***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Melasma ( or chloasma ) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women . The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects . Pycnogenol is a st and ardized extract of the bark of the French maritime pine ( Pinus pinaster ) , a well-known , potent antioxidant . Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition , it recycles vitamin C , regenerates vitamin E and increases the endogenous antioxidant enzyme system . Pycnogenol protects against ultraviolet ( UV ) radiation . Therefore its efficacy in the treatment of melasma was investigated . Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily , i.e. 75 mg Pycnogenol per day . These patients were evaluated clinical ly by parameters such as the melasma area index , pigmentary intensity index and by routine blood and urine tests . After a 30-day treatment , the average melasma area of the patients decreased by 25.86 + /- 20.39 mm(2 ) ( p < 0.001 ) and the average pigmentary intensity decreased by 0.47 + /- 0.51 unit ( p < 0.001 ) . The general effective rate was 80 % . No side effect was observed . The results of the blood and urine test parameters at baseline and at day 30 were within the normal range . Moreover , several other associated symptoms such as fatigue , constipation , pains in the body and anxiety were also improved . To conclude , Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma The objective of the present study was to assess the toxicology of melatonin ( 10 mg ) , administered for 28 days to 40 volunteers r and omly assigned to groups receiving either melatonin ( N = 30 ) or placebo  ( N = 10 ) in a double-blind fashion . The following measurements were performed : polysomnography ( PSG ) , laboratory examinations , including complete blood count , urinalysis , sodium , potassium and calcium levels , total protein levels , albumin , blood glucose , triglycerides , total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and very low-density lipoprotein ( VLDL ) , urea , creatinine , uric acid , glutamic-oxalacetic transaminase ( GOT ) , glutamic-pyruvate transaminase ( GPT ) , bilirubin , alkaline phosphatase , gama-glutamic transaminase ( GGT ) , T3 , T4 , TSH , LH/FSH , cortisol , and melatonin serum concentrations . In addition , the Epworth Somnolence Scale ( ESS ) and a sleep diary ( SD ) were also applied to the volunteers 1 wk before each PSG . In addition , the volunteers were asked about possible side effects ( SE ) that appeared during the treatment . The study was carried out according to the following timetable : Visit 0 , filling out the term of consent and inclusion criteria ; Visit 1 , PSG , laboratory examinations , ESS , SD ,  melatonin serum concentrations ; Visit 2 , SD ,  melatonin serum concentrations , SE ; Visit 3 ,  melatonin serum concentrations , PSG , ESS , SE ; Visit 4 , laboratory examinations , SE , melatonin serum concentrations , SD ; and Visit 5 , PSG , ESS , SE . Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group . No other differences between the placebo and melatonin groups were obtained . In the present study we did not observe , according to the parameters analyzed , any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study BACKGROUND Glutathione ( GSH ) is a naturally occurring thiol that has been reported to cause skin lightening in a manner for which several mechanisms have been proposed . Highest plasma concentrations are achieved with IV administration but are accompanied by greater levels of risk . Oral administration has been less successful in elevating plasma GSH levels . OBJECTIVES The use of a lozenge containing GSH was investigated in order to evaluate the buccal mucosa as a route for GSH administration . Substances that are absorbed through the buccal route go directly into the systemic circulation , effectively bypassing the gastrointestinal tract . METHODS Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge daily for eight weeks . RESULTS Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks . There were no serious adverse events , and laboratory examination findings remained normal . CONCLUSIONS The authors conclude that the lozenge containing glutathione was safe and effective in lightening the skin of Filipino women BACKGROUND UV radiation induces damage to human skin . Protection of skin by an oral photoprotective agent would have substantial benefits . Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos ( PL ) . METHODS A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL ( 7.5 mg/kg ) . At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin . RESULTS A significant decrease in erythema was found in PL-treated skin ( P < .01 ) . Histologically , PL-treated biopsy specimens showed less sunburn cells ( P < .05 ) , cyclobutane pyrimidine dimers ( P < .001 ) , proliferating epidermal cells ( P < .001 ) , and dermal mast cell infiltration ( P < .05 ) . A trend toward Langerhans cell preservation was seen . CONCLUSION Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation BACKGROUND Melasma is associated with epidermal hyperpigmentation , weak basement membrane , vascular proliferation and increased numbers of mast cell . Tranexamic acid ( TXA ) , a plasmin inhibitor , is reported to improve melasma when injected locally . However , the effects of oral and topical TXA on melasma have not been well studied and the underlying mechanism remains unclear . OBJECTIVES To eluci date the effects of oral and topical TXA on melasma . METHODS A clinical study was conducted with 25 women for 8 weeks from March to July 2010 . Volunteers were instructed to take two TXA tablets three times a day and apply a TXA topical agent twice a day for 8 weeks .  Skin pigmentation and erythema was measured using a Mexameter ( ® ) during each visit and skin biopsies were collected from eight subjects before and 8 weeks after treatment . Fontana-Masson , anti-CD31 , antitryptase and antitype IV collagen staining was performed . RESULTS Twenty-two subjects completed the study and no serious adverse events occurred during the study period . The mean lesional melanin index ( MI ) scores decreased significantly . Interestingly , the MI scores for the perilesional skin increased . The erythema index scores of lesional and perilesional skin also showed a similar pattern . Histological analysis showed significant reduction of epidermal pigmentation , vessel numbers and mast cell counts . Type IV collagen staining was not observed in all specimens . CONCLUSION TXA decreased epidermal pigmentation associated with melasma and also reversed melasma-related dermal changes , such as vessel number and increased numbers of mast cells Abstract Objective : To determine whether orally administered glutathione , 500 mg per day for 4 weeks , affects the skin melanin index , when compared with placebo . Methods : This r and omized , double-blind , two-arm , placebo-controlled study was set in the King Chulalongkorn Memorial Hospital , Bangkok , Thail and , a teaching hospital affiliated with a medical school . Sixty otherwise healthy medical students were r and omized to receive either glutathione capsules , 500 mg/day in two divided doses , or placebo for 4 weeks . The main outcome was mean reduction of melanin indices measured at six different sites . Several secondary outcomes , including UV spots , were recorded by VISIA ™ . Efficacies of glutathione and placebo were compared by ANCOVA with baseline values as co-variates . Results : Sixty participants enrolled and completed the study . At 4 weeks , the melanin indices decreased consistently at all six sites in subjects who received glutathione . The reductions were statistically significantly greater than those receiving placebo at two sites , namely the right side of the face and the sun-exposed left forearm ( p-values = 0.021 and 0.036 , respectively ) . This was similarly reflected in the changes in the number of UV spots , as measured by VISIA . Both glutathione and placebo were very well tolerated . Conclusion : Oral glutathione administration results in a lightening of skin color in a small number of subjects . However , long-term safety has not been established and warrants more extensive clinical trials BACKGROUND Melasma is a common , acquired , symmetric hypermelanosis characterized by irregular brown to gray-brown macules on the cheeks , forehead , nasal bridge , cutaneous part of the upper lip , m and ible , and the upper arms . Few trials have been conducted regarding the potential benefits of oral procyanidin in melasma . AIM To assess the safety and efficacy of oral procyanidin + vitamins A , C , E among Filipino patients with epidermal melasma . METHODS A r and omized , double-blind , placebo-controlled trial lasting 8 weeks , involving 60 adult female volunteers with bilateral epidermal melasma , Fitzpatrick skin types III-V , was conducted at the Section of Dermatology , Research Institute for Tropical Medicine , Department of Health , Manila , Philippines . Patients received either the test drug or placebo , twice daily with meals . Changes in pigmentation were measured using a mexameter , the melasma area and severity index ( MASI ) , and a global evaluation by the patient and investigator . Safety evaluations were performed at each follow-up visit . RESULTS Fifty-six patients completed the trial . Mexameter results demonstrated a significant decrease in the degree of pigmentation in the left malar ( 165.85 + /- 70.909 ) and right malar ( 161.33 + /- 61.824 ) regions ( P < 0.0001 ) . MASI scores showed a significant improvement in the left malar ( 2.4862 + /- 1.67816 ) and right malar ( 1.8889 + /- 1.67110 ) regions ( P = 0.001 ) . Procyanidin + vitamins A , C , E proved to be safe and well tolerated , with minimal adverse events . CONCLUSIONS In this 8-week trial period , oral procyanidin + vitamins A , C , E proved to be safe and effective among Filipino women with epidermal melasma Background : Melasma is a common acquired cause of facial hyperpigmentation with no definitive therapy . Tranexamic acid , a plasmin inhibitor , has demonstrated depigmenting properties and combining this oral drug with other modalities of treatment has shown promising results . Objectives : To compare the efficacy of a combination of oral tranexamic acid and fluocinolone-based triple combination cream with that of fluocinolone-based triple combination cream alone in  melasma among Indian patients . Material s and Methods : 40 patients of melasma of either sex attending to dermatology OPD were enrolled in this study . Participants were r and omly divided into two groups with 20 patients in each group . Group A patients were asked to apply the cream only and Group B patients received oral tranexamic acid 250 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01 % , tretinoin 0.05 % , and hydroquinone 2 % once daily for 8 weeks . Response was evaluated using melasma area severity index ( MASI ) at baseline , 4 weeks , and 8 weeks . Results : 40 patients completed the study . The MASI scores at baseline , 4 weeks and 8 weeks in group A were 15.425 + 1.09 , 11.075 + 9.167 and 6.995 + 6.056 respectively and in group B 18.243 + 1.05 , 6.135 + 4.94 and 2.19 + 3.38 . Intergroup comparison showed a faster reduction in pigmentation in Group B as compared to Group A and the results were statistically significant at 4 weeks ( P value 0.014 ) and 8 weeks ( P value 0.000 ) . The efficacy was maintained throughout the 6-month follow-up period . Conclusion : Addition of oral tranexamic acid to fluocinolone-based triple combination cream results in a faster and sustained improvement in the treatment of melasma OBJECTIVE The objective of this study was to determine the safety of oral Polypodium leucotomos extract administered twice daily to healthy adults for 60 days and assess its ability to provide protection against exposure to ultraviolet radiation . DESIGN This was a r and omized , double-blind , placebo- 
    Output:
    
These agents appear to have a beneficial effect on melasma improvement .
In conclusion , oral medications have a role in melasma treatment and have been shown to be efficacious and tolerable with a minimal number and severity of adverse events .