What are the dangers of Depo-Provera?

October 9, 2025 •

3 min read

Depo-Provera's use is associated with significant loss of bone mineral density (BMD), a concern that led the FDA to issue its strongest 'black box' warning. Understanding what are the dangers of Depo-Provera is crucial for anyone considering this contraceptive method.

Quick Summary

An in-depth look at the health risks and side effects associated with the Depo-Provera injection. It covers the FDA black box warning, bone density loss, weight gain, effects on mood, and potential long-term complications.

Key Points

FDA Black Box Warning: Depo-Provera has the FDA's strongest warning due to the risk of significant, and potentially irreversible, bone density loss.
Use Limitation: It is recommended not to use Depo-Provera for longer than two years unless other birth control methods are inadequate.
Weight Gain: Significant weight gain is a common side effect, with studies showing an average gain of 5-8 pounds in the first two years.
Delayed Fertility: Return to fertility can be significantly delayed after stopping the shot, with a median time to conception of 10 months or more.
Menstrual Changes: Irregular bleeding, spotting, or the complete absence of periods (amenorrhea) are very common side effects.
Serious Health Risks: Beyond bone loss, potential dangers include an increased risk of blood clots, depression, and a possible link to certain tumors.
Contraindications: It should not be used by individuals with a history of breast cancer, liver disease, or thromboembolic disorders.

The FDA Black Box Warning: Bone Density Loss

The primary danger highlighted by the FDA is a significant loss of bone mineral density (BMD) with prolonged use. This loss increases with duration of use and may not fully reverse after stopping. This is particularly concerning for young people who are still building bone mass. The FDA advises against using Depo-Provera long-term (over two years) unless other options are unsuitable. Studies show BMD losses of 5.7–7.5% after two years, with incomplete recovery in some areas after discontinuation.

Who is at Higher Risk?

Individuals with existing osteoporosis risk factors, such as family history, alcohol or tobacco use, anorexia, or use of certain medications, should exercise extra caution and discuss alternatives with their healthcare provider.

Common and Serious Side Effects

Depo-Provera is associated with a range of side effects.

Common Side Effects

Frequent side effects, which may improve over time, include:

Menstrual Irregularities: This is very common and can involve irregular bleeding, spotting, or the absence of periods. Amenorrhea occurs in about 55% of users after a year.
Weight Gain: Many users gain weight, with averages of about 5 pounds in the first year and 8 pounds over two years. Some reports indicate an average gain of 16.5 pounds by year six.
Headaches: Headaches are reported by up to 16.5% of users.
Mood Changes: Nervousness, anxiety, and depression are possible side effects.
Other common issues: Abdominal pain, bloating, dizziness, weakness, fatigue, and decreased libido are also common.

Serious Health Risks

More severe potential dangers include:

Blood Clots: Serious events like deep vein thrombosis and pulmonary embolism have been reported. Those with a history of blood clots should avoid Depo-Provera.
Cancer Risk: Some studies suggest a slightly increased risk of breast cancer in recent users, but long-term studies haven't shown an overall increased risk of ovarian or liver cancer.
Brain Tumors (Meningioma): Research indicates a possible link between long-term use and meningioma.
Delayed Return of Fertility: It can take time to become pregnant after stopping. The median time to conception is about 10 months after the last shot.

Comparison with Other Contraceptive Methods

Considering the risks of different birth control options is important.


Method	Primary Risks	Reversibility/Fertility Return
Depo-Provera	Bone density loss (FDA black box warning), weight gain, delayed return to fertility, potential increased risk of blood clots and certain tumors.	Can be delayed; median of 10 months or more.
Combination Pills	Increased risk of blood clots, heart attack, and stroke, especially in smokers and those with certain health conditions. Breast tenderness, headaches, nausea.	Fertility typically returns quickly, within 1-3 months.
Hormonal IUDs (e.g., Mirena)	Device migration or perforation of the uterus (rare), ovarian cysts, irregular bleeding patterns. Some legal challenges link it to pseudotumor cerebri.	Immediately reversible upon removal.
Copper IUD (Non-hormonal)	Heavier or longer periods, increased cramping, especially initially. Risk of pelvic inflammatory disease (PID) if an STI is present during insertion.	Immediately reversible upon removal.

Contraindications: Who Should Avoid Depo-Provera?

Depo-Provera is not suitable for everyone. It should be avoided by individuals with certain medical conditions:

Known or suspected pregnancy
Current or past history of breast cancer
Significant liver disease
Undiagnosed vaginal bleeding
Active thrombophlebitis or a current or past history of thromboembolic disorders (blood clots), stroke, or heart attack

Conclusion

Depo-Provera is an effective contraceptive, but its dangers are significant and documented. The most serious concern is the FDA's black box warning regarding bone density loss, especially for long-term and younger users. Other dangers include substantial weight gain, mood changes, delayed fertility return, and risks of blood clots and cancer. A thorough discussion with a healthcare provider is essential before using or continuing this medication, particularly for longer than two years.

Authoritative Link: Depo-Provera (birth control shot) - Mayo Clinic

Frequently Asked Questions

The most serious danger is the significant loss of bone mineral density (BMD), which prompted the FDA to issue a 'black box' warning. This bone loss increases with prolonged use and may not be completely reversible, potentially leading to osteoporosis and an increased risk of fractures later in life.

Weight gain is a common side effect. Studies show an average gain of about 5.4 pounds in the first year and 8.1 pounds after two years. By year six, the average weight gain can be around 16.5 pounds.

Due to the risk of significant bone density loss, the FDA and manufacturers recommend that Depo-Provera not be used for longer than two years unless other forms of contraception are considered inadequate.

There is often a significant delay in the return of fertility. The median time to conception for those who do get pregnant is 10 months after the last injection, with a range of 4 to 31 months. It can take up to 18 months for 93% of those who wish to conceive to do so.

Yes, changes in menstrual bleeding are the most common side effect. This can include irregular bleeding, spotting between periods, or your periods stopping altogether (amenorrhea). After a year of use, over half of women may stop getting their period.

You should not use Depo-Provera if you are pregnant, have a history of breast cancer, significant liver disease, undiagnosed abnormal vaginal bleeding, or a history of blood clots, stroke, or heart attack.

While some recovery of bone mineral density (BMD) does occur after stopping Depo-Provera, the loss may not be completely reversible, especially in the hip and femoral neck for those who used it for two years or more.