|Year : 2015 | Volume
| Issue : 2 | Page : 85-90
Hormonal profile of melasma in Indian females
Kiran Gopichandani1, Pooja Arora1, Umesh Garga2, Minakshi Bhardwaj3, Neera Sharma4, Ram Krishan Gautam1
1 Department of Dermatology, Post Graduate Institute of Medical Education and Research (PGIMER) and Dr. Ram Manohar Lohia Hospital, New Delhi, India
2 Department of Radiology, Post Graduate Institute of Medical Education and Research (PGIMER) and Dr. Ram Manohar Lohia Hospital, New Delhi, India
3 Department of Pathology, Post Graduate Institute of Medical Education and Research (PGIMER) and Dr. Ram Manohar Lohia Hospital, New Delhi, India
4 Department of Biochemistry, Post Graduate Institute of Medical Education and Research (PGIMER) and Dr. Ram Manohar Lohia Hospital, New Delhi, India
|Date of Web Publication||29-Dec-2015|
9547, Sector C, Pocket 9, Vasant Kunj, New Delhi - 110 070
Source of Support: None, Conflict of Interest: None
Background: Several factors have been implicated in the etiology of melasma which include ultraviolet radiation, genetics, pregnancy, skin type, and drugs. However, there is a paucity of literature regarding the role of endocrine factors. Aim: To study the clinical and hormonal correlation in female patients with melasma. Methods: A total of 30 untreated female patients with melasma were included in the study. The control group included an equal number of age-matched females. Assays of free testosterone, total testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, luteinizing hormone (LH), follicle stimulating hormone, prolactin, 17β-estradiol (E2), progesterone, free triiodothyronine, free tetraiodothyronine, thyroid stimulating hormone were done on the 5th or 6th day of the menstrual cycle in the midfollicular phase. Results: The difference between means of free testosterone, total testosterone, LH, estradiol, progesterone, and free thyroxine of melasma cases and controls was found to be statistically significant. No correlation was found between the severity of melasma and the mean hormone levels. Conclusion: It can be inferred that these hormonal alterations may represent a subclinical evidence of a suppressed hypothalamic-gonadal axis and preclude the role of hormones in the pathogenesis of melasma.
Keywords: Hormones, Indian females, melasma
|How to cite this article:|
Gopichandani K, Arora P, Garga U, Bhardwaj M, Sharma N, Gautam RK. Hormonal profile of melasma in Indian females. Pigment Int 2015;2:85-90
| Introduction|| |
Melasma is one of the most common causes of acquired hyperpigmentation of sun exposed skin, especially face. The entity is known since 1859; however, its etiology remains an enigma till date. Several factors have been reported to be associated with melasma which include ultraviolet radiation (the most important factor), genetic factors, pregnancy, skin type, cosmetics, nutrition, phototoxic and photoallergic medications, oral contraceptives, estrogen and progesterone therapy, hepatic diseases, parasitosis, ovarian tumors, thyroid dysfunction, and vascular factors.,, There are limited studies available which evaluate the role of endocrinal factors in the causation of melasma. A few studies have sought to elucidate the precise role of hormones in influencing the process of melanogenesis. Nevertheless, the majority of information gathered is through indirect inferences concluded from the study of melanocytic hormones (α-melanocyte stimulating hormone [MSH], adrenocorticotropic hormone [ACTH]), insulin-like growth factor, estrogens, and progesterone and through the quantification of tyrosinase-related proteins (TRP-1 and TRP-2)., The role of “hormonal milieu” in the maintenance of melasma in fertile women and men has also been studied in the literature., The role of thyroid hormones has been evaluated by Lutfi et al. who suggested that estrogen, progesterone or both could be the triggering factor in development of melasma in women who have a particular predisposition towards both melasma and thyroid autoimmunity.
Thus, melanocytes in melasma may have undergone functional alteration due to a combination of different etiological factors, some being autoimmune such as thyroid autoimmunity. The studies measuring androgens in females are not available; however, in male patients of melasma, androgens have been measured in a few studies.,,
| Methods|| |
A total of 30 menstruating female patients of age group between 18 and 50 years of age with melasma attending the dermatology outpatient department of our tertiary care hospital were enrolled over a period of 1 year in this prospective study, after taking a fully informed bilingual written consent. Written permission was obtained from the Institutional Review Board and clearance sought from the Ethical Committee. Patients on treatment for melasma, pregnant, lactating, and postmenopausal females were excluded from the study. Exclusion criteria also included patients on oral contraceptives, hormone replacement therapy, those with irregular menstrual cycles and intrauterine devices, and those with a history of alcohol abuses or intake of drugs known to exacerbate melasma. Patients suffering from any other pigmentary disorder or with a history of endocrinopathy were also excluded. Polycystic ovary syndrome (PCOS) was diagnosed based on Rotterdam criteria  (2 of the 3 criteria to be fulfilled: Oligoanovulation and/or anovulation, clinical and/or biochemical signs of hyperandrogenism, polycystic ovarian morphology by ultrasonography) and such patients were excluded. A detailed history was taken and thorough physical examination (to look for signs of hormonal disturbances such as hirsutism, striae, obesity, alopecia, enlarged ovaries) was performed. Wood's lamp examination was done in all patients to determine the type of melasma. A 3 mm punch biopsy was taken from the lesional skin of the face of consenting patients. Melasma Area Severity Index (MASI) was calculated to determine the severity of melasma. Ten ml of blood was taken after overnight fasting on the 5th or 6th day of menstrual cycle for the assessment of various hormones that is, free testosterone, total testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol, progesterone, free triiodothyronine (fT3), free tetraiodothyronine, and thyroid stimulating hormone (TSH) along with other investigations which included complete hemogram, liver function tests, kidney function tests, fasting and postprandial blood glucose, serum electrolytes, lipid profile, and urine examination including microscopy. Ultrasonography of abdomen was also performed on the 5th or 6th day of the cycle in all patients to rule out any organomegaly and that of pelvis to exclude PCOS in the study group. The equal number of age and sex-matched healthy controls were recruited for the study. These included healthy volunteers and healthcare workers without any history of pigmentary or endocrine disorders. The controls were subjected to ultrasonography and hormonal assessment.
The descriptive statistics such as proportions and means were used to assess the association between the hormone levels and the presence or absence of melasma. The difference in the level of hormones between the study and the control group was compared using “Student's t-test” and “Mann–Whitney U-test.” A “P value” of 0.05 or less was considered to be significant for all statistical tests.
| Results|| |
The age of presentation in the present study ranged between 25 and 48 years of age. The mean age of presentation was 34.23 ± 6.44 years. The maximum number of cases (i.e., 53.33% of the total) was in the age group of 31–40 years. The age of onset in the present study ranged between 21 and 45 years of age. The mean age of onset was 30.4 ± 6.9 years. The duration of melasma ranged from 1 to 9 years. The mean duration of melasma before seeking medical advice was 3.83 ± 2.37 years. Twenty patients (90%) were married females and only 10% were unmarried girls. Melasma in 25 (83.3%) patients was related to pregnancy. Seven had onset of melasma during pregnancy while 18 patients had postpregnancy melasma. Five (16.66%) patients that is, 3 unmarried, and 2 nulliparous patients had no relation to pregnancy. The mean age of menarche seen in our patients was 14.43 ± 1.25 years and the range was between 12 and 16 years. No correlation was observed between the age at menarche and the age of onset of melasma (P > 0.05). The family history of melasma in the first degree relatives was noted in 33.33% patients. The mean duration of sun-exposure was 2.53 ± 1.49 h. Forty percentage of our patients complained of exacerbation of melasma during summers while only 2 patients (6.66%) reported increase during winter season. Thirty percentage of patients used cosmetics. The majority of these included over the counter fairness creams, winter cold creams, mustard oil, and coconut oil. The most common pattern of melasma was centrofacial (53.33%) whereas 14 patients had malar type (46.66%) [Figure 1] and [Figure 2]. None of the patients in the present study had mandibular type of melasma. The maximum number of patients that is, 60% had mixed type of melasma while dermal melasma was seen in only 1 patient. Epidermal type of melasma was seen in 36.66% of patients. Only 13 patients consented for biopsy. Eleven patients (84.61%) had features consistent with mixed variety while dermal type of melasma was not seen in any patient. Only 2 patients had features consistent with epidermal variety. Nineteen patients (63.33%) of melasma had anemia (Hb < 12 g%). Three (10%) of patients of melasma had blood glucose levels in the diabetic range (fasting >126 mg% and post-prandial >200 mg%). About 23.33% and 3.33% of the patients were overweight and obese, respectively. The range of body mass index (BMI) was between 18.1 and 30.1 kg/m 2. The mean BMI in our study was 23.11 ± 3.01. None of our patients had any abnormality on pelvic ultrasound. The hormonal assessment of patients and controls is summarized in [Table 1]. The difference between the means of free testosterone, total testosterone, LH, estradiol, progesterone, and free thyroxine of melasma cases and controls was found to be statistically significant. No correlation was found between the severity of melasma (as assessed by MASI score) and the mean hormone levels [Table 2].
|Table 2: Correlation between the severity of melasma (MASI score) and mean hormone levels|
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| Discussion|| |
The mean age of the 30 patients in our study was 34.2 ± 6.4 years and the age of onset of melasma was 30.4 ± 6.9 years which is in agreement with findings of Lufti et al. Pérez et al. reported mean age in melasma as 30.8 years. It is clear from this data that melasma is a disease of young population in the age group of 18–40 years who are likely to be indulging more in outdoor activities both for economic reasons and sporting and leisure activities. Further, pregnancy and the usage of oral contraception are likely in this age group.
The average duration of melasma in our patients was 3.83 years. Seven patients had onset of melasma during pregnancy while 18 patients that is, 72% of the pregnant group of patients had melasma after the pregnancy (postpregnancy). Ortonne et al. had reported pregnancy-related melasma in 68% of 324 patients enrolled during the global survey in their study. They also reported that the most common time of onset of melasma was after pregnancy that is, 42% while 26% had noted melasma during pregnancy. We also found melasma during pregnancy in 23.3% patients.
In our study, family history of melasma in the first degree relatives was found in a third of the patients which is well documented in earlier studies. The mean duration of sun-exposure in 30 patients was 2.53 ± 1.49 h (range: 0.5–6 h). Forty percentage patients noticed summer exacerbation of melasma.,
Nine patients in the study group used different cosmetics which included various fairness cream, mustard oil, and coconut oil. Further, it is interesting to note that cosmetics is used to camouflage melasma, but it should always be kept in mind that same products can induce or exacerbate melasma.
Twenty patients (66.66%) had BMI varying between 18.5 and 24.9 which is within the normal limits. However, 7 patients (23.33%) were overweight and had BMI between 25 and 29.9, while one patient (3.3%) was obese (>30). Three diabetics were detected, one each from the respective BMIs range described above. There is no study available in the literature that evaluates the relation between BMI and melasma. However from the present study, it is clear that the majority of the patients of melasma are likely to have normal BMI.
Thirteen patients of melasma who consented for skin biopsy were examined by hematoxylin and eosin stained sections. Eleven patients (84.61%) out of 13 patients showed features consistent with mixed variety [Figure 3] while none of them had features consistent with dermal type of melasma [Figure 4]. Only 2 patients had features consistent with epidermal variety. Sarkar et al. in their study on melasma in men reported that 20 patients out of 41 patients who consented for skin biopsy had epidermal type of melasma, 9 patients had mixed type, and only 1 patient had dermal melasma, histologically.
|Figure 3: Photomicrograph of skin biopsy showing epidermal thinning and flattening of rete ridges in a patient with epidermal melasma (H and E original magnification, ×1000)|
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|Figure 4: Perivascular melanin deposition in a patient with mixed melasma (H and E original magnification, ×400)|
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Lufti et al., have reported the occurrence of thyroid abnormalities in 58.3% of melasma patients which is almost 2.5 times (23.3%) of what we have found in our study. One person in control group had raised TSH, and another had raised fT3 that is, 6.6% in control group had thyroid abnormalities which is almost 3 times less than that found in the melasma patients in our study. This clearly establishes that the thyroid abnormalities are 3 (our study) to 4 times (Lufti et al.) more common in melasma patients. Pérez et al. in their study in 9 patients with idiopathic melasma found no abnormalities in total T4 and T3 reuptake levels.
Total and free testosterones were measured in all 30 patients. Seventeen patients had lower levels of total testosterone when compared with normal range (0.2–1) ng/ml. There was a significant decrease in total testosterone level (P < 0.001) when compared with control. There are no comparative studies available in the literature in females regarding total or free testosterone levels in melasma; however, studies by Sialy et al. and Sarkar et al. on male patients of melasma had found decreased testosterone levels along with increased LH levels thereby suggesting mild testicular resistance.,
Seven of our patients had decreased levels of DHEAS which was not found to be statistically significant (P > 0.05). Adalatkhah and Amani studied the correlation between melasma, ovarian cysts, and androgenic hormones in 101 cases of melasma and found significant difference in mean serum levels of DHEAS between cases and controls. Their findings are in contrast to our findings and can be explained by their inclusion of patients with acne, hirsutism, and ovarian cysts in melasma. The raised levels could be only due to the markers of androgenecity, and melasma could have been a fortuitous finding.
The levels of LH were measured in 30 patients out of which 1 patient showed increased level (22.8 mIU/ml) when compared with normal range (0.8–15.5 mIU/ml). Sialy et al., Sarkar et al., Pérez et al. and Hassan et al. have found increased levels of LH in their studies, however, the studies of Sialy et al. and Sarkar et al. were on males and they suggested “subtle testicular resistance” which leads to increased LH and its association with melasma.,,, The exact relationship between melasma and LH in induction or in the maintenance of melasma still needs to be elucidated. Pérez et al. found significantly increased levels of LH (P < 0.001) in their study on 9 patients. In our study on 30 patients, 1 patient showed increased level when compared with normal values; however, the mean and standard deviation were 6.14 ± 4.61 while in control group it was 8.46 ± 3.73 and the decrease in LH was found to be statistically significant P < 0.003 thereby suggesting mild pituitary dysfunction but needs to be corroborated further with larger sample size. From our study, it is clear that there is a significant decrease in LH which is in contrast to the findings of Pérez et al. and Hassan et al.,
FSH was also measured in our study and when compared with controls were not found to be significantly different. Pérez et al. measured FSH on day 5 of the menstrual cycle in 9 Puerto Rican females and found normal levels of FSH, as has been seen in our study. Hassan et al. measured FSH on day 5, 7, 9 and 11 of menstrual cycle and found significantly increased levels on day 7 and postulated that FSH along with high 17β-estradiol are needed for the maintenance of melasma. The exact role of FSH in the maintenance of melasma is still not known, however, FSH works along with other hormones in the genesis or maintenance of melasma.
The levels of prolactin in study and control group were not found to be significantly different (P > 0.05). The study by Pérez et al. also found normal levels in all 9 patients when compared with control group. However, the study by Hassan et al. who measured prolactin on day 9 of the cycle revealed that prolactin was significantly decreased when compared to control group. They concluded that some sort of specific 'hormonal milieu' is needed for the maintenance of melasma, but they did not specify the exact role of prolactin in the maintenance of melasma.
Measurement of 17β-estradiol in 30 patients in our study revealed decreased levels in 14 patients while only 2 patients showed increased level. The association between estradiol levels and melasma was found to be statistically significant (P < 0.007). The findings of decreased estradiol levels in melasma patients are in agreement with findings of Pérez et al. It reinforces the view that mild ovarian dysfunction might be an important causative factor in the development of melasma.
In our study, 1 (3.33%) patient with melasma had decreased levels of progesterone (normal level - 0.44–6.47 ng/dL). There was a significant decrease in progesterone level (P < 0.001) when compared with control group. Our findings are contradictory to those reported by Pérez et al. and Hassan et al. who in their studies reported no significant differences in the level of progesterone when measured on day 5 by Pérez et al., Hassan et al. measured progesterone in 36 ovulating women on day 17, 19, and 21 and did not report significant difference after comparing with the control group.
Of 30 cases included in our study group, only 4 patients had increased levels of 17-OHP and 26 patient had normal levels (0.2–1.3 ng/ml). Further, the increased levels of 17-OHP were not found to be statistically significant (P > 0.05) and no comparative study is available in literature. ACTH stimulation test was planned in these 2 patients to rule out nonclassical adrenal hyperplasia but could not be done since the patient was lost on follow-up.
To summarize, the lower levels of LH, estradiol, and progesterone in our cases as compared to controls indicate a suppression of hypothalamic-gonadal axis in these patients and preclude the role of estrogen and progesterone in the pathogenesis of melasma. Other estrogens such as estriol and estrone (which were not measured in the current study) could have a pathogenic role as both cytoplasmic and nuclear receptors for estrogen are known to express in the melanocytes. It is also possible that over expression of the estrogen receptors or increased responsiveness to circulating estrogens could be causally associated with melasma. We also observed low testosterone in our patients as compared to the control group. Both ovaries and adrenals contribute to circulating levels of androgens and low testosterone and estradiol again points toward a suppressed gonadal function.
Limitations and strengths of this study
The sample size is small which was due the limited duration of the study and also limited availability of resources. Serum levels of ACTH, cortisol, and MSH should have been assessed. This could have helped us in reinforcing our conclusions and also would have enabled us to assess the relation between hormonal factors and melanogenesis. These could not be done due to financial constraints.
However, this is the first Indian study that has evaluated the entire hormonal profile in patients with melasma. Our study explored the endocrine influences in this pigmentary disorder and provides evidence to suggest subclinical hypothalamic-gonadal axis suppression which needs to be proved further with randomized studies.
| Conclusion|| |
It can be inferred that the hormonal alterations in melasma may represent a subclinical evidence of a suppressed hypothalamic-gonadal axis and preclude the role of hormones in the pathogenesis of this condition. Further studies with larger number of patients need to be carried out to prove the role of hypothalamic-gonadal axis in melasma.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors acknowledge Dr. Bindu Kulshreshtha, Associate Professor in the Department of Endocrinology in Dr. RML Hospital for the help provided in the interpretation of data.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]