Methotrexate and hair loss is a concern raised by many patients starting this widely used DMARD for conditions such as rheumatoid arthritis, psoriasis, or psoriatic arthritis. Hair shedding is a recognised and common side effect, listed in the UK Summary of Product Characteristics, and can understandably cause distress. Understanding why it happens, how frequently it occurs, and what can be done to manage it — including folic acid supplementation — helps patients make informed decisions alongside their clinical team. This article explains the mechanism behind methotrexate-related hair loss, practical management strategies, when to seek medical advice, and what to expect if treatment is stopped.

Why Methotrexate Can Cause Hair Loss

Methotrexate disrupts folate metabolism and cell proliferation, pushing hair follicles prematurely into the telogen (resting) phase and causing diffuse shedding known as telogen effluvium.

Methotrexate is a disease-modifying antirheumatic drug (DMARD) and immunosuppressant used to treat a range of conditions. Its licensed UK indications include rheumatoid arthritis, severe psoriasis, and psoriatic arthritis; use in conditions such as Crohn's disease or alopecia areata is off-label and undertaken only under specialist supervision.^[1]

At the higher doses used in oncology, methotrexate works primarily by inhibiting dihydrofolate reductase (DHFR), an enzyme essential for folate synthesis, thereby disrupting DNA replication in rapidly dividing cells.^[1] At the lower doses used for inflammatory conditions, its anti-inflammatory action is thought to be mediated largely through increased extracellular adenosine and other immunomodulatory effects — though the anti-folate mechanism remains relevant to certain side effects, including hair loss.

Hair follicles are among the most metabolically active tissues in the body, undergoing continuous cycles of growth (anagen), regression (catagen), and rest (telogen). Because methotrexate interferes with folate metabolism and cell proliferation, it can disrupt the normal hair growth cycle, pushing follicles prematurely into the telogen (resting) phase. This results in a type of hair loss known as telogen effluvium — a diffuse shedding of hair across the scalp rather than patchy or complete baldness.^[1][2]

In some cases, methotrexate may also cause anagen effluvium, where actively growing hairs are shed due to direct disruption of the growth phase. This is less common at the low doses typically used for inflammatory conditions but may occur at higher doses. Hair loss associated with methotrexate is generally dose-dependent.

Isolated mild diffuse shedding is usually a recognised pharmacological consequence of the drug rather than a sign of a more serious problem. However, hair loss occurring alongside mouth ulcers, unusual bruising or bleeding, fever, sore throat, or breathlessness may indicate methotrexate toxicity and warrants prompt medical review (see 'When to Speak to Your GP or Specialist' below).

How Common Is Hair Loss With This Treatment

Alopecia is classified as a common adverse reaction to methotrexate in the UK SmPC, affecting between 1 in 10 and 1 in 100 patients, with real-world prevalence potentially higher.

Hair loss (alopecia) is a well-documented side effect of methotrexate. According to the UK Summary of Product Characteristics (SmPC) for methotrexate, alopecia is classified as a common adverse reaction (affecting between 1 in 10 and 1 in 100 patients). Some observational studies and patient-reported outcome data suggest the real-world prevalence may be higher, particularly when patients are asked directly about subtle changes in hair density.

The likelihood of experiencing hair loss appears to be influenced by several factors:

• Dose: Higher weekly doses are more strongly associated with alopecia

• Folate status: Patients with lower folate levels may be more susceptible

• Concurrent medications: Drugs that interfere with folate metabolism — most notably trimethoprim and co-trimoxazole — can markedly increase the risk of methotrexate toxicity, including hair loss; patients should inform their prescriber and pharmacist about all medicines, including over-the-counter products, before starting or changing treatment^[1][3]

• Route of administration: Most evidence for differences in tolerability between oral and subcutaneous methotrexate relates to gastrointestinal side effects; whether the route of administration meaningfully affects the risk of hair loss is not well established

It is worth noting that the conditions methotrexate is used to treat — particularly psoriasis — can themselves cause hair changes, which can make it difficult to attribute hair loss solely to the medication. Clinicians should consider this when assessing a patient's concerns. Whilst hair loss can be psychologically distressing and may affect quality of life and treatment adherence, it is classified as a common but non-serious adverse effect in most clinical contexts at standard therapeutic doses.

Managing Hair Loss During Methotrexate Therapy

Folic acid 5 mg once weekly on a different day to methotrexate is the standard UK management strategy, reducing hair loss by replenishing folate depleted by the drug.

The most widely recommended and evidence-supported strategy for managing methotrexate-related hair loss is folic acid supplementation. Folic acid helps to replenish the folate that methotrexate depletes, thereby reducing the impact on rapidly dividing cells such as hair follicles, and also helps to reduce other side effects such as mouth ulcers and nausea.

In line with UK guidance from the Specialist Pharmacy Service (SPS), the British Society for Rheumatology (BSR), and the BNF, the standard UK regimen is folic acid 5 mg once weekly, taken on a different day to methotrexate. If side effects including hair loss persist, a specialist may increase this to folic acid 5 mg on up to six days per week (but never on the same day as methotrexate). The appropriate regimen should always be agreed with the prescribing team. Where folic acid supplementation is insufficient or poorly tolerated, a specialist may occasionally consider folinic acid (leucovorin) as an alternative, though this is uncommon and requires specialist oversight.

Before starting additional nutritional supplements, it is advisable to check for correctable underlying deficiencies (such as low ferritin, thyroid dysfunction, or vitamin B12 deficiency) that may be contributing to hair loss, rather than supplementing without investigation.

Beyond supplementation, the following practical measures may help:

• Gentle hair care: Avoiding harsh chemical treatments, excessive heat styling, and tight hairstyles reduces mechanical stress on fragile hair

• Mild shampoos: Gentle, sulphate-free products may help minimise further hair shaft damage

• Nutritional support: Ensuring adequate dietary intake of iron, zinc, and protein supports overall hair health, once deficiencies have been assessed

• Dose review: If hair loss is significant, the prescribing clinician may consider adjusting the methotrexate dose or switching to an alternative DMARD

Patients should be reassured that hair loss associated with methotrexate is usually diffuse and mild rather than complete, and does not indicate the drug is failing to work. For patients who find hair loss particularly distressing, referral to an NHS dermatologist is appropriate; some patients may also find trichology services helpful as an adjunct, though it should be noted that trichologists are not a regulated healthcare profession in the UK. Open communication with the prescribing team is essential to weigh the benefits of continued treatment against tolerability concerns.

When to Speak to Your GP or Specialist

Seek prompt advice if hair loss is sudden, patchy, or accompanied by fever, mouth ulcers, unusual bruising, breathlessness, or jaundice, as these may indicate serious methotrexate toxicity.

Whilst mild hair thinning during methotrexate therapy is generally not a medical emergency, there are circumstances in which patients should seek prompt advice from their GP or specialist. Understanding these triggers is an important part of safe self-management.

Contact your GP or rheumatology/dermatology team promptly if you notice:

• Sudden or rapidly worsening hair loss that seems disproportionate to what was described at the start of treatment

• Patchy hair loss, which may suggest an alternative diagnosis such as alopecia areata or tinea capitis

• Hair loss accompanied by any of the following — these may indicate serious methotrexate toxicity and require urgent review:

• Fever, sore throat, or other signs of infection
• Mouth ulcers
• Unusual bruising or bleeding
• Breathlessness or a persistent new cough
• Yellowing of the skin or eyes, or dark urine (possible signs of liver problems)

• Persistent or severe fatigue

• Signs of scalp infection, including redness, scaling, or pustules

• Significant psychological distress affecting daily functioning or treatment adherence

Methotrexate requires regular monitoring due to its potential for serious adverse effects, including hepatotoxicity, myelosuppression, and pulmonary toxicity. Patients on methotrexate should be enrolled in a shared care monitoring programme involving regular full blood counts (FBC), liver function tests (LFTs), and renal function tests (urea and electrolytes/creatinine). Monitoring is typically more frequent during initiation and dose changes (for example, every one to two weeks initially), then reduced to every two to three months once the dose is stable, in line with BSR and local NHS shared-care protocols. If hair loss coincides with abnormal blood results, this warrants urgent clinical review.

Patients should also be aware that certain medicines — particularly trimethoprim and co-trimoxazole — can dangerously increase methotrexate toxicity. Always inform your prescriber and pharmacist that you are taking methotrexate before starting any new prescription or over-the-counter medicine.

Patients should never stop taking methotrexate abruptly without medical advice, as this can lead to a flare of the underlying condition. Concerns about side effects — including hair loss — should always be discussed with the prescribing team so that an informed, shared decision can be made about continuing, adjusting, or changing treatment.

Does Hair Grow Back After Stopping Methotrexate

Hair loss from methotrexate is reversible for most patients, with regrowth typically observed within three to six months after the drug is stopped or the dose reduced.

For the majority of patients, hair loss associated with methotrexate is reversible. Once the drug is discontinued or the dose is reduced, hair follicles typically resume their normal growth cycle. In telogen effluvium, regrowth is generally observed within three to six months after the trigger is removed — a timeline consistent with the natural duration of the hair growth cycle and the time required for follicles to re-enter the anagen (active growth) phase.

The extent and speed of regrowth can vary between individuals and may be influenced by factors such as age, nutritional status, hormonal health, and whether folic acid supplementation was maintained during treatment. In most cases, hair returns to its previous density and texture, though some patients report that regrown hair may initially appear finer or slightly different in character before normalising over time.

If methotrexate is continued at a lower dose rather than stopped entirely, hair loss may stabilise or partially improve — particularly if folic acid supplementation is optimised concurrently. Permanent hair loss is unlikely at the standard anti-inflammatory doses used for conditions such as rheumatoid arthritis or psoriasis, though persistent loss after stopping treatment warrants assessment for other contributing causes.^[2]

Patients who experience persistent hair loss after stopping methotrexate should be assessed for other common causes, including thyroid dysfunction, iron deficiency, or androgenetic alopecia, all of which may have been masked or exacerbated during treatment. A GP or dermatologist can arrange appropriate investigations to identify any underlying factors.

NICE and NHS Guidance on Methotrexate Side Effects

NICE guideline NG100 recommends methotrexate as a first-line DMARD and emphasises regular monitoring, folic acid supplementation, and patient education about side effects including alopecia.

Methotrexate is a high-risk medicine that requires careful prescribing, monitoring, and patient education. The NICE guideline on rheumatoid arthritis (NG100) recommends methotrexate as a first-line DMARD and emphasises the importance of baseline assessments, regular monitoring, and patient counselling regarding potential side effects — including alopecia, nausea, and hepatotoxicity.

The MHRA has issued Drug Safety Updates and a National Patient Safety Alert highlighting the risk of serious harm and fatalities from daily rather than weekly dosing errors with oral methotrexate. All patients starting methotrexate should receive a patient-specific treatment booklet and alert card, which outlines:

• The critical importance of taking methotrexate once weekly only — daily dosing errors have caused fatalities

• The requirement for regular blood monitoring, including FBC, LFTs, and renal function — more frequently during initiation and dose changes, then every two to three months once stable^[1][3]

• The need to take folic acid supplementation (5 mg once weekly on a different day to methotrexate) to reduce side effects including hair loss and mouth ulcers

• Symptoms that should prompt immediate medical attention, such as fever, sore throat, mouth ulcers, breathlessness, persistent cough, unusual bruising or bleeding, or signs of jaundice

• The importance of avoiding trimethoprim and co-trimoxazole, and of informing all healthcare professionals — including dentists and pharmacists — that you are taking methotrexate

With regard to hair loss specifically, NHS patient information acknowledges alopecia as a recognised side effect and advises patients to report it to their clinical team.^[2] Whilst there is no NICE guidance dedicated solely to methotrexate-induced alopecia, the broader framework of shared decision-making and regular review ensures that side effects are assessed and managed on an individual basis.

Patients are encouraged to engage actively with their monitoring appointments and to raise any concerns — including hair changes — at each review. If you think you have experienced a side effect from methotrexate, you can report it to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk or through the Yellow Card app. Effective management of side effects is central to maintaining long-term treatment adherence and achieving the best possible outcomes for the underlying condition.

Frequently Asked Questions