45(+) and CD56 cells. In the trimegestone-treated endometrium , CD45(+), CD56(+) and CD3(+) cell expression was similar to the proliferat ive and early secretory phases of the natural cycle. However the expression Ki-67 and CD45(+)/Ki-67(+) cells was similar to the menstrual phase of the natural cycle endometrium. Women treated with four doses of trimegestone e xhibited four different bleeding patterns. Therefore the endometrial infilt ration with these cells did not explain the pattern of bleeding in women on this HRT regimen.