Morphologic changes induced by oral long-term treatment with 8-prenylnaringenin in the uterus, vagina, and mammary gland of castrated rats

Menopause. 2006 Jul-Aug;13(4):669-77. doi: 10.1097/01.gme.0000196596.90076.d0.


Objective: The flavonoid 8-prenylnaringenin (8-PN) is found in hops, and hence in beer, and is also increasingly consumed as a food supplement. It is the strongest known phytoestrogen, which makes it a good candidate as an alternative to hormone therapy. Its putatively undesired estrogenic effects in the uterus and mammary gland have not yet been thoroughly investigated. Therefore, we performed a long-term oral administration experiment.

Design: Rats were ovariectomized and fed for 3 months with soy-free chow containing estradiol (E(2)) or 8-PN, both in two doses (8-PN: 6.77 mg or 68.42 mg/kg body weight; E(2): 0.17 mg or 0.7 mg/kg body weight) or no additives. Analysis was mainly focused on morphologic and immunocytochemical parameters. Expression of proliferating cell nuclear antigen as a proliferation marker and of progesterone receptor was quantified in the mammary gland.

Results: Uteri of animals treated with both E(2) doses and the high 8-PN dose had increased weight and showed histologic estrogen-induced features. 8-PN at the high dose induced epithelial polypoid formation unique to this group. Compared to the atrophic controls, both E(2) doses and the high 8-PN dose induced hyperplastic epithelia in the vagina. The high doses of E(2) and 8-PN caused secretion in the mammary gland, whereas proliferation and progesterone receptor expression were stimulated by both E(2) doses and the high 8-PN dose.

Conclusions: E(2) and 8-PN share many effects in the three studied organs, but some differences in the mechanism of action appear to exist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Proliferation / drug effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Estrogen Replacement Therapy
  • Female
  • Flavanones / administration & dosage
  • Flavanones / pharmacology*
  • Humulus*
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / pathology
  • Menopause
  • Ovariectomy
  • Phytoestrogens / administration & dosage
  • Phytoestrogens / pharmacology*
  • Phytotherapy*
  • Rats
  • Rats, Sprague-Dawley
  • Uterus / drug effects
  • Uterus / pathology
  • Vagina / drug effects
  • Vagina / pathology


  • 8-prenylnaringenin
  • Flavanones
  • Phytoestrogens