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What Is the Connection between Methotrexate and Hair Loss?

By S. Berger
Updated May 17, 2024
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Methotrexate is a powerful medication used to treat a variety of medical conditions, such as autoimmune diseases and cancer. It can also have very serious side effects, including immune system weakness and alopecia, or hair loss. The link between methotrexate and hair loss, as well potentially causing other side effects, has to do with the the way the drug works in the body.

Cells manufacture folic acid using the enzyme dihydrofolate reductase, and folic acid is used to create compounds essential to cell life and reproduction, including deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. This medicine prevents dihydrofolate reductase from operating properly, thereby depriving cells of a compound that is necessary for them to flourish. As only cells that are about to divide produce more DNA, this treatment targets rapidly-dividing cells in particular. It is due to this connection to rapidly dividing cells that methotrexate and hair loss become linked.

Both cancer cells and the bone marrow cells that produce cells involved in autoimmune diseases divide quite rapidly. For this reason, methotrexate is an extremely effective against these conditions. Hair follicle cells do not divide as fast as cancerous or bone marrow cells, but they still divide quite rapidly, up to once every day and a half. This medication can therefore easily affect follicle cells, prevent their DNA manufacture so they cannot divide, and keep them from making the proteins they require to survive, as well.

As the hair follicle cells die off, they can no longer hold the hair in place, and hair begins to weaken and fall out. The connection between methotrexate and hair loss is one of the more noticeable side effects. Other side effects, such as nausea and vomiting, are due to the same action of methotrexate, as it affects rapidly-dividing cells in the stomach and intestines.

Unlike some other powerful chemotherapy drugs that target specific locations, injections and oral forms of this drug are used to distribute methotrexate throughout the body. It was first developed to fight cancers of the immune system, such as leukemia, based on this property. This medication's ability to move quickly through the bloodstream and access many parts of the body rapidly means that its side effects tend to be global in nature, even at smaller doses. Regardless of the dosing schedule and size, taking methotrexate and hair loss problems generally are inseparable events. The connection between methotrexate and hair loss is not permanent, however; after treatment ceases, the hair will often grow back, albeit thinner than before.

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