Laying the foundations for a non-hormonal era in contraception

When it comes to something as important as health, why should contraceptive users still have to make compromises?

Hormonal therapy is one of the most groundbreaking innovations of the 20th century. The introduction of hormonal therapy 60 years ago made the pill and many other birth control methods such as the hormonal IUD possible. This method was a revolution at the time: reversible, and extremely effective contraception was now in the hands of women. The flip side is, not everyone has the same experience with the same contraceptive. The current methods can cause serious side effects which leave people in a difficult toss-up between suffering side effects or switching to a less effective method. This is where the problem lies. This is where OUI comes in.

A radically new approach to contraception

Cirqle Biomedical is pursuing a revolutionary solution to put an end to the compromises women make with their contraception: a non-hormonal contraceptive that works in a completely new way. The product, which goes by the name OUI®, is the first of its kind. OUI is a gel that is inserted into the vagina and releases small biopolymers that reinforce the barrier properties of the cervical mucus. The cervical mucus is then made impenetrable for sperm, which prevents sperm cells from travelling through the cervix and fertilising an egg. The biopolymer is a type of sugar molecule derived from fungi or the shell of crustaceans which is known to be highly biocompatible, biodegradable, non-toxic, and is widely used in biomedical applications.

During the non-ovulatory stages of the menstrual cycle, cervical mucus is a thick barrier that sperm cells or bacteria are unable to pass through. During ovulation, cervical mucus becomes more watery to allow sperm to swim through. OUI reverts cervical mucus back to its natural impenetrable state even during ovulation.

OUI® is a first of its kind non-hormonal contraceptive that is targeted to provide effective protection minutes after application by making cervical mucus temporarily impenetrable for sperm cells.

With OUI, we have re-invented blocking sperm. Instead of forming a physical barrier with a foreign object, such as an external or internal condom. OUI reinforces the body’s natural barrier (the cervical mucus) to make it impenetrable for sperm. The contraceptive is currently being tested in large animals. In efficacy trials in which OUI is compared to another spermicide, we have found that OUI is 100% effective at preventing pregnancy in the animals, whereas the spermicide is only 87% effective. These results represent the first demonstration of a novel mechanism of action in contraception in 60 years. About time, too. The physical and psychological effects of the currently available contraceptive methods highlight that it is high time we take women’s health more seriously.

Hormonal contraceptives and physical health

As with all drugs, the response to hormonal contraceptives depends on the individual. Hormonal contraceptives are effective methods of birth control. 9 in 100 users of the pill and less than 1 in 100 users of the hormonal IUD get pregnant each year. Hormonal contraceptives work wonders for some and have benefits in addition to effectively preventing pregnancy. Studies have shown that combined oral contraceptives decrease the risk of ovarian cancer by 20% for every 5 years of use, and of endometrial cancer by 50%(1).

However, others make pretty sizable compromises to prevent pregnancy through using hormonal contraceptives. Many women using progestin-only hormonal methods report unwelcome changes in uterine bleeding patterns and there is robust scientific evidence showing an increased risk of developing breast cancer by 9% when hormonal contraceptives are used for less than a year and up to 38% when used for 10 years(2). Moreover, the FDA estimates that three to nine women out of 10,000 will develop a serious blood clot from using hormonal contraception is every year(3). Given that more than 300 million women use hormonal birth across the world, a potential 90,000–200,000 + people will develop a blood clot while using contraception(4).

The mental health challenge of hormonal contraception

While the physical side effects and risks of hormonal contraceptives have been discussed in moderate depth in the scientific community, it is only in recent times that we have started talking about the mental side-effects and risks.

Researchers have studied whether the risk of being diagnosed with depression is linked with the use of hormonal contraceptives by following the health records of 1 million women in Denmark over 14 years. The researchers found that women who were on hormonal contraceptives were 50% more likely to be diagnosed with depression six months later. Despite the overall risk of developing depression being low, the increase in risk is real, especially for women aged fifteen — nineteen(5). Most often, the mood changes caused by the pill are not as dramatic as developing depression, however, they still can affect the user’s quality of life. For example, data from a double-blinded placebo-controlled study including 340 women showed that the group of women who received hormonal contraception had lower well-being and sexual desire compared to the women that received placebo(6).

Discussions with hormonal contraceptive users have shown that mood-related issues such as anxiety and depression are common. The fundamental question is, “how does taking a hormonal medication, such as the contraceptive pill, influence the brain and the body?”

The hormones used for contraception in addition to preventing pregnancy by suppressing ovulation, have many other roles in regulating the way our body functions, influencing brain functions such as memory, facial recognition and social interaction, stress levels, and the immune system to name a few (Hill, 88–89). Artificially changing the levels of these hormones is likely to interfere with these important functions and lead to risk of various adverse health outcomes, particularly in regards to mental health — a few of which we will now explore.

Emerging research points to changes in brain chemistry caused by the pill which then subsequently may have effects on important processes in the body. One example is the possible effect of the pill on neurotransmitter patterns which can negatively influence women’s mood(7). Dopamine and serotonin are neurotransmitters that are important for creating the sensation of pleasure. The release of these neurotransmitters rewards actions essential for the survival of our species such as eating and having sex. Research has shown that estrogen increases these positive feelings, meaning sex is more enjoyable and certain foods taste better(8), while progesterone has the opposite effect(9). Since the pill works by keeping estrogen levels low and by stimulating progesterone receptors it runs the risk of dampening the reward processes in the brain(10). Therefore, the effect of the pill on dopamine and serotonin signalling may cause women to lose enjoyment in the activities that used to bring them pleasure — which, incidentally, is a common symptom of depression(11).

In addition to the possible effect of the pill on neurotransmitter patterns, researchers have identified differences in the way women using the pill respond to stress. Some studies found that the system that releases the stress hormone cortisol is dysfunctioning(12). In some studies pill-taking women had a blunted response, others had no response and one study found levels of cortisol decreased in response to stress(13). Cortisol helps our bodies deal with stress, therefore lacking this stress response harms your ability to cope with stress. As a result, this broken stress response may be an important factor in developing anxiety and depression(14).

These examples are insights into the current thinking about the potential underlying mechanisms explaining why so many women experience negative mental side-effects from using hormonal contraception. However, the research on understanding how hormonal contraceptives influence mental health is still in its infancy. How the Pill Changes Everything by Dr Sarah Hill compiles numerous studies on the effect of the contraceptive pill on women’s brains and bodies and provides a comprehensive background of women’s hormones(15).

The unmet need in contraception

Contraceptives are rooted in a long history of granting the power of choice. Choosing when to get pregnant, choosing not to get pregnant, choosing to wait to decide if to get pregnant are all ways in which contraceptives enable users to exercise agency over their bodies. It seems counterintuitive that a drug that enables the user to choose the life they want to lead can also change the very way they feel about their life. People who use contraceptives do so to choose who they want to be.

In 2020 we conducted an online survey with 1500 women. The survey results showed that nearly every second woman in the US wants their contraceptive to be hormone-free (49%). However, despite the clear wish from 49 out of 100 women in the US to go hormone-free, only 14 out of 100 women use the current non-hormonal options: copper IUD, fertility awareness methods, spermicide and condoms(16). The large gap between what women wish for their contraceptives, and what contraceptive women use can be explained by the relatively poor alternatives to hormonal contraceptives available today.

The price to pay when deciding to avoid hormones is either side-effects or worries over inefficacy. For instance, 44% of copper IUD users discontinue their treatment within the first 5 years, with approximately 2/3 of women reporting that the reason was pain, bleeding changes or other side effects or because the foreign object had been expelled from their body(17,18). Spermicides are limited in their efficacy, with actual efficacy in between 85–90% only.

49% of women say it is very important that their contraceptive does not contain hormones. However, only 14% of women use non-hormonal alternatives.

The catch 22 of contraception today

There are currently only 4 approaches to contraception for women, also known as mechanisms of action (the way the method works). Disabling sperm is an approach first invented in 1900 and still used by some today. Spermicide is a contraceptive that immobilises and destroys sperm before they reach the entrance of the cervix. The next mechanism of action is inflaming the uterus. First invented in 1910, the IUD is a foreign object inserted into the uterus, which elicits a local inflammatory response and contains either copper that immobilizes sperm or hormones that suppress ovulation. Blocking sperm is another approach to contraception which despite being first widely used in the 1920s is still used today in the form of condoms, diaphragms and other external barriers which prevent sperm from entering the vagina. The final and most modern approach (until OUI came along) is suppressing ovulation. Hormonal therapy, invented in the 1950s, prevents sperm from meeting an egg, by suppressing ovulation. When an egg is not released, sperm cannot fertilise it.

What happens when the solution to a problem causes a new problem? Compromise. With the current contraceptive methods, you are likely to be compromising somewhere. The methods which work effectively to prevent pregnancy, such as IUDs and the pill are effective because they cause massive changes to the women’s physiology, sometimes leading to unpleasant side effects. On the flip side, the methods with fewer side effects are significantly less effective.

In choosing a method with minimal side effects to prevent pregnancy, you may be compromising on the entire reason for taking birth control — effective pregnancy prevention.

More options, fewer compromises

A contraceptive that works wonders for one person, may very well do the complete opposite for another. The same goes for many things related to our body, such as the foods we choose. Thankfully there are so many breakfast options in this world that we can start our day eating whatever makes our body feel the very best. So surely the same should be true for other ways in which we care for our bodies: namely, preventing pregnancy. We should have an array of options available to allow people to make the choice that feels the very best for their body. We have a myriad of options for many of the things we put in our bodies, why not contraceptives?

Ushering in a new era in contraception

Today there is not a good enough alternative to hormonal contraception for many, so they continue using hormonal methods and endure the subsequent unpleasant side-effects because pregnancy prevention is the priority. However, we believe we can do better than this. We aim to develop an alternative that provides effective pregnancy without the compromise of accepting the negative side-effects that currently come with that.

OUI uses a completely new contraceptive technology that aims to empower the user through supporting their health, providing freedom and effectively preventing pregnancy. This breakthrough in cervical mucus engineering sets the stage for a new era in contraception, in which hormonal methods are replaced as the go-to option for women. We imagine a future in which birth control enables the user to thrive, not compromise — a goal that we aim to realise with OUI.

Bibliography

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