Endometrial histomorphometry of trimegestone-based sequential hormone replacement therapy: a weighted comparison with the endometrium of the natural cycle

Histomorphometric changes in the endometrium were evaluated under the effec t of a trimegestone-based sequential hormone replacement therapy (HRT) regi men, and the findings were compared to those in endometrium of the natural cycle. Endometrial samples were taken from postmenopausal women who complet ed a randomized, double blind, dose-ranging study of oral trimegestone (0.0 5, 0.1, 0.25 and 0.5 mg per day) from day 15 to day 28 with continuous micr onized oestradiol 2 mg daily for six treatment cycles. The HRT-treated endo metrium, irrespective of the dose, had a smaller mean total glandular area, smaller average glandular diameter, smaller mean total vascular space area and diameter than the luteal phase. Stromal cellularity was similar in the four dose groups. There were reduced glandular secretions in the endometri um from the high dose group. The relative weighting of these histological p arameters was evaluated by linear discriminant analysis. The weighted value s were dose independent, and may therefore represent either a specific effe ct of trimegestone, number of days administered, or both. We have construct ed an equation to assign a value for a histological parameter which determi nes the position on Linear discriminant functions. These assigned values ca n be used in other sequential HRT regimens to determine the relative influe nce of a given progestogen on endometrial morphology in relation to differe nt phases of the natural cycle.