Comprehensive medication guide to Depo-Estradiol including estimated pricing, availability information, side effects, and how to find it in stock at your local pharmacy.
Estimated Insurance Pricing
$0–$50 copay depending on plan and coverage tier; may be covered under Medicare Part B as a medical benefit when administered in-office. Most commercial plans cover hormone replacement therapy, though coverage for compounded estradiol cypionate specifically varies — a prior authorization may be required.
Estimated Cash Pricing
Brand Depo-Estradiol (discontinued) was $260–$310 per 5 mL vial at retail; compounded estradiol cypionate is typically $30–$80 per vial from compounding pharmacies. With GoodRx, brand pricing was as low as $262; with SingleCare, approximately $254 per vial.
Medfinder Findability Score
40/100
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Depo-Estradiol is the brand name for estradiol cypionate injection, an intramuscular hormone replacement therapy used to treat menopause symptoms, female hypoestrogenism due to hypogonadism, and — off-label — gender-affirming hormone therapy. The brand-name product was manufactured by Pfizer (Pharmacia & Upjohn) but has been discontinued. Compounded estradiol cypionate injection remains available through 503A and 503B compounding pharmacies.
Estradiol cypionate is an ester prodrug of estradiol — the most potent naturally occurring estrogen in the human body. It is available as a 5 mg/mL solution in cottonseed oil for intramuscular injection, providing sustained estrogenic effects for approximately 3-4 weeks per injection. The medication is FDA-approved for moderate to severe vasomotor symptoms associated with menopause and for female hypoestrogenism due to hypogonadism.
Depo-Estradiol is not a controlled substance and carries no abuse or dependence potential. Any licensed prescriber can prescribe it, and it is used in a broad range of clinical settings including obstetrics/gynecology, endocrinology, primary care, and gender-affirming care.
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Depo-Estradiol works through a sustained-release mechanism. When injected intramuscularly, the oil-based solution forms a small depot (reservoir) within the muscle tissue. Estradiol cypionate is highly oil-soluble but only sparingly water-soluble, so it slowly diffuses out of the oil depot and into the bloodstream over 3-4 weeks.
Once in the bloodstream, enzymes rapidly cleave the cypionate ester from the estradiol molecule, releasing active estradiol 17β — identical to the estrogen naturally produced by the ovaries. This active estradiol binds to estrogen receptors (ERα and ERβ) throughout the body, regulating temperature homeostasis (reducing hot flashes), maintaining bone density, supporting vaginal health, and affecting numerous other estrogen-sensitive tissues including the uterus, breast, skin, brain, and liver.
Because injectable estradiol bypasses first-pass liver metabolism (unlike oral estradiol), it is associated with a lower risk of venous thromboembolism (blood clots) and produces more stable hormone levels compared to daily oral tablets. Relief from vasomotor symptoms typically begins within 1-5 days after injection and is maintained for an average of approximately 5 weeks.
5 mg/mL — Intramuscular injection (oil solution)
Standard concentration in 5 mL multi-dose vials in cottonseed oil. Dose per injection depends on indication: 1-5 mg for menopause, 1.5-2 mg for hypogonadism, 2-10 mg for gender-affirming therapy.
Finding Depo-Estradiol in 2026 is significantly more difficult than it was in previous years, primarily because the brand-name product has been discontinued by Pfizer. Standard retail pharmacies (CVS, Walgreens, Rite Aid) no longer carry it, as compounded medications require specialized compounding pharmacies. As of May 2026, estradiol cypionate injection is not on the FDA's official drug shortage list — but this is because the brand was proactively discontinued rather than disrupted unexpectedly. The practical availability challenge is real.
Compounded estradiol cypionate injection is available from 503A patient-specific compounding pharmacies and 503B outsourcing facilities. However, not all compounding pharmacies carry injectable estrogens, and those that do vary in turnaround time (1-7 business days), pricing ($30-$80/vial), and shipping capabilities. Patients in rural areas may have particular difficulty finding a local compounding pharmacy and may need to rely on mail-order options.
The most efficient way to find estradiol cypionate injection near you is to use medfinder, which contacts pharmacies on your behalf to determine which ones can fill your compounded prescription. medfinder has a 99% success rate finding medications and delivers results within 24 hours.
Depo-Estradiol (estradiol cypionate injection) is not a controlled substance, so it can be prescribed by any licensed healthcare provider in the United States without DEA registration or special licensing. Prescriptions can be written electronically and directed to compounding pharmacies that prepare the injectable formulation.
Common prescribers include:
OB/GYNs (most common for menopausal HRT)
Endocrinologists (especially for hypogonadism and gender-affirming care)
Primary care physicians and internists
Nurse practitioners and physician assistants (in most states)
Gender-affirming care specialists
Reproductive endocrinologists
Telehealth is widely available for estradiol cypionate prescriptions. Platforms specializing in menopause care (such as Midi Health) and gender-affirming care (such as Folx Health, Plume, and QueerDoc) can evaluate patients online and send prescriptions directly to compounding pharmacies, including mail-order facilities.
No. Depo-Estradiol (estradiol cypionate injection) is not a controlled substance. It is not scheduled by the U.S. Drug Enforcement Administration (DEA) and has no recognized abuse potential or physical dependence profile. Estrogen is a naturally occurring hormone in the body, and its use in therapeutic doses does not produce euphoria, tolerance, or withdrawal in the way that controlled substances do.
Because Depo-Estradiol is not a controlled substance, any licensed healthcare provider can prescribe it — no DEA registration or special licensing is required beyond a standard medical license. Prescriptions can be written electronically, do not require special prescription forms, and can be refilled in standard ways. There are no federal limits on the quantity or frequency of prescribing, though providers use their clinical judgment to determine appropriate dosing intervals.
The non-controlled status of estradiol cypionate also means there are no special shipping restrictions when obtaining compounded versions by mail order from licensed compounding pharmacies, making mail-order compounding a convenient option for patients who cannot find a local compounding pharmacy.
Most common side effects — often improve as the body adjusts:
Injection site pain, swelling, or redness
Breast tenderness or enlargement
Nausea
Headache
Fluid retention and edema
Bloating
Mood changes or emotional sensitivity
Changes in vaginal discharge
Melasma (skin darkening with sun exposure)
Signs of blood clots: sudden leg pain/swelling, shortness of breath, chest pain
Stroke symptoms: sudden numbness, slurred speech, severe headache, vision changes
Chest pain (possible heart attack)
Abnormal vaginal bleeding in postmenopausal women
Jaundice or signs of liver problems
New breast lumps or breast changes
Severely worsening migraines
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Delestrogen (Estradiol Valerate Injection)
The closest injectable alternative; same intramuscular route and active hormone. Available in 10, 20, and 40 mg/mL concentrations. Dose conversion required: cypionate doses are typically 20-30% lower than equivalent valerate doses.
Estradiol Patches (Climara, Vivelle-Dot)
Transdermal delivery, no injections required. Once or twice weekly. Lower VTE risk profile than oral estradiol. In widespread shortage in 2026 due to surging demand.
Oral Estradiol (Estrace)
Widely available, very low cost ($4-$15/month generic). Taken daily. Undergoes first-pass liver metabolism (slightly higher VTE risk than injectable/transdermal). Good option as a bridge or for patients who cannot access injectable or transdermal.
Estradiol Gel (EstroGel, Divigel)
Applied topically to skin daily. Transdermal absorption (bypasses liver). Low VTE risk. Generally widely available in 2026 even during patch shortage. Good alternative for menopause patients.
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Rifampin
majorPotent CYP3A4 inducer; significantly reduces estradiol blood levels and may cause breakthrough symptoms or treatment failure.
Carbamazepine (Tegretol)
majorCYP3A4 inducer; may reduce estradiol levels significantly. Monitor serum estradiol closely; dose adjustment may be needed.
Warfarin (Coumadin)
majorEstrogens increase clotting factors, potentially reducing warfarin effectiveness. Monitor INR closely when starting, stopping, or changing estradiol dose.
Anastrozole (Arimidex)
majorEstradiol directly counteracts anastrozole's estrogen-lowering mechanism. Contraindicated in patients on aromatase inhibitors for breast cancer treatment.
Levothyroxine (Synthroid)
moderateEstrogens increase thyroxine-binding globulin; hypothyroid patients may need levothyroxine dose increases. Monitor TSH 4-8 weeks after starting or changing estradiol.
Phenytoin (Dilantin)
moderateCYP3A4 inducer; may reduce estradiol blood levels. Monitor hormone levels and symptom control in patients on phenytoin.
St. John's Wort
moderateHerbal CYP3A4 inducer; significantly reduces estradiol levels. Avoid concurrent use with estrogen therapy.
Corticosteroids
minorEstrogens may increase corticosteroid blood levels through CYP enzyme inhibition. Monitor for enhanced corticosteroid effects.
Depo-Estradiol (estradiol cypionate injection) remains an effective and valuable option for hormone replacement therapy, gender-affirming care, and the treatment of female hypoestrogenism — despite the discontinuation of the brand-name product by Pfizer. Compounded estradiol cypionate injection provides the same active ingredient at a lower cost, and is available through accredited 503A and 503B compounding pharmacies across the United States.
The primary challenge in 2026 is access — finding a compounding pharmacy that carries injectable estradiol cypionate, navigating insurance coverage for compounded medications, and ensuring treatment continuity during the transition away from brand-name supply. Patients should work closely with their prescribers to update prescriptions for the compounded formulation and identify reliable pharmacy sources before running low on their current supply.
If you're struggling to find estradiol cypionate injection near you, medfinder can help. medfinder contacts pharmacies on your behalf to find which ones can fill your compounded prescription — saving you time and ensuring you don't go without your medication.
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Our medication guides are researched and written to help patients make informed decisions. All content is reviewed for accuracy and updated regularly. Learn more about our standards
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