Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 29  |  Issue : 2  |  Page : 389--392

A study on the effect of estrogen, progesterone, and their cutaneous receptors in the pathogenesis of melisma


Mohamed A Basha, Rania M Azmy, Mai M Farag 
 Department of Physiology, Faculty of Medicine, Menoufia University, Menufia, Egypt

Correspondence Address:
Mai M Farag
Department of Dermatology, Faculty of Medicine, Mansoura University, Al Azher Street, Bani Ebaied-Mansoura Governorate, 35117
Egypt

Abstract

Objective: The aim of the study was to assess the efficacy of estrogen, progesterone, and their cutaneous receptors in the pathogenesis of melasma. Materials and methods: From January 2013 to June 2013, 40 female patients with melasma and 20 age-matched and sex-matched healthy individuals as the control group were included. Estrogen and progesterone were measured using IMMULITE 2000. Results: Concerning the serum estrogen and progesterone levels, the patients showed a statistically significant increase in progesterone levels with a mean value of 3.65 ± 13.11 when compared with the controls with a mean value of 3.63 ± 2.64. Conclusion: Increase in serum progesterone supports the role of pregnancy in melasma.



How to cite this article:
Basha MA, Azmy RM, Farag MM. A study on the effect of estrogen, progesterone, and their cutaneous receptors in the pathogenesis of melisma.Menoufia Med J 2016;29:389-392


How to cite this URL:
Basha MA, Azmy RM, Farag MM. A study on the effect of estrogen, progesterone, and their cutaneous receptors in the pathogenesis of melisma. Menoufia Med J [serial online] 2016 [cited 2020 Jul 6 ];29:389-392
Available from: http://www.mmj.eg.net/text.asp?2016/29/2/389/192411


Full Text

 Introduction



Melasma is an acquired hypermelanosis occurring symmetrically on sun-exposed areas of the body. Lesions are irregular light-to-dark brown macules and patches, usually involving the forehead, temples, upper lip, and cheek [1]. Melasma can affect any race; Asian and Hispanic female individuals are most commonly affected [2]. Women are affected in 90% of cases, as melasma is rare before puberty and most commonly occurs during their reproductive years [3]. Three patterns of melasma are recognized clinically: a centrofacial pattern, a malar pattern, and a mandibular pattern [4].

Natural and synthetic estrogen and progesterone have been incriminated for the pathogenesis of melasma because of its frequent association with pregnancy, use of contraceptive drugs, use of estrogens in postmenopausal women, and diethylbestrol treatment of prostate cancer [5].

Estrogen receptor (ER) and progesterone receptor (PR) belong to a superfamily of ligand-induced transactivators that exert their regulatory activity on discrete genes through DNA binding at individual hormone-responsive elements [6]. The molecular identification of ER and PR in the human melanocytes is of great importance to understand the mechanisms of induction of hyperpigmentation in melasma. The immunocytochemistry analysis demonstrated that ER and PR were expressed in the cytoplasms and nuclei of human melanocytes. Reverse transcriptase-PCR and sequence analysis confirmed the expression of ER and PR at the transcriptional level. Despite the presence of ER and PR, the physiological and pregnant levels of estrogen and progesterone showed inconsistent effects on the proliferation of tyrosinase activity of cultured human melanocytes [7].

 Materials and Methods



Inclusion criteria

Female individuals with melasma. Patients aged above 30 years.

Exclusion criteria

Pregnancy. Lactation. Oral contraceptive pills and other hormonal treatment. Polycystic ovarian syndrome and/or other endocrinopathies.

Methodology

Forty female patients with melasma and 20 age-matched and sex-matched healthy individuals as the control group were used in this study.

Each of the selected patient was subjected to the following: complete history taking and examination (general examination, dermatological examination).

Scoring of every case was carried out using melasma areas and severity index score (Kimbrough-Green et al., 1994). Area of involvement (A) includes analysis of four areas including the forehead (f) 30%, right malar region (rm) 30%, left malar region (lm) 30%, and the chin (c) 10%. The area of melasma involvement is given a numeric value from 0 to 6 (0 = no involvement, 1 = <10% involvement, 2 = 10–29% involvement, 3 = 30–49% involvement, 4 = 50–69% involvement, 5 = 70–89% involvement, and 6 = 90–100% involvement). Darkness (D) is estimated and given a value from 0 to 4 (0 = absent, 1 = slight, 2 = mild, 3 = marked, and 4 = maximum). Homogenecity (H) is estimated and given a value from 0 to 4 using the same scale as darkness. The melasma areas and severity index score is then calculated by the following formula:

0.3A(f)[D(f)+H(f)]+0.3A(rm)[D(rm)+H(rm)]+ 0.3A(lm)[D(lm)+H(lm)]+0.1A(c)[D(c)+H(c)]

Laboratory measurement (Siemens Healthcare, Erlangen, Germany) of estrogen and progesterone was performed using IMMULITE 2000, which is a solid-phase, two-site chemiluminescent immunometric assay. Sample collection by the use of an ultracentrifuge is recommended to clear lipemic samples. Hemolyzed samples may indicate mistreatment of a specimen before receipt by the laboratory; hence, the results should be interpreted with caution. Centrifuging serum samples before a complete clot forms may result in the presence of fibrin. To prevent erroneous results due to the presence of fibrin, ensure that complete clot formation has taken place before centrifugation of samples. Some samples particularly those from patients receiving anticoagulant therapy may require increased clotting time [8].

Statistical analysis

SPSS software was used to perform statistical analysis. (IBM Corporation, Armonk, New York, United States) Values for all continuous variables are quoted as mean, SD, and minimum and maximum throughout.

The t-test was used to assess the statistical significance of difference between two means. By knowing the (t) test and the degree of freedom, the P-value was calculated from special tables, and hence the significance of the results was determined from the 't' distribution tables.

P-value greater than 0.05 was considered insignificant difference, whereas P-value less than 0.05 was considered significant difference.

P-value less than 0.01 was considered highly significant difference, and P-value less than 0.001 was considered very highly significant difference.

 Results



Patients

There were 40 female patients having melasma and 20 female individuals as the control group. The age of selected patients with a mean value of 36.55 ± 5.77 and 34.30 ± 9.83 years of the control group showed nonstatistical significance.

[Table 1] shows that the serum estrogen levels in patients showed no statistical significance with a mean value of 98.51 ± 211.50 when compared with the controls with a mean value of 83.33 ± 58.70. However, patients showed a statistically significant increase in progesterone levels with a mean value of 3.65 ± 13.11 when compared with the controls with a mean value of 3.63 ± 2.64 (P = 0.03).{Table 1}

 Discussion



The current study aimed to study the role of estrogen and progesterone in the pathogenesis of melasma through measuring their level in serum of studied melasma patients and through immunohistochemical localization of their receptors in tissues to throw spotlight on the pathogenesis of melasma.

In addition, there have been several reports demonstrating that estrogen treatment could lead keratinocytes to produce an increased amount of keratinocyte growth factor, and keratinocyte growth factor could increase pigment production and deposition in vitro and in vivo [9]. However, the results of studies on the effects of progesterone on skin pigmentation have been inconsistent. It has been reported that progesterone increased cell numbers and tyrosinase activity in melanocytes [0]. In contrast, significant inhibitory effects of progesterone on the proliferation of melanocytes in monoculture were also reported [1]. There has been no previous report on the expression of the ER and PR in melasma-affected skin except for one case report on ER expression in melasma-affected skin [2].

In the current study on melasma patients, no significant difference in serum estrogen level was shown, and there was elevation in serum progesterone level against normal control.

Serum estrogen did not differ in cases and control, which is against the results of several in-vitro studies suggesting that estrogen may be involved in the pathogenesis of melasma [3]. In contrast, Perez et al. [4] reported increased serum levels of leutinizing hormone alone and lower levels of serum estradiol in patients with melasma than in normal controls.

Serum progesterone was elevated in patients. This finding also agreed with the finding of Sato et al. [5] who reported that the main cause of melasma is considered to be an increase in progesterone (P4) in the serum during the luteal phase; however, it was in contrast with the study by Wiedemann et al. [1] who suggested that progesterone can inhibit proliferation of human melanocytes, which counteract the stimulator effects of estrogen. They showed that progesterone reduces the rate of proliferation of melanocytes in monoculture, whereas they had no significant effect on the tyrosinase activity.

In contrast, Jee et al. [6] reported that treatment with 17-estradiol for 10 days significantly showed increased neonatal melanocyte number and for 1 day exhibited decreased tyrosinase activity and melanin content. However, they suggested that the tyrosinase activity and melanin content were expressed as per cell. It is suggested that the proliferating activity stimulated by estradiol was greater than that by the tyrosinase activity and the melanin-producing activity. Maeda et al. [7] applied the adult melanocytes of Japanese male foreskin and showed that estradiol in the concentration range of 0.01–1.0 g/ml and 1 g/ml progesterone significantly increased the amount of TRP-1, and no significant effect on DOPA oxidase activity was detected after estradiol and progesterone treatment. In addition, estradiol and progesterone increase the area, the dendrites, and the perimeter per cell.

Kippenberger et al. [3] applied the reverse transcriptase-competitive multiplex PCR to normal human melanocytes and reported that 20 mol/l treatment with diethylstilbestrol and estradiol for 48 h led to about 1.5- to 2.5-fold increase in tyrosinase and TRP-2 transcripts. The authors reported for the first time that the sex steroids cause an increase in melanogenic enzyme transcripts in normal human melanocytes.

An increase in the tyrosinase activity could provoke the switch from pheomelanogenesis to eumelanogenesis. Activation of tyrosinase by estradiol might be an alternative to a direct receptor-mediated mechanism for the growth inhibitory effect observed in vivo and in vitro. The first is that certain prone melanocytes only can respond to estrogen and progesterone with a stimulation of growth. [8].

Progesterone effects on inflammatory cells were determined by administration of progesterone into the female reproductive tract, which resulted in increased numbers of Langerhans cells, a population of dendritic cells (DCs) found in the skin [9]. We have shown direct effects of progesterone on DC function, especially mature DCs. These results include inhibition of proinflammatory cytokine secretion, downregulation of DC-associated activation markers (MHC class II, CD80), and reduced T cell-proliferative capacity by these cells [0].

 Conclusion



The results of our study showed that melasma lesional skin contains more amount of melanin pigment.

The role of hormonal factor in the pathogenesis of the disease may be supported by the increase in serum progesterone, which supports the role of pregnancy in melasma.

In conclusion, this study suggests high evidence of efficacy of progesterone hormone in pathogenesis of melasma.

Conflicts of interest

There are no conflicts of interest.[20]

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