Chang, K. J., Lee, T. T., Linares-Cruz, G., Fournier, S., & de Lignières, B. (1995). Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertility and Sterility, 63(4), 785-791. https://doi.org/10.1016/s0015-0282(16)57482-2
Chang KJ, Lee TT, Linares-Cruz G, Fournier S, de Lignières B. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril. 1995;63(4):785-791. doi:10.1016/s0015-0282(16)57482-2
Chang, King-Jen, et al. "Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo." Fertility and Sterility, vol. 63, no. 4, 1995, pp. 785-791.
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Progesterone gel reduced breast cell division in premenopausal women
In a double-blind trial of 40 premenopausal women having breast surgery, progesterone gel caused less cell division in normal breast tissue than placebo gel. Estradiol gel raised cell division, and adding progesterone to it significantly cut that rise.
Key Findings
Forty premenopausal women were enrolled. The groups analyzed were 8 women on placebo gel, 7 on progesterone gel, 9 on estradiol gel and 9 on estradiol plus progesterone gel.
On the PCNA labeling index, a marker of cycling cells, placebo scored 7.8% ± 4.8%, estradiol 17.4% ± 6.4% and progesterone 1.9% ± 0.8%. Both differed significantly from placebo (P < 0.05).
Adding progesterone to estradiol brought the PCNA labeling index to 6.5% ± 4.4%, a significant reduction from the estradiol group (P < 0.05).
Mitotic index, a count of dividing cells, was significantly lower with progesterone than placebo and higher with estradiol than progesterone (P < 0.05), and comparable to placebo with estradiol plus progesterone.
The mitotic index and the PCNA labeling index correlated significantly, with a correlation coefficient of 0.50 (P < 0.05).
Interpretation
This randomized, double-blind trial assigned women to placebo, progesterone, estradiol or combined gel, so the arms could be compared directly. Women had surgery for a breast lump, and tissue came from a normal-appearing area after 10 to 13 days of gel use. Surgery was timed before presumed ovulation. The gels produced markedly different hormone levels in breast tissue and limited changes in blood. The outcomes were cell-division markers, and each analyzed group held between 7 and 9 women. The authors note that the data give no information about shorter progesterone exposure. Besins-Iscovesco supplied the gel and, with Orient Europharma, supported the study.
RRM Context
Restorative reproductive medicine centers on ovulation, after which progesterone rises in the luteal phase. The authors say their data strongly support a favorable effect of progesterone on the breast cell cycle in a normal luteal phase. They name synthetic progestins as a source of bias in earlier studies. Restorative clinicians keep progesterone and progestin as separate terms.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To study the effect of E2 and P on the epithelial cell cycle of normal human breast in vivo.
Design
Double-blind, randomized study. Topical application to the breast of a gel containing either a placebo, E2, P, or a combination of E2 and P, daily, during the 10 to 13 days preceding breast surgery.
Patients
Forty premenopausal women undergoing breast surgery for the removal of a lump.
Main Outcome Measures
Plasma and breast tissue concentrations of E2 and P. Epithelial cell cycle evaluated in normal breast tissue areas by counting mitoses and proliferating cell nuclear antigen immunostaining quantitative analyses.
Results
Increased E2 concentration increases the number of cycling epithelial cells. Increased P concentration significantly decreases the number of cycling epithelial cells.
Conclusion
Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.
General Gynecology › Breast Health › Breast Cancer Risk · Reproductive Endocrinology › Ovarian Hormones › Progesterone · Therapeutics › Hormonal Agents › Progesterone and Progestins
King-Jen Chang, Tigris T. Y. Lee, Gustavo Linares-Cruz, Sabine Fournier, Bruno de Lignières
K Chang, T Lee, G Linares-Cruz, S Fournier, B Lignières
PMID 7890063 7890063 DOI 10.1016/s0015-0282(16)57482-2 10.1016/s0015-0282(16)57482-2 Chang et al. 1995, Chang 1995
05tr67282 