Can spironolactone cause endometrial hyperplasia?

Spironolactone and Endometrial Hyperplasia

Spironolactone does not cause endometrial hyperplasia based on available evidence. 1

Mechanism of Action and Endometrial Effects

Spironolactone is an aldosterone antagonist that also has anti-androgenic properties, making it useful in several clinical contexts:

• As a heart failure medication (12.5-50 mg) 2
• As an anti-androgen treatment for acne and hirsutism (50-200 mg) 3

Despite early animal studies suggesting potential progestational activity 4, human studies have demonstrated that:

• Spironolactone does not act as a progestin or anti-progestin on human endometrium 1
• When administered to women with estrogen-primed endometrium, spironolactone did not cause secretory transformation of the endometrium 1

Side Effects in Women

Spironolactone can cause several gynecologic side effects, but endometrial hyperplasia is not among them. Common side effects include:

• Menstrual irregularities (15-30% of users) 3
• Breast tenderness (3-5%) 3
• Breast enlargement 3

The menstrual irregularities associated with spironolactone are not due to endometrial hyperplasia but rather may be related to:

• Reduced estradiol levels during treatment 5
• Decreased endometrial thickness 5
• Complex effects on hormone receptors 5

Clinical Implications

When prescribing spironolactone to women:

1. Monitor for common side effects such as menstrual irregularities, which increase with higher doses (relative risk of 4.12 at 200mg/day) 3

2. Consider combined oral contraceptives to help regulate menstrual cycles in women experiencing irregular bleeding 3

3. For patients with hereditary angioedema who experience hirsutism while on androgen therapy, spironolactone (100-200 mg/day) can be used to control hirsutism 2

4. Avoid use during pregnancy due to potential feminization of male fetuses (pregnancy category C) 3

Important Distinctions

It's worth noting that endometrial hyperplasia is typically associated with unopposed estrogen activity. Studies have shown that:

• Unopposed estrogen therapy can lead to endometrial hyperplasia in 14.6% of women 6
• Adding progestins significantly reduces this risk to less than 1% 6
• Spironolactone does not have progestational effects in humans that would either cause or prevent endometrial hyperplasia 1

Conclusion

While spironolactone can cause various side effects in women, including menstrual irregularities, there is no evidence that it causes endometrial hyperplasia. The menstrual changes observed with spironolactone use are more likely related to its effects on estradiol levels and endometrial thickness rather than hyperplastic changes.