Cyestra-35 (Cyproterone Acetate 2mg/Ethinyl Estradiol 35μg): Indications and Contraindications
Indications
Cyestra-35 is indicated for women of reproductive age with moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, particularly when associated with polycystic ovary syndrome (PCOS). 1, 2, 3
Primary Indications:
- Moderate to severe acne vulgaris that is androgen-sensitive in women after menarche 1
- Hirsutism (excessive hair growth) in women of reproductive age 1, 2, 3
- Seborrhea when associated with androgen excess 2, 3
- Menstrual irregularities associated with hyperandrogenism and PCOS 2, 4
Additional Benefits:
- Contraception when hormonal contraception is desired 2, 5
- Reduction of endometrial cancer risk in women with PCOS and irregular menstruation 2
- Improvement in quality of life related to hyperandrogenic skin symptoms 2, 3
Clinical Context:
The combination is particularly effective for women with PCOS-related hyperandrogenic symptoms, providing both dermatologic improvement and menstrual cycle regulation 2, 3. Clinical response for hirsutism typically requires long-term treatment (visible after 4 cycles), while acne improvement may be apparent after the first month 6.
Absolute Contraindications (Category 4 - Unacceptable Health Risk)
Cyestra-35 must not be used in the following conditions: 7, 1
Cardiovascular and Thromboembolic:
- Current or history of thrombophlebitis or thromboembolic disorders 7
- Deep vein thrombosis (DVT) or pulmonary embolism - current or past history 7, 1
- Cerebrovascular disease (stroke or history of stroke) 7, 1
- Coronary artery disease (myocardial infarction or ischemic heart disease) 7, 1
- Known thrombogenic mutations (inherited or acquired hypercoagulopathies) 1
- Valvular heart disease with complications or thrombogenic rhythm diseases 1
- Major surgery with prolonged immobilization 1
- Multiple risk factors for atherosclerosis 1
Age and Smoking:
- Age ≥35 years AND smoking ≥15 cigarettes daily 1, 7
- Smoking increases cardiovascular event risk, particularly myocardial infarction and stroke, with this risk amplifying significantly after age 35 1, 7
Hepatic:
- Hepatic adenomas or carcinomas 7, 1
- Active hepatic disease or dysfunction 1
- Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use 7, 1
- Receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir (with or without dasabuvir) due to ALT elevation risk 7
Malignancy:
- Current diagnosis or history of breast cancer (which may be hormone-sensitive) 7, 1
- Carcinoma of the endometrium or other known/suspected estrogen-dependent neoplasia 7, 1
Other Absolute Contraindications:
- Pregnancy 1, 7
- Undiagnosed abnormal genital bleeding 7, 1
- Adrenal insufficiency 1
- Renal impairment (specific to drospirenone-containing formulations, relevant for similar cyproterone combinations) 1
- Headaches with focal neurologic symptoms or migraine with aura if age ≥35 years 1
Postpartum Timing:
- ≤21 days postpartum regardless of breastfeeding status 1
Relative Contraindications (Category 3 - Risks Usually Outweigh Benefits)
The following conditions require careful risk-benefit assessment, with risks typically outweighing benefits: 1
Cardiovascular Risk Factors:
- Age ≥35 years AND smoking <15 cigarettes daily 1
- Hypertension: Systolic BP 140-159 mmHg or Diastolic BP 90-99 mmHg 1
- Adequately controlled hypertension still represents increased risk 1
- Superficial venous thrombosis 1
- History of VTE with no current risk factors for recurrence 1
Postpartum with Risk Factors:
- Breastfeeding 21-29 days postpartum 1
- Breastfeeding 30-42 days postpartum with other VTE risk factors 1
- Non-breastfeeding 21-42 days postpartum with other VTE risk factors 1
Neurologic:
- Migraine headaches (with or without aura) in women <35 years requires careful evaluation 1
Drug Interactions:
- Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) - reduce contraceptive effectiveness 1
- Rifampicin or rifabutin therapy - significantly reduces effectiveness 1
- Lamotrigine monotherapy - COCs decrease lamotrigine levels, potentially increasing seizure risk 1
Important Safety Considerations
Venous Thromboembolism Risk:
The absolute risk of VTE with combined oral contraceptives is small but real, with estimated incidence of 3-9 per 10,000 person-years in COC users versus 1-5 in non-users 1. This risk is substantially lower than VTE risk during pregnancy (5-20 per 10,000) and postpartum period (40-65 per 10,000) 1. The VTE risk with cyproterone acetate/ethinyl estradiol is comparable to third-generation combined oral contraceptives 4.
Stroke Risk:
Combined hormonal contraceptives containing 30-40μg ethinyl estradiol show moderate stroke risk increase, with risk escalating with higher estrogen doses 1. Each 10μg increase in estrogen content increases stroke risk (OR 1.19 [95% CI 1.16-1.23]) 1.
Required Baseline Monitoring:
- Blood pressure measurement 1
- Pregnancy test (urine or clinical criteria to reasonably exclude pregnancy) 1
- Comprehensive medical history focusing on cardiovascular risk factors, thrombotic history, migraine characteristics, smoking status, and family history 1
- Breast and pelvic examinations are NOT required prior to initiation per current guidelines 1
Ongoing Monitoring:
- Blood pressure assessment at follow-up visits 1
- Assessment of potential health status changes including new cardiovascular risk factors 1
Important Clinical Pearls:
- Tetracycline-class antibiotics do NOT reduce contraceptive effectiveness of combined oral contraceptives 1
- Broad-spectrum antibiotics, antifungals, and antiparasitics show no clinically significant interactions 1
- Treatment duration matters: Hirsutism improvement requires ≥4 cycles, while acne may improve after 1 month 6
Risk-Benefit Context
When prescribing Cyestra-35 exclusively for acne or hirsutism (not for contraception), the cardiovascular and thrombotic risks must be weighed against dermatologic benefits rather than against pregnancy risks. 1 For women requiring both contraception and treatment of hyperandrogenic symptoms, the risk-benefit calculation is more favorable, as the medication addresses multiple therapeutic goals simultaneously 2, 4.