estradiol valerate

Action and Spectrum

Actions and Spectrum:

estradiol valerate is a synthetic form of the naturally occurring estrogen hormone, 17β-estradiol. It is commonly used in hormone replacement therapy (HRT) to treat various conditions related to estrogen deficiency in women.

Action:

estradiol valerate exerts its effects by binding to estrogen receptors in target tissues throughout the body. Once bound to these receptors, it initiates a series of cellular responses that regulate gene expression and modulate various physiological processes.

Some of the primary actions of estradiol valerate include:

• Stimulation of the growth and development of female secondary sexual characteristics, like breast development and body fat redistribution.
• Maintenance of bone density and also prevention of osteoporosis.
• Regulation of the menstrual cycle in the premenopausal women.
• Support the health and function of the female reproductive system.
• Improvement of vaginal atrophy and dryness.
• Potential positive effects on mood, cognition, and overall well-being.

Spectrum:

estradiol valerate is available in various formulations, including oral tablets, transdermal patches, and injectable solutions. The spectrum of estradiol valerate refers to its activity and duration of action, which may vary based on route of administration and the specific product used.

• Oral tablets: estradiol valerate is converted to estradiol in the liver after oral administration. It is then released into the bloodstream, providing a systemic effect. The duration of action of oral estradiol valerate typically lasts about 24 hours, requiring daily dosing.
• Transdermal patches are typically applied to the skin and release estradiol valerate directly into the bloodstream. The patches provide more continuous and steady hormone delivery, with varying patch change intervals (e.g., weekly or biweekly).
• Injectable solutions: estradiol valerate can be administered as an intramuscular injection. The injectable form has a more prolonged action duration than oral tablets or patches, typically lasting for one to four weeks, depending on the specific product and dosage.

Drug Interaction

Adverse Reaction

Frequency not defined

Weight changes

Toothache

Nervousness

Depression

Peripheral edema

Amenorrhea

Influenza

Bloating

Impotence

Syncope

Breast enlargement

Pruritus

Hypertension

Rash

Abdominal cramping

Dry mouth

Muscle cramps

Melasma

Swelling

Breast tenderness

Delayed ejaculation

Headache

Anxiety

Leukorrhea

Breakthrough bleeding

Polydipsia

Vomiting

Nausea

Spotting

Black Box Warning

Black Box Warning:

• Cardiovascular Risks: Estrogen therapy, including estradiol valerate, may increase the risk of cardiovascular events such as heart attacks, strokes, and blood clots, particularly in postmenopausal women. The risk may be higher in women with pre-existing cardiovascular conditions or risk factors.
• Endometrial Cancer Risk: Estrogen therapy used alone in women with an intact uterus may increase the risk of endometrial hyperplasia (abnormal thickening of the uterine lining) and endometrial cancer. Progestin is often prescribed with estradiol valerate in women with an intact uterus to reduce this risk.
• Breast Cancer Risk: Estrogen therapy might be associated with an increased risk of breast cancer. Women with a history of breast cancer or estrogen-dependent tumors should avoid or use estradiol valerate cautiously.

Contraindication / Caution

Contraindication/Caution:

Contraindication

• Hypersensitivity or Allergy: estradiol valerate should not be used in individuals with known hypersensitivity or allergy to estradiol or other medication components.
• Pregnancy: estradiol valerate is contraindicated during pregnancy as it might cause the harm to the developing fetus. If pregnancy is detected during treatment, the medication should be discontinued immediately.
• Estrogen-Dependent Tumors: estradiol valerate is contraindicated in individuals with estrogen-dependent tumors, such as particular breast or uterine cancer types. Estrogen can stimulate the growth of these tumors and worsen the condition.
• Undiagnosed Vaginal Bleeding: estradiol valerate should not be used in individuals with undiagnosed abnormal vaginal bleeding. Before starting treatment, any unexplained vaginal bleeding should be evaluated to rule out potentially serious underlying causes.
• Known or Suspected Hormone-Related Cancers: Individuals with a history of hormone-related cancers, such as breast or uterine cancer, should not use estradiol valerate.
• Liver Disease: estradiol valerate is metabolized in the liver, so individuals with severe liver disease should not use this medication, as it may worsen the condition.
• Thromboembolic Disorders: estradiol valerate is associated with an increased risk of blood clot formation. Therefore, it is contraindicated in individuals with a history of blood clots, deep vein thrombosis, pulmonary embolism (PE), or other thromboembolic disorders.
• Porphyria: estradiol valerate is contraindicated in individuals with a history of porphyria, a group of frequent genetic disorders that generally affect the body’s ability to produce heme, a component of hemoglobin.

Caution

• Cardiovascular Disorders: Estrogen therapy, including estradiol valerate, may increase the risk of cardiovascular events such as heart attacks, strokes, and blood clots. Individuals with a earlier history of cardiovascular disease, hypertension, or other risk factors should be closely monitored while on estrogen therapy.
• Breast Disorders: estradiol valerate can cause breast tenderness and enlargement. Women with a history of breast disorders, including breast lumps, fibrocystic disease, or breast cancer, should have regular breast examinations while on estrogen therapy.
• Endometrial Hyperplasia: Estrogen therapy, when used without a progestin in women with an intact uterus, can increase the risk of endometrial hyperplasia (an abnormal thickening of the uterine lining) and, in some cases, may lead to endometrial cancer. Progestin is often prescribed with estradiol valerate in women with an intact uterus to reduce this risk.
• Gallbladder Disease: Estrogen therapy may increase the risk of gallbladder disease, particularly in postmenopausal women. Individuals with a history of gallbladder disease should be closely monitored while on estrogen therapy.
• Liver Function: estradiol valerate is metabolized in the liver, so individuals with mild to moderate liver impairment should use this medication cautiously. Severe liver disease is a contraindication for the use of estradiol valerate.
• Metabolic Disorders: Estrogen therapy may affect glucose tolerance and lipid metabolism. Individuals with diabetes or a history of lipid disorders should be monitored closely while on estradiol valerate.
• Migraines: Women with a history of migraines, especially those with auras, should use estradiol valerate with caution, as estrogen therapy may worsen or trigger migraines in some cases.
• Uterine Fibroids: Estrogen therapy may cause uterine fibroids to grow and increase in size. Women with a history of uterine fibroids should be monitored while on estrogen therapy.
• Systemic Lupus Erythematosus (SLE): Estrogen therapy may exacerbate SLE or increase the risk of flare-ups in individuals with this autoimmune disease.
• Asthma: Women with asthma should use estradiol valerate cautiously, as estrogen therapy may worsen asthma symptoms in some individuals.

Pregnancy / Lactation

Pregnancy consideration:

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned

Lactation:  

Excreted into human milk: Yes.

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:

estradiol valerate is a synthetic form of the naturally occurring estrogen hormone, 17β-estradiol. Upon administration, estradiol valerate undergoes conversion to its active form, estradiol, in the body. It exerts its pharmacological effects by binding to estrogen receptors in target tissues throughout the body, modulating gene expression, and initiating a cascade of cellular responses. This results in the stimulation of female secondary sexual characteristics, maintenance of bone density, support of the female reproductive system, and relief of menopausal symptoms. estradiol valerate is commonly used in hormone replacement therapy for menopausal women to manage symptoms and prevent osteoporosis, and it is also utilized in transgender hormone therapy to promote feminization.

Pharmacodynamics:

Mechanism of action: The mechanism of action of estradiol valerate is primarily mediated by its conversion to the biologically active hormone, estradiol (17β-estradiol), in the body. estradiol valerate is a prodrug converted into an active form through metabolic processes after administration.

Conversion to estradiol: After administration, estradiol valerate is metabolized in the liver to form estradiol, the primary endogenous estrogen hormone in females. This process involves the hydrolysis of the valerate ester group attached to estradiol valerate, resulting in estradiol release.

Binding to Estrogen Receptors: Once converted to estradiol, it binds to estrogen receptors (ERs) in various target tissues throughout the body. Two main subtypes of estrogen receptors, ER-alpha and ER-beta, are present in different tissues and mediate different biological effects.

Initiation of Cellular Responses: estradiol binding to estrogen receptors initiates a series of cellular responses and intracellular signaling pathways. These responses involve the modulation of gene expression, activation of specific proteins, and regulation of various cellular functions.

Biological Effects: The biological effects of estradiol valerate, mediated through estradiol binding to estrogen receptors, include:

• Stimulation of the growth and development of female secondary sexual characteristics, like breast development and body fat redistribution.
• Maintenance of bone density and also prevention of osteoporosis.
• Regulation of the menstrual cycle in the premenopausal women.
• Support the health and function of the female reproductive system.
• Improvement of vaginal atrophy and dryness.
• Potential positive effects on mood, cognition, and overall well-being.

Adminstartion

Administration:

estradiol valerate is available in various formulations, and the administration method can vary based on the specific product and the purpose of treatment.

• Oral Tablets: Oral estradiol valerate tablets are taken by mouth with water. The tablets are typically available in different strengths, and the dosage prescribed by healthcare provider will depend on the individual’s medical condition and treatment goals. If applicable, taking the tablets as prescribed and simultaneously each day is essential.
• Transdermal Patches: estradiol valerate is also available in the form of transdermal patches. These patches are applied to the skin, and the hormone is absorbed through the skin and into the bloodstream. Transdermal patches offer a steady and continuous release of estradiol over a specific period, and they are available in different strengths and patch change intervals (e.g., weekly or biweekly).
• Injectable Solutions: estradiol valerate can be administered as an intramuscular injection. This method provides a longer action duration than oral tablets or patches, with injection intervals typically ranging from one to four weeks, depending on the specific product and dosage. A healthcare professional usually gives injections in a clinical setting.

The choice of administration method depends on factors such as the individual’s preference, medical condition, and the desired therapeutic effects.

Patient Information Leaflet

Patient information leaflet

Generic Name: estradiol valerate

Pronounced: [ ess-tra-DYE-ole ]

Why do we use estradiol valerate?

estradiol valerate, a synthetic form of the estrogen hormone 17β-estradiol, has several medical uses, primarily in hormone replacement therapy (HRT) for women.

• Menopausal Hormone Therapy: estradiol valerate is used in hormone replacement therapy for women experiencing menopause. Menopause is a natural process when a woman’s ovaries stop producing eggs, and the estrogen levels decline. estradiol valerate helps alleviate menopausal symptoms such as hot flashes, night sweats, vaginal dryness, mood changes, and sleep disturbances.
• Osteoporosis Prevention and Treatment: Estrogen is crucial in maintaining bone density. After menopause, women are at an enhanced risk of osteoporosis due to declining estrogen levels. When used as hormone therapy, estradiol valerate can help prevent bone loss and diminish the risk of fractures in postmenopausal women with osteoporosis or at risk for developing the condition.
• Hypogonadism: It is a condition where the body does not produce enough sex hormones. estradiol valerate can be used as hormone replacement therapy in women with hypogonadism to restore estrogen levels and improve hormone balance.
• Transgender Hormone Therapy: estradiol valerate is sometimes prescribed to transgender women as part of feminizing hormone therapy. It helps promote the development of female secondary sexual characteristics, such as breast growth, body fat redistribution, and softer skin.
• Female Reproductive Disorders: estradiol valerate may be used in certain gynecological conditions, such as primary ovarian failure or amenorrhea (absence of menstrual periods), to help restore estrogen levels and manage related symptoms.
• Contraception: In some cases, estradiol valerate may be combined with a progestin hormone to form a combined hormonal contraceptive. This combination is a birth control method in certain oral contraceptive pills or other hormonal contraceptive formulations.