Molecular action of norgestimate: new developments

Abstract

Background: Acne occurs because the sebaceous glands are overstimulated by high levels of androgens or are hypersensitive to normal levels of testosterone. In women with mild or moderate acne, the association of norgestimate (NG), and ethinyl estradiol (EE) is an effective treatment. This is related to the effect of oral contraceptives on androgen production and transport and the antiandrogenic properties of NG itself.

Design: The present work was undertaken to find out whether NG and its derivative, 17-deacetylnorgestimate(dNG), present steroid activities other than antiandrogen activities, using human progesterone receptor(PR), estrogen receptor α(ERα) and β(ERβ), glucocorticoid receptor(GR) and mineralocorticoid receptor(MR)-responsive cell lines.

Results: We confirmed that NG and its metabolite were progestogen partial agonists (EC₅₀ of 13 and 11.1 nM) and ERα selective agonists (EC₅₀ of 30.4 and 43.4 nM), as well as full antagonists of low affinity for GR (IC₅₀ of 325 and 255 nM) and moderate affinity for MR (IC₅₀ of 81.2 and 83.7).

Conclusion: We demonstrated that NG and dNG have full progestogen and weak estrogenic (through ERα) properties, which could explain in part the efficacy of NG in association with EE for the treatment of moderate acne in women. Moreover, their antagonist MR activity might have a favorable impact on cardiovascular risk, atherosclerosis and lipid profiles.

• Androgen receptor
• estrogen receptor
• hormonal contraception

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.