Comparison of Norethindrone and Desogestrel
Progestin Classification and Properties
- Norethindrone is a first-generation progestin with mild androgenic activity, whereas Desogestrel is a third-generation progestin with very low androgenic properties and potent antiovulatory effects 1, 3
Effectiveness
- Both progestins are effective for contraception when combined with ethinyl estradiol, with a 2012 Cochrane meta-analysis of 31 trials (12,579 women) finding that all combined oral contraceptives effectively reduce acne 3, 1, 2
Side Effect Profile Comparison
- Norethindrone, being mildly androgenic, may worsen acne in some women, whereas Desogestrel has significantly lower androgenic properties 1, 3
- Norethindrone-containing pills may have poorer gynecologic tolerance with breakthrough bleeding, pelvic discomfort, and mastalgia 4
Cardiovascular Risk
- All COCs increase the risk of venous thromboembolism (VTE) compared to non-users, with Desogestrel carrying approximately 50-80% higher VTE risk compared to levonorgestrel-containing COCs 3
- The absolute risk remains low: non-users (1-5/10,000 woman-years), COC users (3-9/10,000 woman-years), Desogestrel-containing COC users (approximately 10/10,000 woman-years) 3
Special Considerations
- For women with hereditary angioedema, progestin-only pills containing Norethindrone are well-tolerated in about two-thirds of patients, and Etonogestrel implants have been well-tolerated by some patients with hereditary angioedema 4
- Women with risk factors for VTE, including age ≥35 years, smoking, history of VTE, thrombophilia, obesity, and hypertension, should consider Norethindrone over Desogestrel due to the lower thrombotic risk 3, 5
Common Side Effects for Both
Drug Interactions
- Both progestins may have reduced effectiveness when combined with medications that induce hepatic enzymes (rifampin, griseofulvin, some anticonvulsants) 6