Effect of progestin on the ovarian epithelium of macaques: cancer prevention through apoptosis?

Published

Journal Article

OBJECTIVE: The apoptosis pathway is a vital mechanism in vivo that functions to eradicate genetically damaged cells prone to malignancy. The purpose of this study was to determine whether oral contraceptives, which confer significant protection against subsequent epithelial ovarian cancer, induce apoptosis in the ovarian epithelium. METHODS: Female cynomolgus macaques (N = 75) were randomized to receive a diet for 35 months containing either no hormones, the oral contraceptive Triphasil (Wyeth-Ayerst Laboratories, Philadelphia, PA), the estrogenic component of Triphasil (ethinyl estradiol) alone, or the progestin component of Triphasil (levonorgestrel) alone, each administered in a cyclic fashion. At study termination, the animals underwent ovariectomy and the ovarian epithelium was examined morphologically and immunohistochemically for apoptosis. The percentage of ovarian epithelial cells undergoing apoptosis was measured in each animal and compared between the treatment groups. RESULTS: The median percentage of ovarian epithelial cells undergoing apoptosis by treatment was control (3.8%), ethinyl estradiol (1.8%), Triphasil (14.5%), and levonorgestrel (24.9%). Compared with control and ethinyl estradiol-treated monkeys, a statistically significant increase in the proportion of apoptotic cells was noted in the ovarian epithelium of monkeys treated with the oral contraceptive Triphasil (P < or = .01) or levonorgestrel (P < .001), with a maximal effect (six-fold) seen in the group treated with levonorgestrel alone. CONCLUSION: Oral contraceptive progestin induces apoptosis in the ovarian epithelium. Given the importance of the apoptosis pathway for cancer prevention, an effective chemopreventive strategy may be possible using progestins or other agents that selectively induce apoptosis in the ovarian epithelium to prevent the development of ovarian cancer.

Full Text

Duke Authors

Cited Authors

  • Rodriguez, GC; Walmer, DK; Cline, M; Krigman, H; Lessey, BA; Whitaker, RS; Dodge, R; Hughes, CL

Published Date

  • September 1998

Published In

Volume / Issue

  • 5 / 5

Start / End Page

  • 271 - 276

PubMed ID

  • 9773403

Pubmed Central ID

  • 9773403

International Standard Serial Number (ISSN)

  • 1071-5576

Digital Object Identifier (DOI)

  • 10.1016/s1071-5576(98)00017-3

Language

  • eng

Conference Location

  • United States