Inhibitory effects of progestogens on the estrogen stimulation of melanocytes in vitro

Background: The use of oral estrogen-progestogen contraceptives may cause melasma, an epidermal hyperpigmentation in sun-exposed areas of the face. It is assumed that elevated estrogen levels lead to the activation of melanocytes, while the role of the gestagen component of contraceptives in pigmentation remains unclear and may vary between the different progestogens. In this study, we analyzed the distinct effects of progesterone and chlormadinone acetate (CMA) on melanocytes in comparison with estrogen. Study Design: Human melanocytes were exposed to different concentrations of 17 beta-estradiol and progestogens and analyzed for proliferation by a fluorometric cell viability assay and for pigmentation by a H-3-labeled tyrosine assay. Subgroups of cells were additionally irradiated with UVA or UVB. Results: Proliferation of melanocytes was induced by 17 beta-estradiol (0.1 and 1 nM) in approximately half of the experiments, while progesterone (100 nM) and CMA (100 nM) reduced the proliferation rate by 38% and 27%, respectively. The pigmentation activity was slightly stimulated by 17 beta-estradiol, whereas progestogens had no effect on the tyrosinase activity. Conclusions: Our data suggest that progesterone and CMA can inhibit proliferation of human melanocytes, which counteracts the stimulatory effects of estrogen. This may be of relevance for the choice of progestogen in oral contraceptives to prevent the development of melasma. (C) 2009 Elsevier Inc. All rights reserved.