cyproterone and ethinyl estradiol

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action: 

cyproterone: cyproterone is an antiandrogenic compound that also exhibits progestogenic activity. It works by binding to androgen receptors and progesterone receptors. As an antiandrogen, cyproterone competitively inhibits the binding of dihydrotestosterone (DHT) to androgen receptors, reducing the effects of androgens in the body.  

ethinyl estradiol: ethinyl estradiol is a synthetic estrogen. It acts by binding to estrogen receptors in target tissues. By mimicking the effects of endogenous estrogen, ethinyl estradiol exerts negative feedback on the hypothalamus and pituitary gland, suppressing the release of gonadotropin-releasing hormone (GnRH), LH, and FSH. This inhibits the development and release of mature oocytes, preventing ovulation. 

Spectrum of Activity: 

• Contraception: The combination of cyproterone and ethinyl estradiol in COCs provides contraceptive effects by inhibiting ovulation and altering the endometrium, thus preventing fertilization and implantation of a fertilized egg. 
• Androgen-Related Conditions: cyproterone, due to its antiandrogenic activity, is also used in the treatment of androgen-related conditions, such as hirsutism (excessive hair growth), androgenic alopecia (male pattern baldness), and certain androgen-dependent skin disorders like acne. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Edema  

Nervousness 

Dizziness 

Breast tenderness 

Varicosity 

Headache 

Depression  

Dysmenorrhea 

Change in libido  

<1% 

Cellulitis 

Cervical dysplasia 

Confusion 

Conjunctival irritation 

Abortion 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Thromboembolic Disorders: cyproterone and ethinyl estradiol are contraindicated in individuals with a history of venous thromboembolism (VTE) or arterial thromboembolism (ATE), including deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), or stroke.  
• Cerebrovascular Disease or Coronary Artery Disease: Individuals with a history of cerebrovascular disease or coronary artery disease, including ischemic heart disease or cerebrovascular accidents, should not use COCs due to the increased risk of cardiovascular events. 
• Estrogen-Dependent Malignancies: COCs containing ethinyl estradiol are contraindicated in individuals with known or suspected estrogen-dependent malignancies, such as breast or endometrial cancer. 
• Liver Disease: Severe liver disease or hepatic dysfunction is a contraindication for using cyproterone and ethinyl estradiol. COCs may worsen liver function and increase the risk of hepatotoxicity. 
• Undiagnosed Vaginal Bleeding: COCs should not be used in undiagnosed abnormal vaginal bleeding, as they may indicate a severe underlying condition that requires evaluation. 

Caution: 

• Hypertension: COCs can increase blood pressure, and caution should be exercised in individuals with pre-existing hypertension.  
• Migraine: Women with a history of migraine, particularly migraine with aura, may have an increased risk of stroke when using COCs.  
• Liver Function: COCs can affect liver function, and caution should be exercised in individuals with pre-existing liver disease or impaired liver function.  
• Hyperlipidemia: COCs can cause changes in lipid profiles, including increased triglycerides and cholesterol levels.

Pregnancy / Lactation

Pregnancy consideration: cyproterone and ethinyl estradiol should not be used during pregnancy 

Lactation: Excretion of the drug in human breast milk is known 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• Synergistic Effects: Combining cyproterone and ethinyl estradiol in COCs provides synergistic effects for contraception. ethinyl estradiol suppresses the secretion of gonadotropins, preventing ovulation, while cyproterone acts as an antiandrogen and progestogen, further enhancing contraceptive efficacy. 
• Endometrial Changes: The combination also causes changes in the endometrium, making it less receptive to implantation and contributing to the contraceptive effect. 

Pharmacodynamics:  

Combining cyproterone and ethinyl estradiol in COCs provides synergistic effects for contraception. ethinyl estradiol suppressing gonadotropins prevents ovulation, while cyproterone’s antiandrogenic and progestogenic activities further enhance contraceptive efficacy. The combination also contributes to changes in the endometrium, making it less receptive to implantation. 

The pharmacodynamics of cyproterone and ethinyl estradiol in COCs work together to inhibit ovulation, alter the endometrium, and provide effective contraception. 

Pharmacokinetics: 

Absorption 

cyproterone is well-absorbed after oral administration. ethinyl estradiol is well-absorbed after oral administration. 

Distribution 

It has a high affinity for plasma proteins and binds extensively to albumin. cyproterone has a large volume of distribution, indicating that it distributes widely in the body. ethinyl estradiol is highly bound to plasma proteins, mainly albumin, and has a large volume of distribution. 

Metabolism 

cyproterone is extensively metabolized in the liver through hydroxylation and conjugation reactions. The primary metabolite is 15β-hydroxy cyproterone acetate. ethinyl estradiol undergoes extensive first-pass metabolism in the liver, primarily through hydroxylation and conjugation reactions. The significant metabolites include ethinyl estradiol 3-sulfate and various hydroxylated metabolites.  

Elimination and Excretion 

cyproterone and its metabolites are primarily excreted in the urine and feces. The elimination half-life is reported to be around 1-2 days. ethinyl estradiol and its metabolites are excreted in the urine and feces. The elimination half-life is reported to be around 24 hours. 

Adminstartion

Administration: 

Administer daily at a consistent time. Take the whole pill. A missing dosage may be administered within 12 hours. If more than 12 hours have passed, discard the unused pill and restart at the regularly scheduled times. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: cyproterone and ethinyl estradiol 

Why do we use cyproterone and ethinyl estradiol? 

cyproterone and ethinyl estradiol are combined as active ingredients in various pharmaceutical products, primarily oral contraceptives. Combining cyproterone and ethinyl estradiol in these formulations offers contraceptive effects and additional therapeutic benefits.  

Contraception: The primary use of cyproterone and ethinyl estradiol is as a combined oral contraceptive (COC). When taken as directed, COCs effectively prevent pregnancy by inhibiting ovulation, altering the cervical mucus to impede sperm penetration, and changing the endometrium to reduce the likelihood of implantation. 

Hormone Regulation: The combination of cyproterone and ethinyl estradiol is also utilized for hormonal regulation in certain medical conditions, such as: 

• Polycystic ovary syndrome (PCOS): PCOS is a hormonal disorder characterized by irregular menstrual cycles, excess androgen production, and ovary cysts. COCs containing cyproterone and ethinyl estradiol can help regulate menstrual cycles, reduce androgen levels, and alleviate PCOS symptoms. 
• Hirsutism: Hirsutism refers to excessive hair growth in a male pattern in women. With its antiandrogenic activity, cyproterone can help reduce hirsutism by blocking the effects of androgens. 
• Acne: cyproterone and ethinyl estradiol combination is also prescribed to manage moderate to severe acne in women, mainly associated with hormonal imbalances.