What Can We Learn from Menstrual Blood?

Initially, Naseri approached menstrual blood as an alternative to venous blood, and set out to see if it could be mined for traditional biomarkers—molecules that point to the presence of a condition or disease. She enlisted Paul Blumenthal, an expert in cervical-cancer prevention and a professor emeritus of obstetrics and gynecology at Stanford’s medical school, in her effort. At first, the pair struggled to find a lab that would analyze their samples. “There was an ick factor,” Naseri recalled; some blood labs said that they didn’t want menstrual blood in their analyzers. Naseri and Blumenthal eventually found a lab that would work with them, and were able to show that menstrual blood can be used to monitor hemoglobin A1C, cholesterol, inflammatory proteins, and thyroid hormones. “If it can be tested for in circulating blood, it’s highly likely that we can find it in menstrual blood,” Blumenthal said. In January, 2024, the F.D.A. approved the use of the Q-Pad to track hemoglobin A1C, which reflects long-term average blood sugar.

Meanwhile, in exploring how period blood could behave like venous blood, Naseri and Blumenthal hit upon something only menstrual blood could do. Blumenthal has travelled to Kenya, Myanmar, and Mexico to train physicians on alternatives to the Pap smear, which screens for cervical cancer but is difficult to implement without adequate training and infrastructure. He quickly realized that menstrual blood, which sweeps through the uterus and cervix, was likely to carry the H.P.V. virus, which can cause the cancer. In 2022, he and Naseri completed a prospective study indicating that the Q-Pad was better at detecting high-risk strains of H.P.V. than either a Pap smear or a self-collected vaginal swab. In 2023, Qvin received F.D.A. clearance to test Q-Pad screening for high-risk H.P.V. in Thailand. Blumenthal now believes that the main challenge will be winning clinicians over to the idea that routine, in-person gynecological testing could be replaced by a mailed-in sample of menstrual blood. “It really is an approach,” he said. “It’s not just a test.”

NextGen Jane, the company that Cate Gogolak found online, took the opposite tack: they started by asking what made period blood biologically unique. After exploring the idea of developing a discreet test for sexually transmitted infections—gonorrhea, chlamydia, and the herpes virus can also hang out around the cervix—they pivoted to trying to create a diagnostic test for endometriosis. There were no diagnostic markers approved by regulatory authorities for the disease. But Ridhi Tariyal, the company’s C.E.O., realized that, because the uterine lining is exquisitely sensitive to changes in hormonal signalling, analyzing menstrual blood might reveal the mass hormonal disruptions that endometriosis is thought to involve. This was a new way of thinking about the uterus—as a dynamic organ whose response to hormones could be measured and interpreted. “A sentinel system,” Tariyal said.

In recent years, endometriosis has become a kind of poster disease for how medicine has gaslit women, prioritizing their ability to reproduce over their pain. Doctors have long punted its symptoms into the realm of the psychological; in the past, antidepressants were common frontline medications, and even now many patients are first sent to therapists. Even well into the nineteen-nineties, endometriosis was called “the career woman’s disease,” and a common “cure” was held to be pregnancy, which temporarily arrests menstruation and changes hormone levels in the body. Women today still report being advised by their doctors to “just get pregnant.”

To Tariyal, endometriosis seemed an ideal target for a women’s-health startup. But unlike Qvin, which could build off of preëxisting tests designed for venous blood, NextGen Jane needed to develop an entirely new test for endometriosis; this test had to work with menstrual blood and would ideally be approved by the F.D.A. This would require standardizing the collection and handling of menstrual blood, and creating a diagnostic test for endometriosis known as a molecular assay. Then, they would need to validate the assay against surgical results from a new set of patients. “It’s very easy to be dismissive of ideas like using menstrual effluence as a diagnostic substrate,” Tariyal told me. “To go from that to actual clinical utility, useful clinical information, is a long road. And people are looking for proof.”

In NextGen’s offices, in Oakland, California, Matt McElroy, a biologist, gestured to what looked a bit like a wine press. “Let’s go by the technical term—arbor press,” he told me. The solid cast-iron machine in front of him could be used to punch holes, crimp jewelry, or stamp leather. He removed a plastic vial from a bag marked “biohazard.” Inside was a blood-soaked tampon, immersed in a preserving solution, which had been air-mailed to NextGen’s Oakland lab by a woman the day before. It had now oxidized to a deep reddish-brown, like rust.

McElroy fitted the cannister with a plastic plug, slid it into the machine’s metal vise, and then cranked a lever, crushing the porous cotton and releasing its contents. He decanted the resulting fluid, which was brown-red and opaque, like aged Merlot, into a test tube. “Looks good,” he said. He held the vial up to a poster showing a rainbow of possible solution colors; a darker hue meant a heavier flow, which meant more blood and uterine lining for the lab to analyze. This one was a C4, out of a range of C1 to C5.

Gogolak, who after sending in her tampons had become an intern at NextGen Jane, stood with us in the lab. “We’re going to have an ombré,” she said, looking at a vial containing fluid the hue of a medium rosé. The samples would now be spun down in centrifuges, and then treated to filter out other proteins, tissue, and cell debris, until they contained only pure genetic material. Most of this would be banked in an industrial freezer rather than analyzed immediately: NextGen hopes to use its menstrual library to build an understanding of “normal” menstruation and develop future tests. Meanwhile, after ten years spent gathering and analyzing thousands of samples, the company believes it has identified an assay of forty-seven biomarkers which can reliably distinguish confirmed endometriosis patients. It is now beginning a validation study to confirm those results.

In the end, the samples Gogolak sent to NextGen Jane were marked “suspected,” as her endometriosis had neither been confirmed nor denied through surgery. While she still holds out hope for an answer, she knows she won’t receive more information until the company is able to release a validated test—which Tariyal says is eighteen months away.

“If you had a diagnosis, how would that help you?” McElroy asked her.

She paused, considering. If she’d been able to take a menstrual-blood test back in her freshman year, when her endocrinologist had had a hunch, it might have changed her path entirely, saving her years of expensive testing and weeks spent bedridden and on opioids. If the test had come back positive, it would have pointed her toward surgery years earlier; if it had come back negative, it would have suggested the need to look for another diagnosis. Instead, she was trapped in what Tariyal calls “analysis purgatory”—the agony of neither knowing nor not knowing.

Months later, Zooming with me from her dorm room, Gogolak lifted her sweatshirt to show me two patches on her midriff that were connected to a square device. Developed by a company called Livia, the tool creates vibrations to help relieve period pain. Next to her door was a portable heating pad, which she grabs on her way to class in the morning when her cramps are at their worst. After her pain and bleeding returned, in September, 2022, she and her parents scheduled a surgery—but then a new birth-control medication started working unexpectedly, bringing her symptoms under control. Still, if she forgets to take her birth control or progesterone for even one day, she can feel the nauseating pulling start to come back.

Gogolak still assumes that, at some point, she’ll have surgery. Today, her fear isn’t that surgeons will find endometriosis but that they will find nothing. In that case, she’ll be back to square one. “I just want to fully, one-hundred-per-cent know I have it or not,” she said.

A truly diagnostic noninvasive test for endometriosis—a test that can lead to a medical decision—may be years away. In the near term, what’s more likely is a screening test—a test that, like a mammogram or Pap smear, can tell you whether you have a high likelihood of having the disease. Yet screening tests have limitations, especially for diseases that aren’t well understood. The Pap smear or H.P.V. test can be incredibly useful because, if you detect cancer or pre-cancer early, you can start down the road to treatment and cure. There is no equivalent road for endometriosis. “The question is, How would this change our recommendations to patients?” Tami Rowen, an ob-gyn who specializes in benign gynecologic diseases, told me.

Even if Gogolak received a definitive diagnosis of endometriosis through surgery, that diagnosis would not tell her which of several treatment options is most likely to work for her. Contraceptive pills can stop working, and even surgery is often not a cure. Another option, if birth control fails to control the symptoms, is a stronger cocktail of drugs that tamp down reproductive hormones; these can suppress menstruation, lower circulating estrogen, and quiet the reproductive system, often plunging a patient into temporary menopause. Such hormonal treatments haven’t changed significantly in forty years. They often come with severe side effects, and it can’t be known in advance whether they will work.

Christine Metz, a reproductive biologist at Northwell Health, on Long Island, is the co-director of ROSE, another research team developing an endometriosis test based on menstrual blood. She told me that, when it comes to endometriosis and other benign gynecological diseases, the knowledge gap goes further than diagnosis. For example, although birth control is widely held to slow down the progression of the disease, there is little evidence that it does so: Metz said that nearly every clinical trial to date on endometriosis treatment, whether surgical or hormonal, has measured not the progression of the disease as such but, rather, relief from pain. “It’s pain, pain, pain,” Metz pointed out. “It’s like if you asked cancer patients how they’re feeling after they took chemotherapeutic agents.”

When it comes to historically misunderstood diseases like endometriosis, there are still more unknowns than knowns. Yet the work that companies like NextGen Jane and Qvin are doing lays the foundation for an expansion in our knowledge. By probing how the uterus responds to hormonal shifts, and by learning the full composition of menstrual blood and how it changes over time, they may make more rigorous research into endometriosis and other reproductive diseases possible. Drop by drop, they are painting a fuller picture of an area of the body that’s been hidden for too long. ♦