Zoely (Nomegestrol Acetate and Estradiol): Indication and Dosage
Zoely is indicated as a combined oral contraceptive containing 2.5mg nomegestrol acetate and 1.5mg estradiol, taken as one tablet daily for 24 days followed by 4 placebo days in a 28-day cycle. 1, 2
Indications
Primary Indication
- Hormonal contraception for women of reproductive age
Secondary Indications
- Management of premenstrual dysphoric disorder (PMDD) 3
- Potential use in post-menopausal hormone therapy (though primarily used for contraception) 4
Dosage and Administration
- Standard regimen: One tablet daily at the same time each day
- Cycle structure: 24 active tablets followed by 4 placebo tablets (24/4 regimen)
- Duration: Continuous use with no breaks between packs
- Starting the pill: Begin on the first day of menstrual bleeding
Pharmacological Properties
Zoely combines two key components:
Nomegestrol acetate (2.5mg):
- 19-norprogesterone derivative with high progesterone receptor activity
- Strong antigonadotropic activity (suppresses ovulation)
- Long half-life (approximately 50 hours)
- Weak anti-androgenic effect
- No binding to estrogen, glucocorticoid or mineralocorticoid receptors 5
Estradiol (1.5mg):
- Natural estrogen (identical to endogenous 17β-estradiol)
- First monophasic combined oral contraceptive to contain natural estradiol instead of ethinyl estradiol 2
Clinical Benefits
- Contraceptive efficacy: At least as effective as other combined hormonal contraceptives 2
- Cardiovascular profile: Potentially improved cardiovascular safety profile due to natural estradiol component rather than ethinyl estradiol 1
- Cycle control: Provides stable menstrual cycles comparable to other combined hormonal contraceptives 5
- Missed pill tolerance: High contraceptive efficacy maintained even when occasional doses are missed due to nomegestrol acetate's long half-life 5
Side Effects and Tolerability
Common side effects:
- Acne
- Altered withdrawal bleeding (shorter, lighter or absent periods)
- Potential mood effects 2
Metabolic effects:
- Minimal impact on hemostasis, lipids, and carbohydrate metabolism 5
Contraindications
As with other combined hormonal contraceptives, Zoely is contraindicated in women with:
- History of or current venous or arterial thromboembolism
- Presence or history of severe hepatic disease
- Known or suspected sex-steroid influenced malignancies
- Undiagnosed vaginal bleeding
- Hypersensitivity to active substances or excipients 6
- History of breast cancer or other estrogen-sensitive cancers 7
- Uncontrolled hypertension 7
Special Considerations
- Cardiovascular risk: Women with cardiovascular risk factors should be carefully evaluated before prescribing Zoely, though the natural estradiol component may offer advantages over ethinyl estradiol-containing contraceptives 6
- Missed doses: Less stringent criteria for backup contraception compared to some other combined oral contraceptives due to the long half-life of nomegestrol acetate 2
- Premenstrual symptoms: May be beneficial for women with PMDD, with studies showing significant reductions in depression, anxiety, and stress scores 3
Clinical Pearls
- Zoely represents an innovation in oral contraception by using natural estradiol instead of synthetic ethinyl estradiol, potentially reducing thrombotic risk
- The 24/4 regimen provides shorter hormone-free intervals which may improve contraceptive efficacy and symptom control
- The combination of nomegestrol acetate with estradiol provides good cycle control despite using natural estradiol, which has been challenging with previous formulations
When considering Zoely for patients, evaluate cardiovascular risk factors carefully and counsel patients about the potential for changes in bleeding patterns, which commonly include lighter or absent withdrawal bleeding.