A decade ago, Elizabeth Summers' options for birth control suddenly narrowed. Doctors diagnosed her with Factor V Leiden, a rare genetic disorder, after discovering blood clots in her lungs. The condition increases the risk of clotting, so physicians told Summers to stay away from the pill and other hormone-laden contraceptives. "Modern medicine has generally failed to provide me with an effective and convenient option," she says.
But new birth control options are emerging for women like Summers. These alternatives promise to provide more choices to women who can't ingest hormones or don't want to suffer their unpleasant side effects.
These new products have their own pros and cons. Still, doctors are welcoming new contraceptives following a long drought in innovation. "It's been a long time since we've had something new in the world of contraception," says Heather Irobunda, an obstetrician and gynecologist at NYC Health and Hospitals.
On social media, Irobunda often fields questions about one of these new options, a lubricating gel called Phexxi. San Diego-based Evofem, the company behind Phexxi, has been advertising the product on Hulu and Instagram after the gel was approved by the Food and Drug Administration in May 2020. The company's trendy ads target women who feel like condoms diminish the mood, but who also don't want to mess with an IUD or hormones.
Here's how it works: Phexxi is inserted via a tampon-like device up to an hour before sex. The gel regulates vaginal pH — essentially, the acidity levels — in a range that's inhospitable to sperm. It sounds a lot like spermicide, which is also placed in the vagina prior to sex to prevent pregnancy. But spermicide can damage the vagina's cell walls, which can increase the risk of contracting sexually transmitted diseases.
"Not only is innovation needed, but women want a non-hormonal option."
Phexxi isn't without side effects either. The most common one is vaginal burning, according to a late-stage trial. It's also possible to develop a urinary tract infection while using the product. That same study found that during typical use, Phexxi is about 86 percent effective at preventing pregnancy. The efficacy rate is comparable to condoms but lower than birth control pills (91 percent) and significantly lower than an IUD (99 percent).
Phexxi – which comes in a pack of 12 – represents a tiny but growing part of the birth control market. Pharmacies dispensed more than 14,800 packs from April through June this year, a 65 percent increase over the previous quarter, according to data from Evofem.
"We've been able to demonstrate that not only is innovation needed, but women want a non-hormonal option," says Saundra Pelletier, Evofem's CEO.
Beyond contraception, the company is carrying out late-stage tests to gauge Phexxi's effectiveness at preventing the sexually transmitted infections chlamydia and gonorrhea.
Phexxi is inserted via a tampon-like device up to an hour before sex.
Phexxi
A New Pill
The first birth control pill arrived in 1960, combining the hormones estrogen and progestin to stop sperm from joining with an egg, giving women control over their fertility. Subsequent formulations sought to ease side effects, by way of lower amounts of estrogen. But some women still experience headaches and nausea – or more serious complications like blood clots. On social media, women recently noted that birth control pills are much more likely to cause blood clots than Johnson & Johnson's COVID-19 vaccine that was briefly paused to evaluate the risk of clots in women under age 50. What will it take, they wondered, for safer birth control?
Mithra Pharmaceuticals of Belgium sought to create a gentler pill. In April, the FDA approved Mithra's Nextstellis, which includes a naturally occurring estrogen, the first new estrogen in the U.S. in 50 years. Nextstellis selectively acts on tissues lining the uterus, while other birth control pills have a broader target.
A Phase 3 trial showed a 98 percent efficacy rate. Andrew London, an obstetrician and gynecologist, who practices at several Maryland hospitals, says the results are in line with some other birth control pills. But, he added, early studies indicate that Nextstellis has a lower risk of blood clotting, along with other potential benefits, which additional clinical testing must confirm.
"It's not going to be worse than any other pill. We're hoping it's going to be significantly better," says London.
The estrogen in Nexstellis, called estetrol, was skipped over by the pharmaceutical industry after its discovery in the 1960s. Estetrol circulates between the mother and fetus during pregnancy. Decades later, researchers took a new look, after figuring out how to synthesize estetrol in a lab, as well as produce estetrol from plants.
"That allowed us to really start to investigate the properties and do all this stuff you have to do for any new drug," says Michele Gordon, vice president of marketing in women's health at Mayne Pharma, which licensed Nextstellis.
Bonnie Douglas, who followed the development of Nextstellis as part of a search for better birth control, recently switched to the product. "So far, it's much more tolerable," says Douglas. Previously, the Midwesterner was so desperate to find a contraceptive with fewer side effects that she turned to an online pharmacy to obtain a different birth control pill that had been approved in Canada but not in the U.S.
Contraceptive Access
Even if a contraceptive lands FDA approval, access poses a barrier. Getting insurers to cover new contraceptives can be difficult. For the uninsured, state and federal programs can help, and companies should keep prices in a reasonable range, while offering assistance programs. So says Kelly Blanchard, president of the nonprofit Ibis Reproductive Health. "For innovation to have impact, you want to reach as many folks as possible," she says.
In addition, companies developing new contraceptives have struggled to attract venture capital. That's changing, though.
In 2015, Sabrina Johnson founded DARÉ Bioscience around the idea of women's health. She estimated the company would be fully funded in six months, based on her track record in biotech and the demand for novel products.
But it's been difficult to get male investors interested in backing new contraceptives. It took Johnson two and a half years to raise the needed funds, via a reverse merger that took the company public. "There was so much education that was necessary," Johnson says, adding: "The landscape has changed considerably."
Johnson says she would like to think DARÉ had something to do with the shift, along with companies like Organon, a spinout of pharma company Merck that's focused on reproductive health. In surveying the fertility landscape, DARÉ saw limited non-hormonal options. On-demand options – like condoms – can detract from the moment. Copper IUDs must be inserted by a doctor and removed if a woman wants to return to fertility, and this method can have onerous side effects.
So, DARÉ created Ovaprene, a hormone-free device that's designed to be inserted into the vagina monthly by the user. The mesh product acts as a barrier, while releasing a chemical that immobilizes sperm. In an early study, the company reported that Ovaprene prevented almost all sperm from entering the cervical canal. The results, DARÉ believes, indicate high efficacy.
A late-stage study, slated to kick off next year, will be the true judge. Should Ovaprene eventually win regulatory approval, drug giant Bayer will handle commercializing the device.
Other new forms of birth control in development are further out, and that's assuming they perform well in clinical trials. Among them: a once-a-month birth control pill, along with a male version of the birth control pill. The latter is often brought up among women who say it's high time that men take a more proactive role in birth control.
For Summers, her search for a safe and convenient birth control continues. She tried Phexxi, which caused irritation. Still, she's excited that a non-hormonal option now exists. "I'm sure it will work for others," she says.
Recent immigration restrictions have left many foreign researchers' projects and careers in limbo—and some in jeopardy.
"I spent about $4,000 on lawyer fees and another $1,200 to pay for the motions I filed," she recalls. "I had to borrow money from my parents and my cousin because without my salary I just didn't have the $7,000 at hand." But the already narrow window of opportunity slammed completely shut when the Trump administration suspended issuing new visas for foreign researchers in June. All Mohan's attempts were denied. In August, she had to leave the country. "Given the recent work visa ban by the administration, all my options in the U.S. are closed," she wrote a bitter note on Twitter. "I have to uproot my entire life in NY for the past 6 years and leave." She eventually found a temporary position in Calcutta, where she can continue research.
Mohan is hardly alone in her visa saga. Many foreign scholars on H- and J-type visas and other permits that let them remain employed in America had been struggling to keep their rights to continue research, which in certain cases is crucial to battling the pandemic. Some had to leave the country, some filed every possible extension to buy time, and others are stuck in their home countries, unable to return. The already cumbersome process of applying for visas and extensions became crippled during the lockdowns. But in June, when President Trump extended and expanded immigration restrictions to cut the number of immigrant workers entering the U.S., the new limits left researchers' projects and careers in limbo—and some in jeopardy.
"We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened."
Rakesh Ramachandran, whose computational biology work contributed to one of the first coronavirus studies to map out its protein structures—is stranded in India. In early March, he had travelled there to attend a conference and visit the American consulate to stamp his H1 visa for a renewal, already granted. The pandemic shut down both the conference and the consulates, and Ramachandran hasn't been able to come back since. The consulates finally opened in September, but so far the online portal has no available appointment slots. "I'm told to keep trying," Ramachandran says.
The visa restrictions affected researchers worldwide, regardless of disciplines or countries. A Ph.D. student in neuroscience, Morgane Leroux had to do her experiments with mice at Gladstone Institutes in America and analyze the data back home at Sorbonne University in France. She had finished her first round of experiments when the lockdowns forced her to return to Paris, and she hasn't been able to come back to resume her work since. "I can't continue the experiments, which is really frustrating," she says, especially because she doesn't know what it means for her Ph.D. "I may have to entirely change my subject," she says, which she doesn't want to do—it would be a waste of time and money.
But besides wreaking havoc in scholars' personal lives and careers, the visa restrictions had—and will continue to have—tremendous deleterious effects on America's research and its global scientific competitiveness. "It's incredibly short-sighted and self-destructing to restrict the immigration of scientists into the U.S.," says Benjamin G. Neel, who directs the Laura and Isaac Perlmutter Cancer Center at New York University. "If they can't come here, they will go elsewhere," he says, causing a brain drain.
Neel in his lab with postdocs
(Courtesy of Neel)
Neel felt the outcomes of the shortsighted policies firsthand. In the past few months, his lab lost two postdoctoral researchers who had made major strides in understanding the biology of several particularly stubborn, treatment-resistant malignancies. One postdoc studied the underlying mechanisms responsible for 90 percent of pancreatic cancers and half of the colon ones. The other one devised a new system of modeling ovarian cancer in mice to test new therapeutic drug combinations for the deadliest tumor types—but had to return home to China.
"By working around the clock, she was able to get her paper accepted, but she hasn't been able to train us to use this new system, which can set us back six months," Neel says.
Her discoveries also helped the lab secure about $900,000 in grants for new research. Losing people like this is "literally killing the goose that lays the golden eggs," Neel adds. "If you want to make America poor again, this is the way to do it."
Cassidy R. Sugimoto at Indiana University Bloomington, who studies how scientific knowledge is produced and disseminated, says that scientists are the most productive when they are free to move, exchange ideas, and work at labs with the best equipment. Restricting that freedom reduces their achievement.
"Several empirical studied demonstrated the benefits to the U.S. by attracting and retaining foreign scientists. The disproportional number of our Nobel Prize winners were not only foreign-born but also foreign-educated," she says. Scientific advancement bolsters the country's economic prowess, too, so turning scholars away is bad for the economy long-term. "We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened," Sugimoto adds—because scientists will look elsewhere. "We are seeing them shifting to other countries that are more hospitable, both ideologically and in terms of health security. Many visiting scholars, postdocs, and graduate students who would otherwise come to the United States are now moving to Canada."
It's not only the Ph.D. students and postdocs who are affected. In some cases, even well-established professors who have already made their marks in the field and direct their own labs at prestigious research institutions may have to pack up and leave the country in the next few months. One scientist who directs a prominent neuroscience lab is betting on his visa renewal and a green card application, but if that's denied, the entire lab may be in jeopardy, as many grants hinge on his ability to stay employed in America.
"It's devastating to even think that it can happen," he says—after years of efforts invested. "I can't even comprehend how it would feel. It would be terrifying and really sad." (He asked to withhold his name for fear that it may adversely affect his applications.) Another scientist who originally shared her story for this article, later changed her mind and withdrew, worrying that speaking out may hurt the entire project, a high-profile COVID-19 effort. It's not how things should work in a democratic country, scientists admit, but that's the reality.
Still, some foreign scholars are speaking up. Mehmet Doğan, a physicist at University of California Berkeley who has been fighting a visa extension battle all year, says it's important to push back in an organized fashion with petitions and engage legislators. "This administration was very creative in finding subtle and not so subtle ways to make our lives more difficult," Doğan says. He adds that the newest rules, proposed by the Department of Homeland Security on September 24, could further limit the time scholars can stay, forcing them into continuous extension battles. That's why the upcoming election might be a turning point for foreign academics. "This election will decide if many of us will see the U.S. as the place to stay and work or whether we look at other countries," Doğan says, echoing the worries of Neel, Sugimoto, and others in academia.
Dogan on Zoom talking to his fellow union members of the Academic Researchers United, a union of almost 5,000 Academic Researchers.
(Credit: Ceyda Durmaz Dogan)
If this year has shown us anything, it is that viruses and pandemics know no borders as they sweep across the globe. Likewise, science can't be restrained by borders either. "Science is an international endeavor," says Neel—and right now humankind now needs unified scientific research more than ever, unhindered by immigration hurdles and visa wars. Humanity's wellbeing in America and beyond depends on it.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]