What combined oral contraceptives (COCs) have lower doses of hormones?

Low-Dose Combined Oral Contraceptives

Combined oral contraceptives (COCs) with ethinyl estradiol doses of 20-35 μg are considered low-dose formulations, with the 30-35 μg pills being the standard first-line option for most patients. 1

Classification of Low-Dose COCs by Estrogen Content

Low-dose COCs can be categorized based on their ethinyl estradiol content:

Very Low-Dose (20 μg ethinyl estradiol)

• Contain 20 μg of ethinyl estradiol combined with various progestins
• Examples include:
  • Ethinyl estradiol 20 μg/levonorgestrel 100 μg 2, 3, 4
  • Ethinyl estradiol 20 μg/desogestrel 150 μg 5

Low-Dose (30-35 μg ethinyl estradiol)

• Contain 30-35 μg of ethinyl estradiol
• Considered the standard "low-dose pill" and first-line option for adolescents 1
• Examples include various formulations with progestins such as:
  • Levonorgestrel
  • Norgestimate
  • Desogestrel
  • Drospirenone

Benefits of Lower-Dose Formulations

Lower doses of hormones offer several advantages:

• Reduced cardiovascular risks: Lower estrogen doses (≤30 μg) may have less impact on blood pressure compared to higher doses 1, 6
• Decreased thrombotic risk: Though all COCs increase VTE risk compared to non-users, lower doses generally carry less risk 6
• Fewer estrogen-related side effects: Less nausea, breast tenderness, and fluid retention

Considerations When Choosing Low-Dose COCs

Progestin Component

The progestin in COCs also affects the overall safety and side effect profile:

• Fourth-generation progestins (e.g., drospirenone): Have anti-mineralocorticoid and anti-androgenic properties 6
• Third-generation progestins (e.g., norgestimate, desogestrel): Have minimal androgenic activity 6
• Second-generation progestins (e.g., levonorgestrel, norgestrel): Higher androgenic activity 6

Efficacy

Despite lower hormone content, low-dose COCs maintain good contraceptive efficacy:

• Pearl index (pregnancies per 100 woman-years) for 20 μg ethinyl estradiol/100 μg levonorgestrel was 0.88 in a large clinical trial 4
• Typical-use failure rates are approximately 9% in adults and may be higher in adolescents due to adherence issues 1

Common Side Effects with Low-Dose COCs

• Bleeding irregularities: More common with very low-dose (20 μg) formulations, especially in the first few cycles 5, 2
• Headache: One of the most common adverse events leading to discontinuation 4

Clinical Pitfalls and Caveats

1. Drug interactions: Lower-dose COCs may have reduced efficacy when used with medications that induce liver enzymes, including certain antiretroviral agents 1

2. Missed pills: Lower-dose formulations may have a narrower margin of error with missed pills, making strict adherence more important

3. Blood pressure monitoring: Even with low-dose formulations, blood pressure should be monitored, as all COCs can cause elevations in blood pressure 1, 7

4. VTE risk: While lower doses reduce risk, all COCs increase VTE risk to some degree (3-9 per 10,000 woman-years compared to 1-5 per 10,000 woman-years in non-users) 6

5. Bleeding patterns: Very low-dose pills (20 μg) may be associated with more breakthrough bleeding, especially in the first few months of use 5, 2

For most patients starting COCs, a formulation containing 30-35 μg of ethinyl estradiol represents an appropriate balance between efficacy, side effects, and safety. For those with specific concerns about estrogen-related side effects or risks, the 20 μg formulations provide an even lower-dose option.