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Depo-Estradiol

estradiol cypionate
Used for Estrogen Replacement, Menopause

Depo-Estradiol (estradiol cypionate) injection is a hormone replacement therapy (HRT). It's used to relieve certain menopause symptoms, such as hot flashes and vaginal dryness. It can also raise estrogen levels in people who aren't making enough hormones. It's injected into the muscle about once every month. You can store Depo-Estradiol (estradiol cypionate) vials at room temperature, away from light. Some side effects of this medication include injection-site pain, headaches, and breast tenderness.

Reviewed by:Last reviewed on October 27, 2024
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What is Depo-Estradiol (estradiol cypionate)?

What is Depo-Estradiol (estradiol cypionate) used for?

How Depo-Estradiol (estradiol cypionate) works

Depo-Estradiol (estradiol cypionate) replaces estrogen hormones that your body loses during menopause or when your body can't make enough estrogen naturally. Replacing estrogen relieves symptoms of menopause, such as hot flashes and vaginal dryness.

Drug facts

Common BrandsDepo-Estradiol
Drug ClassEstrogen replacement
Controlled Substance ClassificationNot a controlled medication
Generic StatusNo lower-cost generic available
AvailabilityPrescription only
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Side effects of Depo-Estradiol (estradiol cypionate)

The following side effects may get better over time as your body gets used to the medication. Let your healthcare provider know immediately if you continue to experience these symptoms or if they worsen over time.

Common Side Effects

  • Injection-site pain
  • Breast tenderness or growth
  • Nausea or vomiting
  • Headaches
  • Stomach cramps
  • Vaginal spotting or irregular bleeding

Less Common Side Effects

  • Dizziness
  • High blood pressure
  • Melasma (dark patches of skin)
  • Trouble tolerating contact lenses
  • Mood changes
  • Swelling from fluids
  • Hair loss

Depo-Estradiol (estradiol cypionate) serious side effects

Contact your healthcare provider immediately if you experience any of the following.

  • Heart attack: chest pain or tightness, pain that radiates up to your shoulder, arm, neck, or jaw
  • Stroke: sudden trouble talking, trouble walking, or numbness on one side of your body or face, severe headache
  • Deep vein thrombosis (blood clot in the leg): leg cramp, swelling, pain, muscle tightness
  • Pulmonary embolism (blood clot in the lung): cough, chest pain, trouble breathing, racing heart
  • Liver or gallbladder problems: yellowing of the skin or the whites of the eyes, tiredness, pain in the right upper stomach, dark urine
  • Unusual vaginal bleeding, vaginal discharge, or pelvic pain

Source: DailyMed

The following Depo-Estradiol (estradiol cypionate) side effects have also been reported

Side effects that you should report to your care team as soon as possible:

  • Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat
  • Blood clot—pain, swelling, or warmth in the leg, shortness of breath, chest pain
  • Breast tissue changes, new lumps, redness, pain, or discharge from the nipple
  • Gallbladder problems—severe stomach pain, nausea, vomiting, fever
  • Heart attackpain or tightness in the chest, shoulders, arms, or jaw, nausea, shortness of breath, cold or clammy skin, feeling faint or lightheaded
  • Heavy vaginal bleeding
  • Increase in blood pressure
  • Liver injury—right upper belly pain, loss of appetite, nausea, light-colored stool, dark yellow or brown urine, yellowing skin or eyes, unusual weakness or fatigue
  • Stroke—sudden numbness or weakness of the face, arm, or leg, trouble speaking, confusion, trouble walking, loss of balance or coordination, dizziness, severe headache, change in vision
  • Sudden eye pain or change in vision such as blurry vision, seeing halos around lights, vision loss
  • Unusual vaginal discharge, itching, or odor

Side effects that usually do not require medical attention (report to your care team if they continue or are bothersome):

  • Bloating
  • Breast pain or tenderness
  • Dark patches of skin on the face or other sun-exposed areas
  • Hair loss
  • Irregular menstrual cycles or spotting
  • Nausea
  • Stomach pain
  • Swelling of the ankles, hands, or feet
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$308.74(Save 17.90%)
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$253.48
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Pros and cons of Depo-Estradiol (estradiol cypionate)

Pros

  • Can be injected at home
  • Typically injected once every 3 to 4 weeks
  • Can be stored at room temperature

Cons

  • Given as an injection
  • Raises the risk of blood clots and strokes
  • If you have your uterus, you have to use Depo-Estradiol (estradiol cypionate) with another hormone called progestin to lower your risk of uterine cancer.
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Pharmacist tips for Depo-Estradiol (estradiol cypionate)

pharmacist
  • Depo-Estradiol (estradiol cypionate) can be given at home. Before using it, your healthcare professional will train you or a caregiver on how to inject this medication safely and properly.
  • Wash your hands with soap and water before giving Depo-Estradiol (estradiol cypionate) to prevent infection. Clean the area where you'll be injecting the medication with an alcohol wipe.
  • Shake the vial before drawing Depo-Estradiol (estradiol cypionate) into a syringe. This can help dissolve any crystals that might've formed during storage. Use a new needle and syringe each time you give yourself Depo-Estradiol (estradiol cypionate).
  • Throw away the used syringes and needles in a protective (sharps) container. Don't throw needles and syringes away in the regular trash to prevent needlestick injuries.
  • Store Depo-Estradiol (estradiol cypionate) at room temperature, away from heat and direct light. Don’t keep the medication in the fridge or freezer because this can affect how well it works. If it gets too cold, it can form crystals. These can be dissolved again by shaking and warming the vial in your hands.
  • Let your healthcare team know if you need surgery. They might ask you to stop using Depo-Estradiol (estradiol cypionate) temporarily, for about 4 to 6 weeks. Estrogen-containing medications can raise your risk of blood clots during and after surgery, especially if you're less mobile for an extended period of time during recovery.
  • Let your prescriber know if you experience unusual vaginal bleeding, lumps in your breast, changes to your vision, or severe headaches after starting Depo-Estradiol (estradiol cypionate). These are not typical side effects and could be a sign of more serious problems.
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Risks and warnings for Depo-Estradiol (estradiol cypionate)

Depo-Estradiol (estradiol cypionate) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.

Uterine or endometrial cancer

  • Risk factors: Estrogen therapy without additional progestin | People with a healthy uterus | Using Depo-Estradiol (estradiol cypionate) for more than 1 year | High estrogen dose

Black Box WarningBecause Depo-Estradiol (estradiol cypionate) injection works like estrogen, it can change the lining of the uterus (endometrium). Uncontrolled growth of the uterus lining can cause uterine or endometrial cancer in people with a healthy uterus. If you have a healthy uterus, your healthcare team will lower your risk of cancer by also prescribing a progestin to balance out estrogen's effect on the growth of the uterine lining. Let your healthcare team know right away if you have symptoms of uterine or endometrial cancer, such as unexpected vaginal bleeding; they can examine you and let you know if you need more medical attention.

Breast cancer

  • Risk factors: Personal or family history of breast cancer | Using estrogen and progestin together for more than one year

Black Box WarningThere's a higher risk of developing breast cancer when taking estrogen medications, such as Depo-Estradiol (estradiol cypionate). To lower your risk of breast cancer, your prescriber will prescribe the lowest dose of estrogen for the shortest period of time possible. It's important that you regularly check your breasts for any changes and get breast scans (mammograms) done. Let your healthcare professional know if you notice any unusual changes in breast shape, size, or color.

Blood clots, heart attacks, and strokes

  • Risk factors: Personal or family history of blood clots | High blood pressure | Diabetes | High cholesterol | Smoking | Larger body size | Systemic lupus erythematosus (SLE)

Black Box WarningDepo-Estradiol (estradiol cypionate) can raise your risk of blood clots, which can lead to a heart attack, stroke, or pulmonary embolism (life-threatening blood clot in the lungs). Your risk for blood clots is higher if you smoke or have had blood clots in the past. Be sure to discuss all your past and present medical conditions with your prescriber before starting Depo-Estradiol (estradiol cypionate). Call 911 or get medical help right away if you have pain in your legs or arms, chest pain, sudden severe headaches, trouble breathing, or sudden changes in your speech or vision.

Risk of dementia

  • Risk factors: Females 65 years of age and older

Black Box WarningPeople taking estrogen/progestin combinations or estrogen-only therapy might be at greater risk for dementia. Your risk is higher if you start hormonal therapy such as Depo-Estradiol (estradiol cypionate) after age 65. Estrogen/progestin combination and estrogen-only therapies shouldn't be used to prevent dementia. Early symptoms of dementia include new forgetfulness, confusion, getting lost, and wandering out into the neighborhood. If the risk of dementia worries you, talk to your HCP.

Gallbladder problems

Depo-Estradiol (estradiol cypionate) can cause you to have problems with your gallbladder. Some people have even needed to have their gallbladder removed after starting this medication. If you experience stomach pain, nausea or vomiting that doesn't go away, fever, or a yellowing of the skin and eyes (jaundice), speak with your prescriber or get medical attention.

Changes in calcium levels in the blood

  • Risk factors: Breast cancer | Cancer that has spread to the bones | Low parathyroid hormone levels

Estrogen therapy can change the calcium levels in your blood. Females with breast cancer that has spread to the bones are at higher risk of very high calcium levels. Symptoms of high calcium levels include feeling tired and having muscle weakness, nausea, vomiting, or constipation.

On the other hand, females with low parathyroid hormone levels from the parathyroid gland are at higher risk of low calcium levels during estrogen therapy. Symptoms of low calcium levels include muscle spasms or twitching and numbness and tingling in your fingers, toes, or around your mouth.

Let your HCP know if you notice any of these symptoms. You might need regular blood tests done so that your HCP can check your calcium levels while you're taking Depo-Estradiol (estradiol cypionate).

Vision problems

Although very rare, some people taking estrogens have had vision problems due to clot formation in the eyes. If you have sudden partial or complete vision loss, bulging eyes, double vision, or migraines, stop Depo-Estradiol (estradiol cypionate) and tell your prescriber.

Low thyroid hormone levels (hypothyroidism)

  • Risk factors: Low thyroid hormone levels

Depo-Estradiol (estradiol cypionate) can affect thyroid hormone levels in your blood. If you take medications for low thyroid hormone levels, you might require higher doses of thyroid replacement therapy. Your prescriber might have you perform regular blood tests to check your thyroid hormone levels.

Fluid Retention

  • Risk factors: History of heart or kidney problems

Depo-Estradiol (estradiol cypionate) might cause some fluid retention, or edema. This could worsen symptoms of certain conditions, like heart conditions (e.g., congestive heart failure) or kidney problems. If you notice unusual swelling in any part of your body or if you suddenly gain weight over a short period of time, let your prescriber know.

Higher risk of side effects

  • Risk factors: History of or current liver problems

Depo-Estradiol (estradiol cypionate) is processed (broken down) by the liver, so if your liver isn't working properly, you might experience more side effects from this medication. Because of this, if you have or have had any problems with your liver, including liver problems during a past pregnancy, you shouldn't use Depo-Estradiol (estradiol cypionate).

High triglycerides

  • Risk factors: High levels of triglycerides

Estrogens can raise the amount of your body's blood fats (triglycerides), which can cause heart problems or inflammation of the pancreas. Your prescriber might order regular blood tests to watch for this while you're using Depo-Estradiol (estradiol cypionate). If you experience sudden stomach or back pain, nausea, vomiting, sudden weight loss, or a fast heart rate, contact your prescriber or get medical care right away.

Worsening of other medical conditions

Taking estrogen-containing medications can worsen certain medical conditions. These include high blood pressure, hereditary angioedema, asthma, diabetes, migraine, and seizures. Before you start Depo-Estradiol (estradiol cypionate), let your healthcare team know about your past medical history so they can talk with you about the risks and benefits of taking this medication.

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Depo-Estradiol (estradiol cypionate) dosage

The average cost for 1 vial of 5ml of 5mg/ml of Depo-Estradiol (estradiol cypionate) is $253.48 with a free GoodRx coupon. This is 17.90% off the average retail price of $308.74.
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DosageQuantityPrice as low asPrice per unit
5ml of 5mg/ml1 vial$253.48$253.48

Typical dosage for Depo-Estradiol (estradiol cypionate)

Your healthcare team will prescribe the lowest dose of Depo-Estradiol (estradiol cypionate) for the shortest period of time needed to treat your symptoms. They'll check in with you every 3 to 6 months to see if they can taper you off this medication.

  • Hot flashes: The typical dose ranges from 1 mg to 5 mg injected into a muscle every 3 to 4 weeks.
  • Low estrogen due to hypogonadism: The typical dose ranges from 1.5 mg to 2 mg injected into a muscle once a month.
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How much does Depo-Estradiol (estradiol cypionate) cost?

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Depo-Estradiol (estradiol cypionate) contraindications

Contraindications are specific health conditions or situations in which a person should not take a medication due to safety concerns. If you have any of the following conditions or if any of the following apply to you, let your healthcare provider know because Depo-Estradiol (estradiol cypionate) will not be safe for you to take.

  • Abnormal vaginal bleeding that your gynecologist doesn’t know about or you haven’t gone to them about
  • Currently have or have had breast cancer
  • Estrogen-dependent cancers (e.g., endometrial cancer, ovarian cancer)
  • High risk for developing a blood clot
  • History of blood clots, stroke, or heart attack
  • Have a bleeding disorder
  • Liver problems
  • Currently pregnant
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What are alternatives to Depo-Estradiol (estradiol cypionate)?

There are a number of medications that your doctor can prescribe in place of Depo-Estradiol (estradiol cypionate). Compare a few possible alternatives below.
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News about Depo-Estradiol (estradiol cypionate)

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References

Best studies we found

American College of Obstetricians and Gynecologists. (2023). Abnormal uterine bleeding.

Atkins, F. M., et al. (1988). Cottonseed hypersensitivity: new concerns over an old problem. The Journal of Allergy and Clinical Immunology.

MedlinePlus. (2022). Hypogonadism.

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.