Estradiol and Medroxyprogesterone (Intramuscular)

Estradiol and medroxyprogesterone is an injectable combination contraception which inhibits egg development in order to prevent unwanted pregnancy.


Estradiol and medroxyprogesterone is a hormonal contraceptive medicine which is administered monthly via an intramuscular injection. It works by stopping eggs from fully developing each month so that they are unable to accept sperm. This prevents fertilization of the egg and therefore prevents pregnancy. Added contraceptive effects include changes to the cervical mucus lining and uterine lining, which makes it more difficult for sperm to reach the uterus and, in the event that an egg does become fertilized, makes it harder for eggs to attach the uterus.

Sometimes hormonal contraceptives like estradiol and medroxyprogesterone are used for purposes other than to prevent pregnancy, such as managing menstrual problems. This is at the discretion of each doctor. In the US, estradiol and medroxyprogesterone's brand name is Lunelle.

Conditions Treated?

  • Pregnancy prevention

Type Of Medicine?

  • Contraceptive injection

Side Effects

Along with its needed effects, estradiol and medroxyprogesterone can cause a variety of unwanted side effects. Some of these are minor, while others are serious and require medical attention. Not all of them may occur, but you should familiarize yourself with all potential side effects so that you can seek medical advice where appropriate.

The following side effects should be reported to a doctor as soon as possible:

  • Hives
  • Itching
  • Persistent pain, bleeding or drainage of other fluid at injection site
  • Puffiness or swelling of eyelids, face, lips or tongue
  • Swelling of face, hands, legs or feet
  • Difficulty swallowing
  • Cough
  • Fast heartbeat
  • Shortness of breath
  • Tightness in chest
  • Wheezing
  • Loss of appetite
  • Nausea
  • Stomach pain
  • Vomiting blood
  • Dark urine
  • Clay-colored stools
  • Rapid weight gain
  • Depression
  • Unusual tiredness or weakness
  • Yellowing skin or eyes (jaundice)
  • Severe migraine headaches
  • Sudden confusion, headache, pain behind eyes, or problems with vision, balance or speech
  • Lump in breast

The following side effects are minor and don't usually need medical attention unless they become very severe or prolonged. You could report them to your doctor if they are very bothersome. Your doctor might consider changing your contraception if they are causing severe inconvenience, or they may be able to recommend lifestyle changes which could reduce or relieve the side effects. Sometimes, minor side effects dissipate once the body adjusts to the new contraception.

  • Headache
  • Dizziness
  • Abdominal pain
  • Enlarged abdomen
  • Breast pain, tenderness or swelling
  • Missed or absent menstrual periods
  • Increased menstrual bleeding
  • Spotting (bleeding in between menstrual periods)
  • Vaginal discharge or itching
  • Nervousness
  • Acne
  • Brown, blotchy spots on skin
  • Allergic rash
  • Hair loss or thinning hair
  • Lack or loss of strength
  • Tiredness

The following are signs of estradiol and medroxyprogesterone overdose, and should be reported to a doctor immediately:

  • Severe nausea
  • Persistent vomiting
  • Menstrual irregularities
  • Abnormal vaginal bleeding

This may not be an exhaustive list of all side effects that estradiol and medroxyprogesterone could cause. If you notice other symptoms not listed here, consult your doctor as soon as possible or report them to the FDA.


The recommended dose of estradiol and medroxyprogesterone is 0.5 ml injected into a muscle every 28 to 30 days. The injection is usually administered by a doctor or nurse in a doctor's office or another clinical environment. The upper arm and the buttocks are the most common injection sites, but your healthcare provider will select an appropriate location.

The very first estradiol and medroxyprogesterone injection is usually given with the first five days of menstrual bleeding. You will, therefore, have to arrange an appointment with your healthcare provider which coincides with your period.

Sometimes doses differ to the recommended 0.5 ml, depending on the unique circumstances and medical history of the patient. Always follow your doctor's instructions, as they will determine the most appropriate dose for you.

Missed doses

It is very important that you have estradiol and medroxyprogesterone injections every 28 to 30 days to prevent unwanted pregnancy. If more than 33 days pass between injections, you may not be able to have another injection until your doctor can rule out pregnancy. You, therefore, may be unable to have another injection until your next period begins. During the interim, you will have to use an alternative method of contraception to protect you against unwanted pregnancy. This will most likely be a barrier method, such as condoms or the diaphragm. You can ask your doctor for advice.


There are many medicines which can interact with estradiol and medroxyprogesterone and cause harmful effects. It is very important to tell your doctor about all the medicines you take, including those prescribed to you, those purchased over the counter, and herbal supplements or multivitamins. It may be helpful to keep a list of medicines to present to each doctor, pharmacist or another healthcare professional you have an appointment with in order that they can avoid prescribing treatments which could lead to harmful interactions.

Before you start estradiol and medroxyprogesterone injections, you should tell your doctor if you take any of the following medicines:

  • Aminoglutethamide (Cytadren)
  • Cyclosporine (Neoral, Sandimmune, Gengraf)
  • Phenylbutazone (Azolid, Butazolidin)
  • Prednisolone (Orapred)
  • St. John's Wort
  • Theophylline (Respbid, Theo-Dur)
  • Antibiotics
  • Seizure medicines
  • Barbiturates
  • HIV medicines

It is not recommended that estradiol and medroxyprogesterone is ever administered at the same time as tranexamic acid, which is a drug used to treat heavy menstrual bleeding. If you take this medicine, your doctor will either choose an alternative contraception method for you, or they will stop prescribing tranexamic acid.

There are many other medicines which aren't recommended for use at the same time as estradiol and medroxyprogesterone, but in some cases, both medicines may still be prescribed if they are both deemed absolutely necessary. In these instances, your doctor may adjust dosages or the times at which you take the medicines in order to minimize harmful side effects or other complications. Always follow your doctor's instructions closely.

Medical interactions

You may not be able to have estradiol and medroxyprogesterone injections if you have any of the following medical conditions:

  • History of blood clot or stroke
  • Very high blood pressure
  • Heart valve disorder
  • Other heart problems, such as:
  • Heart disease
  • Congestive heart failure
  • Angina
  • Heart attack (history of)
  • Circulation problems
  • Breast, uterine or cervical cancer
  • Abnormal menstrual bleeding
  • Kidney disease
  • Liver disease or cancer
  • History of jaundice caused by birth control medicines
  • Seizures or epilepsy


Risk of worsening medical conditions

The following medical conditions may be worsened by combination contraceptives like estradiol and medroxyprogesterone:

  • Abnormal menstrual or uterine bleeding
  • Blood clots
  • Heart or circulation problems
  • High blood cholesterol
  • High blood pressure
  • Gallbladder disease
  • Gallstones
  • Liver disease
  • Mental health problems, such as depression and anxiety

If you have a history of these conditions, your doctor may recommend an alternative contraception method, or they may monitor you closely when you first begin estradiol and medroxyprogesterone injections.


There is evidence to suggest that hormonal contraceptives like estradiol and medroxyprogesterone can increase the risk of various cancers, particularly the following:

The risk of this is higher in patients who have had these types of cancer in the past, or who have a family history of these cancers. If you already have cancer, it is highly unlikely that your doctor will prescribe estradiol and medroxyprogesterone. If you are at a higher risk of cancer, your doctor may still prescribe estradiol and medroxyprogesterone but request more frequent cancer screenings.

You should tell your doctor if you have a history of the following, even if you have not been previously diagnosed with cancer:

  • Fibrocystic breast disease
  • Breast lumps
  • Nodules
  • Abnormal mammogram

Diabetic patients

Use of combination contraceptives like estradiol and medroxyprogesterone can cause an increase in blood sugar. Usually, this is only a very small amount and doesn't normally warrant an adjustment to diabetes medicine. However, diabetic patients should be vigilant in checking their blood sugar levels when they first start taking estradiol and medroxyprogesterone.

Migraine headaches

Sometimes combined contraceptives like estradiol and medroxyprogesterone can cause a build-up of fluid in the body which can worsen migraine headaches. In other instances, hormonal contraceptives can help to reduce migraine headaches. If you are susceptible to migraines and find that they become more frequent or more severe after you start estradiol and medroxyprogesterone injections, consult your doctor.


Estradiol and medroxyprogesterone is administered via injections by a doctor, nurse or other trained healthcare professional. Usually, this takes place in a doctor's office. For this reason, patients should not need to store estradiol and medroxyprogesterone at home.


Estradiol and medroxyprogesterone is a combined hormonal contraception which is administered by injection into the muscles. It works by inhibiting egg development to make it harder for sperm to fertilize eggs. It also increases cervical mucus and uterine lining to make it harder for sperm to reach the eggs and for fertilized eggs to attach to the uterus. All these effects help to prevent unwanted pregnancy.

Usually, 0.5 ml of estradiol and medroxyprogesterone is injected into the muscle of the upper arm or buttocks, once every month. The first injection should be given within the first five days of menstrual bleeding. Subsequent injections should be given once every 28 to 30 days. If there are more than 33 days between injections, doctors will need to check for pregnancy before administering another injection, usually by waiting for a menstrual period. In the interim, patients will have to have use barrier contraception to prevent pregnancy.

Estradiol and medroxyprogesterone is not suitable for people with a history of stroke, blood clots, very high blood pressure, liver disease, or abnormal menstrual bleeding. It shouldn't be administered at the same time as tranexamic acid, and may not be suitable for concurrent use with some antiviral medicines, antibiotics, and barbiturates.

The most common minor side effects associated with estradiol and medroxyprogesterone are a headache, missed menstrual periods, acne, nervousness, and breast swelling. Patients who experience extreme stomach pain, nausea, chest pain, or speech, vision or balance problems should consult a doctor immediately.