Major approaches of molecular and physiopathological mechanisms for hormonal treatment of melasma: a systematic review

Introduction: Epidemiological data showed that melasma occurs in 14.5% -56% of pregnant women and in 11.3% -46% of individuals who take oral contraceptives in different countries. In this respect, by inducing the synthesis of melanogenic enzymes, such as tyrosinase and proteins related to tyrosinase 1 and 2, estrogens stimulate melanogenesis in human melanocytes. The increase in progesterone levels that occurs during pregnancy and the increase in estrogen production that occurs from the eighth to the thirtieth week of pregnancy reflects the progression of hyperpigmentation. Objective: The main predictors, pathophysiological mechanisms, and experimental and clinical results of melasma were addressed through a systematic literature review, discussing the main outcomes of clinical studies. Methods: The present study followed a systematic review model. After literary search criteria using MeSH Terms, a total of 98 clinical studies were compared and submitted to eligibility analysis and, after that, 70 studies were selected, following the rules of PRISMA. The search strategy was carried out in the databases PubMed, Embase, Ovid and Cochrane Library, Web Of Science, ScienceDirect Journals (Elsevier), Scopus (Elsevier), OneFile. Results: Sex hormones, such as estrogens, especially 17-β-estradiol (E2) and progesterone, are factors involved in the regulation of pigmentation. Levels of estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were found to be higher in the serum of women with melasma. Estrogen and progesterone receptors are expressed differently in melasma skin than in perilesional or non-lesional skin. Few authors have analyzed the effects of progesterone on pigmentation, and no data has been reported with concentrations of progesterone found in non-pregnant men and women. An increase in keratinocyte proliferation was observed with baseline progesterone concentrations. It is well known that keratinocytes secrete exosomes and factors that regulate melanogenesis, differentiation, and proliferation of melanocytes. Progesterone is involved in the pathogenesis of melasma, stimulating melanogenesis in epidermal melanocytes. Conclusion: The prevention of melasma can occur by progesterone components in oral contraceptives since progesterone can reduce melanocyte proliferation without significant effects on tyrosine activity. Estrogen can increase melanogenesis in the melanocyte monolayer and induce the production of melanogenic factors by keratinocytes. Estrogen can support hyperpigmentation, increasing the number of blood vessels and, thus, stimulating the secretion of endothelin-1.