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hydroxyprogesterone

Generic Makena
Used for Uterine Cancer, Irregular Menstruation
Used for Uterine Cancer, Irregular Menstruation

Hydroxyprogesterone is an injection used to help regulate menstrual periods and treat uterine cancer. It's given as a shot into your buttocks muscle, and can cause pain or swelling at the injection site as a side effect.

Please note: As of April 2023, hydroxyprogesterone is no longer approved by the FDA to lower chance of pre-term labor.

Reviewed by:
reviewer
Allison Gourley, PharmD
reviewer
Connie Zheng, PharmD
Last reviewed on May 24, 2023
BasicsSide effectsPros & consPharmacist tipsFAQsWarningsDosageContraindicationsAlternativesLatest newsReferencesPricesMedicare
basics-icon

What is Hydroxyprogesterone?

What is Hydroxyprogesterone used for?

  • Lack of menstrual periods due to hormone imbalance

  • Irregular periods due to hormone imbalance

  • Advanced uterine cancer

  • Testing for natural estrogen production

How Hydroxyprogesterone works

Hydroxyprogesterone is a progestin that acts like the natural sex hormone progesterone. The progesterone levels in your body help regulate the lining of your uterus. By helping to balance your natural progesterone levels, hydroxyprogesterone regulates menstrual periods. In uterine cancer, the medication can help block the growth of cancerous cells of the uterine lining.

Are you looking for information on medroxyprogesterone (Provera) oral tablets or medroxyprogesterone (Depo-Provera) injection instead?

Drug Facts

Common BrandsMakena (brand no longer available)
Drug ClassProgestin
Controlled Substance ClassificationNot a controlled medication
Generic StatusLower-cost generic available
AvailabilityPrescription only
basics-icon

What are the side effects of Hydroxyprogesterone?

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

  • Pain where the medication was injected (35%)
  • Swelling where the medication was injected (17%)
  • Hives (12%)

Other Side Effects

  • Itchiness
  • Redness where the medication was injected
  • Nausea
  • Diarrhea

Serious Side Effects

Contact your healthcare provider immediately if you experience any of the following.
  • Allergic reactions
  • Blood clot: Sudden, severe pain and swelling in your leg or arm, chest pain, sudden, severe headaches, trouble breathing, sudden changes in your speech or vision

Source: DailyMed

More on Hydroxyprogesterone side effects

Hydroxyprogesterone: Side effects: pregnant parent uncomfy 1307895136

7 Hydroxyprogesterone Side Effects You Should Know About

Written by Sonja Jacobsen, PharmD, BCPS, BCOP
pros-and-cons

Pros and cons of Hydroxyprogesterone

thumbs-up

Pros

Only needs to be given once per menstrual cycle to treat irregular periods

Other than injection site discomfort, not many side effects

thumbs-down

Cons

Only available as an injection that must be given at your provider's office

Can't be used if you have liver problems

pharmacist-tips

Pharmacist tips for Hydroxyprogesterone

pharmacist

  • Hydroxyprogesterone has to be given by a trained healthcare provider. It's not safe to try to give yourself the injection at home.

    • Hydroxyprogesterone needs to be given on time in order to work properly, regardless of what condition you are using it for. Be sure to go to your injection appointments as instructed by your provider.

      • After your injection, contact your provider if you notice increased discomfort over time, oozing of blood or fluid, or inflammatory reactions at the injection site. This could be signs of an infection.

        • Make sure to tell your provider about your full medical history before starting treatment with hydroxyprogesterone, especially if you have a history of depression because this medication can make depression worse.

          • Sometimes, hydroxyprogesterone can cause you to experience a cough, tight chest, or trouble breathing. This is more likely to happen if your provider gives you a high dose. If you experience trouble breathing after your hydroxyprogesterone shot, call your provider right away.

            faqs

            Frequently asked questions about Hydroxyprogesterone

            Is hydroxyprogesterone FDA-approved to prevent preterm labor?
            No, Makena (hydroxyprogesterone) and its generics are no longer approved to prevent preterm labor as of April 2023. The FDA removed this use because the manufacturer of this medication wasn't able to show that it worked well to help newborns. Hydroxyprogesterone is still approved to help regulate menstrual periods and treat uterine cancer.
            Do hydroxyprogesterone shots make you gain weight?
            Hydroxyprogesterone can cause weight changes, meaning it can cause weight gain and weight loss. If you experience changes in your body weight after your hydroxyprogesterone shot, discuss your concerns with your provider.
            Can hydroxyprogesterone cause diabetes?
            Hydroxyprogesterone can raise your blood sugar levels. This can be dangerous, especially if you have diabetes. Because of this risk, your provider might have you check your blood sugar levels more often during hydroxyprogesterone therapy.
            Can hydroxyprogesterone cause birth defects?
            Research in people who received hydroxyprogesterone at 16 weeks of pregnancy or later show that it isn't likely to cause any serious birth defects. On the other hand, clinical trials suggest that though rare, hydroxyprogesterone might raise the risk of miscarriage compared with placebo. Keep in mind that hydroxyprogesterone is no longer approved for use in pregnancy to prevent early labor. If you've questions about hydroxyprogesterone and pregnancy, talk with your provider.
            Does hydroxyprogesterone cause blood clots?
            People who took progestins, like hydroxyprogesterone, have developed blood clots in different parts of the body, including the brain and lungs. Get medical help right away if you develop sudden, severe pain and swelling in your leg or arm, severe headaches, trouble breathing, or sudden changes in your speech or vision.
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            What are the risks and warnings for Hydroxyprogesterone?

            Hydroxyprogesterone 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.

            risk-warning

            Blood clots

            • Risk factors: Personal or family history of blood clots | High blood pressure | Diabetes | High cholesterol | Smoking | People who are overweight | Systemic lupus erythematosus (SLE)

              Hydroxyprogesterone can raise your risk of blood clots, which can be very dangerous. While there are several conditions that can raise this risk even further, smoking and a history of blood clots are two of the biggest risk factors. Be sure to discuss all your past and present medical conditions with your provider before starting hydroxyprogesterone. Call 911 or get immediate medical attention 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-warning

              High blood sugar

              • Risk factors: Diabetes | Pre-diabetes | Metabolic syndrome

                Hydroxyprogesterone can raise your blood sugar levels. If you are using this medication while pregnant, this raises your risk of developing diabetes during your pregnancy (gestational diabetes). If you have diabetes, hydroxyprogesterone makes it more difficult to control your blood sugar. Let your provider know if you have diabetes or any problems with your blood sugar levels before you start using this medication. You might need to monitor your blood sugar levels more often while using hydroxyprogesterone.

                risk-warning

                Fluid build-up

                • Risk factors: History of heart failure | History of kidney problems

                  Hydroxyprogesterone can cause extra fluid to build up in your body, especially in your legs, ankles, and feet. Fluid build-up is more likely to happen if you have certain conditions, like heart failure or kidney problems. If you know you have problems with fluid build-up or swelling, tell your provider before you start using hydroxyprogesterone. Call your provider or seek medical help right away if you notice unexplainable swelling, quick weight gain (more than 3 pounds in a day or 5 pounds in a week), or sudden trouble breathing.

                  risk-warning

                  Allergic reactions

                  Allergic reactions to hydroxyprogesterone are possible, including life-threatening problems like anaphylaxis or airway swelling. Call 911 if this happens. If you notice hives, a rash, swelling of the lips or tongue, or difficulty breathing after receiving your dose of hydroxyprogesterone, get medical help right away.

                  dosage

                  Hydroxyprogesterone dosage forms

                  Typical dosing for Hydroxyprogesterone

                  • Lack of or irregular menstrual periods:

                    • Single dose treatment or cyclic therapy (taking estrogen therapy): Your provider will inject 375 mg into your buttock muscle one time.

                    • Cyclic therapy (not taking estrogen therapy): Your provider will inject 250 mg into your buttock muscle on day 15 of the 28-day cycle planned by you and your provider. As part of treatment, provider will also give you estradiol valerate (Delestrogen) on different days of the cycle.

                  • Advanced uterine cancer: Your provider will inject 1,000 mg into your buttock muscle one or more times a week. Use no more 7,000 mg per week.

                  • Testing for estrogen production: Your provider will inject 250 mg into your buttock muscle one time. If your body produces estrogen, you can expect a menstrual period 7 to 14 days after the injection. Your provider can order another injection 28 days later if needed.

                  contraindications-icon

                  Hydroxyprogesterone 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 Hydroxyprogesterone will not be safe for you to take.

                  • Current or history of blood clots

                  • Known, suspected, or history of breast cancer or other hormone-sensitive cancer

                  • Undiagnosed abnormal vaginal bleeding unrelated to pregnancy

                  • Past pregnancy where the unborn baby stopped developing (missed abortion)

                  • Liver problems or liver tumors

                  alternatives

                  What are alternatives to Hydroxyprogesterone?

                  There are a number of medications that your doctor can prescribe in place of Hydroxyprogesterone. Compare a few possible alternatives below.
                  Hydroxyprogesterone
                  Used for:

                  • Lack of menstrual periods due to hormone imbalance

                  • Irregular periods due to hormone imbalance

                  • Advanced uterine cancer

                  • Testing for natural estrogen production

                  View Prices
                  Medroxyprogesterone (Provera)
                  Used for:

                  • Lack of menstrual periods due to hormone imbalance

                  • Irregular periods due to hormone imbalance

                  • Protection of the uterus in postmenopausal women who are taking estrogen medications

                  $6.58 Lowest GoodRx priceView Prices
                  Progesterone
                  Used for:
                  $14.10 Lowest GoodRx priceView Prices

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                  References

                  Best studies we found

                  AMAG Pharmaceuticals, Inc. (2022). MAKENA- hydroxyprogesterone caproate injection [package insert]. DailyMed.

                  AuroMedics Pharma LLC. (2022). HYDROXYPROGESTERONE CAPROATE injection [package insert]. DailyMed.

                  AuroMedics Pharma LLC. (2022). PROGESTERONE injection, solution [package insert]. DailyMed.

                  View All References (5)

                  Harris, E. (2023). FDA revokes approval for preterm birth drug Makena. Journal of the American Medical Association.

                  National Cancer Institute Thesaurus. (n.d.). Hydroxyprogesterone caproate. National Cancer Institute.

                  Prasco Laboratories. (2023). HYDROXYPROGESTERONE CAPROATE- hydroxyprogesterone caproate injection [package insert]. DailyMed.

                  U.S. Food and Drug Administration. (2023). FDA commissioner and chief scientist announce decision to withdraw approval of Makena.

                  Vidaeff, A. C., et al. (2013). Critical appraisal of the efficacy, safety, and patient acceptability of hydroxyprogesterone caproate injection to reduce the risk of preterm birth. Patient Preference and Adherence.

                  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.
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