Does spironolactone affect the efficacy of hormonal contraceptives, such as ethinyl estradiol and levonorgestrel?

Spironolactone and Contraceptive Efficacy

Spironolactone does not reduce the efficacy of hormonal contraceptives and can be safely used in combination with them for treating conditions like acne and hirsutism.

Mechanism and Interactions

Spironolactone is an aldosterone receptor antagonist with potent anti-androgenic properties that works through several mechanisms:

• Decreases testosterone production
• Competitively inhibits binding of testosterone and dihydrotestosterone to androgen receptors
• May inhibit 5-alfa-reductase
• Can increase steroid hormone-binding globulin 1

Unlike some medications that can interfere with contraceptive efficacy, spironolactone does not have known interactions that would reduce the effectiveness of hormonal contraceptives.

Evidence for Safety with Combined Hormonal Contraceptives

The American Academy of Dermatology guidelines explicitly state that:

• Combined oral contraceptives (COCs) may be used in combination with other oral acne medications, including spironolactone 1
• The tetracycline class of antibiotics has not been shown to reduce the effectiveness of COCs when taken concomitantly 1
• Only rifampin and griseofulvin are the anti-infectives that interact with COCs, lessening their effectiveness 1

Special Consideration: Drospirenone-Containing COCs

There has been some concern about using spironolactone with drospirenone-containing COCs since drospirenone is an analog of spironolactone, potentially increasing the risk of hyperkalemia. However:

• A study of 27 women with acne treated with both a COC containing drospirenone 3 mg and ethinyl estradiol 30 μg plus spironolactone 100 mg daily showed:
  • No significant elevations of serum potassium
  • No additional side effects significant enough to discontinue treatment 1, 2
• This combination appears to be well-tolerated and effective for treating severe acne in women 2

Benefits of Combined Use

Using spironolactone with hormonal contraceptives offers several advantages:

1. Enhanced efficacy for skin conditions: The combination can be particularly effective for treating acne and hirsutism 3, 4

2. Management of menstrual irregularities: COCs can help regulate menstrual cycles that might be disrupted by spironolactone 5

3. Contraceptive coverage: Since spironolactone carries a risk of feminization of male fetuses if pregnancy occurs, concurrent contraception is important 1

Antiretroviral Considerations

For patients on antiretroviral therapy, it's important to note that:

• Spironolactone itself doesn't affect contraceptive efficacy
• However, certain antiretroviral medications may interact with hormonal contraceptives
• Ritonavir-boosted protease inhibitors, efavirenz, and nevirapine can reduce hormonal contraceptive effectiveness 1
• In these cases, alternative or additional contraceptive methods should be considered 1

Clinical Recommendation

When prescribing spironolactone for conditions like acne, hirsutism, or female pattern hair loss:

• Spironolactone can be safely combined with hormonal contraceptives without concerns about reduced contraceptive efficacy
• The combination may actually be beneficial for managing both the condition being treated and providing effective contraception
• For patients on certain antiretroviral medications, the contraceptive efficacy concern relates to the antiretroviral drug, not to spironolactone

Bottom line: Spironolactone does not reduce the efficacy of hormonal contraceptives such as ethinyl estradiol and levonorgestrel, and the combination can be safely and effectively used in clinical practice.