Pharmaceutical Sciences Faculty Publications

Title

Comparative Effects of Oral Conjugated Equine Estrogens and Micronized 17beta-estradiol on Breast Proliferation: A Retrospective Analysis

Document Type

Article

Publication Date

9-1-2008

Journal Title

Menopause

ISSN

1530-0374

Volume

15

Issue

5

First Page

890

Last Page

898

DOI

10.1097/gme.0b013e318168f0ad

PubMed ID

18520696

Abstract

OBJECTIVE: To evaluate the effects of oral conjugated equine estrogens (CEE) and micronized 17beta-estradiol (E2) on breast proliferation in a postmenopausal primate model.

DESIGN: Data from nine studies were analyzed retrospectively. The primary outcome measure was breast epithelial proliferation determined by immunolabeling for the Ki67 antigen. Other measures included progesterone receptor expression and endometrial thickness (as surrogate markers of systemic estrogen exposure) and urinary estrogen metabolite profile. All CEE doses were given at the human equivalent of 0.625 mg/day (n = 281), whereas E2 was given at the human equivalent of 1.0 mg/day or less (n = 131).

RESULTS: Oral CEE resulted in a modest overall increase in breast epithelial proliferation of 75% that reached significance at P < 0.05 compared with placebo in one of four parallel-arm studies. In contrast, oral E2 resulted in a more substantial increase in breast epithelial proliferation of 259% (all studies) to 330% (parallel-arm studies only) that reached significance at P < 0.05 in all five E2 studies evaluated. Breast epithelial expression of progesterone receptor, a widely used marker of estrogen receptor activity, and endometrial thickness showed similar increases after treatment with CEE and E2 (P < 0.05 in all available studies). Relative amounts of urinary methoxyestrogens and the 2-hydroxyestrogen-to-16alpha-hydroxyestrone ratio were higher after CEE compared with E2 treatment (P < 0.05 for all).

CONCLUSIONS: This retrospective analysis of oral estrogen effects in postmenopausal macaques suggests that standard doses of CEE may result in less estrogen-induced epithelial proliferation in the breast compared with E2.

Keywords

Breast, breast neoplasms, cell proliferation, contraceptive agents, female, endometrium, estrogen replacement therapy, estrogens, medroxyprogesterone acetate, postmenopause, receptors, progesterone, retrospective studies, risk factors

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