On the morning of September 26, 2018, Alexandra (Alex) Williams, a healthy and energetic twenty-year-old college student, collapsed in the driveway of her parent’s home. She was rushed by ambulance to Duke University Medical Center and, for twelve hours, surgery and post-ops teams tried to revive her. At the end of the day, the doctors told Alex’s parents that she had little to no brain activity. On September 27, after being removed from life support, Alex died.
“Alex was a healthy college student who exercised regularly, ate a nutritious diet, and her only prior illness was strep throat when she was four,” says her father, Anthony Williams. Five days after her death, autopsy results revealed that Alex had blood clots in both her lungs. She experienced a pulmonary embolism—an unusual occurrence for people as young as Alex. Mr. Williams explains:
Unbeknownst to us, Alex had gone to a Planned Parenthood clinic nine months prior, where she obtained a prescription for a generic combination hormonal birth-control pill, supposedly one of the “safer” kinds. These pills are often marketed to young women as clearing acne, minimizing mood swings, minimizing weight gain, and preventing the development of certain cancers—sort of a “miracle pill.”
What women often aren’t told is the significant degree to which hormonal contraception (HC), including the Pill, injections, implants, rings, or patches, increases the risk of blood clots in women. It can lead to many serious medical problems, and even death, in healthy young women like Alex.
Birth control-related deaths of young women occasionally make headlines, but they are grossly underreported. There is no systematic surveillance on venous thromboembolism (VTE), which includes deep-vein thrombosis of the leg or pelvis, and its complication, pulmonary embolism (blood clots in the lung), but the CDC reports that 900,000 people experience VTE every year and that up to 100,000 deaths are caused by VTE every year in the United States. For healthy young women like Alexandra, these deaths could be prevented.
Our systematic review of the scientific literature led us to conclude that, in the United States, 136 to 260 healthy women die from VTE caused by hormonal contraception every year. When that risk is combined with the added risk of stroke and heart attack, between three and four hundred women die every year in the United States due to their choice to use hormonal contraception.
To give some perspective, meningitis killed 45 people (of all ages) in 2017. Most states in the US mandate meningitis vaccination for college and university students. Would they consider the same kind of prevention campaigns for the deadly blood clots caused by hormonal birth control?
In our systematic review of the most evidenced-based articles from the 1960s to 2018 comparing users of HC to nonusers, and including more than seventeen million woman-years of observation, we found that using HC increases a woman’s risk of being diagnosed with VTE by three to nine times. For women under thirty, the risk is increased thirteen-fold during the first year of use, when the risk for clot formation is highest.
In the United States, about 21 percent of women of reproductive years are using HC. That works out to about 13 million women. Of those, 5.9 million are between the ages of fifteen and twenty-four, and 4.8 million are between twenty-five and thirty-four.
Obesity can increase the risk of being on hormonal contraception, about doubling the risk of blood clots compared to a woman of normal weight on the pill. When prescribing hormonal birth control, it is not considered cost-effective to check for thrombophilia, a genetic disposition to form blood clots. Yet this condition multiplies the risk of VTE sixty-two fold in the first year.
Some of the newer formulations of hormonal birth control, sometimes called third- or fourth-generation HC (containing desogestrel, gestodene, or drospirenone), have a higher risk of blood clots than second-generation HC (containing levonorgestrel). When a recent study in France showed excessive hospitalizations and death from third- and fourth-generation pills, the French government removed these formulations from the list of reimbursed medications in 2013. Prescriptions for these drugs dropped by 45 percent, as women quickly switched to other forms of birth control.
Not on the Label
While no one wants to start a general panic among birth-control users, we do need to reassess the way patients are warned about the risks of HC and the ways that medical professionals assess and monitor these risks.
For one thing, the language on the black box warning of contraceptives regarding risk of cardiovascular events currently misleads women by making it sound like that risk is limited to those who smoke. Yaz is a Bayer brand that had a major lawsuit, with more than 10,000 settled claims between 2009 and 2016, from patients who suffered a VTE. The warnings on the Yaz label read: “WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS.” While smoking is certainly a risk factor, studies showing prevalence are adjusted for this risk, meaning that many non-smokers (like Alexandra) are at elevated risk as well.
In fact, Lucine Health Sciences studied the medical background of eighty-seven women who experienced a DVT because of hormonal contraceptives and found that 95 percent of them were not smoking at the time of the DVT; 78 percent had never smoked. HC labels should clearly state that anyone taking these medications could experience a potentially life-threatening cardiovascular event and should discuss the risks with a medical provider.
A major and known risk factor for VTE is the genetic blood condition called “activated protein C resistance” or ACP resistance, in which the patient is more likely to experience blood coagulation in presence of certain risk factors. The most common among these conditions, Factor V Leiden, affects an estimated 3-8 percent of the US population with European ancestry. Women who have these genetic attributes are six times more likely to experience a blood clot before they reach sixty-five. In an opinion published in the Journal Expert Opinion on Drug Safety, Dr. Oejvind Lidegaard warns that the use of HC dramatically increases these patients’ risk of VTE. The risk increases with time. After ten years of contraceptive use, 2.5 percent experienced VTE.
Knowing the Risks
After Alex’s death, Anthony Williams ordered blood tests for his second daughter and for his niece. The tests revealed that his niece had ACP resistance, and she stopped using her vaginal ring as a result—a move that may have saved her life.
To better serve women like Alex, the medical community needs to be more aware not only of the risks, but also the breadth of symptoms women can present with if having complications from hormonal birth control. Alexandra started complaining about unexplained back pains about five months after she started the birth-control pills. In August, she went to the ER because her backaches had gotten worse. X-rays were taken of her upper body, and this time she was diagnosed with a lung infection and prescribed antibiotics. No further medical testing was done. Could a more informed doctor have checked her for blood clots?
In 2014, Megan Henry, an Olympic athlete, told Vanity Fair she was “gasping for breath” shortly after she got on the Nuvaring, a hormonal vaginal ring. It took three doctor visits to find a provider who ordered a CT scan and found dozens of blood clots in her lungs, saving her life. It is urgent that all medical professionals are alerted of the relationship between the use of HC and any unexplained symptoms in young women.
Many young women are put on these drugs, even when they are not sexually active, to treat other symptoms, from acne to painful periods, for which there are safer treatments available. When women wish to avoid pregnancy, there are other forms of birth control that can be used with much lower risks and comparable effectiveness. Modern forms of fertility awareness-based methods (FABM), such as the Billings, Creighton, Marquette, and Sympto-Thermal Methods, have no side effects and have typical-use effectiveness rates ranging from 86.8 to 98.4 percent.
In the aftermath of their daughter’s death, Anthony and Lisa Williams wish more women would be informed of these natural alternatives for hormonal health and family planning. They believe Alex—who lived a life dedicated to women’s empowerment—would want that, too.