Evaluating the effect of age on endometrial responsiveness to hormone replacement therapy: A histologic ultrasonographic, and tissue receptor analysis

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Abstract
Our objective was to characterize the endometria of women of various ages placed on similar estrogen/progesterone replacement regimens prior to attempted donor embryo transfer using histologic, ultrasonographic, and steroid receptor markers in order to determine if advancing age has a detrimental effect on uterine responsiveness to pharmacologic sex steroid replacement therapy. This was a prospective open clinical trial. Functionally agonadal women aged 25 to 60 years receiving hormone replacement therapy underwent transvaginal ultrasound examination of the uterus followed by a timed endometrial biopsy on artificial cycle day 21. Endometrial histology and estrogen and progesterone receptors were analyzed from biopsy material. Subjects were assigned to three groups according to age: Group I, aged 25 to 39 years (n =48); Group II, aged 40 to 49 years (n =61); and Group III, aged 50 to 60 years (n =13). Endometrial preparation was accomplished in all patients using the same sequential regimen consisting of oral micronized estradiol and intramuscular progesterone. Similar histologic, ultrasonographic, and steroid receptor characteristics were noted in all groups of patients regardless of age. A normal appearing midluteal secretory endometrium was demonstrated histologically in 85% of biopsies. However, 15% of biopsies exhibited intraluminal papillary excrescences within the glands and/or an increase in the normal gland-to-stroma ratio. Three patients, one from each group, did not initially respond to replacement therapy and required further treatment. Functionally agonadal women exhibit normal or near-normal endometrial responses to sex steroid replacement therapy designed to imitate the natural cycle through the sixth decade of life.