Hormonal and reproductive factors in relation to melanoma in women: Current review and meta-analysis Sara Gandini a, * , Simona Iodice a , Els Koomen b , Alessandra Di Pietro c , Francesco Sera d , Saverio Caini e a Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy b Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands c Division of Sarcoma and Muscolo Cutaneous Melanoma, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy d Medical Research Council Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK e Molecularand Nutritional Epidemiology Unit, ISPO, Scientific Institute of Tuscany, Via di San Salvi 12, 50135 Florence, Italy ARTICLE INFO Article history: Available online 26 May 2011 Keywords: Hormones Oestrogens Menopause Menarche Parity Education Melanoma Meta-analysis ABSTRACT A number of studies have focused on possible relationships between characteristics of female endocrine status and melanoma (CM) risk; however, the link between melanoma, oral contraceptive (OC) and hormonal replacement therapy (HRT) use, and reproductive factors remains controversial. A comprehensive, systematic bibliographic search of the medical literature was conducted to identify relevant studies. Random effects models were used to summarise results. Subgroup, meta-regression and sensitivity analyses have been carried out to explore sources of between-study variation and bias. We included thirty-six observational studies published in the last 30 years. Summarising a total of 5626 melanoma cases, we did not find any significant melanoma risk associated with OC and HRT use. Sev- eral reproductive factors were also investigated, summarising data on 16787 melanoma cases. We found a significantly increased melanoma risk for late age at first birth, and women with more than one child may be at a lower risk for melanoma; however, socio-eco- nomic confounders were found to play a significant role in explaining this association. This study confirmed no increased risk of CM with the use of oral contraceptives and hormone replacement therapy: exogenous female hormones do not contribute to an increased risk of CM. In contrast, significant associations of CM with parity and age at first pregnancy were observed in this meta-analysis finds and warrant further research. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction A number of epidemiological studies from the 1980s focused on possible relationships between characteristics of female endocrine status and melanoma (CM) but substantial contro- versy exists on potential hormonal effects on melanoma risk. The original concerns arose from some case reports of CM in pregnancy and the observation of hyperpigmentation during OC use and reports of nevi darkening and enlarging during pregnancy. 1–3 Additionally, animal experiments have shown increases in melanin production or melanocyte number in associa- tion with oestrogens and oestrogens/progesterone combi- nations. 4,5 Moreover, the influence of female sex steroids on mela- noma is supported by several observational studies. Incidence 0959-8049/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2011.04.023 * Corresponding author: Tel.: +39 02 57489819; fax: +39 02 57489922. E-mail address: sara.gandini@ieo.it (S. Gandini). EUROPEAN JOURNAL OF CANCER 47 (2011) 2607 – 2617 available at www.sciencedirect.com journal homepage: www.ejconline.com