From the Guidelines
Methotrexate use can potentially cause erectile dysfunction (ED) as a side effect, though it's not among the most commonly reported sexual side effects. Methotrexate is an immunosuppressive medication used to treat conditions like rheumatoid arthritis, psoriasis, and certain cancers. The mechanism behind methotrexate-induced ED likely involves its effects on folate metabolism, general fatigue, and overall impact on well-being rather than direct effects on erectile tissue.
Key Considerations
- Patients taking methotrexate who experience ED should discuss this with their healthcare provider, as the problem might be addressed through dose adjustments, folate supplementation (which is typically prescribed alongside methotrexate anyway), or consideration of alternative medications.
- It's essential to note that the underlying condition being treated with methotrexate could also contribute to sexual dysfunction, making it difficult to determine if the medication is the sole cause.
- Never stop taking methotrexate without medical consultation, as abrupt discontinuation can lead to disease flares.
Recommendations Based on Evidence
The most recent and highest quality study available, 1, provides guidelines for the safe and effective prescribing of methotrexate for skin disease, but does not directly address erectile dysfunction. However, general principles of managing side effects and the importance of patient education and monitoring can be applied.
Patient Education and Monitoring
- Explain the potential side effects of methotrexate, including the possibility of erectile dysfunction.
- Advise patients to seek urgent medical attention if they develop signs or symptoms of methotrexate toxicity or other severe side effects.
- Emphasize the need for regular blood tests to monitor for toxicity and the importance of compliance with the prescribed regimen.
Given the lack of direct evidence linking methotrexate to erectile dysfunction in the provided studies, the approach should be cautious and based on the principle of minimizing harm and maximizing benefit for the patient. Therefore, healthcare providers should be aware of the potential for methotrexate to cause erectile dysfunction and manage it accordingly, considering the patient's overall health, the underlying condition being treated, and the potential for other medications or factors to contribute to sexual dysfunction.
From the FDA Drug Label
Urogenital System - severe nephropathy or renal failure, azotemia, cystitis, hematuria, proteinuria; defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction, vaginal discharge, and gynecomastia; infertility, abortion, fetal death, fetal defects Other rarer reactions related to or attributed to the use of methotrexate such as nodulosis, vasculitis, arthralgia/myalgia, loss of libido/impotence, diabetes, osteoporosis, sudden death, lymphoma, including reversible lymphomas, tumor lysis syndrome, soft tissue necrosis, and osteonecrosis.
Methotrexate use can cause erectile dysfunction, as indicated by the reported adverse reaction of loss of libido/impotence 2.
From the Research
Methotrexate and Erectile Dysfunction
- Methotrexate is a disease-modifying antirheumatic drug commonly used to treat rheumatoid and psoriatic arthritis, and its potential side effects include sexual dysfunction 3, 4, 5.
- A systematic review of seven case reports found that erectile dysfunction (ED) was a common presentation in male rheumatological patients treated with methotrexate, with 45.4% of patients experiencing ED 3.
- Another study reported two cases of sexual impotence and gynecomastia in patients with psoriatic arthritis treated with methotrexate, highlighting the potential consequences of methotrexate-induced sexual dysfunction 4.
- A case report described a 58-year-old man who developed erectile impotence nine months after starting methotrexate treatment, which subsided after discontinuation of the treatment but returned when it was reintroduced 5.
Prevalence of Erectile Dysfunction in Rheumatoid Arthritis Patients
- A study of 231 rheumatoid arthritis patients found that 53.8% of men and 45.7% of women reported sexual dysfunction, with erectile dysfunction being a significant correlate of pain score, cardiovascular disease, age, disease activity, fatigue score, and tender joint count in men 6.
- Another study found that the incidence of erectile dysfunction was not statistically increased in men with rheumatoid arthritis compared to age-matched comparators, but men with both rheumatoid arthritis and erectile dysfunction had a decreased risk of heart failure, myocardial infarction, and death 7.
Association between Methotrexate and Erectile Dysfunction
- While the exact mechanism of methotrexate-induced erectile dysfunction is unknown, the available evidence suggests that methotrexate may contribute to the development of erectile dysfunction in some patients 3, 4, 5.
- Further studies are needed to confirm the association between methotrexate and erectile dysfunction, investigate its pathophysiological basis, and assess the safest dosages and most appropriate management strategies 3.