In the last years there has been an extraordinary development in the synthesis of
new progestins. These compounds are classified, in agreement with their structure,
in various groups which include progesterone, retroprogesterones, 17alpha-hydroxyprogesterones,
19-norprogesterones, 17alpha-hydroxyprogesterone derivatives, androstane and estrane
derivatives. The action of progestins is a function of many factors: its structure,
affinity to the progesterone receptor or to other steroid receptors, the target tissue
considered, the biological response, the experimental conditions, dose, and metabolic
transformation. The information on the action of progestins in breast cancer patients
is very limited. Positive response with the progestins: medroxyprogesterone acetate
and megestrol acetate was obtained in post-menopausal patients with advanced breast
cancer. However, extensive information on the effect of progestins was obtained in
in vitro studies using hormone-dependent and hormone-independent human mammary cancer
cell lines. It was demonstrated that in the hormone-dependent breast cancer cells,
various progestins (nomegestrol acetate, tibolone, medrogestone, promegestone) are
potent sulfatase inhibitory agents. The progestins can also involve the inhibition
of mRNA of this enzyme. In another series of studies it was also demonstrated that
various progestins are very active in inhibiting the 17beta-hydroxysteroid dehydrogenase
for the conversion of estrone to estradiol. More recently it was observed that the
progestins promegestone or medrogestone stimulate the sulfotransferase for the formation
of estrogen sulfates. Consequently, the blockage in the formation of estradiol via
sulfatase, or the stimulatory effect on sulfotransferase activity, by progestins can
open interesting and new possibilities in clinical applications in breast cancer.