Assessment of the activity of an oral contraceptive on the levels of oxidative stress and changes in oxidative stress after co-treatment with two different types of physiological modulators with antioxidant action.

BACKGROUND: The aims of this research were to document the nature of oxidative stress (OS) while taking an estrogen/progestagen-combined oral contraceptive (OC) and to evaluate the action of two different products composed of a combination of antioxidant, vitamins and natural products in physiological quantity and classified as antioxidant/food supplement. For this reason, the two products are classified as physiological modulators (PM), able to restore the balance between antioxidants and reactive oxygen species in the organism. STUDY DESIGN: The Reactive Oxygen Metabolites-derived compound test, a photometric assay that measures the hydroperoxides levels in biological fluids, was used to determine the OS. OS was analyzed every 3 days (from t(1) to t(27)) for 28 days on 10 healthy volunteers during three successive OC treatment cycles with a contraceptive (Microgynon®: ethinylestradiol 50 mcg plus levonorgestrel 125 mcg). In the first cycle, the OC was administered by itself; in the successive two cycles, the OC was administered in association in an open crossover study with two different types of PMs with antioxidant action. The main difference in the composition of the two products is the presence/absence of catechins from green tea. RESULTS: With just OC treatment, all the volunteers showed an increase in the OS values from 240±22.3 (mean±SD) Carratelli Units. (normal value) up to values >400 Carratelli Units (severe OS), then returned to normal when the OC therapy was suspended. The concomitant use of the two PMs showed that only the product containing green tea catechins was able to reduce the OS values, on average, by approximately 50% (t test p<.05). CONCLUSION: We conclude that to control the OS generated by OC, specific types of physiological modulators are needed.

Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.

Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.