PROJECT
Female Hormone Therapy

Selecting a progestin for female hormone therapy (HT) involves several considerations. In addition to its efficacy, and of paramount importance, a progestin for HT should exhibit the highest benefit-to-risk ratio.

Physiological levels of progestins can promote either proliferation or differentiation in breast tissue. A progestin for HT should either have no growth-promoting effects or exert an antiproliferative effect on breast tissue. Studies of combined estrogen and progestin treatments have indicated an increased risk of breast cancer with long-term use of hormone replacement therapy (HRT). In abnormal breast tissue, certain progestins can decrease or increase tumor growth.

The antiprogestin CDB-2914 is a progesterone receptor modulator (PRM). To determine the potential for safe inclusion of CDB-2914 in contraception and HRT, the biological properties of this PRM on growth and hormone responsiveness of human mammary adenocarcinoma (MCF-7) cells were further studied. Utilizing this breast cancer model system, several biological parameters shown to be useful prognostic indicators for breast cancer progression were monitored. Using flow cytometry, the cell cycle status of synchronized MCF-7 cells following a 24-hour treatment with 17β-estradiol (E₂), progesterone, or CDB-2914 was analyzed. In contrast to E₂, CDB-2914 had no mitogenic effect upon MCF-7 cells when used alone or in combination with E₂. New data from these molecular biology studies suggest that CDB-2914 may offer additional advantages for contraception and hormone replacement. 

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Population Council researchers

Anke Diemert (fellow), Deborah Lazzarino, Patricia L. Morris, Régine Sitruk-Ware

Donors

National Institute of Child Health and Human Development/US National Institutes of Health

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