Navigating Thrombotic Risk in Family Planning Decisions
Imagine being one of the millions of women worldwide who faces a painful dilemma every month: endure debilitating migraine attacks with visual disturbances, or risk potentially life-threatening blood clots from your birth control. This is the reality for countless women with migraine with aura (MA) who seek effective contraception.
For decades, doctors have wrestled with a complex question: do the newest combined hormonal contraceptives pose significant thrombotic risks for these women?
The controversy dates back to the 1960s when high-dose contraceptive pills first raised safety concerns. Today, despite modern formulations containing much lower hormone doses, uncertainty persists in exam rooms and research labs alike. Understanding this risk isn't just about avoiding potential harm—it's about empowering women with accurate information to make confident choices about their reproductive health.
This article explores the delicate balance between providing effective contraception and minimizing thrombotic risk for women with migraine with aura. We'll examine the latest research, break down a landmark study, and help you understand what science currently says about this complex medical decision.
A neurological condition with sensory disturbances preceding headaches.
Medications containing estrogen and progestin to prevent pregnancy.
How contraceptives affect blood clotting and increase stroke risk.
Migraine with aura is more than just a severe headache—it's a complex neurological condition characterized by temporary sensory disturbances that typically occur before the headache phase. These aura symptoms can include:
According to the International Classification of Headache Disorders, these symptoms must develop gradually over at least five minutes and last between 5-60 minutes 6 . Importantly, migraine with aura carries a twofold increased risk of ischemic stroke compared to migraine without aura, though the absolute risk remains small in otherwise healthy young women 6 .
Combined hormonal contraceptives (CHCs) contain both estrogen and progestin components. When first introduced in the 1960s, these medications contained high estrogen doses—up to 150 micrograms of mestranol. Today's formulations are dramatically different, with many containing 20 micrograms or less of ethinyl estradiol 6 .
High-dose estrogen formulations (up to 150μg mestranol) with significant side effects.
Lower estrogen doses and introduction of levonorgestrel as progestin component.
New progestins like desogestrel and gestodene with different risk profiles.
Ultra-low dose estrogen (≤20μg) and newer progestins like drospirenone.
Estrogen in combined contraceptives affects the coagulation system through several mechanisms. It increases levels of procoagulant factors (II, VII, VIII, and X) while decreasing natural anticoagulants (antithrombin and protein S) 1 . This creates a state of increased coagulability, particularly concerning for women who may already have elevated vascular risk due to migraine with aura.
The thrombotic risk is influenced by estrogen dose, progestin type, delivery method, and treatment duration. Oral progestin-only contraceptives carry minimal to no thrombotic risk, while transdermal, vaginal, and intrauterine options need further study 1 .
In 2025, researchers conducted a groundbreaking nationwide cohort study in Denmark to examine VTE risk across contemporary hormonal contraceptives 3 . Their approach leveraged comprehensive national registries, creating an unprecedented opportunity to analyze real-world data.
The study included 1.4 million females aged 15-49 years followed for over 8.4 million person-years—an exceptionally large sample size that provides substantial statistical power. Researchers excluded women with a history of thrombosis, cancer, thrombophilia, or other major health conditions that might confound results.
1.4 million participants
8.4 million person-years of follow-up
2,691 VTE events recorded
The findings revealed striking differences in VTE risk across contraceptive types. Compared to non-users of hormonal contraception, women using combined pills had a fivefold increased risk of VTE, with variations based on specific formulations 3 .
Data adapted from 3
| Contraceptive Method | Standardized Incidence Rate (per 10,000 person-years) | Adjusted Incidence Rate Ratio (vs. non-users) |
|---|---|---|
| No hormonal contraception | 2.0 | Reference (1.0) |
| Combined pills | 10.0 | 5.4 |
| Vaginal ring | 8.0 | 4.5 |
| Patch | 8.1 | 4.5 |
| Progestin-only pill | 3.6 | 2.5 |
| Intrauterine device (IUD) | 2.1 | 1.4 |
| Implant | 3.4 | 2.1 |
| Injection | 11.9 | 5.1 |
The Danish study confirmed that all combined hormonal contraceptives increase VTE risk, but the magnitude varies substantially by formulation. The highest risks were associated with injectable contraceptives and combined pills containing certain progestins.
When examining estrogen dose, researchers found that 20μg estrogen formulations generally carried lower risk than 30-40μg formulations, though the progestin type remained an important determinant. For example, a 20μg ethinyl estradiol/levonorgestrel pill showed significantly lower risk (IRR: 2.5) than a 20μg ethinyl estradiol/desogestrel combination (IRR: 6.3) 3 .
| Progestin Type | Rate Ratio of Thrombosis vs. Levonorgestrel | Risk Level |
|---|---|---|
| Levonorgestrel | 1.00 (reference) | Low |
| Norethindrone | 0.98 | Low |
| Norgestimate | 1.19 | Moderate |
| Drospirenone | 1.64 | Moderate |
| Desogestrel | 1.82 | High |
| Gestodene | 1.86 | High |
| Cyproterone acetate | 1.88 | High |
Data adapted from 1
These findings highlight the importance of individualized contraceptive selection based on a woman's specific risk profile, rather than one-size-fits-all recommendations.
For women with migraine with aura, contraceptive decisions require careful risk-benefit analysis. While combined hormonal contraceptives remain generally contraindicated for this population according to current guidelines, the Danish study and other recent research suggest the situation is more nuanced than previously thought.
The estrogen dose and progestin type significantly influence thrombotic risk. Some experts now suggest that ultra-low-dose formulations (containing ≤20μg ethinyl estradiol) may be appropriate for select women with migraine with aura, particularly if they have no additional stroke risk factors 6 .
Modern contraceptive counseling for women with migraine with aura should incorporate:
Including aura characteristics, frequency, and relationship to menstrual cycle
Screening for smoking, hypertension, obesity, and personal/family history of thrombosis
Presenting absolute—not just relative—risks to help women understand individual risk profile
While the Danish registry study provides valuable insights, important questions remain unanswered. Future research should:
Examine whether continuous ultra-low-dose estrogen formulations might reduce aura frequency by stabilizing estrogen levels.
Explore how newer contraceptives containing estradiol valerate (rather than ethinyl estradiol) affect thrombotic risk in women with MA.
Investigate biological mechanisms linking migraine, aura, and coagulation abnormalities.
Conduct randomized trials specifically designed to evaluate the safety of various contraceptive options in women with different migraine subtypes.
The relationship between migraine with aura and hormonal contraceptive-related thrombosis represents a classic example of medical decision-making in the face of uncertainty. While risks exist, they must be balanced against the very real benefits of effective contraception and the potential for certain formulations to improve migraine control.
The Danish registry study and other contemporary research provide clinicians and patients with more nuanced data to guide these complex decisions. Rather than absolute prohibitions, we're moving toward an era of personalized contraceptive counseling that considers a woman's complete clinical picture.
As research continues to evolve, the goal remains constant: empowering women with migraine with aura to make informed choices that support both their reproductive autonomy and their overall health. Through continued scientific investigation and open doctor-patient communication, we can ensure that contraceptive decisions are based on evidence rather than fear.
| Factor | Higher Risk Considerations | Lower Risk Considerations |
|---|---|---|
| Migraine characteristics | Recent increase in aura frequency or severity | Stable, infrequent aura with long-standing pattern |
| Additional risk factors | Smoking, hypertension, diabetes, personal or family history of thrombosis | No additional cardiovascular risk factors |
| Contraceptive options | Combined hormonal contraceptives with higher estrogen doses or higher-risk progestins | Progestin-only methods, levonorgestrel IUD, non-hormonal options |
| Patient priorities | Strong preference for combined methods for cycle control or other benefits | Willingness to consider multiple contraceptive options |