A BITTER PILL

The trial-and-error approach to picking a hormonal contraceptive that works for you could be about to end

Hormonal contraception is a well-documented nightmare, with cautionary tales about the pill, the coil and the implant shared between women like Tripadvisor reviews. Now, one start-up is using cutting-edge data science to help women discover the method that will work best for their body, and WH has a front-row seat

hTe winding streets behind King ’s Cross station aren’t much to look at. Just 10 minutes north of Google and Youtube’s slick towers exists a desolate road, decorated only with the triumvirate of developing-london hallmarks: incomplete luxury flats, faded warehouses and a mini chain supermarket. A couple of doors down from said store sits an office space just as unremarkable. Workers are hunched over laptops, their ear holes plugged with plastic to help them focus on the task at hand, and the fruit basket contains a few Golden Delicious, a browning banana and a turgid gaggle of conference pears.

These staid surroundings are home to University College London’s ‘Hatchery startup incubator’. Don’t speak tech? It’s a programme that helps to fund a select few of the university’s promising alumni to grow their big ideas into legit businesses. WH is here to learn more about a fledgling project called Pexxi (yourpexxi.com), whose team wants to change your life by changing your contraception. The idea is to develop a science-led algorithm to replace the current birth control gamble of pot luck and trial and error via a ‘smart decision-making platform’. The Pexxi team believe 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 (and identify those to avoid).

‘We still treat contraception as if preventing pregnancy is the only goal, without considering reproductive, physical or mental health,’ explains founder Shardi Nahavandi, a 29-year-old student-turnedbiotech 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.’ Nahavandi’s determination hasn’t gone unnoticed. On the day WH drops by her office, she apologises for being tired; Pexxi won a healthcare innovation prize from the University of Cambridge the night before. Other winners included a company that prints replacement hearts for ill babies and a team that developed an algorithm that detects five types of cancer, and while the menstrual cycle might not seem as life and death as this, the process of finding hormonal contraception that works with your body rather than against it can be frustrating at best, debilitating at worst.

UNFAIR PLAY

Hormonal contraception has been a mainstay of many women’s lives since the combined oral contraceptive pill became available in the UK in 1961. Between then and now, there have been multiple developments. The progestogen-only pill came in 1969; longer-acting options, including an intrauterine device that releases the hormone levonorgestrel, aka the Mirena coil, arrived in 1990; and the weekly contraceptive patch came in 2002. From then to now, hormonal contraceptives have gone from emblem of women’s empowerment to something many feel is anathema to freedom. There are the standard problems across all doctor-prescribed medication: the postcode lottery, the belief that one pill works for all. Only, with contraception, the situation is starker – it isn’t supposed to be a quick fix for certain symptoms, it’s meant to be a long-term solution.

And how do women choose between different types? For years, it was based on whisperings. You know the name of the pill your friend blamed for making her balloon in her early twenties, and your cousin warned you against the Mirena coil after weeks of tempestuous moods and errant bleeds. But their bodies aren’t your body; every woman is different and what works for one doesn’t for 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. Most notably, those concerning mental health, highlighted by the #madaboutthepill campaign from the now-defunct young women’s digital brand The Debrief and BBC Radio 4’s Woman’s Hour.

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

Dr Lisa Owens, endocrinology researcher at Imperial College London. Indeed, the broader NHS position remains that oral contraceptives have no mental health impacts. Equivalent data for longer-acting forms of

The contraceptive pill is no longer an emblem of women’s empowerment

contraception, such as the coil, doesn’t exist, she says, due to the fact that they’re used less. Figures published in March back this up, showing that 90% of women who receive contraception from their GP or a pharmacy take either the combined or progestogen-only pill.

But why does a shudder ripple through the shoulders of some women on hearing the word ‘Microgynon’, while your best mate’s got on just fine with the daily dose she’s taken since she was 16? Experts don’t know yet. ‘There’s no doubt a subgroup of women who are more vulnerable to both their own hormones and the synthetic ones contained in contraceptives,’ explains Dr Michael Craig, clinical lead and consultant psychiatrist at the Female Hormone Clinic at London’s Maudsley Hospital. ‘What we don’t know is how big this group of women is, or what’s different about them.’

ALTERNATIVE FACTS

More certain is that women are hungry for an alternative, a get-out from the gamble. Just look at the surge of enthusiasm that greeted the launch of the nowcontroversial Natural Cycles app in 2017 (by summer 2018, it had reportedly attracted over 800,000 users), with its tag line: ‘No hormones, just science.’ Granted, it was created by a top physicist who helped find the Higgs boson particle, but its mechanism, whereby users take their temperature using a basal thermometer, input it into the app and are then told whether they’re good to have unprotected sex or not, drew unfavourable comparisons to the so-called rhythm method (where women track their menstrual cycle to predict ovulation) – an approach that’s been used with varying degrees of success for centuries. Many commentators weren’t surprised when a spate of unplanned pregnancies were reported, and the Advertising Standards Authority banned an advert for the app that claimed it was ‘highly accurate’. So, when WH caught wind of a start-up aimed at making existing contraceptives work better for women, it’s no surprise that our interest was piqued.

It’s worth noting that Nahavandi isn’t fuelled by some do-gooder altruism; she needs this as much as you do. She’s taken the contraception gamble and lost, multiple times, including an experience with a pill that left her with impaired vision for three days and another she blames for exacerbating a metabolic disorder, causing weeks of gastric symptoms so aggressive she couldn’t leave the house, oh, and hair loss. And if a leader is only as good as their team, Nahavandi must be chuffed that she’s formed quite the formidable gynae health power squad. There’s a consultant gynaecologist who’s also vice president of the European Society of Contraception and Reproductive Health, a clinical senior lecturer in psychiatry at Imperial College London currently studying the link between female hormones and mental health, a medical doctor and serial entrepreneur with a PHD in biomedical engineering, and a women’s health advocate who’s raised over £35 million for the UN. Beyond the inner circle, there are links with Genomics England, Harvard University and The Wellcome Trust. Yep, power squad.

PRECISELY DOES IT

So, how do they 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 elements to find a type that fits.

The first step is to make sure that the hormones in your pill or coil align with your own so as to avoid the aforementioned consequences of trying your hand at the contraception gamble, and losing. 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 your hormonal profile – essentially, where your levels of progesterone and oestrogen are at. From there, your profile is mapped on to the index of hormonal contraceptives the algorithm knows about (it’s constantly fed with the latest research) to find your best match.

While hormone compatibility negates the infamous in-your-face symptoms, the genetic testing element of

Pexxi (involving a simple swab of the mouth using a kit you’re sent in the post) provides an extra level of long-term security – important, as contraceptive side effects aren’t always noticeable. Say your DNA test (and the medical questionnaire you complete alongside it) 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, for example, increase blood pressure, which could increase your risk. Clever, right?

Such an approach may sound futuristic, but experts believe it’s going to change the world of medicine – and soon. ‘Pharmacogenomic research is starting to reveal how genetic differences influence women’s unique responses to specific medications,’ explains Dr

Peter Fish, the doctor-turnedentrepreneur in Pexxi’s power squad. ‘The US Food and

Drug Administration recently listed a few hundred drugs with pharmacogenomic considerations [read: drugs that research suggests 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.’ Indeed, earlier this year, health secretary Matt Hancock announced his plans to roll out predictive genetic testing across the NHS.

NEW RULES

Never mind the studies or developing the algorithm, Nahavandi insists that the hardest aspect of the process so far has been getting people to take her seriously. She first came across the bias against female-specific healthcare in academia. Frustrated by doctors’ lack of interest in the way her hormones were affecting her health – and

freshly graduated with a master’s degree in business and health technology – Nahavandi began a second master’s course in endocrinology in an attempt to find answers herself. She approached a prominent professor in the field of stress to ask if he would be prepared to be involved with her research. ‘I wanted to know if he was interested in feeding in his work on how cortisol interacts with progesterone, so that we could adjust our algorithm for this,’ she recalls. ‘He said that his team didn’t study women because they “didn’t really understand the menstrual cycle”.’

She’s felt similarly frozen out in the business world. Despite Pexxi’s proposal speaking directly to a basic need of 26% of the world’s population (that’s the proportion of people who, according to Unicef, are women of menstruating age), multiple business consultants have struggled to grasp that what they’ve created is a viable commercial enterprise. ‘One adviser right at the beginning said: “What are you doing? Are you a charity?”’ she recalls, eye-roll barely restrained. ‘I’m determined to help women feel in control of their contraceptive choices. I am passionate. But we’re not a charity. In fact, we could be very profitable.’ If the men in suits – or more likely box-fresh Nikes – aren’t getting it just yet, it shouldn’t be long before they do. ‘Funding for femtech is growing rapidly, passing £750 million in the past three years,’ explains Shruthi Parakkal, lead femtech market analyst at consultancy Frost & Sullivan, one of the first companies to recognise the potential of the sector. ‘There’s been a recognition of the need for gender-specific solutions when it comes to addressing the particular needs of women.’ Two of the biggest names in the burgeoning industry, menstrual tracking app Clue and the aforementioned Natural Cycles, are worth £23 million and £28.5 million, respectively.

TIME FOR CHANGE?

Forces of disruption – to borrow the tech-world parlance – 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 femtech? Dr 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.’ Dr 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 target them better, mitigate the risks more effectively and reduce side effects. Right now, if you’re in one of these subgroups, the consequences for you are very significant.’ Quite.

Back to the here and now, and the public mood around hormonal contraception is best summed up with the prefix ‘anti’. Be it measles vaccines, antidepressants or doctor-prescribed contraceptives, there appears to be a growing sense of mistrust around the pharmaceutical and medical industries, and much of it is coming from women. That’s not to equate your city executive pal who gets on just fine using Natural Cycles with a Midwestern soccer mom who spends her days posting articles linking MMR with autism (for which there’s zero evidence, by the way). But zoom out and there’s a discernible thread of dissent running between the two. Perhaps it’s not altogether surprising; this magazine has published award-winning reporting on the lack of seriousness with which female pain and female-specific conditions are handled by the medical establishment. (We’re not all talk, either; our Editor-in-chief is working with a parliamentary task force to help level out the gender imbalance when it comes to healthcare access.) Women don’t spend years between symptom presentation and diagnosis and wait longer than men in A&E and remain loyal, in belief and action, to top-down medical institutions.

Perhaps, in this climate, it’s more urgent than ever to make the case for the state of play not being a simple binary of ‘bad’ doctor-dispensed hormonal contraceptives and ‘good’ non-hormonal solutions. That the answer lies in honing the process, not dropping out of the system entirely. ‘The biggest thing missing in women’s health is trust,’ Nahavandi reflects. ‘And how do you change that?’ By signalling game over for the contraceptive gamble, could her service be part of a wave that helps rebuild it? We’ll have to get back to you on that. But while 2019 might not hold all the answers just yet, at least someone is asking the question.