A review of the endometrial histologic effects of progestins and progesterone receptor modulators in reproductive age women

Contraception. 2015 May;91(5):360-7. doi: 10.1016/j.contraception.2015.01.008. Epub 2015 Jan 14.


This review compares the histologic changes that occur in the endometrium following ovulation and progesterone secretion with contraceptive progestins and progesterone receptor modulators (PRMs) that may be used as contraceptive agents in women. The morphologic endometrial changes vary by the progestin type, dosage and duration; are often subtle and difficult to interpret; and may also vary depending on whether or not estrogen is used. The prolonged use of ethinyl estradiol and a progestin as a combined oral contraceptive results in common endometrial histologic findings that include glandular and stromal atrophy and spiral arteriole underdevelopment. Intrauterine systems releasing levonorgestrel have similar changes that are related to the proximity of the device to the endometrium, while progestin-only implants result in atrophy with marked vascular changes characterized by underdevelopment of spiral arterioles and dilated, thin-walled vessels near the surface epithelium. Lower doses of levonorgestrel delivered by a vaginal ring allow ovulation, and the endometrial changes appear to reflect the impact of the endogenous hormones. PRMs have been investigated as potential female contraceptives. PRM-associated endometrial changes include an inactive endometrium with cystically dilated glands, lined by epithelium with increased apoptosis in a background of compact nondecidualized stroma. Histologic differences between PRMs appear to depend on the degree of progesterone receptor agonistic activity.

Keywords: Contraceptive; Endometrium; Histology; Progesterone; Progestins; Selective progesterone receptor modulators.

Publication types

  • Review

MeSH terms

  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / classification
  • Contraceptive Devices, Female
  • Endometrium / drug effects
  • Endometrium / pathology*
  • Estrogens / pharmacology
  • Female
  • Humans
  • Ovulation / drug effects
  • Progestins / pharmacology*
  • Receptors, Progesterone / agonists*
  • Receptors, Progesterone / antagonists & inhibitors*


  • Contraceptive Agents, Female
  • Estrogens
  • Progestins
  • Receptors, Progesterone