Estradiol and progesterone regulate the proliferation of human breast epithelial cells

Jean-Michel Foidart; Claude Colin; Xavier Denoo; Joëlle Desreux; Aude Béliard; Sabine Fournier; Bruno de Lignières

doi:10.1016/s0015-0282(98)00042-9

General Gynecology · Breast Health

Estradiol and progesterone regulate the proliferation of human breast epithelial cells

Foidart JM, Colin C, Denoo X, Desreux J, Béliard A, Fournier S, de Lignières B

Published May 20, 1998 Fertility and Sterility, 69(5), 963-969

DOI 10.1016/s0015-0282(98)00042-9 PMID 9591509

RRM Academy Synopsis

Progesterone limited estradiol-induced breast cell growth in menopause

In a double-blind randomized trial of 40 postmenopausal women, progesterone limited the cell growth that estradiol stimulated in normal breast tissue. Women applied a gel with placebo, estradiol, progesterone, or both hormones to both breasts daily for 14 days before breast surgery for esthetic reasons or a benign lesion. Researchers then measured growth markers in the tissue removed.

Key Findings

Forty of the 44 enrolled women completed the trial. Four were excluded for persistent ovarian activity. The groups held 10 (placebo), 13 (progesterone), 10 (estradiol), and 7 (estradiol with progesterone) women.
The proliferating cell nuclear antigen labeling index, a marker of cycling cells, averaged 11.5% with estradiol, 1.5% with progesterone, 1.3% with estradiol plus progesterone, and 0.1% with placebo (P<0.001).
The estradiol group's index exceeded placebo, progesterone, and the combination (each P<0.001). Both progesterone-containing groups stayed above placebo (P<0.001 and P=0.003) and did not differ from each other (P=0.112).
The mitotic index averaged 0.6 per 1,000 cells with estradiol. The progesterone and combined groups did not differ significantly from untreated women.
Plasma progesterone was significantly higher (P<0.001) in the progesterone and combined groups than in the estradiol and placebo groups. Tissue progesterone did not differ significantly because of wide variation between women.

Interpretation

The trial was double-blind and randomized. Groups held 7 to 13 postmenopausal women who were not on hormone replacement therapy. The endpoints were cell growth markers in normal breast tissue after 14 days of gel. The authors suggest that progesterone may counteract estradiol-induced growth and may protect against hyperplasia (tissue overgrowth). They write that progesterone and synthetic progestins may produce different responses. Conflicting data from other techniques do not allow a definitive conclusion on whether progestins are breast mitogens (growth stimulators), the authors add.

RRM Context

Restorative reproductive medicine (RRM) centers on ovulation, the event that produces the body's own progesterone. The trial adds tissue data on how progesterone and estradiol act in normal breast cells. The authors separate progesterone from synthetic progestins. RRM keeps that same distinction in its terminology.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To study the effects of estradiol and progesterone on the proliferation of normal human breast epithelial cells in vivo.

Design

Double-blind randomized study.

Setting

Departments of gynecology and of cell biology at a university hospital.

Patients

Forty postmenopausal women with untreated menopause and documented plasma FSH levels of >30 mIU/mL and estradiol levels of <20 pg/mL.

Interventions

Daily topical application to both breasts of a gel containing a placebo, estradiol, progesterone, or a combination of estradiol and progesterone during the 14 days preceding esthetic breast surgery or excision of a benign lesion.

Main Outcome Measures

Plasma and breast tissue concentrations of estradiol and progesterone. Epithelial cell cycles were evaluated in normal breast tissue by counting mitoses and performing quantitative proliferating cell nuclear antigen immunolabeling analyses.

Results

Increasing the estradiol concentration enhanced the number of cycling epithelial cells, whereas increasing the progesterone concentration significantly limited the number of cycling epithelial cells.

Conclusions

Exposure to progesterone for 14 days reduced the estradiol-induced proliferation of normal breast epithelial cells in vivo.

Topics

General Gynecology › Breast Health › Breast Cancer Risk · Reproductive Endocrinology › Ovarian Hormones › Estrogen · Therapeutics › Hormonal Agents › Progesterone and Progestins

Jean-Michel Foidart, Claude Colin, Xavier Denoo, Joëlle Desreux, Aude Béliard, Sabine Fournier, Bruno de Lignières

J Foidart, C Colin, X Denoo, J Desreux, A Béliard, S Fournier, B Lignières

PMID 9591509 9591509 DOI 10.1016/s0015-0282(98)00042-9 10.1016/s0015-0282(98)00042-9 Foidart et al. 1998, Foidart 1998

Keywords

Aged, Aged, 80 and Over, Breast/cytology/drug Effects, Cell Division/drug Effects, Double-Blind Method, Epithelial Cells/drug Effects, Estradiol/blood/pharmacology, Female, Humans, Middle Aged, Progesterone/blood/pharmacology, Progesterone, Estradiol

Estradiol and progesterone regulate the proliferation of human breast epithelial cells

Progesterone limited estradiol-induced breast cell growth in menopause

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Related research

Keywords