Methotrexate's Effects on Menstruation
Yes, methotrexate can affect menstruation, potentially causing menstrual abnormalities including amenorrhea in some patients. This effect appears to be related to both cumulative dose and duration of therapy, with higher disease activity also being a significant factor 1.
Mechanisms of Menstrual Effects
Methotrexate may affect menstruation through several mechanisms:
- Impact on ovarian function: As a folate antagonist, methotrexate targets rapidly dividing cells, which can include ovarian cells 1
- Hormonal changes: Studies have shown that FSH levels have a significant positive correlation with cumulative methotrexate dose and duration of therapy 1
- Diminished ovarian reserve: Higher levels of FSH, which indicate diminished ovarian reserve, are associated with disease activity, cumulative dose, and duration of methotrexate therapy 1
Clinical Presentation
Menstrual abnormalities associated with methotrexate may include:
- Secondary amenorrhea: Complete absence of menstruation after previous normal cycles 2
- Irregular cycles: Changes in frequency, duration, or flow of menstruation
- Menopausal symptoms: Over 50% of patients in some studies report menopausal symptoms, particularly hot flushes 1
Risk Factors
Factors that may increase the risk of menstrual abnormalities with methotrexate include:
- Higher disease activity: Multivariate analysis showed disease activity (DAS 28) was significantly associated with FSH levels 1
- Longer duration of therapy: Significant positive correlation with FSH levels 1
- Higher cumulative dose: Significant positive correlation with FSH levels 1
- Older age: Menstrual abnormalities are more likely to occur in older premenopausal patients 3
Management Considerations
For patients experiencing menstrual abnormalities while on methotrexate:
- Monitor reproductive hormones: Consider checking FSH and LH levels if menstrual abnormalities occur
- Pregnancy considerations: Methotrexate is absolutely contraindicated during pregnancy due to its teratogenic effects 4, 5
- Contraception requirements: Effective contraception must be used while taking methotrexate 4
- Discontinuation timing: Women should discontinue methotrexate at least 3 months before attempting conception 4
Important Caveats
- Reversibility: Some menstrual abnormalities may be reversible after discontinuation of methotrexate, though data is limited
- Individual variation: Not all patients will experience menstrual changes
- Confounding factors: Underlying disease activity may independently contribute to menstrual abnormalities
Clinical Implications
For women of reproductive age taking methotrexate:
- Counsel about potential menstrual changes before starting therapy
- Monitor menstrual patterns during treatment
- Remember that methotrexate is contraindicated in pregnancy and requires effective contraception 4
- If pregnancy is desired, discontinue methotrexate at least 3 months before attempting conception 4
In summary, methotrexate can affect menstruation through its impact on ovarian function and hormone levels, with effects potentially related to dose, duration, and disease activity. Healthcare providers should monitor and counsel patients accordingly.