Those who are in chronic pain — again, mostly women — are viewed as unreliable, as an unwise investment, as a burden, as complainers, as unfixable. —Sonya Huber, “Pain Woman Takes Your Keys and Other Essays from a Nervous System”

In 1999, Anjali Enjeti, of Atlanta, Georgia, rushed to the emergency room after vomiting for hours and an excruciating pain in her chest had migrated to her abdomen. At the ER, she waited eight hours in agony as doctors told her that her symptoms were likely the stomach flu.

Thirty-six hours later, after interacting with more than 12 doctors, Etali found herself “alone in a hospital room, gasping in pain” so severe she couldn’t even answer the medical staff’s questions.

“I just [laid] in the bed with my eyes closed, thinking, please let me die now,” Etali told me by email.

Though Etali’s white blood cell count was “through the roof” and a series of pelvic exams ruled out STDs or a burst ovarian cyst, doctors still had not reached a diagnosis. “Most of the time I spent in the hospital, I was told I had an STD,” she says, though she was married and monogamous. It would be nearly a day and a half before physicians took Etali’s pain seriously.

Women’s pain has long been treated as psychosomatic. The very fact of having a uterus was once deemed explanation enough for a panoply of mental health issues — the root for “hysteria” is the Greek hystera, or womb. Historically, women’s pain was “cured with herbs, sex, or sexual abstinence” and “punished and purified with fire for its association with sorcery,” write the authors of “Women and Hysteria in the History of Mental Health,” published in 2012.

Even today, pain in or around a woman’s reproductive organs is often written off as hormonal and not urgent, though having female reproductive organs is not required for a woman’s pain to be overlooked. Those who have undergone hysterectomies, as well as transgender women, gender fluid, and nonbinary folx who may be perceived as female also report feeling that they’re taken less seriously than their male or masculine-presenting counterparts. Indeed, a 2001 study in the Journal of Law, Medicine, and Ethics found that women are medicated for pain less frequently than men, admitted to hospitals less than often than men, and “treated less aggressively in their initial encounters with the health-care system until they prove they are as sick as male patients.”

While pain is subjective and relies upon such measures as self-reporting and tolerance levels to approximate pain (heat, cold, electrical stimulation) in laboratory settings, the scientific literature admits that women have long been underrepresented in medical studies, often under the guise of protecting future reproductive potential at the cost of women’s present health.

Pain in the Brain

Much of the research on women and pain has been performed on female rats or on human women in laboratory settings that only approximate naturally occurring pain. A 2014 study in Experimental Neurology showed that female rats experience reduced pain relief from opioid analgesia as compared to their male counterparts. The researchers also found reduced activation in female rats’ mu opioid system — the body’s natural pain-relief pathway, which is responsible for releasing endogenous opioids — as compared to male rats. These female rats also had fewer mu opioid receptors for opioids to bind with. In fact, one of the study’s authors, Anne Z. Murphy, an associate professor at Georgia State University’s neuroscience institute, told me by phone, “If you take those receptors out in a male rat, you can make them very much like females.”

The same study zeroed in on another essential pain circuit in the brain and spinal cord that is different in female rats: the midbrain periaqueductal gray (PAG). The PAG is activated by acute pain and is involved in both naturally occurring and administered opiates. Studies consistently report that output neurons in this region — which lead to an increased feeling of pain — were “significantly greater in females” in a region of the PAG dense with mu opioid receptors.

Further, morphine produces greater analgesia in male rats compared to females, and a similar effect was observed in humans.

The question of why is not so simple. Biological mechanisms clearly play a role, but many other factors come into play in human women, such as the sex of the experimenter, the setting of the experiment, and other psychosocial factors, like that women are socially permitted to express pain more than men. “Women are more likely to seek medical attention for a pain syndrome than a male, while males are more likely to self-medicate,” says Murphy.

Murphy and her co-author concluded that “the endogenous opioid system is sex dependent and likely contributes to increased pain sensitivity in females.”

“Just” Hormonal

Kate Collins of Kentucky fought for 10 years, beginning at age 18, to have a hysterectomy to stop “extreme pain and extreme bleeding” that caused vomiting and depression. Her periods could last as long as nine months, with abdominal bloating so hard and painful that she was unable to stand. Over the next decade, Collins recounted by email, doctors frequently told her such things as “some women just have bad periods” and “there’s nothing more we can do for you.” Many refused to give her a hysterectomy due to her young age: “One doctor told me when I was 19 to have a baby that I didn’t want and couldn’t afford,” says Collins. Another asked, “Aren’t you worried about what your future husband might want?”

Since tests did not reveal any abnormalities, doctors continued to throw up their hands or put her on birth control pills. “As long as the tests came back normal, people didn’t believe me.” A decade later, Collins finally found a doctor who offered her a hysterectomy. “I feel wonderful. I got my life back,” she says.

Many women have their pain dismissed as hormonal — which can be code for “emotional” or “not real.” However, a growing body of research acknowledges that hormones may play a very real part in pain sensitivity. While research into the mechanisms of pain is subject to variability as women’s hormones fluctuate across the menstrual cycle or during hormone treatments, women’s sensitivity to pain may be heightened by gonadal steroid hormones, which are produced by sex organs. A 2010 study in the journal Metabolism notes that boys and girls, who have the same approximate chance of migraines prior to puberty, see a dramatic change after puberty: The risk of migraines is three times higher in women than in men. Even more telling, according to the same study, transgender women undergoing hormone treatment with the female sex hormones estradiol and antiandrogens experienced more frequent incidences of chronic pain than transgender men treated with testosterone.

Furthermore, women’s inflammatory processes are more active than men’s, which is linked to greater incidences of inflammatory autoimmune diseases known to cause chronic pain, such as rheumatoid arthritis, lupus, and collagen vascular disorders, as well as an overall increased pain sensitivity.

While there is plenty of piecemeal evidence of variance in pain sensitivity between the sexes, there is still a great deal of research to be done and psychosocial factors to be taken into consideration. If nothing else, women’s testimonies about their pain and its treatment suggests a need for better training among medical professionals.

Etali’s excruciating pain was textbook appendicitis.

Even after she was seen by multiple doctors, her complaints couldn’t convince them of the urgency of her pain. “Typically when patients are even suspected of appendicitis, they are sent immediately to surgery,” says Etali. After that experience, she “began to look at the medical field with far more skeptical eyes.”

And just a few months after Etali’s appendectomy, her husband, a second-year medical student at the time, witnessed a case of appendicitis in his residency that presented with the same symptoms as hers. That patient was a man. “[He] was in surgery a few hours later,” says Etali. “My husband couldn’t believe it. He was so angry.”

Stories like Etali’s are not uncommon. Research has shown that women report pain that is more severe, more frequent, and of a longer duration than men report—yet women feel their pain is often underreported and undertreated, even in life-threatening situations. It’s hard not to tie these examples to institutionalized sexism, which influences not only how clinicians treat patients but also how women internalize their pain experience. Do women feel pain more intensely than men, or are they simply more socialized to express it? We may never know the exact answer to the first question, but we’d be foolish to ignore the second.