Journal of Clinical and Aesthetic Dermatology

FEB 2018

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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55 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2 R E V I E W while two patients also had an affected male relative. 25 However, to date, there have been no gene association studies on melasma. The variation in positive genetic predisposition across various studies and populations could be due to the multifactorial causation of melasma, suggesting that the development of the disease might be related to epigenetic hormonal control and other environmental stimuli, such as UV radiation. Sun exposure is known to be an important etiological factor in causing melasma, irrespective of sex. 18 UV radiation (UVA and UVB) increases proliferation and melanocyte activity, causing epidermal pigmentation, that occurs more intensely in melasmic areas with melasma than in unaffected skin. 26,27 This is further substantiated by the findings that melasma usually improves during the winter and worsens during the summer months(or during other periods of intense sun exposure). Moreover, prevalence is high in tropical regions and high elevation areas. 17 Recently, infrared radiation and visible light have been found to cause melasma, although not as severely as UV radiation. 28 In a majority of studies on men with melasma, sun exposure was documented as the main cause. In a study by Sarkar et al, 5 48.8 percent of the male patients reported sun exposure compared to 23.9 percent of female patients. Among these 41 men with melasma, 24 (58.5%) were outdoor workers and 12 (29.3%) lived in high elevation regions of north India. Similar findings were reported in two other studies where 45.16 percent (n=31) and 81.4 percent (n=) of the subjects had histories of chronic sun exposure. 16,17 In women, hormonal factors, such as pregnancy, oral contraceptive pills, hormonal therapy, and mild ovarian dysfunction, are considered to be some of the most common etiological factors in the development of melasma. 29 Hormonal imbalances between estrogen and testosterone might play a role in the development of melasma in men. Estrogen is known to lower blood testosterone and suppress the secretion of leuteinizing hormone (LH) and follicle stimulating hormone (FSH), which further increases estrogen levels by reversing the LH- and FSH- induced suppression. The effects of estrogen on melanocytes and induction of pigmentation in melasma are well-documented. 31 Several aspects of melanocyte function respond directly to estrogenic stimulation, which takes place through the estrogen receptors present on the melanocytes in the cytoplasm and nucleus. Estrogen increases melanin synthesis by stimulating the activity of tyrosinase enzyme. Further, it increases the extrusion of melanin from the cells. Several studies have found increased estrogen levels in women with melasma. Tadokoro et al 32 indicated that testosterone affects human melanocytes by reducing the level of intracellular cyclic adenosine monophosphate and tyrosinase activity, thereby decreasing melanogenesis. The two studies noted low testosterone levels in Indian men with melasma (Table 2). In one of these studies, hormonal evaluation in men with melasma revealed increased LH and low testosterone in four men (9.7%). 5 The second study evaluated 15 men with melasma (aged 20–40 years, 2-month to 1.5-year melasma duration, 11 age-matched controls), and found a significantly high level of circulating LH coupled with low levels of testosterone and normal LH/ FSH ratio compared to controls. These findings suggests the presence of subtle testicular resistance in men with melasma. 30 Presence of mild subclinical ovarian dysfunction was reported in a study of nine women with idiopathic melasma; the women showed increased levels of LH along with lower estradiol levels compared to normal age- and sex-matched controls. 31 This is in contrast to a majority of studies that have reported increased levels of estrogen in female patients, which implies that melasma patients have some degree of mild endocrinopathy. Besides the endogenous hormonal factors, exogenous or iatrogenic administration of hormonal medications have shown to induce melasma. Several cases of melasma following hormone therapy (e.g., estrogen therapy, 33 fosfestrol tetrasodium, 34 an androgenic agent, Andro-6, 35 and finasteride 36 ) have been reported. Finasteride is hypothesized to increase testosterone, which is available for aromatization to estradiol, resulting in the subsequent induction of melasma pigmentation. 36 The use of cosmetics and consumption of certain drugs and other photosensitizing substances have also been implicated in melasma induction. An Indian study observed that the use of mustard oil for body and hair massage was more common in men with melasma (43.9%) than women (31.4%), though the difference was statistically insignificant (Table 1). 5 Mustard oil acts as a photosensitizer, which can lead to facial pigmentation, predominantly on the forehead and the temporal region of the face. Labeled as toxic melanoderma in India, this form of pigmentation is difficult to differentiate from melasma. However, since the use of mustard oil was found in a significant number of patients in this study, one might postulate that mustard oil plays a role in the development of melasma among patients who use it. 5 Further studies are needed to substantiate the relationship between mustard oil and melasma. The possibility of exogenous substances causing melasma in men is lower than that of women due to comparatively lesser use of cosmetics among men. Studies have not been able to establish any association between the melasma and the use of any chemical. In the study by Vazquez et al, 16 use of cosmetics like soaps, shaving creams, aftershave, and perfumes were documented in 25 (92.6%) men with melasma. Use of a single cosmetic could not be identified among the patients, and none of the patients attributed the development of melasma to the use of cosmetics. 16 The drug phenytoin has shown to be a causative agent in 6.45 percent and 7.3 percent of men with melasma in two Indian studies. 5,17 Recently, imatinib has also been shown to induce melasma. 37 Certain chronic illnesses have been identified in men with melasma (3 men had a thyroid disorder, 1 had inflammatory bowel disease, and 1 had recently recovered from typhoid). In women with melasma, chronic illness was observed in 20.1 percent (n=32) (Table 2). However,the TABLE 2. Hormonal evaluation in men with melasma REFERENCE COUNTRY NUMBER OF PATIENTS RESULTS TESTOSTERONE LH FSH E2 Sialy et al, 30 2000 India 15 Low High - - Sarkar et al, 5 2010 India 41 Low High - - Ogita et al, 33 2015 Japan 1 Low Low Low Low LH: luteinizing hormone; FSH: follicular stimulating hormone; E2: Estradiol

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