Marvelon

Indications

• Menopausal symptoms
• Osteoporosis prophylaxis
• Irregular menstruation
• Vulvovaginal atrophy
• Postmenopausal urogenital conditions

Dosage

Adults: The typical adult dosage of estradiol is 2 mg daily, initiated on day 1-5 of the menstrual cycle or at any time if cycles have ceased or are infrequent, taken with

Mechanism of action

Estradiol exerts its effects by binding to estrogen receptors, specifically estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), as well as the G protein-coupled estrogen receptor (GPER). This binding triggers the receptor-ligand complex to translocate to the nucleus, where it regulates gene transcription and the synthesis of specific proteins that mediate estradiol's physiological effects.

Pharmacodynamics

Estradiol acts on estrogen receptors to alleviate vasomotor symptoms such as hot flashes and urogenital symptoms including vaginal dryness. It has beneficial effects on bone density by inhibiting bone resorption and improving plasma lipid profiles. Additionally, estradiol decreases follicle-stimulating hormone (FSH) levels by suppressing its formation in the anterior pituitary gland. Notably, it may increase the risk of cardiovascular events, venous thromboembolism, and stroke, necessitating caution in high-risk populations.

Pharmacokinetics

Estradiol is rapidly absorbed when administered orally, with a bioavailability affected by first-pass metabolism in the liver. It is extensively metabolized in the liver, conjugated to form estrone and estrone sulfate, and eliminated through urine. The half-life of estradiol varies depending on the route of administration, with peak plasma concentrations occurring within 1-3 hours post-administration. Continuous use can lead to accumulation and requires careful monitoring of therapy duration and dosage adjustments.

Contra-indications

• History of thromboembolic disorders
• Known or suspected estrogen-dependent tumors
• Undiagnosed abnormal genital bleeding
• Severe liver dysfunction
• Pregnancy

Adverse effects

• Nausea
• Headaches
• Weight changes
• Breast tenderness
• Mood alterations
• Vaginal discharge
• Oedema
• Skin reactions
• Thromboembolic events
• Cerebrovascular accidents
• Endometrial hyperplasia
• Angioedema

Interactions

• Antiepileptics (carbamazepine, phenytoin, etc.) may decrease efficacy of estradiol
• Bosentan may decrease efficacy of estradiol
• Modafinil may decrease efficacy of estradiol
• Rifamycins may decrease efficacy of estradiol
• St. John's Wort may decrease efficacy of estradiol
• Ritonavir may decrease efficacy of estradiol

Precautions

• Monitor for signs of thromboembolic events
• Evaluate for endometrial hyperplasia in women with a uterus
• Consider cardiovascular risks before initiating therapy
• Assess liver function prior to use
• Use with caution in patients with a history of depression

Pregnancy

Estradiol is contraindicated in pregnancy due to potential harm to the fetus and increased risk of thromboembolic events.

Breast-feeding

Estradiol is excreted in breast milk; caution is advised when used by nursing mothers as it may affect milk production.

Storage

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

Formulations

• Tablets (1 mg, 2 mg)
• Vaginal ring (continuous use, replaced every 3 months)

Indications

• Atopic dermatitis
• Contact dermatitis
• Psoriasis
• Seborrheic dermatitis
• Nummular eczema

Dosage

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

Adults: Apply a thin layer to the affected area once or twice daily, as directed by a healthcare professional.

Mechanism of action

Desonide exerts its effects by binding to cytosolic glucocorticoid receptors, forming a complex that migrates to the nucleus and interacts with genetic elements on DNA. This interaction leads to the activation and repression of specific genes. The anti-inflammatory action is thought to result from the induction of lipocortins, proteins that inhibit phospholipase A2, ultimately reducing the production of pro-inflammatory mediators like prostaglandins and leukotrienes by preventing the release of arachidonic acid from membrane phospholipids.

Pharmacodynamics

As a corticosteroid, desonide is effective in reducing inflammation and pruritus in various skin conditions. Its action as a topical agent allows for localized treatment with minimal systemic absorption, thus reducing the risk of systemic side effects typically associated with corticosteroids.

Pharmacokinetics

Desonide is primarily applied topically, which limits its systemic absorption. When used as directed, it demonstrates rapid onset of action at the site of application. The pharmacokinetics of desonide in terms of absorption, distribution, metabolism, and excretion are less documented due to its topical use, though systemic absorption is generally low compared to systemic corticosteroids.

Adverse effects

• Burning sensation
• Itching
• Dryness
• Skin atrophy
• Striae
• Hypopigmentation

Precautions

• Avoid use on infected areas unless treated appropriately
• Use with caution in patients with a history of hypersensitivity to corticosteroids
• Long-term use may lead to systemic absorption and adrenal suppression

Pregnancy

Use during pregnancy only if the benefits outweigh the risks, as corticosteroids can potentially affect fetal development.

Breast-feeding

Desonide is excreted in 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

• Topical cream
• Topical ointment
• Topical lotion

Indications

• Contraception
• Regulation of menstrual cycles
• Management of polycystic ovary syndrome
• Management of endometriosis

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing recommendations.

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

Mechanism of action

Ethinyl estradiol exerts its effects by binding to estrogen receptors in target tissues, leading to changes in gene expression. This action promotes the development of secondary sexual characteristics and regulates the menstrual cycle. It also inhibits ovulation by suppressing gonadotropin release from the pituitary gland, thereby reducing follicular maturation and ovum release.

Pharmacodynamics

Ethinyl estradiol influences the reproductive system by stabilizing the endometrial lining, making it less conducive to implantation. It also affects the cervical mucus, making it thicker and less penetrable to sperm. The pharmacodynamic effects are dose-dependent, contributing to contraceptive efficacy and menstrual regulation.

Pharmacokinetics

Ethinyl estradiol is well-absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 2 hours after oral administration. It undergoes extensive first-pass metabolism in the liver, resulting in a bioavailability of approximately 40-60%. The drug is primarily metabolized by cytochrome P450 enzymes, particularly CYP3A4, and has a half-life of about 13 to 27 hours. Ethinyl estradiol is excreted mainly in urine and feces.

Interactions

• fostemsavir + ethinylestradiol from a combined hormonal contraceptive: Moderate (increases concentration)

Pregnancy

Ethinyl estradiol is generally not recommended during pregnancy due to potential risks to the fetus.

Breast-feeding

Ethinyl estradiol may pass into breast milk; caution is advised.

Storage

Store at room temperature, away from light and moisture.

Mechanism of action

Like other topical corticosteroids, desonide has anti-inflammatory, antipruritic and vasoconstrictive properties. The drug binds to cytosolic glucocorticoid receptors. This complex migrates to the nucleus and binds to genetic elements on the DNA. This activates and represses various genes. However corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacodynamics

Desonide is a synthetic nonfluorinated corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents.

Mechanism of action

Estrogen is found in the the breast, uterine, ovarian, skin, prostate, bone, fat, and brain tissues. The main source of estrogen in adult women during the reproductive period of life is the ovarian follicle, which secretes 70 to 500 mcg of estradiol each day. After menopause, however, the majority of endogenous estrogen is produced by transformation of androstenedione (which is secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women. Estradiol, however, is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, the higher estrone concentration in postmenopausal population, can cause various undesirable effects. These effects may include hot flashes, chills, vaginal dryness, mood swings, irregular menstruation, and chills, in addition to sleep problems. Estradiol workings by binding to subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). It also exerts potent agonism of G Protein-coupled estrogen receptor (GPER), which is recognized an important regulator of this drug's rapid effects. Once the estrogen receptor has bound to its ligand, it enters the nucleus of the target cell, regulating gene transcription and formation of of messenger RNA. This mRNA makes contact with ribosomes producing specific proteins that express the effect of estradiol upon the target cell. Agonism of estrogen receptors increases pro-estrogenic effects, leading to the relief of vasomotor and urogenital symptoms of a postmenopausal or low estradiol state. 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. 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

Pharmacodynamics

Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia). Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption and may have beneficial effects on the plasma lipid profile. Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland. **A note on hyper-coagulable state, cardiovascular health, and blood pressure** Estradiol may cause an increased risk of cardiovascular disease, DVT, and stroke, and its use should be avoided in patients at high risk of these conditions. Estrogen induces a hyper-coagulable state, which is also associated with both estrogen-containing oral contraceptive (OC) use and pregnancy. Although estrogen causes an increase in levels of plasma renin and angiotensin. Estrogen-induced increases in angiotensin, causing sodium retention, which is likely to be the mechanism causing hypertension after oral contraceptive treatment.