What are the contraindications for Depoprovera (medroxyprogesterone acetate)?

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Last updated: November 3, 2025View editorial policy

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Contraindications for Depo-Provera

Depo-Provera (medroxyprogesterone acetate) is absolutely contraindicated in patients with active thrombophlebitis, current or history of thromboembolic disorders, cerebral vascular disease, known or suspected breast malignancy, known hypersensitivity to the medication or its ingredients, significant liver disease, and undiagnosed vaginal bleeding. 1

Absolute Contraindications

The FDA drug label clearly defines the following as absolute contraindications:

  • Thromboembolic conditions: Active thrombophlebitis, current or history of thromboembolic disorders, or cerebral vascular disease 1

  • Breast malignancy: Known or suspected malignancy of breast 1

  • Hypersensitivity: Known hypersensitivity to medroxyprogesterone acetate or any of its ingredients 1

  • Liver disease: Significant liver disease 1

  • Undiagnosed vaginal bleeding: Any undiagnosed vaginal bleeding 1

Additional Important Contraindications from Clinical Guidelines

Beyond the FDA-labeled absolute contraindications, NCCN guidelines identify additional clinical scenarios where medroxyprogesterone should be carefully considered or avoided:

  • History of stroke or myocardial infarction: These cardiovascular events are listed as contraindications in the context of progestin-based therapy 2

  • Pulmonary embolism or deep vein thrombosis: History of these thromboembolic events contraindicates use 2

  • Active smoking: Smoking is identified as a contraindication, particularly when combined with other risk factors 2

  • Neurofibromas or meningiomas: Depo-Provera should generally be avoided in individuals with a history of these tumors due to evidence suggesting it may stimulate tumor growth, particularly with high-dose depot injections 3

Critical Clinical Considerations

Pregnancy must be excluded before administration: The first injection should be given only during the first 5 days of a normal menstrual period or within the first 5 days postpartum 1

  • In exclusively breastfeeding postpartum mothers, administer during or after the sixth postpartum week 1

  • If the interval between injections exceeds 13 weeks, pregnancy must be ruled out before the next dose 1

Long-term use limitations: Use for longer than 2 years is not recommended unless other birth control methods are considered inadequate, due to significant bone mineral density loss 1

Common Pitfall to Avoid

Do not assume all progestin-based contraceptives carry equal contraindications—depot formulations like Depo-Provera appear to pose greater risks for certain conditions (such as neuro tumors) compared to oral contraceptives or IUDs 3. The high-dose depot formulation is specifically problematic for patients with progesterone receptor-positive tumors 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Depo Provera Safety in Patients with Neuro Tumors

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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