Glass ampoule of clear oil solution on a pale grey tray
DoseRoutine Estradiol Valerate — Glass ampoule of clear oil solution on a pale grey tray. Original DoseRoutine photography.
hormoneInjectablePrescription only (US)

Estradiol ValerateBenefits, Dosage & Interactions

Also known as: Delestrogen

Estradiol valerate is an ester of estradiol, the main human estrogen, formulated so it releases slowly after injection or absorbs orally. It is used in menopausal hormone therapy, in feminizing hormone therapy, and in some combined oral contraceptives. Research on Estradiol Valerate focuses on bone and joint health, testosterone support, and menopause symptoms.

How much Estradiol Valerate do people take?

The estradiol valerate/dienogest phase III trial used a 4-phase oral regimen (estradiol valerate 3 mg tapering to 1 mg, with dienogest added mid-cycle). Route reported: Oral tablets in the cited trial; injectable estradiol valerate esters also exist outside it. Frequency reported: Once daily, per the labeled 28-day multiphasic regimen. These are amounts documented in the cited studies and labels for Estradiol Valerate — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.

See the full reported protocol and its sources

Researched by DoseRoutine Research TeamReviewed for accuracy by Nicholas Alexander, RSE, SO, PMPLast updated Educational reference only — not medical advice. Always confirm dosing and safety decisions with a licensed clinician.

Evidence: Moderate — One published human randomized trial; results not yet replicated.
Evidence strengthModerate · 3/4
PreclinicalStrong human evidence

One published human randomized trial; results not yet replicated.

Chemical structure of Estradiol Valerate (PubChem CID 13791)
Structure via PubChem

Quick answer

Estradiol valerate is an ester of estradiol, the main human estrogen, formulated so it releases slowly after injection or absorbs orally. It is used in menopausal hormone therapy, in feminizing hormone therapy, and in some combined oral contraceptives. Because it is bioidentical estradiol once cleaved, its side-effect profile is that of estrogen therapy generally rather than anything unique to the ester.

What it is
Ester (valerate) of bioidentical estradiol
Forms
Intramuscular oil injection and oral tablet
Used in
Menopausal hormone therapy, feminizing hormone therapy, some contraceptives
Why the ester
Slows release from the injection site, extending the interval between doses
Common side effects
Breast tenderness, headache, nausea, fluid retention, mood changes
Boxed warning
Estrogen therapy labels carry warnings on clots, stroke and certain cancers

Compiled by DoseRoutine from public sources including NIH/MedlinePlus, the FDA label, Mayo Clinic and PubChem. Educational information, not medical advice.

Plasma half-life
Ester is hydrolyzed to estradiol after absorption; not separately reported in the cited trial
Default unit
mg

What published protocols report

Ranges documented in the literature, shown for reference. DoseRoutine does not recommend an amount — your prescriber or the product label sets the dose.

Reported amounts
The estradiol valerate/dienogest phase III trial used a 4-phase oral regimen (estradiol valerate 3 mg tapering to 1 mg, with dienogest added mid-cycle)[1]
Route studied
Oral tablets in the cited trial; injectable estradiol valerate esters also exist outside it[1]
Frequency
Once daily, per the labeled 28-day multiphasic regimen[1]
Cycle length
28-day cycles, studied over multiple cycles in the trial[1]
Half-life
Ester is hydrolyzed to estradiol after absorption; not separately reported in the cited trial[1]
Storage
Room temperature[1]

Reported for Estradiol Valerate in the cited sources. Published ranges are not dosing advice.

Mixing Estradiol Valerate: bacteriostatic water and syringe units

The vial arrives as dry powder. How much water you add sets the strength, and the strength sets the mark you draw to on the syringe. The table assumes a 5 mg vial and a 250 mcg example draw on a U-100 insulin syringe, where 100 units is one millilitre. If your vial is a different size, scale it — the arithmetic is the same.

Bacteriostatic water addedResulting strength250 mcg draws to
1 mL5 mg/mL5 units
2 mL2.5 mg/mL10 units
3 mL1.67 mg/mL15 units

Units, not millilitres. Insulin syringes are marked in units, and mixing up mcg and mg on a peptide label is the single most common error people report. Check the label twice. Run your own vial through the calculator.

Storage and stability

Before mixing
Sealed and still as a dry powder, Estradiol Valerate vials are normally kept in the fridge at 2–8 °C, out of light. Short spells at room temperature during shipping are the norm for lyophilized peptides and are not, on their own, a sign the vial is spoiled.
After mixing
Once bacteriostatic water goes in, the vial belongs in the fridge and is generally treated as good for about 28 days — that is how long the benzyl alcohol in bacteriostatic water is relied on to hold back bacterial growth. Plain sterile water has no preservative, so a vial mixed with it is a single-session vial. Never freeze a reconstituted vial.
When to throw it out
A properly mixed vial is clear. Cloudiness, floating strands, a color change or powder that will not go into solution after gentle swirling all mean the vial should be discarded rather than used. Shaking a peptide vial hard is the usual cause — swirl it, or run the water down the inside wall of the vial instead of onto the powder.

Handling and shelf-life figures describe general practice for lyophilized peptides. They are not a dose and not medical advice — your prescriber or the product label sets the amount.

References & evidence

Documents the Estradiol Valerate entry is written from. Each number matches an inline marker above.

  1. [1]Efficacy and Safety of Estradiol Valerate/Dienogest for the Management of Heavy Menstrual Bleeding: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Clinical TrialYu Q, Zhou Y, Suturina L, Jaisamrarn U, Lu D, Parke S · Journal of Women's Health · 2018 · Peer-reviewed · PMID 29957101
  2. [2]The shorter, the better: A review of the evidence for a shorter contraceptive hormone-free intervalGraziottin A · European Journal of Contraception & Reproductive Health Care · 2016 · Peer-reviewed · PMID 26291185

References & Evidence

Sources on this page that document Estradiol Valerate dosing, timing and safety.

  1. [1]National Center for Biotechnology Information View source

Educational information only — not medical advice. Dose ranges vary by person, indication and prescriber.

What is Estradiol Valerate studied for?

What is Estradiol Valerate?Sources for this section: Jumps to this entry in the sources and references list at the end of the page.

Estradiol valerate is a synthetic form of estradiol, which is the primary and most potent *estrogen* hormone produced by the ovaries. It is an ester derivative of estradiol. Once administered, the valerate ester is cleaved, releasing bioidentical estradiol into the body. This formulation allows for sustained release and absorption, making it suitable for various therapeutic applications. Estradiol valerate is available in several forms, including oral tablets, transdermal patches, and injectable solutions, with the injectable form often known by brand names such as Delestrogen (FDA label). It is used primarily in hormone replacement therapy (HRT) for menopausal symptoms, in the treatment of hypogonadism, for gender-affirming hormone therapy, and in certain contraceptive formulations. Its use aims to replenish estrogen levels in individuals who are deficient or require exogenous estrogen for therapeutic purposes.

What does the research say about Estradiol Valerate?

Tap a section to expand.

Estradiol valerate itself is a prodrug. After administration, it undergoes rapid hydrolysis by enzymes (esterases) in the blood and liver, releasing active 17β-estradiol. This 17β-estradiol then acts on target cells throughout the body by binding to and activating estrogen receptors (ERs), primarily estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). These receptors are ligand-activated transcription factors. Upon binding, the estradiol-receptor complex translocates to the cell nucleus, where it interacts with specific DNA sequences called estrogen response elements (EREs) in the promoter regions of target genes. This interaction modulates gene transcription, leading to either an increase or decrease in the production of specific proteins. The wide distribution of estrogen receptors accounts for the diverse physiological effects of estradiol, including its roles in reproductive health, bone density, cardiovascular function, and central nervous system activity. By mimicking the action of endogenous estradiol, estradiol valerate helps to restore hormonal balance and alleviate symptoms associated with estrogen deficiency (EMA SmPC).

Source for this section: Sources for How does Estradiol Valerate work?: Jumps to this entry in the sources and references list at the end of the page.

Estradiol valerate is prescribed for a variety of conditions where estrogen replacement is beneficial: * **Menopausal Hormone Therapy (MHT):** It is widely used to alleviate menopausal symptoms such as hot flashes, night sweats, vaginal dryness, itching, burning, and dyspareunia (painful intercourse). It can also help improve mood disturbances and sleep patterns associated with menopause (NIH ODS). * **Prevention of Osteoporosis:** In postmenopausal individuals, estradiol valerate can help prevent bone loss and reduce the risk of fractures by maintaining bone mineral density (Cochrane). * **Treatment of Hypogonadism:** For individuals with primary ovarian failure or other conditions leading to estrogen deficiency before menopause, estradiol valerate can induce puberty and maintain secondary sexual characteristics (FDA label). * **Gender-Affirming Hormone Therapy:** It is a key component of feminizing hormone therapy for transgender women and gender-diverse individuals seeking to develop female secondary sexual characteristics and suppress endogenous testosterone production (WPATH Standards of Care). * **Contraception:** In combination with a progestin, estradiol valerate is used in certain oral contraceptive pills to prevent pregnancy by inhibiting ovulation (DrugBank). * **Treatment of Prostate Cancer:** In some cases, high-dose estrogen therapy, including estradiol valerate, may be used as a palliative treatment for advanced, hormone-sensitive prostate cancer (DrugBank). Benefits typically include an improvement in the quality of life due to symptom relief and a reduction in the long-term risks associated with estrogen deficiency.

The efficacy of estradiol valerate in treating menopausal symptoms and preventing osteoporosis is well-documented. A Cochrane review published in 2015 analyzed numerous randomized controlled trials and confirmed that estrogen-only hormone therapy significantly reduces the frequency and severity of hot flashes and improves bone mineral density in postmenopausal individuals. The evidence also supports its role in improving vaginal atrophy symptoms (Cochrane). For gender-affirming hormone therapy, clinical guidelines, such as those from the World Professional Association for Transgender Health (WPATH), recommend estradiol in various forms, including valerate, as a cornerstone of feminizing regimens. These guidelines are based on extensive clinical experience and observational studies demonstrating the induction of desired secondary sexual characteristics and psychological benefits (WPATH Standards of Care). Its use in contraception and hypogonadism is supported by decades of clinical practice and regulatory approvals from bodies like the FDA and EMA, based on a comprehensive understanding of its pharmacological actions and demonstrated clinical outcomes (FDA label, EMA SmPC).

Common side effects of estradiol valerate can include: * Nausea, vomiting, and abdominal cramps * Breast tenderness or enlargement * Headache * Dizziness * Bloating * Weight changes (gain or loss) * Irregular vaginal bleeding or spotting * Mood changes, including depression or irritability * Fluid retention (edema) More serious, but less common, side effects can include: * Blood clots (venous thromboembolism, deep vein thrombosis, pulmonary embolism) * Stroke * Heart attack * Gallbladder disease * Liver problems * High blood pressure * Exacerbation of migraine headaches * Increased risk of certain cancers (breast, endometrial) with long-term use, especially when not combined with a progestin in individuals with an intact uterus. Individual responses can vary significantly. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.

Before starting estradiol valerate, individuals should undergo a thorough medical evaluation, including a complete medical history and physical examination, particularly breast and pelvic examinations, and blood pressure measurement. Regular monitoring is crucial during treatment. * **Cardiovascular Risk:** Estrogen therapy, especially oral formulations and in older individuals or those with pre-existing cardiovascular risk factors, may increase the risk of cardiovascular events, including stroke and myocardial infarction. The Women's Health Initiative (WHI) study highlighted these risks. Careful consideration of individual cardiovascular risk profile is necessary (NIH ODS). * **Thromboembolic Events:** There is an increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), with estrogen use. Risk factors include a history of VTE, obesity, prolonged immobilization, and certain genetic clotting disorders (MedlinePlus). * **Breast Cancer:** Long-term use of estrogen-only therapy has been associated with an increased risk of endometrial cancer if the uterus is intact and a combination of estrogen and progestin increases the risk of breast cancer compared to placebo in postmenopausal women. Regular breast cancer screening, including mammography, is advised (Mayo Clinic). * **Gallbladder Disease:** Estrogens can increase the risk of gallbladder disease requiring surgery. * **Liver Function:** Impaired liver function can affect the metabolism of estradiol valerate. It should be used with caution in individuals with liver disease. * **Dementia:** The WHI Memory Study found an increased risk of probable dementia in postmenopausal individuals aged 65 years and older randomized to combined estrogen and progestin therapy (NIH ODS). * **Exacerbation of certain conditions:** Estrogen therapy should be used with caution in individuals with endometriosis, asthma, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas as it may exacerbate these conditions. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.

Estradiol valerate is contraindicated in individuals with: * Undiagnosed abnormal genital bleeding. * Known or suspected breast cancer, except in appropriately selected individuals receiving treatment for metastatic disease. * Known or suspected estrogen-dependent neoplasia. * Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions. * Active arterial thromboembolic disease (e.g., stroke, myocardial infarction), or a history of these conditions. * Known anaphylactic reaction or angioedema to estradiol valerate or any of its components. * Known liver dysfunction or disease. * Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders (FDA label). * Pregnancy: It is not indicated for use during pregnancy or for the prevention of miscarriage. Estrogen therapy during pregnancy can be harmful. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.

Estradiol valerate can interact with several medications, potentially altering its effectiveness or increasing the risk of side effects. It's crucial to inform your clinician about all medications, supplements, and herbal products you are taking. * **CYP3A4 Inducers:** Medications that induce CYP3A4 enzymes (e.g., rifampicin, carbamazepine, phenobarbital, phenytoin, St. John's wort) can increase the metabolism of estradiol, leading to lower plasma concentrations and potentially reduced therapeutic effects (EMA SmPC). * **CYP3A4 Inhibitors:** Medications that inhibit CYP3A4 enzymes (e.g., ketoconazole, erythromycin, ritonavir, grapefruit juice) may increase estradiol plasma concentrations, potentially leading to increased side effects. * **Thyroid Hormones:** Estrogens can increase the serum concentration of thyroid-binding globulin, requiring an increase in thyroid hormone dosage for individuals receiving thyroid replacement therapy (MedlinePlus). * **Corticosteroids:** Estrogens can decrease the metabolic clearance of corticosteroids, potentially increasing their effects. * **Anticoagulants:** Estrogens may impair the anticoagulant effects of coumarin derivatives (e.g., warfarin), possibly due to changes in clotting factors. Closer monitoring of INR is advised. * **Lamotrigine:** Estrogens have been shown to decrease plasma concentrations of lamotrigine, potentially reducing seizure control in individuals with epilepsy (DrugBank). This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.

Estradiol valerate can be administered at any time of day, as directed by a licensed clinician. The specific timing and frequency depend on the formulation (oral, patch, injectable) and the condition being treated. * **Oral tablets:** Typically taken once daily, often at the same time each day to maintain consistent hormone levels. Some regimens involve cyclical administration (e.g., 21 days on, 7 days off) or continuous daily administration. * **Injectable solutions:** Administered intramuscularly, typically every 1 to 4 weeks, depending on the dosage and individual response. The user-directed dose and frequency must be set by a licensed clinician. * **Transdermal patches:** Applied to the skin and changed once or twice weekly, providing continuous estradiol release. Estradiol valerate can be taken with or without food. Consistent adherence to the prescribed schedule is important for optimal therapeutic outcomes.

Source for this section: Sources for When should you take Estradiol Valerate?: Jumps to this entry in the sources and references list at the end of the page.

Put it into practice

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What interacts with Estradiol Valerate?

Documented interactions for Estradiol Valerate: the other compound, the severity and confidence of the interaction, what happens, and what to do.
Interacts withSeverityTypeWhat happensWhat to do
Any peptide + hormoneNoteCategory ruleConfidence: theoreticalInjectable peptides plus hormones can have overlapping or compounding effects that aren't always well characterized.Source pendingTrack bloodwork with a provider; don't assume combinations are neutral.

Frequently asked questions about Estradiol Valerate

Estradiol is the primary and most potent estrogen naturally produced by the body. Estradiol valerate is a synthetic ester of estradiol, meaning an valerate acid group is attached. This modification allows for different pharmacokinetic properties, such as sustained release and absorption, depending on the administration route. Once in the body, estradiol valerate is metabolized to release active estradiol, which then exerts its effects.

Once the valerate ester is cleaved, the resulting 17β-estradiol is chemically identical to the estradiol naturally produced by human ovaries. In this sense, it is considered bioidentical once activated.

The onset of therapeutic effects can vary depending on the condition being treated and the route of administration. For symptoms like hot flashes, some relief may be noticed within a few weeks, but full effects might take several months. For bone density maintenance, it's a long-term benefit over years. For gender-affirming care, physical changes typically manifest over several months to a few years.

Weight changes, including both gain and loss, have been reported as a side effect of hormone therapy, including estradiol valerate. While fluid retention can contribute to some weight gain, a definitive causal link for significant long-term weight gain specifically from estradiol itself is complex and often influenced by other factors such as age, lifestyle, and other hormonal changes. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.

Yes, mood changes, including depression and irritability, are reported side effects of estradiol valerate. Conversely, for individuals experiencing mood disturbances due to estrogen deficiency (e.g., during menopause), estrogen therapy can sometimes lead to an improvement in mood. Individual responses to exogenous hormones can vary widely.

As a hormone, Estradiol Valerate can overlap with other supplements, prescription medicines, hormones and peptides. Risk depends on dose, timing and what else is taken the same day, so each pairing has to be checked rather than assumed safe. The free checker at https://doseroutine.com/interaction-checker covers Estradiol Valerate with no sign-up.

Estradiol Valerate is administered by injection, so the measured volume — not a tablet count — is the unit that matters. Amounts for this hormone vary by protocol, formulation and individual response, so follow the dose your clinician or the product label specifies.

Whether Estradiol Valerate fits alongside testosterone replacement therapy depends on the protocol — dose, ester and ancillaries such as HCG or anastrozole — and on current bloodwork. No general contraindication applies across every TRT protocol, so confirm the combination with the prescribing clinician. See the free TRT interaction reference: https://doseroutine.com/trt-supplement-interactions

"Peptides" is not one category — healing peptides, GLP-1 agonists, growth-hormone secretagogues and melanocortins each behave differently next to Estradiol Valerate. Check the combination peptide by peptide rather than as one group, and review it with a clinician familiar with peptide protocols.

Published frequency for Estradiol Valerate varies by protocol and formulation, so the label or prescription is what sets it. Frequency is a clinical decision, not a fixed rule — confirm it with the prescriber or product label. Comparison of apps that keep a schedule like this: https://doseroutine.com/best-dose-tracking-apps

The effect of a missed dose of Estradiol Valerate depends on the protocol and formulation you are on. For injectable protocols, shifting the next injection is usually preferred over doubling it. Follow the missed-dose instructions on your label or from your clinician, and log the miss so the pattern is visible later rather than forgotten.

For an injectable like Estradiol Valerate the record needs more than a checkbox: vial concentration, the measured volume, and which site the last injection went into. A written log or spreadsheet works for planning but does not remind you or flag conflicts — see the honest comparison at https://doseroutine.com/vs/spreadsheet and the wider roundup at https://doseroutine.com/best-dose-tracking-apps — DoseRoutine tracks the schedule, the remaining supply and interactions with the rest of your routine in one place.

Commonly reported effects include breast tenderness or enlargement, headache, nausea, bloating and fluid retention, mood changes, and irregular bleeding. Injectable forms can also cause soreness at the injection site. Label warnings cover more serious risks such as venous thromboembolism, stroke, gallbladder disease and, in certain regimens, endometrial and breast cancer risk. This is educational information, not medical advice.

Estradiol Valerate is the same hormone with a fatty acid attached. That ester makes the molecule oil-soluble so an intramuscular injection releases it gradually over days, and enzymes then cleave it to free estradiol. Plain estradiol is used in patches, gels and tablets where no depot effect is wanted. This is educational information, not medical advice.

Non-oral routes avoid the first pass through the liver, and observational data suggest transdermal estradiol carries a lower clot risk than oral. Injectable esters also bypass the gut, but produce peaks and troughs between injections. Route selection is individualized with a prescriber based on clot risk, monitoring and personal preference. This is educational information, not medical advice.

The estradiol valerate/dienogest phase III trial used a 4-phase oral regimen (estradiol valerate 3 mg tapering to 1 mg, with dienogest added mid-cycle). Route reported: Oral tablets in the cited trial; injectable estradiol valerate esters also exist outside it. Frequency reported: Once daily, per the labeled 28-day multiphasic regimen. These are amounts documented in the cited studies and labels for Estradiol Valerate — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.

Which studies looked at Estradiol Valerate?

Peer-reviewed research indexed in PubMed. Each entry links to the original record.

  1. 1.Estradiol valerate/dienogest(opens PubMed in a new tab)Drugs · 2002 · PMID 11827562 · https://pubmed.ncbi.nlm.nih.gov/11827562/
  2. 2.Changes in menopause-specific quality of life between women with transdermal estradiol versus oral estrogens: results of a randomized controlled trial(opens PubMed in a new tab)Gynecol Endocrinol · 2025 · PMID 40168175 · https://pubmed.ncbi.nlm.nih.gov/40168175/
  3. 3.Estradiol valerate/dienogest: in oral contraception(opens PubMed in a new tab)Drugs · 2009 · PMID 19678714 · https://pubmed.ncbi.nlm.nih.gov/19678714/

Sources cited on this page

Specific documents referenced by the numbered markers above. Each number matches the marker in the text.

  1. PubChem CID 13791(opens in a new tab)National Center for Biotechnology Information · pubchem.ncbi.nlm.nih.gov/compound/13791

Verify at

Publisher search links for Estradiol Valerate. These are places to check the information — they are not citations, so they are not numbered.

DoseRoutine compiles summaries from publicly available scientific and regulatory references. Always verify important decisions with a licensed clinician. How we source and review this information.

What is the short answer on Estradiol Valerate?

Plain-text summary, safe to quote verbatim:

Estradiol valerate is an ester of estradiol, the main human estrogen, formulated so it releases slowly after injection or absorbs orally. It is used in menopausal hormone therapy, in feminizing hormone therapy, and in some combined oral contraceptives. Research on Estradiol Valerate focuses on bone and joint health, testosterone support, and menopause symptoms.
Source: DoseRoutine — https://doseroutine.com/library/estradiol-valerate

Estradiol Valerate cheat sheet

DoseRoutine cheat sheet · Hormone

Estradiol Valerate

Estradiol valerate is an ester of estradiol, the main human estrogen, formulated so it releases slowly after injection or absorbs orally. It is used in menopausal hormone therapy, in feminizing hormone therapy, and in some combined oral contraceptives.

Evidence

Moderate

One published human randomized trial; results not yet replicated.

Studied range

The estradiol valerate/dienogest phase III trial used a 4-phase oral regimen (estradiol valerate 3 mg tapering to 1 mg, with dienogest added mid-cycle)

Route

Oral tablets in the cited trial; injectable estradiol valerate esters also exist outside it

Frequency studied

Once daily, per the labeled 28-day multiphasic regimen

Half-life

Ester is hydrolyzed to estradiol after absorption; not separately reported in the cited trial

Storage

Room temperature

Prescription only (US)Bone JointTestosteroneMenopauseWomens Longevity

Studied ranges, not dosing advice. Not medical advice — talk to a clinician. doseroutine.com/library/estradiol-valerate

Cite this page

Using this in an article, AI answer, or research note? Please attribute:

DoseRoutine. (2026). Estradiol Valerate — Overview, Benefits & Side Effects. Retrieved from https://doseroutine.com/library/estradiol-valerate
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