What Is Depo-Estradiol? Uses, Dosage, and What You Need to Know in 2026

Depo-Estradiol is the brand name for estradiol cypionate injection, an intramuscular hormone replacement therapy used by patients managing menopause symptoms, hypogonadism, and — off-label — gender-affirming hormone therapy. This comprehensive guide covers everything you need to know about this medication in 2026.

What Is Depo-Estradiol?

Depo-Estradiol is an injectable form of estrogen. Its active ingredient, estradiol cypionate, is a synthetic ester of estradiol — the most potent naturally occurring estrogen in the human body. The cypionate ester is attached to estradiol to slow its release from the injection site, extending its duration of action to approximately 3-4 weeks with a single intramuscular injection.

The medication is suspended in cottonseed oil and was commercially manufactured by Pfizer as Depo-Estradiol. The brand has since been discontinued, but compounded estradiol cypionate injection remains available through 503A and 503B compounding pharmacies.

What Is Depo-Estradiol Used For?

Depo-Estradiol is FDA-approved for two indications:

Moderate to severe vasomotor symptoms of menopause: This includes hot flashes, night sweats, flushing, and other symptoms caused by declining estrogen during menopause or surgical menopause (after removal of the ovaries). Within 1-5 days after injection, relief of vasomotor symptoms typically begins and is maintained for an average of 5 weeks.

Female hypoestrogenism due to hypogonadism: This includes conditions where the ovaries are underactive or absent, such as Turner syndrome, primary ovarian insufficiency, or removal of the ovaries before natural menopause. Estrogen therapy maintains feminization and prevents bone loss.

Beyond these FDA-approved uses, Depo-Estradiol is widely used off-label for:

Gender-affirming hormone therapy (GAHT): Injectable estradiol is a preferred route for many transgender women and nonbinary individuals seeking feminization. Per Endocrine Society and WPATH guidelines, estradiol cypionate and estradiol valerate are endorsed interchangeably at doses of 2-10 mg weekly or 5-30 mg every 2 weeks.

Puberty induction in girls with delayed puberty: Starting at very low doses (0.2 mg/month), gradually increased over 2 years to adult maintenance doses.

Depo-Estradiol Dosage Guide

Depo-Estradiol is available as a 5 mg/mL solution for intramuscular injection in 5 mL multi-dose vials. Dosing varies by indication:

Menopause (vasomotor symptoms): 1-5 mg IM every 3-4 weeks. Lowest effective dose should be used, with attempts to discontinue every 3-6 months.

Female hypogonadism: 1.5-2 mg IM monthly.

Gender-affirming hormone therapy: 2-10 mg IM weekly or every 1-2 weeks (off-label); starting doses closer to 3-5 mg/week are often recommended to avoid supratherapeutic estradiol levels.

Puberty induction: 0.2 mg IM monthly, gradually increased over approximately 2 years to adult maintenance dose.

Injections are given deep into the muscle — typically the upper outer quadrant of the gluteal muscle, the thigh, or the upper arm. The vial should be warmed and shaken before use to redissolve any crystals that may have formed during storage.

How Long Does Depo-Estradiol Last?

After a single 5 mg injection, estrogenic effect lasts approximately 3-4 weeks on average. Relief of vasomotor symptoms typically begins within 1-5 days and may be maintained for 5 weeks or longer. For most people, this allows a monthly injection schedule, though some find symptoms return sooner and may benefit from every 3-week injections.

Who Should NOT Take Depo-Estradiol?

Depo-Estradiol is contraindicated in the following situations:

Undiagnosed abnormal vaginal bleeding

Known or suspected breast cancer or estrogen-dependent cancer

Active or history of deep vein thrombosis (DVT) or pulmonary embolism (PE)

Active or recent (within one year) stroke or heart attack

Liver dysfunction or disease

Pregnancy

Known hypersensitivity to estradiol, chlorobutanol (the preservative), or cottonseed oil

Is Depo-Estradiol a Controlled Substance?

No. Depo-Estradiol (estradiol cypionate) is not a controlled substance and is not scheduled by the DEA. It has no abuse potential or dependence risk. Any licensed prescriber can prescribe it, and prescriptions can be sent electronically without special DEA forms.

What's the Difference Between Depo-Estradiol and Other Estrogen Forms?

All forms of estradiol therapy ultimately deliver the same active hormone. The main differences lie in the route of administration, frequency, blood level stability, and side effect profiles:

Injectable (Depo-Estradiol): Monthly or more frequent; bypasses liver; predictable absorption; peaks and troughs between injections

Transdermal patch: Weekly or twice-weekly; steady levels; bypasses liver; in shortage in 2026

Oral: Daily; widely available; first-pass liver metabolism (slightly higher VTE risk); lower cost

Gel/spray: Daily topical application; transdermal; bypasses liver; widely available

Finding Depo-Estradiol in 2026

With the brand discontinued, patients now obtain estradiol cypionate injection through compounding pharmacies. Use medfinder to find pharmacies near you that can fill your prescription. For more on the current availability situation, see why Depo-Estradiol is hard to find in 2026.