Evaluating the Effect of Age on Endometrial Responsiveness to Hormone Replacement Therapy: A Histologic Ultrasonographic, and Tissue Receptor Analysis

J Assist Reprod Genet. 1993 Jan;10(1):47-52. doi: 10.1007/BF01204440.


Objective: 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.

Study design: 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.

Results: 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 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.

Conclusion: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aging / pathology
  • Aging / physiology*
  • Endometrium / anatomy & histology
  • Endometrium / diagnostic imaging
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Estrogen Replacement Therapy*
  • Female
  • Humans
  • Middle Aged
  • Progesterone / therapeutic use*
  • Prospective Studies
  • Receptors, Steroid / metabolism*
  • Ultrasonography


  • Receptors, Steroid
  • Progesterone