Short answer: Depo-Provera CI has a boxed warning: it can cause significant bone mineral density loss that may not fully reverse. In the label's trials of over 3,900 women, the most common side effects were irregular bleeding (57.3% at 12 months), no periods (55% at 12 months, 68% at 24), weight gain over 10 lb at 24 months (37.7%), headache (16.5%), abdominal pain (11.2%) and nervousness (10.8%).
What Depo-Provera CI is approved for: Depo-Provera CI is a birth control shot approved to prevent pregnancy in females of reproductive potential (section 1). The label does not recommend it as a long-term method (longer than 2 years) unless other options are considered inadequate.
Source
DEPO-PROVERA CI (medroxyprogesterone acetate) injectable suspension, for intramuscular use, prescribing information and Patient Information. Pfizer (Pharmacia & Upjohn). DailyMed, version published August 28, 2026. DailyMed setid 199cf13e-0859-4a73-9b45-e700d0cd1049
WARNING: LOSS OF BONE MINERAL DENSITY
Women who use Depo-Provera CI may lose significant bone mineral density. Bone loss is greater the longer it is used and may not be completely reversible. It is unknown whether use during adolescence or early adulthood, a critical time for building bone, will lower peak bone mass and raise the risk of osteoporotic fracture later in life. Depo-Provera CI is not recommended as a long-term (longer than 2 years) birth control method unless other options are considered inadequate (Boxed Warning and section 5.1).
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Depo-Provera CI.
| Adverse reaction | Incidence (%) |
|---|---|
| Menstrual irregularities: bleeding | 57.3% at 12 months, 32.1% at 24 months |
| Menstrual irregularities: amenorrhea | 55% at 12 months, 68% at 24 months |
| Increased weight >10 lb at 24 months | 37.7% |
| Headache | 16.5% |
| Abdominal pain/discomfort | 11.2% |
| Nervousness | 10.8% |
| Dizziness | 5.6% |
| Libido decreased | 5.5% |
Two clinical trials, over 3,900 women aged 15 to 51, 150 mg every 3 months for up to 7 years (median 13 months). The label says these may or may not be related to the drug. There is no placebo column.
| Adverse reaction | Incidence (%) |
|---|---|
| Asthenia/fatigue | 4.2% |
| Leg cramps | 3.7% |
| Nausea | 3.3% |
| Leukorrhea | 2.9% |
| Breast pain | 2.8% |
| Bloating | 2.3% |
| Backache | 2.2% |
| Edema | 2.2% |
| Dysmenorrhea | 1.7% |
| Depression | 1.5% |
| Acne | 1.2% |
| Vaginitis | 1.2% |
| No hair growth/alopecia | 1.1% |
| Rash | 1.1% |
| Hot flashes | 1.0% |
| Arthralgia | 1.0% |
| Insomnia | 1.0% |
| Time on Depo-Provera CI | Average weight gain |
|---|---|
| 1 year | 5.4 lb |
| 2 years | 8.1 lb |
| 4 years | 13.8 lb |
| 6 years | 16.5 lb |
Reactions that led at least 2% to leave the trials: bleeding (8.2%), amenorrhea (2.1%) and weight gain (2.0%). In a large trial, 2% withdrew because of excessive weight gain (section 5.12).
Return of fertility is likely to be delayed. Of women who stopped to become pregnant and conceived, 68% may conceive within 12 months, 83% within 15 months and 93% within 18 months of the last injection. The median time to conception was 10 months (range 4 to 31), unrelated to how long it was used.
In a US study, recent users (last use within five years) who used it for 12 months or longer had a statistically significant increase in breast cancer risk. The label says a doubling of risk would take breast cancer in women aged 20 to 49 from about 72 to about 144 cases per 100,000.
Reported after approval: osteoporosis including fractures; injection site abscess, infection, lumps, pain and lasting skin dimpling; blood clots including deep vein thrombosis and pulmonary embolus; allergic reactions including angioedema; lack of return to fertility; and others listed in Table 3.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Who should not use it. Depo-Provera CI is not used with active vein inflammation or a current or past blood clot disorder or cerebrovascular disease, known or suspected breast cancer, allergy to medroxyprogesterone acetate or its ingredients, significant liver disease, or undiagnosed vaginal bleeding.
Loss of bone mineral density. It lowers estrogen and is linked to significant bone loss. In adolescents who used it for more than 2 years, hip bone density had not fully recovered 5 years after stopping; in adults, recovery after 2 years was partial. Bone density is checked when long-term use is needed.
Blood clots. Serious clotting events have been reported, though it has not been shown to cause them. It is not given again pending an eye exam after sudden vision loss, bulging eyes, double vision or migraine.
Cancer risks. People with current or past breast cancer do not use it. Some studies suggest a slightly higher breast cancer risk, especially in recent users of 12 months or more. A nonsignificant rise in cervical cancer risk was seen with first use before 35. No overall rise in ovarian or liver cancer was found.
Meningioma. Meningiomas (brain tumors that are usually benign) have been reported after repeated use, mainly long-term. It is stopped if one is diagnosed.
Ectopic pregnancy. Prescribers are alert to ectopic pregnancy in users who become pregnant or have severe abdominal pain.
Anaphylaxis. Severe allergic reactions have been reported and need emergency treatment.
Injection site reactions. Lasting injection site reactions can happen if the drug ends up under the skin instead of in the muscle.
Liver. It is stopped if jaundice or liver problems develop, and not restarted until liver tests are normal and the drug is ruled out as the cause.
Depression. People with a history of depression are monitored, and it is not given again if depression returns.
Bleeding changes. Most users have disrupted bleeding patterns: no periods, irregular bleeding or spotting, prolonged bleeding or heavy bleeding. With longer use, fewer have irregular bleeding and more have no periods.
Blood sugar. Lower glucose tolerance has been seen in some users, so people with diabetes are monitored carefully.
No STI protection. It does not protect against HIV or other sexually transmitted infections.
From the Patient Information that comes with Depo-Provera CI:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.