Family physician Montida Fleming, MD, who played a role in norgestrel (Opill)'s road to FDA approval, presents what providers need to know about this soon-to-be-available option, from mechanisms of action to the data on efficacy and safety. She also discusses Opill's advantages in a world where patients face numerous barriers to prescription contraceptives and in a political climate that has made reliable methods more crucial than ever. Hear her thoughts on how medical professionals can help ensure equitable access for patients of all ages, gender identities, income levels and personal circumstances.
Thank you so much for having me. Um, so I go by my, um, my Fleming. I use the pronouns. I am a, um, assistant clinical professor at UCSF in the Department of Family and Community Medicine. I primarily work, um, with the Family Medicine residency program at San Francisco General Hospital, and I also work um, at UC Berkeley in the Student Health Center, um, on top of a number of other, um, different jobs. Um, but I, um, I am definitely happy to be here, um, have been, I'm sort of a part of some of the advocacy efforts that led to the passage of this, um, of this medication over the counter, and so I'm Really excited to um share a little bit about um the process, um, and, uh, and a little bit about this medication as it becomes available to our patients. Um, I definitely want to leave uh plenty of room for questions at the end. Um, so any, um, questions, big or small, that come up, definitely feel free to add them in the Q&A. OK. Oh. Um, here are our objectives, um, to really understand the context for the FDA approval of the op pill for over the counter use, um, as our, as the United States' very first over the counter, um, hormonal contraceptive option. Um, understand the mechanism of Action of progesterone-only pills as kind of a reminder, um, reviewing the safety and efficacy data for this particular progesterone-only pill, um, and then just kind of discussing the implications in a, in a broader context, um, with, um, the current reproductive health access crisis that we are currently facing in this country. Um, and this image is from, um, a, uh, uh, an or a coalition, um, called Free the Pill that is, was hosted at Ibis Reproductive Health, um, who really laid the groundwork for, um, a lot of the research and advocacy efforts that led to the passage of this pill. Um, so just to kind of put this into context, so over the counter contraception and and specifically over the counter hormonal contraception as a concept is definitely not new on a global scale, um, although we were a little bit slow to adopt here in the United States. Um, so this is a map that, um, is based off of a 2012 survey, um, where they took a look at all of the different countries um in the world to see what is, um, what hormonal contraception options exist for folks uh to access over the counter. Um, and It demonstrated that over 100 countries have over the counter access to oral contraceptives in one way, shape or form, either legally available without prescription or without any sort of health screening. Uh, which accounts for 24% of the country's 8% legally available without prescription, but with a health screening, um, and then 38%, while technically, um, legally, uh, legally speaking, not necessarily available without a prescription, um, many of the retail outlets and pharmacies do sell, um, contraception over the counter. Um, Uh, and it is readily available for folks. Um, since this map was published, um, the United Kingdom has also joined the ranks of, of countries that have started to offer over the counter, um, hormonal contraceptive options with two different progesterone-only pills that are now available, um, within that, um, within that country to, um, over the counter, um, Uh, patients, um, and now the United States is, is the most recent one. So, um, this is really exciting to kind of, uh, join this global effort and, and, you know, uh, global compilation of, of data essentially on the safety of, of using, um, some of these medications over the counter. Um, and the, the, uh, route to get this FDA approval also is not something that, um, is new or novel. It definitely didn't come out of the blue. This is actually part of over 20 years of, um, of research and Effort on behalf of researchers, scientists, um, the pharmaceutical company, um, as well as, um, as well as local grassroots advocates to get this to happen, and it just only recently ended up making news and so more people sort of knew about it. Um, this, uh Essentially, in order to switch a medication from prescription only to over the counter use, it requires robust research demonstrating that the product meets the criteria for over the counter use, and that includes that people can understand how to use the product by reading the drug facts label on the back of the pack and can understand it and use it safely, um, are independently able to determine whether Out oversight from a healthcare provider if the pill is appropriate for them to use or not by reading that label and that they can take the product as indicated on the label and those are the criteria that it needs to meet and then once the once all of that research is sort of compiled and the pharmaceutical company and the researchers feel that they have made a compelling enough argument. Then they submit a completed application to the FDA, after which it's a 10 month review process to make a determination of whether or not to approve it, and it was, it was sort of unclear when it first kind of came to the FDA. The application came to the FDA in 2022, whether or not they would go forward and, and approve it, and they really sought a lot of Advice and testimony from uh scientists and, uh, healthcare leaders in the field in order to make a determination. Um, and, and really, um, so a lot of strong evidence was really presented to make the case that, that this medication is in fact safe for over the use, um, over the counter use, um, and can really go a long way in, um, in helping folks realize their reproductive autonomy. So just a quick kind of pharmacology review how progesterone-only pills work. Um, so, Uh, the primary method that progesterone-only pills, um, work to prevent pregnancy is by thickening the cervical mucus. This essentially creates a barrier or a wall through which, um, sperm is really finds a difficult time to enter. There are a number of secondary, um, mechanisms as well, um, although are sort of less prominent as compared To, uh, combine hormonal contraceptives, and this includes preventing ovulation via feedback inhibition of the, um, gonadal pituitary, uh, the hypothalamic pituitary gonadal axis, um, so feedback inhibiting GNRH, um, from the hypothalamus, um, as well as LH and FSH from the pituitary. Um, it also thins the endometrial lining, creating a, an inhospitable, um, Uh, home for a pregnancy, and it affects tubal motility, meaning that even if an ovulation does occur, um, that, that released egg has a really hard time making its way through the um through the fallopian tube to even get to a place where it could be implanted. So there are a number of mechanisms of action, but the primary driver of uh, of the contraceptive efficacy of progesterone-only pills is really that cervical mucus thickening. Um. There are a few different formulations that are commercially available in the United States. Um, norithedrone is kind of the one that most of us have the most familiarity with. Um, so this is, uh, the mini pill, um, is, is the, is the name that we often hear it by. It is a lower dose than the progestins in combined, um, hormonal contraceptives. It does require strict adherence and so typically we say that um if you aren't able to take it within a 3 hour, the same 3 hour time window day to day, that it may have decreased efficacy. Um and so um you would, you know, consider using a backup method for up to 48 hours if you do take that pill within outside of that 3-hour time window. Um, that it, it is a pill that is. Taken continuously, so there is no um hormone-free interval, so there's no sort of um uh period where you stop the pill or at least stop the hormonally active pill for a withdrawal bleed, and this can sometimes lead to some more irregular um bleeding patterns. Studies have shown that, uh, that the mini pill is not, um, very Uh, potent or not very reliable at inhibiting ovulation, about 40 to 50% of people taking norithedrone at 0.35 mg continue to ovulate, um. And, and again, the primary mechanism of action is the cervical mucus thickening, um, because of that. Um. Norgestrel 0.75 mg. This is the medication that is going to be in the oak pill. It is actually technically not commercially available at this current time. It was up until about 2005, and the manufacturers actually took it off of the market, not for any sort of safety reasons at all, um, but they, um, they just decided to, I guess, hang on until they were able to get it. Approved for over the counter use, um, but similar medications are regularly available abroad in European countries as well as Canada. Um, and, uh, this, uh, this medication at this dose has been shown to inhibit ovulation in about 2/3 of people, so 66% of people will have their ovulation inhibited, so a little bit more reliable um ovulation inhibition as compared to no syndrome, um, but Um, and it will still be labeled for, um, to, uh, for like a 3-hour window period, um, of adherence. Although there have been studies, and I'll review this in a little bit, um, that indicates that it may actually be, um, in, in reality, much more forgiving than this, than this, um, 3-hour time period, but just, um, we don't have enough data to, to change the label at this time. Uh, similar to noinrone, it's a medication. That you take continuously without any withdrawal period. Um, so it may also have some more irregular bleeding patterns. Um, and then the very last one, was also a relatively newer approved medication, risperinone. Um, this is a progesterone medication that is taken at a much higher dose than typical, um, uh, pro, progestin components of a combined hormonal contraceptive. So it's 4 Milligrams. The brand name is Flinn. It's only available by brand at this time, so it can be a little bit more expensive for folks. Um, it does actually prevent ovulation reliably, and that is the main mechanism of action of that one. So it's a little bit different. The mechanism of action is, is a little bit more similar to combined hormonal contraceptives, and it has a 24 hour time window, um, due to its longer half-life. And so, um, it's not sort of um. Maintained to that 3-hour time window as the other um progesterone-only pills. And so, uh, and it, and it also has a 4-day hormone-free period for more scheduled withdrawal bleeds in the hopes that that leads to a more regular bleeding pattern, although. Studies have demonstrated that people still continue to have some unscheduled bleeds in the studied populations with this, with this medication. So it more mimics the estrogen-containing birth control pills in, in the ways in which it, um, it works, the flexibility in taking it, um, and, um, uh, and it is often um kind of on the more expensive side because it's still under, under brand patent. And so with Norgestrel, um, which is, again, the, the progestin that will be in the over the counter o pill, um, it, uh, the studies have actually demonstrated a really low failure rate. Um, and so the, an actual use study demonstrated a Pearl index of 4.4%. That means 4.4%. Failure rate per 100 women years, um, which is, you know, the way that we, uh, report failure rates for all contraceptives and, and as a comparison point, um, that we sort of think about the, the typical versus perfect use of, of contraception options and we say that most likely, um, most people are gonna fall with. Within the typical use. And so that's usually the number that we end up thinking about and sticking to. So for all progesterone-only pills as well as combined hormonal contraceptives, so estrogen-containing contraceptives, is about 7% with typical use. Condoms are about 14%, and spermicides are about 28%. So as we can see, um, It is much more effective than um the other over the counter um contraceptives that are currently available, including condoms and spermicides. And so, um, and it's, it's very similar to other um prescription strength um oral contraceptives as well. Um, they, there was also a study, and this is kind of about the, the flexibility with adherence timing. There was a study that looked at deliberate non-adherence, um, with a 6-hour delay, uh, um, uh, from the time window when the pill was supposed to be taken, as well as a full 24 hour delay. And actually, they, they took a look at ovulation rates as well as the, um, uh, the cervical mucus. Thickness, um, which they scored in the study and it actually demonstrated that even with a 24 hour delay, there was really little effect on the contraceptive protection of uh of the, the Norgestrel pill and so it probably does have a little bit more um more window period than what. It will be labeled for and because this is a, a single study, it's not correlated to clinical outcomes. It's more just looking at sort of measures of cervical mucus thickness and whether or not an ovulation occurred, um, and no other similar studies have been done to corroborate the findings. It's kind of just not enough data to actually change the labeling yet. Um. Data does support that um people who have access to over the counter contraception use it and use it really reliably and actually much more reliably than people who use prescription contra hormonal contraceptives, and that is often because there are less barriers. To over the counter access as compared to um prescription access and so, you know, if a person is able to regularly um just go to the pharmacy or store and purchase their next pack without having to wait for a provider to get through their their um full inbox to find that they have requested. Um, a, a new prescription or a refill, um, that is now, you know, sometimes a few days or a few weeks later than what the person had actually wanted, um, then, uh, or, or past, um, them running out of that medication, um, then they actually end up having less missed doses, um, and, and more reliable use. Um, So we know that this, um, this is something that is really represents a promising, um improvement for efficacy because the more missed doses there are, more delays that people have in obtaining their next pack of pills, the less likely they are to have an interim unintended pregnancy. Um, it's also extremely safe. The progesterone-only pills are typically the pills that we usually prescribe for folks who have underlying health conditions anyways, right? And so, um, there is only really one strict contraindication, um, as, uh, on the CDC medical eligibility criteria, and that is current active breast cancer. Um, there are a few other, uh, kind of precautions um to think about as well. Um, and typically these, these precautions are not necessarily because it makes it unsafe in any way. It just may mean that the, um, these underlying conditions may make the contraception a little bit less effective, um. But the contraception does not actually have an impact on worsening these underlying health factors. So for instance, um, people who have a, a gastric bypass or malabsorptive procedure, and this is specifically like a R and Y gastric bypass rather than like a sleeve or another restrictive procedure. Procedure, um, it may, um, uh, it, it may decrease the efficacy, um, by impacting the amount of the progesterone that's able to be absorbed, um, by the gut, um, although there's some conflicting results on the efficacy for that anyways. Um, Anticonvulsants, certain anticonvulsants, um, can, uh, decrease, uh, the efficacy of the contraceptive as well. Um, this encompasses most anticonvulsants except for lamotrigine, which, um, does not have that interaction, um, for progesterone-only pills. Same thing with rifampin and some of the other, um, uh, uh, similar category anti. Tuberculosis medications can decrease the efficacy of the contraceptive. Um, decompensated cirrhosis is really just more of a theoretical concern due to the liver metabolism of progestins, but there have been good, reliable studies that demonstrate that progestin contraceptives do not affect disease progression or severity of the underlying liver disease, and so, Um, and so it's, it, it is a reasonable option, um, for folks, uh, to use and, and certainly when we sort of think about these, pregnancy is certainly high risk for many of these patient populations and so thinking about the relative risks and benefits of, you know, the medications, um, uh, taking the medication, taking the contraceptive as compared to having a pregnancy, um, uh, really often weighs in. In favor of going ahead with the uh with the contraception. Um, hepatocellular adenoma, there's actually no data for progesterone-only pills. Combined oral contraceptives can lead to the development of hepatocellular adenomas, um, but it's sort of unknown whether progesterone-only have, um, have similar effects, and the, the, the thought is that most likely it's related to the estrogen component. combined pills, um, but just because we don't have enough data to know, um, is why it's a category 3. and then same thing, antiphospholipid antibody positive. Um, these folks have really high thrombosis risk. It's really, um, uh, um, unwise to use estrogen-containing, um, birth control pills for, for this category of folks, and we have good evidence showing that there's a really low, um, And, and almost negligible impact for thrombosis risk with progestins. Progestins can be safely used for folks with other um BTE risk factors, but again, just because we don't have specific data about this category of, um, of people, uh, that, uh, the CDC conservatively puts it as a category 3. Um, there have also been studies that patients can really reliably self-screen themselves for these rare contraindications, and so, um, data supports the reliability of self-screening that, um, that is similar to provider-based screening, um, and, and also includes youth, right? So. Youth, adolescents, um, minors, um, have also been shown to be able to reliably self-screen themselves, um, just as well as a provider can for these rare contraindications, um, in order to, um, prevent, um, uh, prevent, uh, use, um, in a way that is not intended. Um, and the medication is also really safe and effective in breastfeeding, in breastfeeding patients as well. And so, you know, this becomes really important because there are many, many barriers to prescription contraception that people face, right? And this is why it is so important to have access to over the counter pills for people to be able to really take this matter into their own hands and access a reliable, safe, and effective. Forms of pregnancy prevention without the need of, of, uh, you know, a medical provider intervention. And so studies have shown that nearly 1 in 3 individuals have reported significant barriers to accessing contraception and for the number of people of childbearing childbearing age who wish to Uh, or childbearing potential who wish to prevent pregnancy, that's really a huge number of people in the United States who have had already experienced significant barriers to accessing contraception. Um, some of the most common barriers that have been reported include stigma, um, you know, stigma related to contraception use can lead to a sense of shame or Embarrassment to obtain the services or fill prescriptions at the pharmacy counter, um, difficulties with appointment availability, so thinking about wait times for appointments, inability to take off time at work or school in order to get to an appointment during, um, you know, during usual business, uh, clinic business hours, transportation barriers and cost of transportation. And especially if folks don't have a regular primary care provider or they're not really sure where to go if they don't really access healthcare and um for any other reason, these can all be um appointment-related barriers. Um, and then if they don't have insurance or they're underinsured with high deductible plans, um, the cost of the visit itself may be way too expensive for folks to even access. Um, And then there are some insurance coverage gaps, right? So, um, when the Affordable Care Act was passed, um, it did lead to the requirement of private insurance carriers to cover FDA approved contraception with at least some option, at least one option of every single category of contraception that is available to be covered without cost sharing to the patient. But there's been really uneven coverage and coverage gaps for some people's preferred contraception method due to some language in the law that allows insurance to dictate the terms of coverage, um, leading to an insurance-based barriers, and that includes, you know, um, if they have one generic that is available at no cost, but alternative. Formulations may not be covered, um, and a person's, uh, preferred, um, contraception, um, maybe another one that's not cost. Sometimes it involves, um, doing, uh, prior authorizations which may or may not be accepted, um, requires, um, trying, uh, uh, a higher prefer a more preferred form of on formulary before, uh, before going to another one that is less preferred. Um, all of these things lead to a lot of barriers for folks accessing the contraception that they want and need. And in addition, religious exemptions exist um for some employer-based insurance plans, and that, and they, and that continues to leave many people of reproductive potential without any covered options. Um, confidentiality ends up being a huge issue as well, and particularly when we think about, um, adolescents and, and young people, um, You know, contraception and sexual health falls under um confidential care, um, but considering, um, you know, whether, uh, the name of the clinic um that shows up on a person's insurance or um explanation of benefits, um, may, uh, may, um, uh, make it obvious what sorts of services are being sought out or, um, or, uh. Uh, utilized transportation barriers to a clinic, right, if um young folks maybe don't have access to a car, don't have a driver's license, may not have funds or money in order to be able to get transportation, in order to be able to pick up or fill a prescription at the pharmacy, um. Without the knowledge or help of an adult, um, that those are all things that, um, young people face, um, that are, uh, that continue to be barriers for prescription access. Um, and then, uh, additional confidentiality issues when it comes to people facing reproductive coercion and IPV, um, you know, um, they may be, um, prevented by partners from seeking healthcare, um, or, um, or for seeking confidential healthcare, um, from having their visit, um, be, be kept. Confidential or, or, um, or uh being in the room alone with a healthcare provider um may all be barriers as well. Um, and, and discrimination being um another common uh barrier that has been reported, um, particularly a survey of youth, um, reported facing difficulties, um, you know, On top of kind of lack of transportation and difficulties with scheduling appointments from stigma from both parents and healthcare providers, and more than half of those surveyed young people reported that one or more of those barriers actually prevented them from getting birth control at all. Black and Latina people and those of low English language. Good proficiency have been demonstrated to report lower rates of high quality contraceptive counseling that focuses on their values and their preferences um and so um they may be more likely to have discriminatory experiences, um, including having stereotyped assumptions being made. About them being pressured to use certain types of contraceptives over others, being more likely to be counseled towards a LARC contraception, and all of this has been documented in the literature, and transgender non-binary people who can become pregnant also face discrimination and stigma, sometimes have healthcare providers who lack training and providing gender inclusive care. And a lot of these things can be addressed by having availability of over the counter um hormonal contraception option, um, when folks don't have to um face these potentially stigmatizing um and discriminatory healthcare experiences by being able to just go to their local um corner pharmacy, um, pick up a medication from the shelf, um, and just bring it to the register without having to sort of face all of these, um, these barriers. So, you know, what could this equitable access look like? Um, so it's not enough to just have had this, uh, this path, um, but there are many steps that we need to take in order to ensure that the, the medication, even though it is approved and available, that it's actually accessible to people, um, because if it's not accessible, then it's really kind of what's the point, right? Um, and Again, while the ACA requires insurance coverage of FDA approved contraception without cost sharing, um, insurance companies are able to still require a prescription in order to cover the, the pill, and, and again, we just talked through all of the reasons why why getting a prescription is not easy for a lot of people and prevents a lot of people from being able to actually access contraception at all. Additionally, pharmacy employees. Must be adequately prepared and educated, um, so as not to create any additional barriers, um, often unintentional barriers by, um, having inaccurate information, um, uh, that they tell patients by having, um, the medication behind the pharmacy counter rather than on the shelf where people can sort of access it themselves. Um, and, and, and this is not coming without basis, right? When, um, over the counter. Plan B or emergency contraception was initially approved. We saw all of these things. There was a study of essentially um researchers who acted as secret shoppers for the emergency contraception pills and heard all sorts of of um inaccurate information told to them by, um, by pharmacy employees, um, and, and actually had a really difficult time accessing the medication even though it had already been approved, um, for over the counter use. Um. There is a um a bill uh that has been introduced, um, in order to help address some of these concerns. It's called the Affordability Access Act, and that would remove the prescription requirement, um, so essentially it would legislate, um, that insurance providers cannot require A prescription in order to have it covered, um, that it would also prohibit retailers that sell over the counter birth control pills from interfering in any way with people trying to purchase them, um, and ensure that any FDA approved over the counter contraception, so including a pill and anything that may come after this, um, would be covered by private insurance without a prescription, um, and without stipulations. And so, um. If that passes, that would be an incredible step in the right direction to make sure that the that the medication is actually accessible to the folks who need it. Um, Beyond insurance coverage, it's also really critical that any future over the counter birth control pill is priced affordably so that people who, who don't have insurance or can't use insurance are still able. To access the, the care that they need and want. Um, this onus will be on the drug manufacturer, um, whose name is Prigo. Um, the cost hasn't yet been announced, and the thought is that the, um, the, the medication will come to the over the counter market sometime in early 2024. You know, we're only a month away. For less than 2 weeks away from that time point and they still haven't announced a cost, um, and so we have yet to see what that will look like, but if we also look at um emergency contraception, if that is sort of any indicator, over the counter Plan B can cost up to $40 to $50 for one pill. Right, so, um, you know, and that, that for many people is extremely inaccessible pricing. Um, there was a survey, um, that the Kaiser Family Foundation did that found that 84% of people are not able or willing to pay more than $20 a month for For their hormonal contraception, right? So, um, if they price it more than $20 a month, um, then the majority of people, uh, are, uh, you know, particularly for those who don't have insurance, um, are underinsured, uh, are likely not gonna be able to access these medications, and we see these things really, um, really bear out in disparities, particularly in places where there has not been Medicaid expansion, right? Certain, in certain states that also face the highest rates of maternal morbidity and mortality, um, the highest rates of, of, um, health disparities as related to social and structural determinants of health. Um, and so, um, It will be really important to continue to advocate with the with the pharmaceutical company to make sure that the pricing is, is equitable and accessible for folks. It also needs to be accessible on the shelf rather than behind the counter without ID requirements or age requirements. Again, we've sort of seen a lot of um. A lot of efforts in kind of the voter suppression realm of requiring IDs, um, and that is something that, um, we have not been able to, um, uh, that people are not able to kind of access the care that they, uh, sorry, um, that people are, um. Sorry, I just had a distraction behind me and lost my train of thought, um, that, um, There are a number of people um who may not necessarily have a, a, a state ID um who may need to access these medications. Um, And then, um, and particularly young people and adolescents may not necessarily have an ID, um, in order to access these medications. Um, and then, um, particularly folks who are at risk of experiencing, um, stigma and discrimination, including, um, black, indigenous, and people of color, um, transgender or non-binary folks or gender expansive folks, people with disabilities Abilities, um, just making sure that folks are able to easily access the medication without being subjected to negative healthcare experiences. Um, again, being able to just kind of grab what you need off of the, off of the shelf along with any other things that you're gonna be grabbing at the pharmacy rather than having to go and speak to a pharmacist, speak to a pharmacy staff at that, um, behind the counter. Um, and then having home delivery services available also without pharmacy restrictions can additionally improve access for everybody. So, um, All of this is really, really timely because we are living in an unprecedented time here in the United States where people are unable to access a critical piece of their reproductive health care, which is abortion care, and In a large, large swath of the country, right? Um, and it is in a lot of these states that have these complete bans, um, where a lot of those significant healthcare disparities occur, where also are the same places that uh Medicaid has not been expanded, right? And so these are also folks who are at high risk of being unable to access this medication if it's priced unaffordably and if they're, um, and if they're, if they don't have insurance because they are in that Medicaid gap due to their state not expanding Medicaid for them. Um, so currently, uh, in the United States, there are 14 states with complete abortion bans, 10 states with partial bans, um, or bans that, um, that are complete, that are currently enjoined in court proceedings. Um, And, um, and despite all of this, there is recent data that actually the total number of abortions in the United States have increased in the last year since since Dobbs struck down Roe v. Wade and since abortion access has not been protected across the country. And so, um, what that means is that many people who are um getting abortions are traveling across state lines to do so if they're even able to, but many of the same barriers that we've already talked, talked about, um, in terms of accessing prescription birth control. are also the same barriers that people face when they are trying to access abortion care. And so for a lot of people, travel is just not an option and folks are being forced to carry pregnancies to term against their will. And so what that means is that having a more accessible option. To prevent pregnancy, one that is highly effective, reliable, and safe, and much more effective than most of what we have, um, you know, over the counter, um, is incredibly important for, for the people who wish to prevent pregnancy. Um, and, and, and the impact again will be seen for a really long time. There have been studies that show that there are generational Consequences when a desired abortion is denied to, to folks. And so preventing a pregnancy, um, that, um, in which a person would want to seek an abortion and are then denied one, becomes incredibly important as well. Um, so that is all I have. Um, I would love to open it up to any questions that might come through.
