Menstrual Cycle Changes with Spironolactone
Yes, menstrual irregularities are the most common side effect of spironolactone, occurring in 15-40% of patients, and should be expected and discussed before starting treatment. 1
Frequency and Nature of Menstrual Changes
Menstrual irregularities occur in 15-30% of patients according to the most recent American Academy of Dermatology guidelines, though some studies report rates as high as 40.6% compared to 0% with placebo. 1 The specific pattern most commonly reported is metrorrhagia with shortened cycles (14-day cycles), which while not medically dangerous, can be intolerable to patients. 2
- In one prospective study of 26 women receiving 100mg twice daily, 56% developed metrorrhagia with 14-day cycles, leading to dose reduction or discontinuation in 68% of patients. 2
- Another survey of 54 patients found that 91% experienced side effects, with 80% being hormonal in nature (menstrual disturbances, breast enlargement and tenderness). 3
- Polymenorrhea (frequent menstrual periods) is described as the "major side effect" in multiple studies. 4
Dose-Dependent Relationship
The risk of menstrual irregularities is strongly dose-dependent, with a relative risk of 4.12 (95% CI 3.27-5.19) in women receiving 200mg/day compared to lower doses. 1 This dose-response relationship is critical for clinical management:
- At 100mg twice daily (200mg total), menstrual irregularities occurred in 56% of patients. 2
- At 50mg twice daily (100mg total), only 20% developed metrorrhagia. 2
- Lower doses (75-100mg daily) are as effective as higher doses (150-300mg daily) but with substantially fewer side effects. 5
Effective Mitigation Strategy
Concomitant use of combined oral contraceptives (COCs) or hormonal intrauterine devices can minimize the incidence of menstrual irregularities. 1 This is a key management strategy:
- Studies show a lower incidence of menstrual abnormalities when spironolactone is used with contraceptive pills. 3
- The American Academy of Dermatology specifically recommends concurrent COC use to both regulate menses and prevent pregnancy. 1
- Concomitant use of spironolactone with drospirenone-containing COCs is safe, with no elevations in serum potassium identified in 27 patients. 1
Practical Counseling Points
Start with 100mg daily (or 50mg twice daily on cycle days 4-21) to balance efficacy with tolerability, as this minimizes menstrual side effects while maintaining therapeutic benefit. 1, 5, 2
- Menstrual irregularities tend to occur early in treatment, so regular review during the initial 3 months is advised. 3
- If menstrual irregularities develop, consider dose reduction to 50-75mg daily rather than discontinuation, as this often achieves a compromise between disease control and side effects. 3
- Alternatively, add cyclical estrogen/progesterone therapy to continuous spironolactone therapy. 2
Mechanism
The menstrual irregularities are not due to progestational activity of spironolactone itself, as studies demonstrate no secretory transformation of appropriately estrogen-primed endometrium with oral spironolactone. 6 Rather, they result from the drug's anti-androgenic effects and antagonism of progesterone receptors. 1