What are examples of low-dose combined oral contraceptives?

Low-Dose Combined Oral Contraceptives

Low-dose combined oral contraceptives (COCs) are defined as those containing 35 μg or less of ethinyl estradiol, with examples including pills containing 17β-estradiol with acetate nomegestrol or dienogest, and ethinyl estradiol-based COCs with progestins such as levonorgestrel, norgestimate, or drospirenone. 1

Common Low-Dose COC Formulations

First-Choice Options

• 17β-estradiol-based COCs:
  • 17β-estradiol + acetate nomegestrol
  • 17β-estradiol + dienogest

Second-Choice Options

• Ethinyl estradiol-based COCs:
  • Ethinyl estradiol 20 μg + levonorgestrel 100 μg 2, 3
  • Ethinyl estradiol 30-35 μg + levonorgestrel 1
  • Ethinyl estradiol 30-35 μg + norgestimate 1
  • Ethinyl estradiol 20-30 μg + drospirenone 4, 5

Clinical Considerations for Low-Dose COCs

Efficacy

• Low-dose COCs are highly effective contraceptives with typical failure rates of 5-9% 6
• The Pearl index (pregnancies per 100 woman-years) for ethinyl estradiol 20 μg/levonorgestrel 100 μg is 0.88 2

Benefits of Low-Dose Formulations

• Lower hormone exposure while maintaining contraceptive efficacy
• May have fewer estrogen-related side effects
• 17β-estradiol-based COCs are considered first-choice options for patients with iatrogenic premature ovarian insufficiency requiring contraception 1
• Transdermal estrogens have better profiles for bone mass accrual and avoid first-pass hepatic metabolism 1

Potential Side Effects

• Common transient adverse effects include:
  • Irregular bleeding (especially in first 3 months)
  • Headache
  • Nausea 1
• Drospirenone-containing COCs may have a higher risk of venous thromboembolism compared to levonorgestrel-containing COCs 4

Important Contraindications

Low-dose COCs should not be prescribed for patients with:

• Severe uncontrolled hypertension (≥160/100 mmHg)
• Ongoing hepatic dysfunction
• Complicated valvular heart disease
• Migraines with aura or focal neurologic symptoms
• Thromboembolism or thrombophilia
• Complications of diabetes
• Complicated solid organ transplantation 1

Practical Prescribing Information

Initiation

• Can be started on the same day as the visit ("quick start") in healthy, non-pregnant adolescents and women
• A backup method (condoms or abstinence) should be used for at least the first 7 days 1
• No gynecologic examination is required to determine eligibility for COC use 1

Follow-Up

• A routine follow-up visit 1-3 months after initiating COCs is useful for addressing adverse effects or adherence issues 1
• Enhanced counseling about expected bleeding patterns can improve treatment adherence 6

Clinical Pearls

• Breakthrough bleeding is common in the first 3 months and is a leading cause of discontinuation 7
• Smoking is not a contraindication to COC use in women younger than 35 years old 1
• The risk of venous thromboembolism with COC use (3-4 per 10,000 woman-years) is lower than during pregnancy (10-20 per 10,000 woman-years) 4
• Consider prescribing up to 1 year of COCs at a time to improve access and continuation 1

When choosing a low-dose COC, consider the patient's medical history, risk factors, and potential side effects to select the most appropriate formulation.