Podcast Summary: Dr. Chapa’s OBGYN Clinical Pearls

Episode: WARNING: DepoP and Meningiomas
Date: December 18, 2025
Host: Dr. Chapa

Overview

In this episode, Dr. Chapa addresses the evolving evidence connecting Depo Provera (medroxyprogesterone acetate), a widely used injectable contraceptive, with the risk of developing meningiomas—benign, but occasionally aggressive, primary brain tumors. Prompted by the FDA’s new decision to require a warning label for Depo Provera, Dr. Chapa reviews existing research, explains the biological plausibility, and provides guidance for clinicians and patients in light of these developments.

Key Discussion Points

1. Background on Depo Provera and Meningiomas

• Depo Provera: Approved in 1992, used by about 1 in 4 sexually active women in the US at some point ([00:39]).
• Meningiomas: Most common type of primary brain tumor in women, largely benign (Grade 1 in 80-85%), with a small percentage behaving atypically or malignantly ([00:48]).

2. Recent Regulatory Changes

• FDA previously denied the label warning due to reliance on observational data ([02:23]).
• December 17, 2025: FDA follows Europe and Canada’s lead and mandates a warning about meningioma risk on Depo Provera packaging ([05:29]).
  • “Regulators through the FDA said, yeah, we need to follow what other countries have already done.” ([05:29])

3. Review of Key Research Findings

ACOG’s Position ([04:44])

• Association found between medroxyprogesterone acetate and meningiomas, but absolute risk remains low.
• French study:
  • 5/10,000 Depo users vs. 1/10,000 non-users developed meningioma.
  • "That is a 5 fold increase, even though relative risk is different than absolute number." ([05:07])
• “It’s important to interpret the results of this study with caution...”
• There’s still a difference between association and causation ([06:01]).

Three Major Population-Based Studies

• 2025 US Cohort Study (JAMA Neurology) ([08:36])
  • Relative risk: 2.43 (95% CI: 1.7-3.3)—narrow, and suggests increased risk, but lower confidence interval includes 1.
• Swedish Registry Study
  • Odds ratio: 5.49 (CI: 4.5 - 6.6)—narrow and well above 1; strongly suggests association ([09:11]).
• French Case-Control Study
  • Odds ratio: 5.0 (CI: 2.2 - 13.56)—association, but wide interval reduces precision ([09:44]).
• Takeaway: All studies suggest association, not causation; absolute risk is low but relative risk is elevated ([10:23]).

Important Risk Modifiers ([10:45])

• Risk is related to prolonged use (more than 4 years) or initiation over age 31.
• Not a concern with a single or short-term dose.
• "Both of those things seem to matter here. And I would tell patients that the absolute risk still remains low." ([11:22])

4. Practical Recommendations ([10:23], [11:29])

• Continued access to birth control is vital.
• Consider alternative contraceptives—Depo is elective, and patients (especially adolescents) can opt for others if concerned.
• Best practice: Use Depo for the shortest time possible and ideally before age 31.
• “If you’re going to use depo, knock yourself out. But try to use it for the shortest amount of time possible, and try to start that under the age of 31, because those seem to be the two big qualifying risk factors here.” ([10:45])
• Always share absolute risk numbers with patients for context.

5. Biological Plausibility ([15:21])

• Meningiomas express progesterone receptors: 75% have progesterone receptors, providing a mechanism for potential influence by progestins.
  • “Yes, meningiomas like them some progesterone, okay?” ([15:24])
• Some tumors show regression or decreased size after stopping Depo use ([15:44]).
• Data point to a dose-response relationship: biggest risks with contraceptive (IM or subQ) doses of medroxyprogesterone acetate ([16:01]).

Specificity of Risk

• Applies only to Depo Provera in IM or subQ forms.
• Does NOT apply to:
  • Oral medroxyprogesterone acetate (no significant risk found: odds ratio close to 1)
  • Combined oral contraceptives
  • Etonogestrel implants
  • Intrauterine systems ([17:06])
• “This is strictly for Depo Provera as either IM or the sub Q form. This is only for Depo Provera in the IM or sub Q form, not oral Provera, not IUDs, not combined birth control pills and not the etonorgestrel implant.” ([17:06])

6. Clinical Communication & Counseling ([10:23], [17:48])

• Foster shared decision-making: inform patients honestly, explain the difference between relative and absolute risk.
• Do not sensationalize or “freak patients out”; provide balanced context.
• “For a long time, there was an association between tobacco smoking and lung cancer… And now, of course, we know that it's not just an association… it is a true causation.” ([11:54])
• “Don’t send me an ugly message… I get it. These are associations. But after a while you have to say, man, there’s a lot here.” ([15:14])

7. Summary Points ([17:41])

• Risk is important but low in absolute numbers.
• Use alternatives when possible, especially in high-risk groups (long-term use, age >31).
• The new FDA label change is a significant shift aligning the US with other Western countries.

Notable Quotes & Timestamps

• On new FDA label change:
  "This is a very, very big deal. As the association, as the data continues to build against Depo Provera, this association is pretty scary." — Dr. Chapa ([01:31])

• On risk communication:
  “Good birth control is super important. Number two, it's all elective. It's birth control. Pick something else.” ([07:53])

• Explaining relative vs. absolute risk:
  "That is a 5 fold increase even though relative risk is different than absolute number." ([05:07])

• On biological plausibility:
  “Meningiomas like them some progesterone, okay? So they've got little progesterone towers. And so these things go nuts. 75% of meningiomas express progesterone receptors.” ([15:24])

• Clarification for clinical application:
  “This is strictly for Depo Provera as either IM or the sub Q form, not oral Provera, not IUDs, not combined birth control pills and not the etonorgestrel implant.” ([17:06])

Key Timestamps

• [00:39] - Background on Depo Provera and meningiomas
• [04:44] - ACOG’s statement & French study data
• [08:36] - US cohort study (2025, JAMA Neurology)
• [09:11] - Swedish registry findings
• [09:44] - French case-control study
• [10:45] - Practical guidance for patient counseling
• [11:54] - Association vs causation (cigarette lung cancer analogy)
• [15:14] - Biological plausibility and receptor expression
• [16:01] - Dose-response relationship and why route matters
• [17:06] - What the risk does and doesn’t apply to

Conclusion

Dr. Chapa urges clinicians to stay updated, practice shared decision-making, and appropriately balance the real-but-rare risks of Depo Provera against its benefits and alternatives. The episode contextualizes the new FDA warning, emphasizing clarity, cautious interpretation of evolving evidence, and prioritizing patient-centered care.