Effects of etonogestrel treatment in the reproductive organs and uterine arteries of nonoophorectomized guinea pigs.

ABSTRACT

The endometria of women treated with long-term progestin-only contraceptives (LTPOCs) display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow, oxidative stress, and unpredictable focal abnormal endometrial bleeding. Because human studies on the effects of LTPOC treatment are constrained for ethical and practical reasons, we assessed the suitability of nonoophorectomized guinea pigs (GPs) to best mimic the hormonal milieu of women. The present study demonstrates that treatment of GPs parallels the morphological changes following LTPOC treatment of the human endometrium and ovaries. Specifically, treatment resulted in larger hyperemic, uteri compared with controls. Histopathologic and immunohistochemical analysis demonstrated fewer endometrial glands, decreased luminal mucus, increased numbers of blood vessels, and focal hemorrhage. While increased staining for the cell mitosis marker, Ki67, was present in the zona functionalis, no such increase occurred in the basalis. Lastly, effects on vasomotor features of uterine arteries suggest changes that favor increased resistance and reduced blood flow promoting decreased ability to withstand elevations in transmural pressure.