10 Depo-Provera Side Effects to Consider: Weight Gain, Headaches, and More

With so many options for birth control (contraception), choosing one can be overwhelming. If you’re looking for longer-acting birth control, you may consider Depo-Provera (medroxyprogesterone acetate), an injection that’s given every 3 months.

Before getting started, it’s good to know about potential side effects. Most Depo-Provera side effects, such as menstruation changes and headaches, are possible with all hormonal birth control methods. But Depo-Provera has a long-term risk that other contraceptives don’t: bone density loss.

Depo-Provera side effects at a glance

Depo-Provera (also called “the Depo shot”) is a progestin-only contraceptive. Most of its side effects are mild and similar to other birth control methods that contain hormones. They often get better or go away as your body adjusts to the medication.

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Common Depo-Provera side effects include:

• Irregular or no menstruation

• Breakthrough bleeding or spotting

• Weight gain

• Fluid retention or bloating

• Headaches

• Abdominal (stomach) pain

• Low libido (sex drive)

• Breast tenderness

• Acne

• Changes in vaginal discharge

• Injection site reactions

• Nausea

• Dizziness

• Back pain

• Joint pain

• Leg cramps

• Menstrual cramps

• Nervousness

• Fatigue

• Trouble sleeping

• Weakness

• Hair loss

• Vaginal discomfort or pain

• Hot flashes

Rare but serious Depo-Provera side effects include:

• Heart attack

• Allergic reactions

• Stroke

• Blood clots

• Mood changes, including new or worsening depression

• Higher risk of certain cancers

• Seizures

Depo-Provera also has a boxed warning for bone density loss. This is the FDA’s most serious warning for medications. While rare, this side effect can raise your risk of bone fractures (breaks).

Below, we’ll discuss 10 Depo-Provera side effects in more detail.

1. Menstruation changes

It's common to experience changes in menstruation with Depo-Provera. This is especially noticeable in the first year after starting it.

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• Other long-term risks: Bone density loss is one of Depo-Provera’s more serious risks. Learn more about other long-term side effects of birth control.

• Getting birth control without an office visit: There are several ways to access effective birth control without going in to see a healthcare professional. Read about the options in your area.

• The cost of Depo-Provera: Find out how much Depo-Provera costs without insurance — plus ways to save.

You may experience lighter menstruation or even no menstruation at all. But heavier bleeding is possible, too. It’s also common for bleeding to be irregular and for spotting to happen.

It’s perfectly safe not to menstruate if you’re using Depo-Provera. In fact, you may be considering the birth control shot because of this side effect. But if menstruation changes seem bothersome or make you uncomfortable, let your prescriber know. They may suggest a different birth control method.

2. Weight gain

Weight gain is a common Depo-Provera side effect. In fact, nearly 38% of clinical trial participants reported gaining at least 10 lbs after 2 years of receiving the shot.

Some people also experience bloating and fluid retention while using Depo-Provera. This can contribute to weight gain. But fluid retention typically happens shortly after starting hormonal contraception. It usually lessens or resolves as your body adjusts to the medication.

While the shot may contribute to weight gain, eating a balanced diet and exercising regularly may help minimize it. If you’re concerned about gaining weight with Depo-Provera, talk with your healthcare team.

3. Headaches

Headaches are another common Depo-Provera side effect. And they’re possible with all hormonal birth control methods. Headaches are most common during the first 2 to 3 months of starting a new hormonal contraceptive. They should lessen or stop as your body gets used to the medication.

If headaches persist for more than a few months, seem to get worse, or are severe, talk to your healthcare team. Depo-Provera may not be the right birth control method for you.

4. Low libido

Low libido is another common Depo-Provera side effect. But it happens less frequently than those discussed above. Low libido can be concerning and impact your relationships and quality of life.

If you’ve noticed a change in your libido since starting Depo-Provera, contact your prescriber. They may suggest a different birth control method. They may also recommend certain lifestyle changes, such as dedicating time for sex and intimacy, that can help support your overall sexual health.

5. Breast tenderness

Breast tenderness or pain is another possible Depo-Provera side effect. This is more likely to happen in the first few months after starting it. Breast discomfort is usually mild and should fade with time.

Wearing bras without underwire and looser fitting shirts may be more comfortable until breast tenderness improves. You can also ask a healthcare professional about taking an over-the-counter (OTC) pain reliever, such as ibuprofen (Advil, Motrin). Occasional use of these medications can help relieve this discomfort.

If breast pain seems severe or you notice lumps in your breasts, contact your healthcare team right away. These are not typical Depo-Provera side effects and can indicate that something more serious is going on.

6. Acne

While some forms of hormonal birth control can help with acne, Depo-Provera may make it worse. The progestin in the shot (medroxyprogesterone) can act like testosterone in the body. This can lead to certain side effects, including acne.

Acne from Depo-Provera can usually be managed with OTC acne treatments. Your healthcare team can help recommend one for you. But if your acne is too bothersome, let your prescriber know. They may recommend another birth control method that has a lower risk of acne.

7. Discharge changes

Changes in vaginal discharge are a less common Depo-Provera side effect. You may notice a change in the color, consistency, or amount of discharge. This isn’t usually something to be worried about. But wearing panty liners may help you feel more comfortable.

If your discharge has an odor or a cottage cheese consistency, let your primary care provider know. This isn’t an expected side effect of Depo-Provera. And it could mean you have a yeast infection or bacterial vaginosis.

8. Injection site reactions

Injection site reactions can happen where you received your Depo-Provera shot. Symptoms include redness, swelling, and pain. They typically last about 1 to 2 days and will go away on their own without any treatment. Taking OTC pain relievers and applying ice packs to the area can help lessen discomfort.

If symptoms get worse or spread to other parts of your body, contact your prescriber right away. These could be signs of a potential allergic reaction. If you experience trouble breathing or swelling of your face, lips, or throat, call 911. These are symptoms of a life-threatening reaction and require immediate care.

9. Mood changes

Mood changes are a serious Depo-Provera side effect. Some women using hormonal birth control have reported changes in mood, including new or worsening depression symptoms. But the evidence regarding how much birth control contributes to depression is mixed. Some studies have found no link between hormonal contraception and depression, while others have found one.

If you have a history of depression, let your prescriber know before you start Depo-Provera.  And if you notice any unusual changes in your mood or behavior after starting it, contact your healthcare team right away.

For additional resources or to connect with mental health services in your area, call SAMHSA’s National Helpline at 1-800-662-4357. For immediate assistance, call the National Suicide Prevention Lifeline at 988, or text “HOME” to 741-741 to reach the Crisis Text Line.

10. Bone density loss

Depo-Provera’s label has a boxed warning about the potential for bone density loss. Bone density, or bone mineral density (BMD), is a measurement of the amount of certain minerals in your bones. Healthcare professionals use BMD as a snapshot of how strong your bones are. It can also help identify your risk for bone fractures.

The risk of lower BMD is a long-term Depo-Provera side effect. But studies suggest this is likely reversible if you’ve used the birth control shot for fewer than 2 years. After that point, there’s a risk that BMD loss may be permanent or only partially reversible. This could raise your risk of developing osteoporosis or experiencing fractures.

To help lower your risk of this serious Depo-Provera side effect, it’s recommended to limit your use of the shot to under 2 years. But there are times where the benefits of long-term use may outweigh these risks.

It’s important to discuss your personal risks for this side effect with your prescriber. They can help you weigh the pros and cons and determine how long you should continue using Depo-Provera.

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Written by:

Kristine Foley, PharmD

Kristine Foley is a licensed pharmacist with over 13 years of community pharmacy experience. She earned her Doctor of Pharmacy degree from Rutgers University.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Bailey E. Eason, PharmD, MS, BCPS

Bailey Eason has been licensed for 6 years and has held licenses in three states (North Carolina, Virginia, and Illinois). She has held positions as a health-system pharmacy administration resident, operating room pharmacy manager, pharmacy manager of clinical operations: surgery, neurology and controlled substances, and most recently as program director  of drug diversion for a large academic health system.

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