Usage
- Ethinyl Estradiol + Etonogestrel is prescribed for contraception (preventing pregnancy). It is also sometimes used to manage menstrual irregularities, though this is an off-label use.
- Pharmacological Classification: Combined Hormonal Contraceptive (CHC), containing both an estrogen and a progestin.
- Mechanism of Action: Primarily prevents ovulation by suppressing the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, thus reducing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. Secondarily, it thickens cervical mucus, hindering sperm penetration, and alters the endometrial lining, making implantation less likely.
Alternate Names
- Combined hormonal contraceptive vaginal ring
- Brand Names: NuvaRing, EluRyng, Annovera (Segesterone Acetate/Ethinyl Estradiol Vaginal System)
How It Works
- Pharmacodynamics: Suppresses the hypothalamic-pituitary-ovarian (HPO) axis, resulting in inhibition of ovulation. Thickens cervical mucus and thins the endometrium, creating a less hospitable environment for sperm transport and implantation.
- Pharmacokinetics: Etonogestrel and ethinyl estradiol are absorbed through the vaginal mucosa. Etonogestrel is metabolized primarily by hepatic CYP3A4 enzymes. Ethinyl estradiol undergoes hepatic metabolism, including conjugation, and is primarily excreted in urine. The vaginal ring provides sustained release of both hormones over three weeks.
- Mode of Action: The estrogen component, ethinyl estradiol, primarily inhibits FSH release, preventing follicle development. The progestin component, etonogestrel, mainly inhibits LH release, preventing ovulation. Both hormones contribute to the changes in cervical mucus and endometrium.
- Receptor Binding/Enzyme Inhibition: Ethinyl estradiol and etonogestrel bind to estrogen and progesterone receptors, respectively, mediating their effects on the reproductive system.
- Elimination Pathways: Primarily hepatic metabolism and renal excretion for both hormones.
Dosage
Standard Dosage
Adults:
One vaginal ring is inserted into the vagina and left in place for 3 weeks, followed by a 1-week ring-free interval. A new ring is inserted 1 week after the last ring was removed, even if bleeding has not stopped.
Children:
Not indicated for use before menarche. Adolescent dosing is similar to adult dosing.
Special Cases:
- Elderly Patients: Not typically used in postmenopausal women.
- Patients with Renal Impairment: No specific dosage adjustments are usually needed.
- Patients with Hepatic Dysfunction: Use with caution in mild to moderate hepatic impairment. Contraindicated in severe hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in women with cardiovascular risk factors, hyperlipidemia, diabetes, and a history of depression or migraines with aura.
Clinical Use Cases Ethinyl Estradiol + Etonogestrel vaginal ring is primarily used for contraception. Its use is not indicated for the scenarios you described (Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations).
Side Effects
Common Side Effects:
Headache, nausea, breast tenderness, vaginal irritation or discharge, weight changes, mood changes, decreased libido.
Rare but Serious Side Effects:
Blood clots (deep vein thrombosis, pulmonary embolism, stroke, heart attack), toxic shock syndrome, allergic reactions (including angioedema and anaphylaxis), liver problems (including cholestatic jaundice and hepatic adenoma), gallbladder disease.
Long-Term Effects:
Increased risk of cardiovascular events in smokers over 35 years of age. Potential for increased risk of cervical cancer with long-term use.
Adverse Drug Reactions (ADR):
Severe allergic reactions, blood clots, and liver problems.
Contraindications
Breast cancer (current or past), severe liver disease, undiagnosed abnormal vaginal bleeding, pregnancy, hypersensitivity to drug components, high risk of arterial or venous thrombotic disease, smokers over 35, uncontrolled hypertension, certain drug combinations used to treat chronic hepatitis C (e.g. ombitasvir/paritaprevir/ritonavir with or without dasabuvir).
Drug Interactions
Certain medications can decrease the effectiveness of Ethinyl Estradiol + Etonogestrel, such as some anticonvulsants (e.g., phenytoin, carbamazepine, topiramate), rifampin, certain HIV medications, and St. John’s wort. Conversely, Ethinyl Estradiol + Etonogestrel may alter the levels of certain other drugs, such as cyclosporine and lamotrigine. Alcohol and grapefruit juice can also interact.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated)
- Fetal Risks: Contraindicated during pregnancy as there is no need for contraception during pregnancy. Limited evidence suggests no increased risk of birth defects with inadvertent exposure.
- Breastfeeding: Can reduce milk production. Not recommended for breastfeeding mothers, especially in the first few weeks postpartum due to increased thromboembolism risk. Progestin-only contraceptives are generally preferred.
Drug Profile Summary
- Mechanism of Action: Suppresses HPO axis, inhibits ovulation, thickens cervical mucus, alters endometrium.
- Side Effects: Headache, nausea, breast tenderness, vaginal irritation, mood changes, rare but serious side effects like blood clots.
- Contraindications: See “Contraindications” section.
- Drug Interactions: Certain anticonvulsants, rifampin, certain HIV medications, St. John’s wort, among others.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Not recommended during breastfeeding.
- Dosage: One ring vaginally for 3 weeks, followed by a 1-week ring-free interval.
- Monitoring Parameters: Blood pressure, signs of blood clots, liver function tests (if indicated).
Popular Combinations
Not applicable. Ethinyl Estradiol + Etonogestrel is a combination product itself and isn’t typically used with other hormonal contraceptives.
Precautions
Screen for contraindications and risk factors before initiating therapy. Monitor blood pressure. Counsel patients on proper insertion and removal techniques, potential side effects, and drug interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ethinyl Estradiol + Etonogestrel?
A: One vaginal ring is inserted and left in place for 3 weeks, followed by a 1-week ring-free interval. A new ring is inserted 1 week after the last ring was removed.
Q2: What should a patient do if the ring slips out?
A: If the ring is out for less than 3 hours, rinse it with cool to lukewarm (not hot) water and reinsert it as soon as possible. If the ring has been out for more than 3 hours or if the duration of expulsion is unknown, contraceptive efficacy may be reduced. A backup method of contraception is recommended until the ring has been used continuously for seven days. If expulsion occurs within the first two weeks of use, consider the possibility of pregnancy.
Q3: Can Ethinyl Estradiol + Etonogestrel be used while breastfeeding?
A: It is not recommended as it can decrease milk production and poses a thromboembolic risk, particularly in the early postpartum period.
Q4: What are the most serious side effects of Ethinyl Estradiol + Etonogestrel?
A: Blood clots (DVT, PE, stroke, heart attack), toxic shock syndrome, severe allergic reactions, liver problems (including hepatic adenoma).
Q5: Who should not use Ethinyl Estradiol + Etonogestrel?
A: Women with contraindications listed above, including smokers over 35, those with a history of breast cancer or blood clots, and those with severe liver disease.
Q6: Does Ethinyl Estradiol + Etonogestrel protect against sexually transmitted infections (STIs)?
A: No. Barrier methods, such as condoms, are necessary for STI protection.
Q7: What if a patient misses a period while using the ring?
A: If the ring has been used according to instructions and two periods are missed, pregnancy must be ruled out.
Q8: Can other vaginal products be used while using the ring?
A: Concurrent use with certain vaginal products, such as antifungal medications, might interfere with the effectiveness of the vaginal ring, so caution should be exercised.
Q9: Does the exact placement of the ring in the vagina matter?
A: Precise placement is not crucial for effectiveness, however, it should be inserted far enough into the vagina to minimize the chances of expulsion.
Q10. When should a woman start using the ring?
A: Ideally, the ring should be inserted on the first day of the menstrual cycle. If inserted later, an additional barrier method of contraception is recommended for the first 7 days.
