Tucked away in an unremarkable office block in London, a team of bright young science minds are working on a breakthrough for women. They’re part of a fledgling project called Pexxi, which aims to change your life by changing your contraception. The idea? To replace the current birth control gamble of pot luck and trial and error via a ‘smart decision making platform’. The Pexxi team believes that, by combining data science with hormonal and genetic testing, they can help women match with the most appropriate form of hormonal contraception for them.
It’s a simple but revolutionary idea because, so far, the process of finding hormonal contraception that works with your body rather than against it has been frustrating at best and debilitating at worst. “We still treat contraception as if preventing pregnancy is the only goal, without considering reproductive, physical or mental health,” explains Pexxi founder Shardi Nahavandi, a 29-year-old student-turned-biotech-entrepreneur. “I want to help women feel in control of their contraceptive choices and to contribute to the body of research so that we can better understand the female body.”
Hormonal contraception has been a mainstay of many women’s lives since the combined oral contraceptive pill became available in Australia in 1961. Since then, there have been multiple developments, including the progestogen-only pill (aka the mini pill) and longer acting options such as IUDs and implants. But how do women choose between different types and brands? For years, it was based on whisperings. You know the name of the pill your friend blamed for making her balloon, and your cousin warned you against an IUD after weeks of errant bleeds. But every body is different, and what works for one person may not suit another. Without any better way of filtering their options, millions of women have been locked into a contraception gamble, the myriad potential fallouts of which have become notorious, with reports of side effects ranging from depression to severe haemorrhaging. In the eyes of many of those who research and dispense hormonal contraception, the fears about its links to mental health conditions such as depression are just that: fears.
“Only one study has shown a clear, causal link between depression and oral contraceptives,” explains endocrinology researcher Dr Lisa Owens. Equivalent data for longer-acting forms of contraception, such as the IUD, doesn’t exist, she says, due to the fact they are used less. Why hormonal birth control can mess with some women and play nicely with others is still a medical mystery.
“There’s no doubt [there is] a subgroup of women who are more vulnerable to both their own hormones and the synthetic ones contained in contraceptives,” explains psychiatrist Dr Michael Craig. “What we don’t know is how big this group of women is, or what’s different about them.”
Precisely does it
More certain is that women are hungry for an alternative. Just look at the surge of enthusiasm that greeted the 2014 launch of the Natural Cycles app: by mid-2018, the ‘digital contraception’, which uses an algorithm to predict fertile windows, had reportedly attracted more than 800,000 users with its tagline, ‘No hormones, just science’. (Unfortunately, the bubble burst when a spate of unplanned pregnancies were reported and an ad claiming the app was ‘highly accurate’ was banned.) So, the idea of making existing contraceptives work better for women clearly has us intrigued. How do Nahavandi and her team plan to meet one of womankind’s greatest needs?
The theory is that your body responds to different kinds of contraception based on both its hormonal balance and genetic make-up – and Pexxi tests both to find a type that fits. The first step is to make sure that the hormones in your pill or device align with your own, to avoid running into nasty side effects. You do this via a DIY hormone test (for which you spit into a tube) and the results give Pexxi’s algorithm an accurate idea of where your levels of progesterone and oestrogen are at. From there, your profile is mapped onto the index of hormonal contraceptives the algorithm knows about (it’s constantly fed with the latest research) to find your best match. The genetic testing element of Pexxi (involving a simple mouth swab) provides an extra level of longterm security – important, as contraceptive side effects aren’t always noticeable. Say your DNA test highlights a vulnerability to cardiovascular problems.
Pexxi will then cross-reference your list of hormonally compatible contraceptive options with this in mind, and rule out any known to increase blood pressure, which could raise your risk. Clever, right? Such an approach may sound futuristic, but experts believe it’s going to change medicine – and soon. “Pharmacogenomic research is starting to reveal how genetic differences influence women’s unique responses to specific medications,” explains Dr Peter Fish, a biomedical engineer working with Pexxi. “The US Food and Drug Administration recently listed a few hundred drugs with pharmacogenomic considerations [read: drugs that may behave differently according to someone’s genetics]. It currently includes just one contraceptive, but I expect this will expand rapidly as precision medicine becomes more mainstream.”
Time for change?
Industry ‘disrupters’ don’t always get the warmest reception in their respective fields. So, what do female health medics of the, er, classical tradition think of this new dawn of fem tech? Owens is cautiously optimistic. “In theory, everyone’s doctor can help them narrow down and make the right contraceptive choice, but that doesn’t always happen in reality,” she admits. “Any resource that helps is fantastic – as long as it’s done in conjunction with universities using rigorous scientific evidence.” Craig echoes her sentiment: “If we can somehow separate out the different subgroups of women – those who are prone to depression and those prone to blood clots – based on more than simply asking about their family history, then we will be able to mitigate the risks more effectively and reduce side effects.” It’s worth noting that Nahavandi isn’t fuelled by some do-gooder altruism – she too has taken the contraception gamble and lost, multiple times, including an experience with a pill that left her with impaired vision for three days. So she gets why many women’s attitudes towards hormonal contraception could now best be summed up as ‘anti’. “The biggest thing missing in women’s health is trust,” Nahavandi acknowledges. “And how do you change that?” By signalling game over for the contraceptive gamble, her service might just be part of a wave that helps rebuild that trust. Wish her luck.
“For eight years, I’ve been trying to find a contraceptive that works for me. After six months taking a combined pill, a large blood clot came out of me when I wasn’t even on my period. Distressed, I switched to the progestogen-only pill (POP). [While on it] I would just cry for no reason – it was as if I had completely changed personality. After a year of ‘pulling out and hoping for the best’, I had an IUD inserted, which I’ve been on for four years. The impact on my moods isn’t as dramatic, but I wouldn’t exactly recommend it; my anxiety is exacerbated, sex can be painful and, two years in, ultrasounds revealed that I’d developed cysts on my ovaries. The pain when one collapsed was like nothing I’d experienced. Then, three years in, I bled continuously for three months. I’d be tempted to try Natural Cycles, but I’m concerned about the risk of falling pregnant. I’m due to have my IUD taken out and I’m dreading [deciding my next move].”Elizabeth Harper, 26, university administrator
Know your options
Endocrinologist Dr Lisa Owens offers an evidence-based briefing on the different contraceptives a doctor will offer you.
Combined oral contraceptive pill
What? A mix of oestrogen and progestogen that prevents ovulation.
Watch-outs: Nausea, headache, breast tenderness and irregular bleeding are common.
What? Works in the same way as the combined pill, but only releases progestogen.
Wins: It may be suitable if you react badly to the combined pill, and certain types may help manage painful periods.
Watch-outs: Pills must be taken at the same time each day. Random bleeding and breast tenderness may occur when you begin taking it.
What? A long-acting contraceptive that prevents fertilisation by releasing levonorgestrel.
Wins: It can be kept in for up to five years and the failure rate is low.
Watch-outs: Irregular bleeding is common in the first six months. One in eight users will develop an ovarian cyst. Most of these cysts are symptomless and 94 per cent of them will disappear within a few months.
What? A piece of plastic inserted in the upper arm that works primarily by preventing ovulation with progestogen.
Wins: Very low failure rate, and there’s no evidence of a delay in return to normal fertility after removal.
Watch-outs: Menstrual bleeding may stop, become more or less frequent, or prolonged during implant use.
What? Made of copper and plastic, it stops fertilisation through copper’s effect on the egg and sperm.
Wins: Pregnancy rates for IUDs with copper are between 0.1 per cent and 1 per cent after the first year of use. There are no hormones involved, so no related side effects. It may reduce the risk of some cancers.
Watch-outs: Irregular bleeding, and if pregnancy does occur, there’s an increased risk that it’ll be ectopic.