At present, more than 200
progestin compounds are synthetized, but their
biological effects are different: this is function of their structure, receptor affinity, metabolic transformations, the target tissues considered, dose. The action of
progestins in
breast cancer is controversial; some studies indicate an increase in
breast cancer incidence, others show no differences, and yet others indicate a decrease. Many studies agree that treatment with
progestins plus
estrogens at a low dose and during a limited period (less than 5 years) can have beneficial effects in peri- and post-menopausal women. It was demonstrated that various
progestins (e.g.
nomegestrol acetate,
medrogestone,
promegestone), as well as
tibolone and its metabolites, can block the
enzymes involved in
estradiol bioformation (
sulfatase, 17beta-
hydroxysteroid dehydrogenase) in
breast cancer.
Progesterone is converted into various metabolic products: in normal breast tissue the transformation is mainly to 4-ene derivatives, whereas in the
tumor tissue 5alpha-pregane derivatives are predominant.
Aromatase activity is the last step in the formation of
estrogens by the conversion of
androgens. In recent studies it was shown that 20alpha-dihydroprogesterone, a metabolite found mainly in normal breast tissue and having anti-proliferative properties, can act as an anti-
aromatase agent. The data suggest the possible utilization of this compound in
breast cancer prevention. In conclusion, in order to clarify and better understand the response of
progestins in
breast cancer (incidence and mortality), as well as in
hormone replacement therapy or in endocrine dysfunction, new clinical trials are necessary using other
progestins in function of the dose and period of treatment.