ISPO

The problem of transposition of steroid mediated antiproliferative activities to the clinical outcome - the example of the hybrid progestin dienogest

Doris Huebler, Michael Oettel and Thomas Graeser

Department of Research and Development, Jenapharm GmbH & Co. KG, 07745 Jena, a Subsidiary of Schering AG Berlin, Germany

Dienogest (17 &alpha-cyanomethyl-17 &beta-hydroxy-4,9-estradien-3-one) combines the benefits of 19-norprogestins with the typical properties of the 17 &alpha-hydroxyprogesterone derivatives. Dienogest is the first representative of the so-called hybrid progestins and is entering the oral contraceptive market in combination with ethinyl estradiol (Valette®, Celimona®) and the hormone replacement segment in combination with estradiol valerate (Lafamme®, Climodien®). In a variety of in-vitro as well as in-vivo models using endometrial as well as mammary endpoints dienogest shows distinct antiproliferative activities. In clinical studies, the proliferative action of concomitant estrogen on the endometrium is clearly abolished by dienogest (histologically atrophic state of the endometrium, reduced serum glycodelin levels). Additionally, the IGF-1 serum concentrations are reduced. In a double blind clinical study using fine needle biopsy specimens (performed by Bo von Schoultzs group at Karolinska Institutet) Ki67 as a chosen marker for the proliferation of mammary cells was significantly elevated after three months of the treatment with the combination of estradiol valerate plus dienogest. On the other hand, there was a drop of Ki67 positive cells after 6 months' treatment.

For more information, contact ivonne.heothch@jenapharm.de

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prevention.

http://www.cancerprev.org/Journal/Issues/26/101/1093/4552