About 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.
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 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 2021, 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.
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. 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.
This article was first published by Leaps.org on August 31, 2021.
Brittany Trang was staring at her glass test tube, which suddenly turned opaque white. At first, she had thought that the chemical reaction she tested left behind some residue, but when she couldn’t clean it off, she realized that the reaction produced corrosive compounds that ate at the glass. That, however, was a good sign. It meant that the reaction, which she didn’t necessarily expect to work, was in fact, working. And Trang, who in 2020 was a Ph.D. researcher in chemistry at Northwestern University, had reasons to be skeptical. She was trying to break down the nearly indestructible molecules of per- and polyfluoroalkyl substances or PFAS—the forever chemicals called so because they resist heat, oil, stains, grease, and water, and thus don’t react or break down in the environment.
“The first time I ran this, I was like, oh, like there's a bunch of stuff stuck to the glass, but when I tried to clean it, it wasn’t coming off,” Trang says, recalling her original experiment and her almost-disbelief at the fact she managed to crack the notoriously stubborn and problematic molecules. “I was mostly just surprised that it worked in general.”
In the recent past, the world has been growing increasingly concerned about PFAS, the pollutants that even at low levels are associated with a litany of adverse health effects, including liver damage, thyroid disease, high cholesterol, pregnancy complications and several cancers. Used for decades in manufacturing and in various products such as fire retardant foam, water-repellant clothes, furniture fabrics, Teflon-coated pans, disposable plates, lunch containers and shoes, these super-stable compounds don’t degrade in the environment. The forever chemicals are now everywhere: in the water, in soil, in milk, and in produce.
As of June 2022, the Environmental Working Group, a nonprofit watchdog organization, found 2,858 locations in 50 states and two territories to be heavily contaminated with PFAS while many farmers had been forced to dump their milk or spinach because the levels of these compounds were in some cases up to 400 times greater than what’s considered safe. And because PFAS are so pervasive in the environment and the food we eat, they are in our bodies too. One study found some levels of PFAS in 97 to 100 percent of participants tested.
Because these compounds were made to be very stable, they are hard to destroy. So far, the only known way to break down PFAS has been to “cook” them under very harsh conditions. The process, known as pyrolysis, requires upwards of 500 degrees Centigrade, high pressure and absence of oxygen, which is energy expensive. It involves sophisticated equipment and the burning of fossil fuels. Trang, who worked in the laboratory of William Dichtel, managed to break PFAS at 120 degrees Centigrade (248 F) without using strong pressure. After she examined the results of her process with various techniques that help quantify the resulting compounds and confirmed that PFAS had indeed degraded into carbon and the corrosive fluorine that clouded her glass, she was thrilled that it worked in such simple conditions.
“That's really what differentiates our finding from everything else that's out there,” Dichtel said about their discovery at a press conference announcing the study last month. “When we're talking about low temperatures, we're at 120 degrees Celsius and sometimes even quite a bit lower than that, and especially ambient pressure.”
The process used by Trang’s team was the exact opposite of the typical organic synthesis method.
Trang’s journey into PFAS degradation began with a paper she read about the nuances of the chemicals’ molecular structure. A long molecule comprised primarily of carbon and fluorine atoms, along with oxygen and hydrogen, it has what Trang describes as a head and a tail. At the head sits a compound called carboxylic acid while the fluorine atoms make up the tail portion, with the atomic bonds so strong they aren’t possible to break without harsh treatment. But in early 2020, Trang read that a solvent called dimethylsulfoxide, or DMSO, commonly used in labs and industry, can make the carboxylic acid “pop off” its place. The DMSO doesn’t react with carboxylic acid but sort of displaces it, leaving the rest of the typically indestructible PFAS molecule vulnerable.
Trang found that its exposed fluorine tail would react with another common chemical compound, sodium hydroxide, causing a cascade of reactions that ultimately unravel the rest. “After you have decarboxylated the head, the hydroxide is able to react with the tail,” Trang says. “That's what sets off a cascade of reactions that degrades the rest of the molecule.”
That pathway took time to figure out. Trang was able to determine that the molecule carboxylic acid head popped off, but before she was able to figure out the rest, her lab and the entire Northwestern University went into lockdown in early March of 2020. “I was able to do three experiments before the shutdown,” she recalls. For the next few months, she sat at home, reading scientific literature to understand how to continue the degradation process. “I had read a bunch of literature and had a bunch of ideas for what may or may not work,” she says. By the time she could return to work, she had a plan. “I added sodium hydroxide in my batch of experiments when the lab reopened.”
The process used by Trang’s team was the exact opposite of the typical organic synthesis method. “Most organic chemists take two molecules and squish them together to make one big molecule. It’s like taking two Legos and putting them together to make one thing that was larger,” she says. “What we are doing is kind of smashing the Lego with two bits and looking at what was left to figure out how it fell apart.” The team published their discovery in the journal Science.
Although very promising, the process isn’t quite ready for industrial applications, and will take time to adapt, Trang says. For starters, it would have to be scaled up to continuously clean large quantities of water, sewage or other substances that can be contaminated with PFAS. The process will also have to be modified, particularly when it comes to removing PFAS from drinking water because as an industrial chemical, DMSO is not suitable for that. Water companies typically use activated carbon to filter out PFAS and other pollutants, so once that concentrated waste is accumulated, it would be removed and then treated with DMSO and hydroxide to break down the molecules. “That is what our method would likely be applied to,” Trang says—the concentrated waste rather than a reservoir because “you wouldn't want to mix DMSO with your drinking water.”
There are some additional limitations to the method. It only breaks down one class of forever chemicals, but there are others. For example, the molecules of perfluoroalkane sulfonic acids, or PFSA, don’t have a carboxylic head that DMSO can displace. Instead, PFSA have a sulphonic acid as their molecular head, which would require a different solvent that still needs to be discovered. “There is certainly the possibility of activating sulphonates in similar ways [to what] we've done [with] carboxylates,” Dichtel said, and he hopes this will happen in the future. Other forever chemical types may have their own Achilles’ heels, waiting to be discovered. “If we can knock that sulphonated headgroup off the molecule and get to the same intermediates we get to in this study,” Dichtel added, “it's very reasonable to assume that they'll degrade by very similar pathways.” Perhaps another team of inquisitive chemists will take on the challenge.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- A new mask can detect Covid and send an alert to your phone
- More promising research for a breakthrough drug to treat schizophrenia
- AI tool can create new proteins
- Connections between an unhealthy gut and breast cancer
- Progress on the longevity drug, rapamycin
And an honorable mention this week: Certain exercises may benefit some types of memory more than others