YAZ

Indications

• Hormonal contraceptive
• Menstrual disorders
• Acne vulgaris
• Polycystic ovary syndrome (PCOS)
• Endometrial hyperplasia prevention

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to the specific product guidelines for dosing, as it may vary based on the formulation and indication.

Mechanism of action

Drosperinone works by binding to progesterone receptors, leading to the inhibition of ovulation through the suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. Additionally, it alters the endometrial lining to prevent implantation of a fertilized egg. Its anti-androgenic activity helps in regulating sebum production and reducing acne.

Pharmacodynamics

Drosperinone exhibits progestational effects, leading to changes in the endometrium and influencing menstrual cycle regulation. Its anti-androgenic properties also help to mitigate symptoms of conditions such as polycystic ovary syndrome (PCOS) and severe acne. The drug shows a favorable side effect profile compared to other progestins, particularly with regards to weight gain and mood disturbances.

Pharmacokinetics

Drosperinone is well absorbed following oral administration, with a bioavailability of approximately 76%. It is extensively metabolized in the liver, primarily via the cytochrome P450 system, and has a half-life of about 30 hours. The drug is eliminated in urine, with metabolites being excreted as glucuronides. Food does not significantly affect its absorption.

Contra-indications

• Hypersensitivity to drosperinone or any of its components
• History of venous thromboembolism
• Severe renal impairment
• Adrenal insufficiency
• Pregnancy
• Active or recent arterial thromboembolism
• Liver tumors or severe liver disease

Adverse effects

• Nausea
• Headache
• Mood changes
• Breast tenderness
• Weight gain
• Menstrual irregularities
• Thromboembolic disorders
• Hyperkalemia

Interactions

• Potassium-sparing diuretics
• ACE inhibitors
• Angiotensin receptor blockers
• NSAIDs
• Other drugs that affect potassium levels
• CYP3A4 inhibitors and inducers

Precautions

• Monitor potassium levels in patients with renal impairment or taking other medications that increase potassium
• Caution in patients with a history of depression
• Regular monitoring for signs of thromboembolism
• Consider risks versus benefits in women with risk factors for thromboembolism

Pregnancy

Drosperinone is contraindicated in pregnancy due to the risk of teratogenic effects.

Breast-feeding

Drosperinone may pass into breast milk; caution is advised when used by nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablets containing drosperinone
• Combination products with estrogen

Indications

• Hormonal contraception
• Menstrual cycle regulation
• Hormone replacement therapy
• Management of menopausal symptoms
• Treatment of polycystic ovary syndrome
• Endometriosis management
• Dysfunctional uterine bleeding

Dosage

Adults: The dosing of ethinylestradiol varies based on the formulation and indication. Commonly, it is administered in combination with progestins for contraception, typically as a daily oral tablet containing 20 to 35 micrograms of ethinyles

Mechanism of action

Ethinylestradiol acts as a synthetic estrogen by binding to estrogen receptors in estrogen-responsive tissues. It suppresses gonadotropic hormone secretion from the pituitary gland, leading to decreased luteinizing hormone levels. This results in reduced endometrial vascularization and prevents ovulation by inhibiting the hormonal changes necessary for ovarian follicle maturation. Additionally, it thickens cervical mucus to impede sperm movement and alters the endometrium to prevent implantation.

Pharmacodynamics

Ethinylestradiol has a long duration of action and a wide therapeutic index. It effectively decreases luteinizing hormone and gonadotropic hormone levels, thereby preventing ovulation and altering reproductive tract conditions. Patients using ethinylestradiol should be made aware of potential thrombotic risks, particularly in specific populations such as smokers and those with a history of thromboembolic disorders.

Pharmacokinetics

Ethinylestradiol is well absorbed when taken orally, with peak plasma concentrations occurring approximately 1 to 2 hours after administration. It has a high plasma protein binding rate, predominantly to sex hormone-binding globulin. The drug undergoes extensive hepatic metabolism, primarily by cytochrome P450 enzymes, and has a half-life of about 10-20 hours. Excretion is primarily via the kidneys, with metabolites being eliminated in urine.

Contra-indications

• Pregnancy
• History of thromboembolic disorders
• Active liver disease
• Severe hypertension
• Undiagnosed vaginal bleeding
• Hormone-sensitive cancers (e.g., breast cancer)
• Known hypersensitivity to ethinylestradiol or any component of the formulation

Adverse effects

• Nausea
• Headache
• Breast tenderness
• Mood changes
• Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism)
• Increased risk of certain cancers (e.g., breast and endometrial cancer)
• Hypertension
• Skin reactions (e.g., rash)

Interactions

• Antibiotics (e.g., rifampicin) may reduce effectiveness
• Anticonvulsants (e.g., phenytoin, carbamazepine) may reduce effectiveness
• St. John's Wort may reduce effectiveness
• Fostemsavir increases ethinylestradiol concentration
• Certain antiretrovirals may interact with ethinylestradiol

Precautions

• Monitor for signs of thromboembolism
• Caution in patients with a history of migraines
• Caution in patients with liver disease
• Regular breast examinations and mammograms are recommended
• Consider risks versus benefits in patients with a family history of breast cancer
• Use with caution in patients with hypertension, renal disease, asthma, epilepsy, and systemic lupus erythematosus

Pregnancy

Ethinylestradiol is contraindicated in pregnancy due to potential risks to the fetus and maternal health.

Breast-feeding

Caution is advised as ethinylestradiol may be excreted in breast milk. It is recommended to weigh the benefits of the treatment against potential risks to the nursing infant.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Tablets
• Transdermal patches
• Gels
• Sachets

Mechanism of action

Ethinylestradiol is a synthetic estrogenic compound. Use of estrogens have a number of effects on the body including reduced bone density. Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg. Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium. It also increases sex hormone binding globulin. Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites estrone and estriol at the receptor level. ... After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. The pharmacologic effects of ethinyl estradiol are similar to those of endogenous estrogens. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. Estrogens have an important role in the reproductive, skeletal, cardiovascular, and central nervous systems in women, and act principally by regulating gene expression. Biologic response is initiated when estrogen binds to a ligand-binding domain of the estrogen receptor resulting in a conformational change that leads to gene transcription through specific estrogen response elements (ERE) of target gene promoters; subsequent activation or repression of the target gene is mediated through 2 distinct transactivation domains (ie, AF-1 and AF-2) of the receptor. The estrogen receptor also mediates gene transcription using different response elements (ie, AP-1) and other signal pathways. Recent advances in the molecular pharmacology of estrogen and estrogen receptors have resulted in the development of selective estrogen receptor modulators (eg, clomiphene, raloxifene, tamoxifen, toremifene), agents that bind and activate the estrogen receptor but that exhibit tissue-specific effects distinct from estrogen. Tissue-specific estrogen-agonist or -antagonist activity of these drugs appears to be related to structural differences in their estrogen receptor complex (eg, specifically the surface topography of AF-2 for raloxifene) compared with the estrogen (estradiol)-estrogen receptor complex. A second estrogen receptor also has been identified, and existence of at least 2 estrogen receptors (ER-alpha, ER-beta) may contribute to the tissue-specific activity of selective modulators. While the role of the estrogen receptor in bone, cardiovascular tissue, and the CNS continues to be studied, emerging evidence indicates that the mechanism of action of estrogen receptors in these tissues differs from the manner in which estrogen receptors function in reproductive tissue. /Estrogen General Statement/ Intracellular cytosol-binding proteins for estrogens have been identified in estrogen-responsive tissues including the female genital organs, breasts, pituitary, and hypothalamus. The estrogen-binding protein complex (ie, cytosol-binding protein and estrogen) distributes into the cell nucleus where it stimulates DNA, RNA, and protein synthesis. The presence of these receptor proteins is responsible for the palliative response to e

Pharmacodynamics

Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation. It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects. Patients should be counselled regarding the risks of thrombotic events.