Increased Risk of Blood Clots Linked to Combined Use of Painkillers and Birth Control

People who use certain painkillers alongside high-dose hormonal birth control may have a greater risk of blood clots, a new study finds.

Before you begin mixing medications, a quick review to ensure there's no risk of negative interaction between the drugs is always a good idea. While this may be more common for prescription medication, commonplace drugs—like painkillers—deserve the same assessment before introducing them to your routine.

Because sometimes, even the most frequently used over-the-counter drugs can spark issues when mixed.

A new study published in the British Medical Journal, found that people who use non-steroidal anti-inflammatory drugs (NSAIDs) alongside high-dose hormonal contraceptives have a greater risk of venous thromboembolism (VTE) blood clots than individuals who don’t take NSAIDs while on contraception, who take NSAIDs alone, or who take NSAIDs while on progestin-only hormonal contraception.

NSAIDs include common over-the-counter pain medication, such as aspirin (Bayer), ibuprofen (Motrin, Advil), and naproxen sodium (Aleve).

“[Women] in need of hormonal contraception and regular use of NSAIDs should switch to a low/no-risk hormonal contraceptive or relieve their pain/inflammation without NSAID use,” Amani Meaidi, MD, PhD, study author, told Health.

In order to assess whether or not high-dose contraceptives and painkillers resulted in blood clots, researchers used national medical records to track first-time diagnoses of VTE among 2 million women aged 15 to 49 years living in Denmark between 1996 and 2017.

The women had no history of blood clots, cancer, hysterectomy, or fertility treatment. Factors such as age, education level, pregnancy history, prior surgery, high blood pressure, and diabetes were considered in the research.

Of the people analyzed, 529,704 women used NSAIDs while taking hormonal contraception. Most frequently taken NSAIDs included:

The association with VTE was strongest for diclofenac compared with ibuprofen and naproxen.

The study authors categorized the use of hormonal contraception according to the association with VTE in the following ways:

“Most patients are on low-dose contraception,” said Jennifer Wu, MD, OB/GYN at Northwell Lenox Hill Hospital. “The study shows that low-risk birth control and NSAIDs do not really increase [risk of blood clots] much more than the risk of [of blood clots from] just taking NSAIDs.”

For instance, the study found the following:

“This potentially suggests a synergistic drug interaction between these two drug classes,” said Meaidi.

It's worth noting that research has looked into contraceptives' correlation with blood clots before.

Meaidi explained that the progestin-only injection, which delivers a high dose and potency of progestin, has previously been linked to an increased risk of VTE.

However, she noted that the progestin-only intrauterine device, which delivers a small dose of progestin to the blood, has been linked to reduced risk of VTE.

In the new research, when it comes to progesterone-only hormonal contraceptives being used with NSAIDs, Meaidi said this is associated with a much lower risk of VTE (3 per 100,000 women per week) compared with concomitant use of NSAID and combined hormonal contraception (up to 23 per 100,000 women per week).

“[We] found that the highly increased risk of venous thromboembolism with NSAIDs was even higher in women using combined hormonal contraception than in women using progestin-only formulations or no hormonal contraception,' she said.

Because the study is an observational study, the authors can only establish correlation, not cause. Limitations to the study, such as missing information about smoking and obesity, could have affected the results.

Wu explained that sometimes a person might have several things occurring that increase their risk of blood clots.

“Say you’re on one of the higher-risk methods of birth control and then you get into a car accident and break your leg and you’re taking lots of NSAIDs to control pain, and you’re immobilized cause your leg is broken,” she said. “You then have three different inciting factors for blood clots.”

While patients may not be aware that their birth control method could cause harm in situations like this, Wu said healthcare providers are aware and will act in the patient’s best interest.

“These are decisions for the healthcare provider,' she said. 'Most will be cognizant of that fact and will take patients off birth control if they are having a surgery that will keep them immobilized or if they will be taking a lot of medicine.'

For women taking low-dose contraception, Wu explained their risk for VTE does not increase if they take NSAIDs.

“You don’t really have a lot of alternatives to NSAIDs,' she said. 'To tell a patient ‘you have a terrible headache, but it’s going to really increase your risk of blood clots, so don’t take any Motrin or Advil,’ is hard.'

The alternative to NSAIDs is pain medications like the opioid narcotic oxycodone, which is highly addictive if abused. In 2022, nearly 80,000 people died from an overdose involving an opioid.

“In hospitals, they give NSAIDs around the clock to patients who had surgery because they are trying to keep their pain at a manageable level and trying to decrease the use of narcotics,” said Wu. 

Patients and doctors are weighing a lot of factors when it comes to pain control, Wu said. For women on birth control in need of pain management, it is essential to talk to a healthcare provider about your best options.