Methotrexate (MTX) is a medication used to treat conditions, including certain cancers and autoimmune disorders like rheumatoid arthritis and psoriasis. MTX works by targeting rapidly dividing cells to slow disease progression. A common concern for patients starting this treatment is hair loss, and MTX can cause hair thinning or shedding. The hair loss is usually mild, not leading to complete baldness for most patients, and is typically temporary.
The Mechanism of Hair Follicle Interference
Methotrexate’s therapeutic effect and its capacity to cause hair loss stem from its function as a folic acid antagonist. The drug works by inhibiting the enzyme dihydrofolate reductase (DHFR), which converts dietary folate into its active form. This active folate is necessary for the synthesis of DNA and RNA, which are the building blocks for cell division and replication.
Hair follicles are among the fastest-dividing cells in the body, particularly during the anagen, or growth, phase of the hair cycle. Because MTX interferes with the cell’s ability to create new DNA, it slows down the proliferation of hair matrix cells. This disruption weakens the hair shaft as it is being formed, leading to breakage and shedding.
MTX’s primary goal is to suppress overactive immune cells or halt the growth of cancer cells. Unfortunately, the drug cannot distinguish between these target cells and other quickly multiplying, healthy cells. This mechanism causes the hair follicle to produce a defective or fragile hair shaft, which is the root cause of MTX-related hair loss.
Types of Alopecia and Prevalence
The hair loss experienced by patients on Methotrexate can manifest in two main ways, depending largely on the dose and duration of treatment. The first type is Anagen Effluvium, which is the abrupt and widespread shedding of hairs currently in their growth phase. This is associated with the high-dose MTX protocols used in chemotherapy, where the direct toxicity to the hair follicle is more severe.
The second, and more common type for patients using lower-dose MTX for conditions like rheumatoid arthritis, is Telogen Effluvium. This involves a premature shift of growing hairs into the resting (telogen) phase, leading to diffuse thinning across the scalp a few weeks or months after starting the medication. This type of loss is characterized by generalized thinning rather than distinct bald patches.
The prevalence of hair loss with low-dose MTX is relatively low, affecting approximately 1% to 3% of patients with rheumatological conditions. In these cases, the effect is often minor and presents as mild thinning or increased shedding. The risk and severity of hair loss are generally understood to be dose-dependent, meaning higher weekly doses carry a greater risk of more pronounced shedding.
Mitigating Hair Loss and Recovery
The most common strategy for mitigating Methotrexate side effects, including hair loss, is routine folic acid supplementation. Folic acid is co-prescribed with MTX to replenish the body’s folate stores without compromising the drug’s anti-inflammatory or cytotoxic effects. A typical regimen involves taking 1 milligram of folic acid daily or 5 milligrams once per week, usually taken on a day separate from the MTX dose.
If significant hair thinning is still occurring despite supplementation, a physician may suggest a higher “rescue” dose of folic acid or an alternative form, such as folinic acid. Patients should always consult their healthcare provider before making any changes to the folic acid dose or schedule. Dose adjustment of the MTX itself or a switch to an alternative medication may be considered if the hair loss is causing significant distress.
The prognosis for hair loss caused by Methotrexate is temporary and reversible. Once the MTX dosage is reduced or the medication is discontinued, the hair follicles recover and resume normal activity. Regrowth typically begins within weeks to a few months after the drug is stopped. Even if the medication is continued, the hair can often stabilize or partially regrow as the body adjusts to the treatment.