Mechanism of action of minoxidil , rogain

Since these initial studies, much research has been done to identify exactly how the topical application of minoxidil can lead to increased hair growth. One important hypothesis is based on its vasodilatory properties. Diazoxide is another antihypertensive potassium channel opener which increases blood flow and is reputed to increase hair growth. Laser Doppler velocimetry studies showed an increase in cutaneous blood flow after applying 1%, 3%, and 5% minoxidil solutions to the scalps of 16 balding men.16 All three groups showed increases compared to a control group, and the 5% group showed the greatest increase. A significant increase in blood flow occurred as soon as 15 minutes after application, and lasted for up to an hour. The role of minoxidil in angiogenesis is further supported by evidence that it upregulates the expression of vascular endothelial growth factor mRNA in human hair dermal papilla cells.

Minoxidil sulfate is the active metabolite that stimulates hair follicles. The conversion of minoxidil to minoxidil sulfate is catalyzed by sulphotransferase enzymes, which exist in the scalp. In scalp skin of the stump-tailed macaque, this enzyme has been localized mainly to the hair follicle, which contains 50% to 85% of the enzyme (versus 10-20% in the epidermis and dermis). Immunolocalization studies of minoxidil sulphotransferase demonstrated that the lower outer root sheath is the most likely site of conversion of minoxidil to its sulfated form. Just as is the case with dihydrotestosterone (DHT), there are interindividual variations in scalp sulphotransferase levels. Patients with a better response to topical minoxidil were found to have a greater level of enzyme activity.

Cultures of human epidermal cells treated with minoxidil have been shown to survive longer than control cultures. Minoxidil slows the senescence of keratinocytes and reduces the rate at which cells are lost from the germinative pool. This is similar to what has been found with epidermal growth factor. Minoxidil has been shown to increase the proliferation of dermal papilla cells of the human hair follicle. Specifically, minoxidil increased levels of Erk and Akt phosphorylation, with an increased ratio of Bcl-2/Bax, prolonging anagen and preventing cell death with antiapoptotic effects. This same study found that minoxidil elongated individual hair follicles in organ culture.

Minoxidil may also enhance cell proliferation. The uptake of tritiated minoxidil and its conversion to minoxidil sulfate has been found to be relatively higher in the hair follicles than in the epidermis and dermis. This group also found that minoxidil caused the enhancement of DNA synthesis in the follicular and perifollicular cells but not in the epidermal keratinocytes. Another study showed a marked dose-dependent second peak of DNA synthesis 8 to 10 days later in epidermal cells cultured with minoxidil. There were two morphologically distinct cell types, suggesting that minoxidil can affect epidermal cells in culture by altering their growth pattern and phenotypic appearance.

Whether the minoxidil indeed prolongs anagen or simply shortens telogen is still a matter of debate. It has been shown to shorten the length of telogen phase in the follicular cycle of rats but did not prolong the anagen phase. Rather, there was found to be a premature entry of resting hair follicles back into the anagen stage, with an increased rate of DNA synthesis during the anagen stage. However, another study in balding stump-tailed macaques found that treatment with minoxidil increased the proportion of hair follicles in anagen, reduced the number of telogen follicles, and increased the follicle size overall. This suggests at least a relative shift chronologically from telogen to anagen. Abell supported the finding of increased anagen/telogen ratios after 12 months of minoxidil treatment in balding men. However, the main finding was an increase in mean hair diameter, which was evident at 4 months. Other histologic studies also demonstrated an increase in the shaft diameter from 0.029 mm at baseline to 0.043 mm at 12 weeks and 0.042 mm at 24 weeks.

Lastly, it is possible that minoxidil plays an immunoregulatory role in the hair follicle. In vitro studies demonstrate that minoxidil had a suppressive effect on normal human T-lymphocytes in vitro. This may explain minoxidil’s reported efficacy in treating some patients with AA.  This is supported by histologic findings of a reduced perifollicular infiltrate.  There is also evidence that minoxidil can selectively inhibit prostacyclin production by cells in culture. Somewhat like aspirin, minoxidil has been found to prevent the aggregation of platelets by causing a reduction in the synthesis of prostaglandin E2 and thromboxane B2.36 This inhibitory effect on the cyclooxygenase enzyme awaits further study. Regardless of its exact mechanism of action, there is sound histologic and clinical evidence that minoxidil works. A complete list of proposed mechanisms is provided in Table below.

Minoxidil: proposed mechanisms of action

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Vasodilatory properties

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Angiogenic properties

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Enhanced cell proliferation and DNA synthesis

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Potassium channel opener

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Antiandrogen effects

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Suppression of collagen synthesis

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Immunosuppressive effects