How does Enpresse (levonorgestrel and ethinyl estradiol) compare to Ortho Tri-Cyclen (norgestimate and ethinyl estradiol) for a female patient of reproductive age requiring birth control?

Comparison of Enpresse vs. Ortho Tri-Cyclen

Both Enpresse (levonorgestrel/ethinyl estradiol) and Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) are equally effective triphasic combined oral contraceptives with comparable safety profiles, and the choice between them should be based primarily on insurance formulary coverage, as there is no clear evidence that one formulation is superior to the other for contraceptive efficacy, morbidity, or mortality. 1

Contraceptive Efficacy

• No significant difference exists in contraceptive effectiveness between these two triphasic formulations. Both contain 35 mcg ethinyl estradiol and are classified as low-dose combined oral contraceptives (COCs) with similar mechanisms of action—primarily ovulation suppression. 1, 2

• Among low-dose pills, there are no clear data suggesting one formulation is superior to another for contraceptive use, making it appropriate to choose based on the lowest copay on a patient's insurance formulary. 1

• The typical-use failure rate for COCs is approximately 9%, which applies to both formulations when used as directed. 1

Key Formulation Differences

Progestin Component:

• Enpresse contains levonorgestrel in a triphasic regimen (doses vary across the cycle). 1
• Ortho Tri-Cyclen contains norgestimate in a triphasic regimen (180/215/250 mcg). 2, 3

Clinical Significance:

• Both levonorgestrel and norgestimate are recommended progestins by adolescent medicine providers when combined with 30-35 mcg ethinyl estradiol. 1
• Norgestimate is rapidly metabolized to norelgestromin and norgestrel (which is the same active compound as levonorgestrel), suggesting similar biological activity. 2

Cycle Control and Side Effects

Breakthrough Bleeding:

• Ortho Tri-Cyclen demonstrates good cycle control with breakthrough bleeding/spotting occurring in approximately 14-17% of cycles. 3, 4
• Direct comparative data between Enpresse and Ortho Tri-Cyclen for cycle control is not available in the provided evidence.

Common Side Effects:

• Both formulations containing 35 mcg ethinyl estradiol are associated with approximately 50% higher rates of bloating, breast tenderness, and nausea compared to 20 mcg formulations. 5
• These side effects are related to the estrogen dose rather than the specific progestin component. 5

Non-Contraceptive Benefits

Both formulations provide equivalent benefits:

• Decreased menstrual cramping and blood loss. 1
• Protection against endometrial and ovarian cancers with use >3 years. 1
• No increased risk of breast cancer. 1
• Completely reversible with no negative effect on long-term fertility. 1

Acne Treatment:

• Ortho Tri-Cyclen has FDA-approved indication and proven efficacy for treating moderate acne vulgaris, with 62% reduction in inflammatory lesions versus 38.6% with placebo. 6
• Enpresse's efficacy for acne has not been specifically studied in the provided evidence, though levonorgestrel-containing COCs may also improve acne through androgen suppression. 1

Safety Profile

Both formulations share identical contraindications and risks:

• Thromboembolic disease risk (1-2% fatal per 10,000 woman-years). 1
• Contraindicated in women with hepatic impairment, as steroid hormones may be poorly metabolized. 2
• Safe for use in women of reproductive age with no contraindications to COC therapy. 2
• Little or no increased risk of birth defects if inadvertently used during early pregnancy. 2

Practical Considerations

Starting Regimen:

• Many experts recommend starting with a monophasic pill rather than triphasic formulations, then changing regimens as indicated to address patient adverse effects or preferences. 1
• Same-day initiation is recommended for both formulations. 1

Missed Pill Management:

• Instructions are identical for both formulations, as they are both triphasic COCs with 21 hormonal pills. 1
• If ≥2 consecutive pills missed (≥48 hours): take most recent missed pill, use backup contraception for 7 days, and consider emergency contraception if missed during first week with unprotected intercourse in previous 5 days. 1

Clinical Decision Algorithm

1. Check insurance formulary coverage—choose the option with lowest or no copay. 1
2. If acne is a concern—Ortho Tri-Cyclen has proven efficacy and FDA approval for moderate acne treatment. 6
3. If patient has history of poor adherence—consider switching to a long-acting reversible contraceptive (LARC) method rather than choosing between these two similar COCs. 1
4. If patient experiences side effects on one formulation—switching to the other may be attempted, though consider switching to a lower estrogen dose (20-25 mcg) or monophasic formulation instead. 1, 5

Common Pitfalls to Avoid

• Do not assume triphasic formulations are superior to monophasic—many experts actually prefer starting with monophasic pills for simplicity. 1
• Do not overlook insurance coverage—medication adherence is significantly affected by out-of-pocket costs, and these formulations are clinically equivalent. 1
• Do not continue COCs in women who frequently miss pills—consider LARC methods (IUD, implant) instead for better real-world effectiveness. 1