Introduction
Male Androgenic Alopecia (MAA) is one of the most common causes of hair loss in men affecting 23%-87% of people in different populations. This form of hair loss is sometimes associated with other symptoms of increased androgen (dihydrotestosterone) such as acne, seborrhea, and hirsutism. The effects of androgen on the hair include shortened anagen period, prolonged telogen phase and reduced terminal hair follicles and increased vellus hair follicles. In MAA, the hairs in the frontal and frontoparietal areas first retreat and then the hair in the vertex area begins to become thinner and then sheds. At the end, terminal hair become fur and shed. Topical minoxidil and oral finasteride have been approved by the Food and Drug Administration agency for the treatment of MMA; however, it has several cutaneous side effects including itching, scaling and erythema, which cause the discontinuation of its consumption. Anti-inflammatory drugs such as topical steroids, can be used to reduce the side effects of minoxidil. they are very helpful in reducing the symptoms of itching, inflammation and scaling, but their long-term use has complications such as skin atrophy, telangiectasia, and pigmentary disorders. For this reason, its use is limited.
Chamomile is one of the oldest, most widely used and documented medicinal plants in the world, which interrupts the cyclooxygenase and lipoxygenase cycles, inhibiting histamine release and decreasing prostaglandin and leukotriene (the main inflammatory mediators) and can be used with anti-inflammatory properties to treat skin and mucosal inflammation. Since no study has been conducted on the effect of chamomile on cutaneous side effects of minoxidil and its topical form has been used in the treatment of many inflammatory diseases, and given that addition of 7% Chamomile extract to minoxidil solution is safe and non-allergenic, this study attempted to examine the effect of the concomitant administration of 5% minoxidil solution and 7% chamomile on the side effects of minoxidil.
Materials and Methods
In this double-blind randomized clinical trial, participants were 100 men with MMA referred to the dermatology clinic of Vali-e Asr Hospital in Arak, Iran during 2016-2018. The inclusion criteria were: having age 18-40 years, type 2 MMA based on the Hamilton-Norwood classification, and hair loss duration of less than 10 years. The exit criteria included the use of medical treatment or surgical for hair loss in the past 6 months, a history of heart disease or use of blood pressure lowering medications, and a history of allergy or sensitivity to minoxidil or chamomile 7%. Of 100 samples, 51 were treated with 5% minoxidil solution plus 7% chamomile extract, and 49 samples with 5% minoxidil solution only (matched controls). The drug used in each group was a solution in dark glasses that the physician and patient were unaware of the type of it, and only the pharmacy partner was aware. Based on the written instructions, patients were asked to apply 1 ml of the solution every 12 hours on different parts of the scalp and then massage. Both groups were treated and followed for six months and the variables were examined at each time and then patient was given the treatment again. The variables were: Itching, erythema, and scaling. The first was asked from the patients and the others were examined by a dermatologist. After collecting data, they were analyzed in SPSS v.18 software using statistical tests (chi-squared, independent t-test, and logistic analysis).
Ethical Considerations: This study has received its ethical approval from the Research Ethics Committee of Arak University of Medical Sciences (code: IR.ARAKMU.REC.1395.456) and is a registered clinical trial (code: 2017042420258N41).
Results
Marital status, age, and height were not significantly associated with hair loss, but it had significant relationship with duration of hair loss, body mass index, family history (positive), and cigarette smoking. At the end of the second month in the intervention group, itching was significantly reduced, but scaling and erythema did not differ. At the end of the fourth and sixth months, all three skin complications were reduced in the intervention group compared to the control group, which was statistically significant. In other words, the addition of chamomile to the minoxidil solution has led to a reduction in skin complications, especially erythema.
Discussion
In this study, 100 men with MAAin two groups of intervention (n=51) and control (n=49) were treated and followed-up for 6 months. In both groups of minoxidil alone (control) and minoxidil plus chamomile (intervention) scaling and itching gradually decreased during the six-month follow-up. Erythema was increased in the control group, while it was also decreased in the intervention group. Addition of 7% chamomile to the minoxidil solution resulted in a decrease in the skin complications of scaling, itching and erythema, and this decrease was statistically significant compared with the control group. 
conclusion
It seems that concomitant administration of 7% chamomile extract and 5% minoxidil solution leads to a reduction in the severity and duration of cutaneous side effects caused by minoxidil solution use in treatment of MAA. It can increase the patient's compliance to the treatment and eventually the chance of MAA treatment.


Ethical Considerations
Compliance with ethical guidelines
This study has received its ethical approval from the Research Ethics Committee of Arak University of Medical Sciences (code: IR.ARAKMU.REC.1395.456) and is a registered clinical trial (code: 2017042420258N41).
Funding
This study received no financial support from any organization.
Authors' contributions
The authors observed the standards of writing based on the recommendations of the International Committee of Medical Journal Publishers and all contributed equally to the writing of this article.
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgements
The authors would like to thank the Deputy for Research and Technology of Arak University of Medical Sciences for their valuable support and Behvarzan Pharmaceutical Company for their cooperation.

References