Side Effects of Zoely (Nomegestrol Acetate and Estradiol)
Zoely is generally well tolerated with the most common side effects being acne and abnormal withdrawal bleeding (typically shorter, lighter, or absent periods), along with standard combined oral contraceptive side effects including irregular bleeding, headache, and nausea. 1, 2, 3
Common Side Effects
Most Frequently Reported
- Acne: This is one of the most commonly reported adverse events with Zoely, and appears to occur more frequently compared to drospirenone/ethinylestradiol combinations 3
- Abnormal withdrawal bleeding: Most often manifesting as shorter, lighter, or absent periods 2, 3
- Irregular bleeding: Common transient effect, particularly during the first 3-6 months of use 4
- Headache: A typical side effect of combined hormonal contraceptives 4
- Nausea: Expected with combined hormonal contraceptives, though generally less severe than with higher-dose estrogen formulations 4
Important Tolerability Features
- Weight: Zoely causes minimal to no weight gain, with most women reporting no negative impact on weight 2, 5
- Mood changes: Have not been reliably linked to combined hormonal contraception in general 4
- Blood pressure: Minimal influence on blood pressure has been observed 5
Metabolic and Laboratory Effects
Zoely demonstrates favorable metabolic profiles:
- Lipid metabolism: Remains largely unchanged 5, 6
- Carbohydrate metabolism: Not significantly affected 5, 6
- Bone mineral density: Minimal influence 5
- Hemostasis: Remains largely unchanged, though all combined oral contraceptives carry some thrombotic risk 6
Serious Side Effects and Contraindications
Venous Thromboembolism Risk
- The baseline incidence of venous thromboembolism in adolescents is up to 1 per 10,000 woman-years 4
- Combined oral contraceptives increase this risk three to fourfold, or up to 4 per 10,000 woman-years 4
- Zoely contains estradiol rather than ethinylestradiol, which is postulated to be potentially safer, though definitive long-term safety data are still being established 2, 6
Absolute Contraindications
Zoely should not be used in patients with:
- Severe and uncontrolled hypertension (systolic ≥160 mm Hg or diastolic ≥100 mm Hg) 4
- Ongoing hepatic dysfunction 4
- Complicated valvular heart disease 4
- Migraines with aura or focal neurologic symptoms 4
- Thromboembolism or thrombophilia (e.g., factor V Leiden mutation, antiphospholipid antibody syndrome, or protein C, protein S, or antithrombin 3 deficiency) 4
- Complications of diabetes (nephropathy, retinopathy, neuropathy, or other vascular disease) 4
Clinical Advantages
- High contraceptive efficacy: Particularly effective in overweight and obese patients 5
- Good cycle control: Achieved with the monophasic 24/4 regimen 5, 6
- Fast recovery: Rapid return of ovarian activity and ovulation after discontinuation 5
- Endocrine function: Does not adversely affect endocrine gland functioning 5
Special Considerations
- Breast tissue effects: Nomegestrol acetate, like natural progesterone, does not appear to stimulate proliferation of cancerous breast cells, unlike some other synthetic progestogens 6
- Antibiotic interactions: No definitive evidence of decreased contraceptive effectiveness with antibiotics except rifampin 4
- Drug interactions: Combined oral contraceptives can decrease the effectiveness of some medications (e.g., lamotrigine) 4