In 1960, the first oral contraceptive was released. What we refer to as ‘The Pill’ became accessible to the general public, and before you knew it, a societal revolution ensued. The first Pill was developed from the research of Scientist, Carl Djerassi. In 1951, he had been the first to successfully synthesise an artificial progesterone compound, norethindrone – a crucial step in developing the Pill.
The decades following the Pill’s release saw vast improvements in its safety. The levels of progestin and oestrogen were lowered; hormone levels were adjusted in relation to the stage of the user’s menstrual cycle; and the progestin-only pill was created. When taken correctly, the Pill is 99% effective, although in reality it is closer to 91-95%. But nonetheless, when compared to condoms (which are around 82% effective with typical use) the Pill looks like a pretty good bet.
But the Pill is not perfect – ask anyone who has tried it.
In 1989, almost four decades after his work on norethindrone, Djerassi wrote a paper called ‘The Bitter Pill.’ “All we can expect well into the beginning of the 21st century,” the disheartened scientist concluded, “are minor modifications of existing methods [of contraception] that will not ‘affect our total dependence on conventional 19th and 20th-century approaches to birth control.”
In a 2022 report on global contraceptive use, the United Nations found the most common contraceptive method to be female sterilisation at 22.9%.[1] Male condoms were found to be used by 21.8%, IUDs by 16.8%, and the Pill by 15.7%. Whilst all of these methods have been drastically improved since their inventions, they are all, as Djerassi predicted, methods originating in the 19th or 20th centuries. Was he right? Are we living with yesterday’s birth control?
I put this idea to Dr Daniel Johnston, Chief of the Contraception Research Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ‘For males,’ Johnston told me, ‘we have vasectomy, condoms, and coitus interruptus. Right? That’s it.’ We have had all three methods for over a century – ‘there is nothing new, essentially.’ Johnston, however, pushed back against my dismissive stance on developments or lack thereof in hormonal female contraception. Whilst ‘the same basic mechanism has been used [in the Pill and other hormonal methods] since 1960,’ this does not mean new drugs aren’t still being developed.
Johnston levelled with my frustration at the timeline drug development takes; scientists would ‘like to make them completely better, but the way they’re trying to change the market is to make these small improvements’ such as creating new active molecules and delivery methods.
In 2001 and 2002 respectively, the vaginal ring and birth control patch were released. Both methods rely on the same basic mechanism as the Pill but the former only requires changing once a month and the latter, once a week.
A more recent example of the development of the Pill is Opill. Approved by the FDA in 2023, Opill is the first non-prescription daily oral contraceptive, expected to hit the market in 2024. A nonprescription Pill could increase the accessibility of and change social attitudes towards contraception.
Two key developments Johnston is interested in is the idea of non-hormonal contraceptives and on-demand contraceptives. The hormonal IUD, Pill, implant, patch, injection, and vaginal ring are all long-term, hormonal contraceptives.
Whilst offering users more hormonal options, these developments do not contradict Djerassi’s pessimism in 1989, which touches on the ‘modifications’ of existing methods rather than completely new forms of contraception.
So, what might ‘new’ contraceptives look like?
Hormones such as progestin and oestrogen do not work solely within the reproductive system but affect multiple bodily functions. By comparison, if scientists can locate a specific protein required to create functional sperm or a developmentally competent egg and specifically disrupt its job – and only its job – the whole chain of the reproductive system is disrupted. This is the idea behind non-hormonal contraceptives. These products would reduce fertility whilst also hopefully reducing the side affects associated with current hormonal contraceptives, potentially making them more suitable for those who struggle with options presently available.
In Cornell University, researchers have successfully inhibited an enzyme called soluble adenylyl cyclase in mice. This rendered sperm temporarily immobile, making the mice temporarily infertile. The drug took around thirty minutes to work and lasted up to three hours – not as long as scientists would like. Ideally, the product would last around 8-12 hours to allow the user to take the product in advance. If, for example, the user could take the drug in the late afternoon, they would be covered until the following morning. If this could be done and the drug passed human trials, it could be the first on-demand, non-hormonal male contraceptive.
Another example of a non-hormonal, on-demand contraceptive in development is the Human Contraceptive Antibody – essentially, an antibody which is a protein on the surface of sperm. The antibody was discovered when a fertility clinic noticed it in the cervix of a woman presenting with infertility. The idea goes that the film would be inserted before sex to release the molecule that creates an unsuitable environment for sperm. Like the trial in mice at Cornell, it would work as a short-term contraceptive with minimal risk of side effects.
Such technologies are still a few years away, depending on scientific development and trial processes. However, the possibilities regarding new contraceptive developments are exciting.
Ovaprene, a non-hormonal contraceptive developed by Daré Biosciences, is further along in its trial processes. The product is an intervaginal ring covered by mesh (think of a trampoline) that releases ascorbic acid and ferrous gluconate, creating a toxic environment to sperm. Unlike Johnston’s interest in on-demand contraceptives, the product lasts a month. It has, however, shown promising results in pre-clinical trials, and if it reaches the market, it could be the beginning of the next generation of contraceptives.
Perhaps Carl Djerassi was wrong. Whilst these products are still a while away, maybe we will see new, novel, and revolutionary developments in contraception this side of 2050 after all.
[1]United Nations, (2022). ‘World Family Planning 2022’. pp.17 https://www.un.org/development/desa/pd/sites/www.un.org.development.desa.pd/files/files/documents/2023/Feb/undesa_pd_2022_world-family-planning.pdf
