Background: The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women... Show moreBackground: The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women, a contribution of sex hormones has been proposed.Objectives: We undertook this systematic literature review to investigate: (1) the role played by male and female sex hormones in the pathogenesis of SSc; (2) how sex hormone levels change in SSc patients and how hormonal variations modify the progression of SSc; (3) the effect of therapies targeting sex hormones on the disease course.Methods: A literature search was performed in Pubmed, Embase, Web of Science, and Cochrane library databases. Given the heterogeneity in study design, different quality assessment tools were applied where appropriate.Results: We retrieved 300 articles and 30 were included in the review. The available evidence points to a fibrogenic, but also a vasodilatory, role of estrogens in SSc. With the limitation of small sample sizes, women with SSc tend to have lower levels of androgens and non-significantly higher levels of estradiol compared to healthy controls, while in men we found increased levels of estradiol and discordant results for androgens. After menopause the skin score seems to decrease and prevalence of pulmonary artery hypertension seems to rise, which might be prevented by the use of hormone replacement therapy. No recent high-quality trial evaluated the efficacy of hormone-targeting therapies in SSc.Conclusions: Few translational studies of varying quality evaluated the role of sex hormones in SSc showing possible profibrotic and vasodilatatory effects of estrogens, but more research is needed to elucidate the extent of this contribution. Insights on the influence of sex hormones, along with the availability of new compounds acting on estrogen pathways, might provide ideas for additional studies on the application of sex hormone-targeting therapies in SSc. (C) 2019 Elsevier Inc. All rights reserved. Show less
Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of... Show moreCutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are lacking, melanoma prevention may be the key issue in melanoma disease control. Although sun protection programs have increased awareness, they have not resulted in a decreased melanoma incidence. In addition, most melanoma risk factors are not amenable. Alternative approaches such as cancer chemoprevention are, therefore, important research topics. Several agents, such as statins, non-steroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors, have been claimed to have chemopreventive properties. However, it is unknown which of these have the best potential to be useful. This thesis presents: - epidemiologic cancer registry-based studies from The Netherlands on the epidemiology of extracutaneous melanoma and on the burden of disease due to cutaneous melanoma - a qualitative review discussing candidate drugs for melanoma chemoprevention, their possible mechanisms of action, and evidence for their chemopreventive efficacy, safety and tolerability - pharmacoepidemiological studies testing hypotheses on chemopreventive activityof several drugs on melanoma - pharmacoepidemiological studies on the association between estrogen use and melanoma. Show less
