What is the effect of Spironolactone (SPIR, a potassium-sparing diuretic) on menstrual cycle irregularities?

From the Guidelines

Spironolactone can cause menstrual irregularities in 15-30% of women, and this side effect is dose-dependent, with higher doses increasing the risk of menstrual cycle issues. This medication, commonly prescribed for conditions like acne, hirsutism, and polycystic ovary syndrome (PCOS), works by blocking androgens (male hormones) and can lead to changes in menstrual patterns 1. Common menstrual issues include irregular periods, spotting between periods, heavier or lighter bleeding, and occasionally missed periods. These effects typically occur because spironolactone alters the hormone balance that regulates the menstrual cycle.

Key Considerations

• The risk of menstrual irregularities is higher with doses of 200mg/day, with a relative risk of 4.12 (95% CI 3.27-5.19) compared to lower doses 1.
• The concomitant use of a combined oral contraceptive (COC) or hormonal intrauterine device can minimize the incidence of menstrual irregularities 1.
• If you're experiencing significant menstrual disruptions while taking spironolactone, don't stop the medication abruptly but consult your healthcare provider, as they may adjust your dosage or recommend alternative treatments 1.

Management and Prevention

• Women taking spironolactone should use reliable contraception, as the drug may cause birth defects if taken during pregnancy 1.
• Most menstrual irregularities stabilize after a few months as your body adjusts to the medication.
• The starting dose of spironolactone is typically 100mg/day, and doses up to 200mg/day can be used, but side effects increase with higher doses 1.

From the Research

Spironolactone and Menstrual Cycle Issues

• Spironolactone has been reported to cause menstrual cycle issues, including metrorrhagia, in some women 2.
• A study found that 56% of women experienced metrorrhagia with 14-day cycles while taking 100 mg of spironolactone twice daily on days 4-21 of their menstrual cycles 2.
• Another study found that spironolactone had a slight but statistically insignificant effect on hirsutism, but it did cause spotting in one-third of the treatment cycles 3.
• The incidence of metrorrhagia was lower in women taking 50 mg of spironolactone twice daily on days 4-21 of their menstrual cycles, with only 2 out of 10 women developing metrorrhagia 2.
• A systematic review and meta-analysis found that the main side effects of spironolactone reported by the studies were menstrual irregularity, mild nausea, vomiting, and diarrhea 4.
• Spironolactone has been found to improve premenstrual syndrome (PMS) symptoms, including negative mood symptoms and somatic symptoms, in some women 5.

Dosage and Administration

• It is recommended that spironolactone be administered cyclically at a starting dosage of 50 mg twice daily on days 4-21 of the menstrual cycle to minimize the risk of menstrual cycle issues 2.
• Alternatively, cyclical estrogen/progesterone therapy may be added to continuous spironolactone therapy to help regulate the menstrual cycle 2.

Effects on Menstrual Cycle

• Spironolactone has been found to cause changes in menstrual cycle length and regularity, including shorter cycles and metrorrhagia 2, 3.
• However, some studies have found that spironolactone has no significant effect on menstrual cyclicity or ovulation 3, 4.