Usage
Cyproterone + Ethinyl Estradiol is prescribed for women of reproductive age to treat moderate to severe acne (with or without seborrhea), hirsutism (excessive hair growth), and androgenetic alopecia (female pattern hair loss) related to androgen sensitivity. It is also used as an oral contraceptive in women being treated for these androgen-dependent conditions. It may also be used in managing symptoms of polycystic ovary syndrome (PCOS).
Pharmacological Classification:
- Anti-androgen
- Estrogen
- Combined oral contraceptive
Mechanism of Action:
Cyproterone acetate is an anti-androgen that competes with androgens for binding to androgen receptors, thus reducing androgenic effects. Ethinyl estradiol, a synthetic estrogen, enhances cyproterone’s effect by increasing sex hormone-binding globulin (SHBG) levels, further reducing free androgen activity. The combination also provides contraception by inhibiting ovulation and altering cervical mucus, creating an environment unfavorable for fertilization and implantation.
Alternate Names
- Co-cyprindiol
- Ethinylestradiol/cyproterone acetate (EE/CPA)
Brand Names:
- Diane-35
- Estelle-35
- Dianette
How It Works
Pharmacodynamics: Cyproterone competes with androgens at receptor sites, decreasing their effects on target tissues like skin, hair follicles, and sebaceous glands. Ethinyl estradiol suppresses gonadotropin release, leading to reduced ovarian androgen production. The estrogen component also increases SHBG, further lowering free androgen levels.
Pharmacokinetics: Both drugs are absorbed orally. Cyproterone is extensively metabolized in the liver, primarily by CYP3A4. Ethinyl estradiol undergoes hepatic metabolism, with some enterohepatic recirculation. Both drugs are primarily eliminated through the kidneys and in feces.
Mode of Action: Cyproterone acts as a competitive antagonist at androgen receptors. Ethinyl estradiol modulates gene transcription through estrogen receptor binding, affecting SHBG synthesis.
Receptor binding/Enzyme Inhibition: Cyproterone binds to androgen receptors. Ethinyl estradiol indirectly influences androgen activity by increasing SHBG levels.
Elimination Pathways: Both drugs are primarily eliminated via hepatic metabolism and subsequent renal and biliary excretion.
Dosage
Standard Dosage
Adults: One tablet daily, containing 2 mg cyproterone acetate and 0.035 mg ethinyl estradiol, for 21 consecutive days, followed by a 7-day pill-free interval.
Children: Use only after menarche, at the same adult dose.
Special Cases:
-
Elderly Patients: Not indicated after menopause.
-
Patients with Renal Impairment: Use with caution. Dosage adjustments may be needed depending on the degree of impairment.
-
Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Use with caution in mild to moderate impairment.
-
Patients with Comorbid Conditions: Caution in patients with cardiovascular risk factors (e.g., hypertension, diabetes, smoking), history of thromboembolism, migraine with aura, or liver disease.
Clinical Use Cases
Cyproterone + Ethinyl Estradiol is not indicated for use in the clinical settings of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for the management of androgen-dependent dermatological conditions.
Dosage Adjustments
Dosage adjustments may be necessary in patients with renal or hepatic impairment.
Side Effects
Common Side Effects:
- Nausea, vomiting
- Headache
- Breast tenderness
- Weight changes
- Mood swings
- Breakthrough bleeding/spotting
Rare but Serious Side Effects:
- Blood clots (deep vein thrombosis, pulmonary embolism, stroke)
- Liver dysfunction
- Jaundice
- Allergic reactions
Long-Term Effects:
- Increased risk of cardiovascular events in certain patient populations (e.g., smokers over 35 years of age)
Adverse Drug Reactions (ADR):
- Severe allergic reactions (anaphylaxis)
- Thromboembolic events
Contraindications
- Pregnancy and breastfeeding
- History of or current venous or arterial thromboembolism
- Liver disease (active or history of liver tumors)
- Breast cancer (known or suspected)
- Undiagnosed abnormal vaginal bleeding
- Migraine with aura
- Smokers over 35 years old
- Hypersensitivity to cyproterone acetate or ethinyl estradiol
Drug Interactions
- Enzyme-inducing drugs (e.g., rifampicin, phenytoin, carbamazepine, griseofulvin, St. John’s Wort) may decrease efficacy and increase the risk of breakthrough bleeding.
- Some antibiotics (e.g., ampicillin, tetracyclines) can alter the enterohepatic circulation of the drug, affecting its effectiveness.
- Concomitant use with medications metabolized by CYP3A4 may result in altered metabolism of either agent.
Pregnancy and Breastfeeding
Pregnancy Safety Category: X (Contraindicated). It may cause fetal harm.
Breastfeeding: This medication is contraindicated while breastfeeding.
Drug Profile Summary
- Mechanism of Action: Anti-androgen and estrogenic effects, ovulation inhibition.
- Side Effects: Nausea, headache, breast tenderness, thromboembolic events.
- Contraindications: Pregnancy, thromboembolic disorders, liver disease, breast cancer.
- Drug Interactions: Enzyme-inducing drugs, some antibiotics.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 1 tablet daily for 21 days, followed by a 7-day break.
- Monitoring Parameters: Blood pressure, liver function tests, signs of thromboembolism.
Popular Combinations
Not applicable. It is typically used as a single combination product.
Precautions
- Monitor blood pressure and assess risk factors for thromboembolism.
- Monitor liver function, especially in patients with pre-existing liver conditions.
- Discontinue if signs of thromboembolism or liver dysfunction occur.
- Counsel patients on the importance of consistent daily intake for optimal efficacy.
- Advise patients to use backup contraception during the first 7 days of initial use and when starting a new pack after missing pills.
- Screen for contraindications and risk factors before initiating treatment.
- Advise patients to report any unusual vaginal bleeding, severe headaches, or signs of thromboembolic events.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cyproterone + Ethinyl Estradiol?
A: One tablet daily for 21 consecutive days, followed by a 7-day pill-free interval.
Q2: How long does it take to see improvement in acne and hirsutism?
A: It may take 3-4 months or longer to see noticeable improvement in acne. Hirsutism may take even longer to respond.
Q3: Can this medication be used for contraception alone?
A: While it is effective for contraception, it is not recommended solely for this purpose due to a higher risk of thromboembolic events compared to other oral contraceptives.
Q4: What should a patient do if she misses a pill?
A: If a pill is missed for less than 12 hours, take the missed pill as soon as possible, and continue with the regular schedule. If missed for more than 12 hours, follow product-specific instructions provided in the patient leaflet or consult a healthcare professional. Additional contraceptive measures might be necessary.
Q5: What are the serious side effects to watch out for?
A: Signs of blood clots (e.g., leg pain or swelling, chest pain, shortness of breath), severe headaches, visual disturbances, jaundice, and severe allergic reactions should be reported immediately.
Q6: Can smokers use this medication?
A: Smoking significantly increases the risk of cardiovascular complications with this medication, especially in women over 35 years old. It is generally contraindicated in smokers over this age.
Q7: Can this medication affect mood?
A: Yes, mood changes, including depression, irritability, or emotional lability, can occur as side effects.
Q8: What are the key patient counseling points for Cyproterone + Ethinyl Estradiol?
A: Emphasize the importance of taking the pill at the same time each day, reporting any unusual side effects, and using additional barrier methods if pills are missed or during concomitant use of enzyme-inducing medications. Discuss the risks and benefits of the medication thoroughly, including the increased risk of thromboembolism.
Q9: How long should treatment be continued?
A: Treatment should be reevaluated periodically. For acne, it can be discontinued 3-4 cycles after acne resolution. For other conditions, the duration depends on the individual patient’s response and clinical need.
