What it's for (Indications)
- Cyproterone acetate (CPA) and ethinyloestradiol (EE) combination therapy is indicated for the treatment of moderate to severe acne (associated with seborrhoea) and hirsutism in women of reproductive age, particularly those who have not responded to topical treatment or oral antibiotics.
- It is also indicated for polycystic ovary syndrome (PCOS) when anti-androgenic effects are desired, along with the need for contraception.
- Due to its contraceptive properties, it is essential that women requiring anti-androgen treatment also require contraception.
- This medication is not intended for use solely as a contraceptive in women without androgen-dependent conditions, as other combined oral contraceptives may offer a more favorable risk-benefit profile concerning thromboembolic events.
- Treatment should be discontinued 3-4 cycles after the treated condition has resolved and anti-androgen effects are no longer needed, and alternative contraception should be considered if pregnancy prevention is still required.
- Its use should be carefully balanced against its known risks.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | The typical dosage regimen involves taking one tablet daily for 21 consecutive days, followed by a 7-day tablet-free interval. Each tablet usually contains 2 mg of cyproterone acetate and 35 micrograms (mcg) of ethinyloestradiol. During the 7-day tablet-free interval, a withdrawal bleed similar to menstruation typically occurs. The next pack of tablets should be started on the day after the 7-day break, regardless of whether the bleeding has stopped. For initial treatment, the first tablet should be taken on the first day of a woman's natural cycle (i.e., the first day of menstrual bleeding). Adherence to the prescribed regimen is crucial for both contraceptive efficacy and therapeutic outcomes. Missing tablets, especially early in the cycle or late in the cycle before the pill-free break, can reduce contraceptive protection and impact the anti-androgenic effect. Dosage adjustments are not typically made for this fixed-dose combination; however, clinical response and side effects should be monitored regularly by a healthcare professional. |
Safety & Warnings
Common Side Effects
- This medication can cause a range of side effects, some common and others potentially serious.
- Common side effects often include nausea, abdominal pain, headache, migraine, breast tenderness or pain, mood changes (including depression), weight gain or loss, and changes in libido.
- Less common but still reported effects include skin reactions (rash, urticaria), fluid retention, and changes in vision.
- Serious side effects, which require immediate medical attention, include venous thromboembolism (VTE) such as deep vein thrombosis (DVT) and pulmonary embolism (PE), arterial thromboembolism (ATE) such as myocardial infarction (heart attack) and cerebrovascular accident (stroke), hypertension, liver tumors (benign or malignant), gallbladder disease, pancreatitis (especially with severe hypertriglyceridemia), and severe allergic reactions.
- The risk of these serious events, particularly VTE, is notably higher with this combination than with other low-dose combined oral contraceptives.
- Patients should be educated on the signs and symptoms of these serious conditions.
Serious Warnings
- Black Box Warning: Serious Warnings: Increased Risk of Thromboembolism. This medication carries a significantly increased risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, compared to other low-dose combined oral contraceptives. The risk is highest during the first year of use and upon re-initiation after a four-week or longer interval. It also carries an increased risk of arterial thromboembolism (ATE), including myocardial infarction and stroke. Due to these serious risks, cyproterone acetate and ethinyloestradiol should only be used in women who require anti-androgenic treatment for conditions such as severe acne or hirsutism and for whom other treatments have been unsuccessful or are contraindicated, and who also require contraception. It must not be used solely for contraception. Before initiating treatment, a thorough assessment of individual risk factors for thromboembolism (e.g., smoking, obesity, family history, prolonged immobilization, advanced age) is imperative. Patients must be carefully monitored for signs and symptoms of thrombotic events, and the medication should be discontinued immediately if such events are suspected. Treatment should be limited to the period during which anti-androgenic effects are clinically necessary, and generally should not exceed 3-4 cycles after the condition has resolved.
- Patients should be thoroughly evaluated before initiating therapy with cyproterone acetate and ethinyloestradiol, and regularly monitored thereafter.
- The risk of venous thromboembolism (VTE) is significantly increased with this medication compared to other combined oral contraceptives (COCs), particularly in the first year of use and upon re-initiation or switching.
- Risk factors for VTE, including obesity, increasing age, prolonged immobilization, surgery, and a family history of VTE, must be carefully assessed.
- The medication is contraindicated in women over 35 years who smoke.
- It should be used with extreme caution in patients with hypertension, diabetes mellitus (especially with vascular complications), dyslipoproteinemia, or a history of depression, as these conditions can worsen.
- Discontinue treatment if severe depression occurs.
- Hepatic function should be monitored due to the potential for liver damage or the development of liver tumors.
- This medication can affect glucose tolerance; diabetic patients require close monitoring.
- Migraines, especially with aura, are a contraindication due to increased stroke risk.
- Patients should be advised to discontinue the medication and seek immediate medical attention if symptoms suggestive of thromboembolic events, severe headache, unexplained visual disturbances, or jaundice occur.
How it Works (Mechanism of Action)
The therapeutic effects of cyproterone acetate and ethinyloestradiol are achieved through a dual mechanism. Cyproterone acetate (CPA) is a potent anti-androgen that acts primarily by competitively inhibiting the binding of androgens (like testosterone and dihydrotestosterone) to their receptors in target tissues, thereby reducing the effects of endogenous androgens. Additionally, CPA exhibits progestogenic activity, which, in combination with ethinyloestradiol (EE), suppresses the hypothalamic-pituitary-ovarian axis. This suppression leads to a reduction in gonadotropin secretion (luteinizing hormone and follicle-stimulating hormone), consequently decreasing ovarian androgen production. Ethinyloestradiol, a synthetic estrogen, further contributes to the contraceptive effect by stabilizing the endometrium, ensuring cycle control, and enhancing the anti-androgenic effects of CPA by increasing sex hormone-binding globulin (SHBG) levels. Increased SHBG binds to androgens, reducing their free, active concentration. The combined hormonal actions also suppress ovulation, thicken cervical mucus, and alter the endometrium, providing highly effective contraception while addressing androgen-dependent conditions.