Estradiol valerate is estradiol, the main human estrogen, with a valeric acid (pentanoate) ester attached. In an oil injection the ester slows release from the muscle, so one shot raises estrogen levels for about a week. In the US it is sold as an intramuscular injection under the brand Delestrogen and as generics, and as part of the oral contraceptive Natazia.
The injection is FDA-approved for menopausal symptoms, for low estrogen caused by hypogonadism, castration or ovarian failure, and for palliative treatment of advanced prostate cancer. It is also one of the two injectable esters used in feminizing gender-affirming hormone therapy, where recent cohort studies suggest the guideline doses are higher than most patients need. It is not an anabolic steroid, it is not a controlled substance, and it carries the class boxed warning for estrogens.
This page summarizes what the FDA label, pharmacokinetic studies and clinical cohorts report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Estrogen (17β-estradiol ester) |
| Brand / approval | Delestrogen, NDA 009402 (first approved 1954); generic injections; oral in Natazia (NDA 022252, 2010) |
| Route | Intramuscular injection (deep gluteal) in oil; oral tablet in Natazia |
| Strengths | 10, 20 and 40 mg/mL in sesame or castor oil |
| Labeled dose | 10–20 mg every 4 weeks (menopause, hypoestrogenism); 30 mg or more every 1–2 weeks (prostate cancer) |
| Half-life | Not stated on the label; after 5 mg IM, levels peak in ≈2 days and stay elevated 7–8 days |
| Estradiol content | ≈76% of the ester’s weight (10 mg ester ≈ 7.6 mg estradiol) |
| US status | Prescription drug; not a controlled substance |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Chemically, estradiol valerate is estradiol 17-pentanoate: formula C₂₃H₃₂O₃, molecular weight 356.5 g/mol (PubChem). Estradiol alone weighs 272.4 g/mol (PubChem). The ester therefore makes up about 24% of the weight, and each 10 mg of estradiol valerate delivers about 7.6 mg of estradiol.
The ester itself has no hormonal activity. Given intravenously, estradiol valerate is split by enzymes into 17β-estradiol and valeric acid, and the estradiol is then handled like the body’s own (Düsterberg et al., Horm Res 1985). Once released, estradiol binds the two estrogen receptors in target tissues. It also feeds back on the pituitary to lower LH and FSH, the hormones that drive the ovaries and testes (Delestrogen label).
The US labeled products come in three strengths, each in a 5 mL multiple-dose vial:
| Strength | Oil carrier | Other ingredients |
|---|---|---|
| 10 mg/mL | Sesame oil (915 mg) | Chlorobutanol 5 mg (preservative) |
| 20 mg/mL | Castor oil (730 mg) | Benzyl benzoate 224 mg; benzyl alcohol 20 mg |
| 40 mg/mL | Castor oil (522 mg) | Benzyl benzoate 447 mg; benzyl alcohol 20 mg |
Delestrogen’s 40 mg/mL strength is now listed as discontinued at FDA, with a Federal Register determination that it was not withdrawn for safety or effectiveness reasons; generic 40 mg/mL vials remain approved (Drugs@FDA, NDA 009402).
The library has separate pages for estradiol cypionate, the longer-acting injectable ester, and topical estradiol.
Pharmacokinetics
The label says only that a single intramuscular injection of estradiol valerate or cypionate “is absorbed over several weeks,” and gives no half-life. Estradiol is metabolized mainly in the liver, partly by CYP3A4, into estrone and estriol, and is excreted in urine as sulfate and glucuronide conjugates.
The clearest head-to-head data come from a 1980 study that gave a single 5 mg IM dose of one of three estradiol esters in arachis oil to women whose own ovarian hormones were suppressed by an oral contraceptive (Oriowo et al., Contraception 1980):
| Ester (n) | Time to peak estradiol | Duration of elevated levels | Peak height |
|---|---|---|---|
| Benzoate (10) | ≈2 days | 4–5 days | Higher than cypionate |
| Valerate (9) | ≈2 days | 7–8 days | Higher than cypionate |
| Cypionate (10) | ≈4 days | ≈11 days | Lowest |
No subject had elevated estradiol or estrone two weeks after any of the three esters. The authors concluded that the valerate gave the most predictable profile. In practice this means a faster, higher peak and a shorter tail than cypionate at the same dose.
Route matters a great deal:
- Injection. Metabolism of the released estradiol was the same after IV and IM dosing (Düsterberg et al., Horm Res 1985).
- Oral. Oral estradiol valerate undergoes extensive first-pass metabolism in the liver, so much of it circulates as estrone and estrone sulfate rather than estradiol. Daily oral dosing did not cause accumulation (same study; Delestrogen label).
Approved medical use
Injection (Delestrogen and generics)
The label lists four indications and doses (Delestrogen label):
| Indication | Usual labeled dose |
|---|---|
| Moderate to severe menopausal hot flashes | 10–20 mg every 4 weeks |
| Moderate to severe vulvar and vaginal atrophy of menopause | 10–20 mg every 4 weeks (topical vaginal products should be considered if this is the only symptom) |
| Hypoestrogenism from hypogonadism, castration or primary ovarian failure | 10–20 mg every 4 weeks |
| Advanced androgen-dependent prostate cancer (palliation only) | 30 mg or more every 1–2 weeks |
The label adds several conditions on use:
- Start at the lowest dose; the lowest effective dose has not been determined for any indication.
- Women with a uterus should also receive a progestin to reduce the risk of endometrial cancer.
- Try to taper or stop every 3–6 months for menopausal symptoms.
- Base dosing on clinical response, not on serum estradiol or FSH levels.
Oral (Natazia)
Natazia combines estradiol valerate with the progestin dienogest in an oral contraceptive tablet pack. It is approved to prevent pregnancy and to treat heavy menstrual bleeding in women who choose an oral contraceptive. In its two pivotal studies, the Pearl Index (pregnancies per 100 woman-years) was 1.64 in North America and 1.04 in Europe (Natazia label).
What the research shows
Monthly injectable contraception
Outside the US, 5 mg estradiol valerate is combined with 50 mg norethisterone enanthate as a once-a-month contraceptive injection. A three-year phase III trial followed 931 women in five Latin American countries for 15,787 woman-months (von Kesseru et al., Contraception 1994):
| Outcome | Result |
|---|---|
| Pregnancies | 1 (0.08 per 100 woman-years) |
| Amenorrhea | 2.8% of cycles |
| Weight gain over 2 kg | 36.8% of women |
| Continuation at 12 / 24 / 36 months | 64.7% / 31.0% / 20.4% |
A Cochrane review of 12 randomized trials found that this combination caused less overall discontinuation and more regular bleeding than the other marketed monthly injectable (medroxyprogesterone acetate plus estradiol cypionate), though not in every trial (Gallo et al., Cochrane 2013).
Gender-affirming hormone therapy
The 2017 Endocrine Society guideline lists parenteral estradiol valerate or cypionate at 5–30 mg IM every 2 weeks or 2–10 mg IM weekly. It targets estradiol of 100–200 pg/mL and testosterone under 50 ng/dL (Hembree et al., JCEM 2017, as summarized by Rothman et al., Transgend Health 2024 and Kanin et al., J Endocr Soc 2025). No randomized dose-finding trial of injectable estradiol exists. The data are retrospective cohorts, and they consistently find that doses at the low end of that range are enough.
| Study | Design and n | Dose | Main finding |
|---|---|---|---|
| Kanin et al., 2025 | Retrospective, 29 treatment-naive patients (28 on valerate) | Mean 4.3 mg/week at start, 3.7 mg/week at end | First on-treatment estradiol averaged 347 pg/mL; only 21% were in the 100–200 pg/mL goal. All reached testosterone under 50 ng/dL. |
| Misakian et al., 2025 | Retrospective multisite, 357 patients (valerate or cypionate) | Median 4 mg/week | Median estradiol 232 pg/mL. Testosterone under 50 ng/dL in 82.6%, with or without an antiandrogen. |
| Krikorian et al., 2026 | Retrospective, 459 patients per protocol | 3 or 4 mg/week valerate | Estradiol 100–357 pg/mL in 78.3% (3 mg) and 76.0% (4 mg). Testosterone under 50 ng/dL in 83.6% and 90.0%. |
A scoping review by endocrinologists who treat this population concluded that the guideline starting doses likely produce supraphysiologic estradiol across much of the injection cycle. It suggested starting at 5 mg weekly or less, by either IM or subcutaneous injection, and titrating to levels (Rothman et al., Endocr Pract 2024). In a Mayo Clinic cohort of 130 patients on injectable estradiol, subcutaneous (median 3.75 mg/week) and intramuscular (median 4 mg/week) dosing gave estradiol and testosterone levels that did not differ significantly (Herndon et al., Endocr Pract 2023). Subcutaneous use is not described on the US label.
These studies also show the point most relevant to men: estradiol alone, through feedback on the pituitary, suppressed testosterone under 50 ng/dL in most people at a median of about 4 mg per week.
Side effects and risks
Boxed warning
The injection carries the boxed warning shared by estrogen products (Delestrogen label):
- Endometrial cancer. Unopposed estrogen raises the risk in women with a uterus.
- Cardiovascular disease, breast cancer and dementia. Estrogens with or without progestins should not be used to prevent cardiovascular disease. The warning rests on the Women’s Health Initiative (WHI) trials of oral conjugated estrogens, not on estradiol valerate itself, but the label says the risks should be assumed similar for other estrogens.
The label reproduces the WHI estrogen-plus-progestin results in 16,608 postmenopausal women followed for 5.2 years:
| Event | Relative risk (95% CI) | Placebo, per 10,000 woman-years | Hormones, per 10,000 woman-years |
|---|---|---|---|
| Coronary heart disease events | 1.29 (1.02–1.63) | 30 | 37 |
| Stroke | 1.41 (1.07–1.85) | 21 | 29 |
| Pulmonary embolism | 2.13 (1.39–3.25) | 8 | 16 |
| Deep vein thrombosis | 2.07 (1.49–2.87) | 13 | 26 |
| Invasive breast cancer | 1.26 (1.00–1.59) | 30 | 38 |
| Hip fracture | 0.66 (0.45–0.98) | 15 | 10 |
In the WHI memory substudy of women 65 and older, probable dementia was diagnosed in 45 vs 22 per 10,000 woman-years (RR 2.05, 95% CI 1.21–3.48).
Endometrial cancer
Unopposed estrogen raises endometrial cancer risk about 2- to 12-fold, and 15- to 24-fold with use for 5–10 years or more. The risk persists for at least 8–15 years after stopping. Adding a progestin lowers the rate of endometrial hyperplasia, a possible precursor.
Blood clots
Estrogens increase clotting factors and lower antithrombin. The label advises stopping estrogens at least 4–6 weeks before surgery linked to clot risk or during prolonged immobilization, where feasible.
Data in transgender women are observational and not specific to the valerate ester:
- A meta-analysis estimated venous thromboembolism at 2.3 per 1000 person-years (95% CI 0.8–6.9), with high heterogeneity between studies (Khan et al., Clin Chem 2019).
- In a Kaiser Permanente cohort of 2842 transfeminine members, the 8-year excess risk of venous thromboembolism was 16.7 per 1000 people compared with cisgender men (95% CI 6.4–27.5) (Getahun et al., Ann Intern Med 2018).
Use in men at high doses
For prostate cancer the label notes that large estrogen doses (5 mg conjugated estrogens per day) increased nonfatal heart attack, pulmonary embolism and thrombophlebitis in a large trial in men. Breast tenderness and enlargement, fluid retention and changes in libido are listed adverse reactions. Estrogen also suppresses LH and FSH, and with them the body’s own testosterone production.
Other risks on the label
- Gallbladder disease: a 2- to 4-fold higher risk of gallbladder disease needing surgery in postmenopausal women.
- Triglycerides: estrogen can raise triglycerides, which in people with pre-existing hypertriglyceridemia can lead to pancreatitis.
- Liver: contraindicated in liver disease; caution with a history of cholestatic jaundice.
- Blood pressure, fluid retention and glucose tolerance should be watched.
- Vision: retinal vascular thrombosis has been reported.
- Thyroid: estrogen raises thyroid-binding globulin, so people on thyroid replacement may need a higher dose.
Who should not use it
The label contraindicates use in people with:
- undiagnosed abnormal genital bleeding;
- known, suspected or past breast cancer, or other estrogen-dependent cancer;
- active or past deep vein thrombosis or pulmonary embolism;
- stroke or heart attack within about the past year;
- liver dysfunction or disease;
- known or suspected pregnancy.
Interactions
Estrogens are partly metabolized by CYP3A4. Inducers such as St. John’s wort, phenobarbital, carbamazepine and rifampin may lower estrogen levels. Inhibitors such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may raise them.
For Natazia, the boxed warning is about cigarette smoking: combination oral contraceptives should not be used by women over 35 who smoke, because of the risk of serious cardiovascular events (Natazia label).
Legal status and use outside medicine
Estradiol valerate is a prescription drug in the US. Estradiol does not appear in the DEA’s Schedule III list of anabolic steroids (21 CFR 1308.13), and estrogens are not named on the WADA 2026 Prohibited List. WADA’s S4 class bans substances that block estrogen, such as aromatase inhibitors and SERMs, not estrogens themselves.
Product obtained without a prescription is not regulated for dose, sterility or identity.
Key takeaways
- Estradiol with a short-to-medium ester. About 76% of the labeled milligrams is estradiol. After a 5 mg IM injection, levels peak in about 2 days and stay elevated about a week, shorter than cypionate.
- Approved for menopause, hypoestrogenism and prostate cancer. The usual labeled dose is 10–20 mg every 4 weeks for women and 30 mg or more every 1–2 weeks for prostate cancer palliation.
- Lower doses than the guideline often suffice in gender-affirming care. Cohorts show about 3–4 mg weekly reaches target estradiol in most patients and suppresses testosterone under 50 ng/dL in roughly 80–90%.
- Class boxed warning applies. Endometrial cancer with unopposed estrogen, plus stroke, clots, breast cancer and dementia from the WHI trials of oral estrogens.
- Strongly suppresses testosterone in men. Estrogen feedback on the pituitary lowers LH, FSH and the body’s own testosterone.
- Not scheduled and not WADA-listed. It is a prescription drug, not a controlled anabolic steroid.
Sources
- Par Health / Endo. Delestrogen (estradiol valerate injection, USP) prescribing information, revised 05/2024. DailyMed; Drugs@FDA, NDA 009402.
- Bayer HealthCare Pharmaceuticals. Natazia (estradiol valerate and estradiol valerate/dienogest) tablets prescribing information, NDA 022252. DailyMed; Drugs@FDA.
- National Center for Biotechnology Information. Estradiol valerate, PubChem CID 13791. PubChem.
- National Center for Biotechnology Information. Estradiol, PubChem CID 5757. PubChem.
- Oriowo MA, Landgren BM, Stenström B, Diczfalusy E. A comparison of the pharmacokinetic properties of three estradiol esters. Contraception. 1980;21(4):415–424. PubMed.
- Düsterberg B, Schmidt-Gollwitzer M, Hümpel M. Pharmacokinetics and biotransformation of estradiol valerate in ovariectomized women. Horm Res. 1985;21(3):145–154. PubMed.
- von Kesseru E, Aydinlik S, Etchepareborda JJ. Multicentred, phase III clinical trial of norethisterone enanthate 50 mg plus estradiol valerate 5 mg as a monthly injectable contraceptive; final three-year report. Contraception. 1994;50(4):329–337. PubMed.
- Gallo MF, Grimes DA, Lopez LM, et al. Combination injectable contraceptives for contraception. Cochrane Database Syst Rev. 2013;(3):CD004568. PubMed.
- Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869–3903. PubMed.
- Rothman MS, Hamnvik OR, Davidge-Pitts C, et al. Revisiting injectable estrogen dosing recommendations for gender-affirming hormone therapy. Transgend Health. 2024;9(6):463–465. PubMed.
- Rothman MS, Ariel D, Kelley C, et al. The use of injectable estradiol in transgender and gender diverse adults: a scoping review of dose and serum estradiol levels. Endocr Pract. 2024;30(9):870–878. PubMed.
- Kanin M, Slack M, Patel R, et al. Injectable estradiol dosing regimens in transgender and nonbinary adults listed as male at birth. J Endocr Soc. 2025;9(5):bvaf004. PubMed.
- Misakian AL, Ariel D, Sullivan EA, et al. Injectable estradiol monotherapy effectively suppresses testosterone in gender-affirming hormone therapy. Endocr Pract. 2025;31(11):1462–1469. PubMed.
- Krikorian J, Casetti A, Dickstein A, et al. Revisiting injectable estradiol valerate dosing for gender-affirming hormone therapy: a retrospective cohort review. Endocr Pract. Published online June 10, 2026. PubMed.
- Herndon JS, Maheshwari AK, Nippoldt TB, et al. Comparison of the subcutaneous and intramuscular estradiol regimens as part of gender-affirming hormone therapy. Endocr Pract. 2023;29(5):356–361. PubMed.
- Khan J, Schmidt RL, Spittal MJ, et al. Venous thrombotic risk in transgender women undergoing estrogen therapy: a systematic review and metaanalysis. Clin Chem. 2019;65(1):57–66. PubMed.
- Getahun D, Nash R, Flanders WD, et al. Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med. 2018;169(4):205–213. PubMed.
- Drug Enforcement Administration. Schedules of controlled substances: Schedule III. 21 CFR 1308.13. eCFR.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA.