Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast is Narrator - ? 00:12 provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Speaker 1 00:32 Welcome to HelixTalk episode 175 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is hormonal harmony, a pharmacist guide to hormonal contraception. Dr. Khyati Patel 00:43 And in this two part episode, yes, we have part one part two, we're going to review some of the most important clinical pearls and pharmacotherapy and all the important practice aspects of hormonal contraceptive. And we're also going to discuss just a tidbit brief information about the most recently, FDA approved over the counter hormonal contraceptive product called Opill. As we said, this is a two part episode, and we're really excited about it, especially because we are joined by two special guests. Today. We have Dr. Nicholas super, who is an ambulatory care pharmacist who works at the Women's Health Clinic at Hines VA; he has about 13 years of experience working in women's health area, and we also have Dr. Danielle Candelario with us again. She's an associate professor and colleague at the College of Pharmacy who teaches hormonal contraceptive pharmacotherapy to our students. She's also practicing pharmacist at the Lake County Health Department in Illinois. So welcome to both of you, Dr. super and Dr. Candelario. We're so grateful to have your expertise today. Thanks for having us pleasure to be here. Thanks so much. Speaker 1 01:49 You know, kind of segueing on a previous episode, Episode 145 we actually talked about an Illinois law that went into effect about, you know, legal and practice aspects of the pharmacists ability to prescribe hormonal contraception that was part of the Illinois Pharmacy Practice Act. Update. Since then, 29 states have now allowed pharmacists to prescribe contraceptives. And you know, one of the goals that we have for this episode is to help pharmacists better understand hormonal contraception, whether you're prescribing it or if you're talking to a provider or a patient about the wide variety of contraceptive options that are out there in the market. And specifically in this episode, we're focusing on hormonal contraception. Dr. Khyati Patel 02:30 And doctor, Kane, you know, you and I, when we, you know, recorded that 145 we knew we wanted to record this episode because, you know, I work in primary care, but I'm not in touch with, I don't see patients who are on this medications. I don't get to start them or address some of the issues that we have, and that's why we have these experts today. And so you and I had fun, you know, coming up with this, you know, content and stuff, but we are also very happy to have the expertise of our guests today. And so we thought, you know, rather than jumping right into the products. It's important to cover some of the background here, and what is that ovulation cycle? Because all your hormones are tied into the cycle. So I'm going to have Dr. Candelario kind of kick us off with explaining very briefly what this ovulation cycle is, and that would help understand how the contraceptives work. Speaker 2 03:20 Thanks, Dr. Patel. I'll try to take a cursory overview of the ovulation cycle for this podcast. So generally, the length of a menstrual cycle is about 28 days. It can range anywhere from 21 to 40, some shorter, some longer. And there is this complex relationship between the hypothalamus, the anterior pituitary, and the ovaries, and you get gonadotropin hormone releasing hormone from the hypothalamus that's going to trigger release of the luteinizing hormone and follicle stimulating hormone, and that's stimulating the anterior pituitary gland and LH and FSH both impact ovulation. There are three phases to the menstrual cycle in this order. So there's the follicular phase, ovulation and the luteal phase, or sometimes what people will call the post ovulatory phase. That's the last one. So the follicular phase actually begins the first day of menses, so day one, once the woman has the menstrual cycle, that's considered to be the follicular phase. And that's where you get follicular stimulating hormone, because you're trying to get trying to get a peak stimulation of several follicles to grow. One follicle ends up dominating and growing up to be the larger of that of the follicles, and that large follicle is going to release estradiol, inhibiting all the other follicles to grow. Then you go through the ovulation phase, and that's generally around day 14. So kind of right in the middle of that menstrual cycle, your estradiol levels are going to rise again from that one dominant follicle, and that's going to lead to the cessation of the menstruation, and then you're going to get increased luteinizing hormone from the pituitary gland, and that's to get and cause ovulation from the follicle. The last phase is the luteal phase, and that generally, is about 15 day in the cycle, and you're going to get that corpus luteum that's formed from the remnants of the follicle in that ovary, and that corpus luteum is going to produce progesterone and estrogen. The progesterone is necessary to maintain the uterine lining, and it also prevents gonadotropin releasing hormone, follicle stimulating hormone, and luteinizing hormone production from the pituitary if there is no implantation. So if there's no embryo, the corpus luteum will degenerate, the progesterone levels will drop, and then that's when menstruation is triggered. Speaker 1 05:44 So then, of course, as pharmacists, we're always thinking about, you know, the physiology of a given organ system, and then potentially, how we can use that knowledge of physiology to help inform the drug targets, right? So with that understanding of the cycle, how can we use that to our advantage, in terms of how these hormonal contraceptives actually modify the process of that normal physiology? Speaker 2 06:09 When we talk about oral contraceptives in particular, we'll talk about estrogen and progestin, and both of those to your point, are active in the menstrual cycle. So estrogen, normally in the menstrual cycle, you get this estradiol surge, which we talked about, is from that dominant follicle, and that can cause ovulation through the LH surge. But when you're giving estrogen and an oral contraceptive, you're actually maintaining a constant level of that estrogen, so you're blocking that LH surge, and thus blocking ovulation. Another component in oral contraceptives can be progestin, and progesterone is naturally released during the luteal phase. So if you have and give progestin, then you're modifying the endometrial lining. You could also be inhibiting follicle stimulating hormone production necessary for follicle development. So both estrogen and progestin have other proposed mechanisms in preventing pregnancy, but these tend to be the two most dominant, Dr. Khyati Patel 07:11 and as the name of the episode is considered hormonal contraceptive, that's what we are here to talk about. But we can't move past the whole picture. So for completeness sake, Dr. super, what are some of the non hormonal, or quote, unquote, non pharmacologic options that are used for contraceptive purposes? Speaker 3 07:30 So of course, a lot of our patients either can or don't want to use hormonal options for contraception. And so there are a lot of options which you're probably familiar with, starting with kind of the old classics. You know the rhythm method is when we think of when we think of the calendar method, this is one that's led to many large families over the years, generally not considered very effective to track based on a woman's ovulatory cycle. You know, on calendar and saying, you know, when they're going to be most fertile and least fertile, and basic intercourse scheduled on that so that, on average, we think estimate leads to about 25 pregnancies in any of every 100 cases or so over a year that use rhythm methods. So 75% effective at best. Let's say similar numbers for basal body temperature monitoring, cervical mucus monitoring as well, also about 25% pregnancy rate there with those topical spermicides are another option, also not super effective. You might get maybe 2728 pregnancies out of 100 cases with this. And then copper IUD is one that is actually quite effective. Kind of the opposite side of the spectrum here. Copper IUDs are very effective, but for patients who use IUDs, one of the issues we find is that with the copper, although it's super effective, because copper inhibits sperm motility, we don't get any of the cycle regulatory effects you get from, say, a progestin IUD so women tend to have more bleeding issues with copper IUDs than other options. So super effective as far as non hormonal agents go. If a patient's got contraindications, this is a great option for someone who can't use estrogen progestins, but bleeding issues are fairly common. And then we have your barrier methods, condoms and diaphragms. These improve the efficacy from your classic kind of rhythm, non hormonal methods up to around 80% let's say so. You might get 2022, pregnancies out of 100 cases with condom diaphragm use. And then finally, surgical methods, you know, vasectomy, hysterectomy, these are going to be, you know, almost 100% effective, of course, getting right to the root of the fertilities. And so that's pretty much, is the gamut of non hormonal options. And the rest of the talk will be about all the other options, which tend to be quite a bit more effective, as we'll see. Dr. Khyati Patel 09:43 So that's great. Dr. super for covering some of the non hormonal or non farm options, as the episode title suggests. We are here to talk in two part episode talk about the hormonal contraceptive options. And you know, we kind of hope to maintain that flow going forward. And. But just an overarching overview, I know we're going to go into the detail of each of them in a bit. Dr. super what are the different hormonal contraceptive options available? And roughly, just like you describe the efficacy of the non hormonal ones, what are some of the efficacy percentages with the hormonal options? Speaker 3 10:19 Blanket statement here is a lot more effective than non hormonal options, with the exception of IUD and surgeries. So thinking of your classic birth control options, your pills, those are going to be around. This is either combined estrogen progestin pills or progesterone only pills are going to be over 90% effective in the real world if you use them appropriately. So seven to nine pregnancies at 100 cases of using these for a year, this is either combined estrogen progestin or progestin only pills. And similarly, for the combined estrogen, progesterone, ring and the patch as well, all those are right around 91 92% effective in the real world. And moving on to IUDs, which are progesterone only. Your progesterone only IUDs, or your progestin only implants, are going to be right around 98 99% effective, because you don't have any lapses in coverage, no worries about compliance issues. And really, they act at that end of the cycle. They never let the cycle restart. So basically, you're suppressing the site hormonal, the menstrual cycle continually, so there's extremely little risk of pregnancy in the course of the use of these IUDs and implants. And we also have the injectable progestins like depo provera, which are convenient, compliance wise, probably around 90 92% effective in the real world as well, similar to your orals and your your ring and your patch, but carry some significant side effects and the inconvenience of coming into the office for a lot of patients. So overall, you know, whereas with non hormonals, we're talking in the 70s to 80% efficacy in the hormonal area, we're talking 90 plus. And then you get to the IUD implant, you're really close to 100% almost surgical efficacy. And with Speaker 2 12:03 effectiveness of these methods, you may see two different types of data. So you'll see with perfect use effectiveness, and then you'll see with common use effectiveness. And I think Dr. super did a really nice job of walking us through the common use effectiveness. So real world effectiveness, which is what you're typically going to see in your patient populations. Patients may skip a dose or miss a dose, they may not place a patch or ring at the right time. And so thinking about the typical effectiveness is important in practice, and being able to realize that for your patient. Speaker 1 12:41 So before we jump into specific hormonal contraception, I think it's important to just mention that there's a bunch of decision points and factors and patient specific things to consider when evaluating a patient for hormonal contraception. We're going to go through a larger list in part two of this episode. But Dr. Candelario, can you just mention a couple things that come to mind when evaluating a patient for hormonal contraception. Speaker 2 13:06 I think there's kind of two factors to consider when evaluating a patient for hormonal contraceptives. Number one is their personal preference. So we talked about non hormonal contraceptives and hormonal but taking into account what their personal preferences are for what they want to take. Also considering the effectiveness and how each method is utilized is important for each patient, but namely for the hormonal contraceptives. We also need to look at medical history. So we may need to do some type of assessment of cardiovascular risk, estrogen dependent cancer risks that may involve also checking blood pressure and lipids. So some of it can be done by interviewing the patient and having some of their medical history, but I think it's a larger conversation with your patient about determining what works best for them, what works best with their lifestyle, and what's their preference. Dr. Khyati Patel 13:59 So I think with that, we are ready to dive into these hormonal contraceptive options, one by one. And the first one, which is probably by large by the category, is the combined oral contraceptive. Sometimes in the literature, you might see this as CoCs and as the word says combine. It is a combination of estrogen and progesterone. We spoke about the role of estrogen and progesterone in the menstrual cycle earlier, but when we were talking about as a pharmacotherapy option, estrogen in particular, is available commonly as ethinyl estradiol. So you'll see this abbreviated as capital E E as well as estradiol valerate. And then we go into the specifics of, you know, here's the low dose and here's the high dose. So the dose ranges up to 50 microgram. But we do have certain products available that are considered low doses, which contain 25 microgram or less of the ethinyl estradiol, Dr. Super. Can you go in a little bit more detail as to who do we select the low dose estrogen product for? Who do we select the high dose oxygen product for? Speaker 3 15:09 Going back in time, you know, 50 plus years ago, when we first had birth control pills developed for decades thereafter, we didn't know that it mattered. You know that low estrogen doses could possibly have any benefit, so we tend to use high estrogen doses. Now the Women's Health Initiative study a couple decades back, kind of made us all a little squeamish about using too much estrogen. There was this concern about increased thromboembolic risk, increased cardiac risk, so that kind of ushered in this new era of a lower estrogen products, these less than 25 microgram estrogen products. And so these are widely available now. And it wasn't just that that drove through the change as well, though it was also a matter of estrogens carry side effects as well. Pretty commonly, we'll see some nausea with with estrogens and kind of your classic birth control symptoms, breast tenderness, breast swelling. So given this web so many women have complaints of these things, there is an increasing tendency to use lower doses to start. So my personal practice in practice and clinic is to start with a low dose. Now we would historically think you're going to reserve those low doses for people who are maybe perimenopausal or are smaller batch or smaller body weight, just needing lower doses overall. But my preference is to start with lowest dose possible and see if we get efficacy with that, and assess tolerability as well. Because if someone's not going to tolerate a 20 microgram estrogen, then we can. We have a pretty good sense that we have limited options going there, from there, and you might need to go to progestin only option. Speaker 2 16:39 And I think one of the main questions we get about low dose estrogen is, is there any difference in effectiveness compared to the higher dose and so generally, the literature does not find a difference in contraceptive effectiveness when compared to higher doses. So if we can reduce and limit the side effects and the amount of estrogen that a woman is exposed to, I think that that benefits our patients. The literature does, however, say that lower dose groups may have a higher rate of early discontinuation, and that may be because of the irregular irregularities and bleeding, but that's something that we have to weigh when we're looking at the other estrogenic side effects, as you mentioned, breast tenderness and headache. Speaker 3 17:25 Yeah, and those high doses, I really, in practice, only see them in patients who maybe need some extra coverage. Let's say they have an interactive drug on board that's going to reduce the contraceptive efficacy. That's a case where you may want to use a high dose estrogen, or in someone whose cycle isn't adequately regulated, and we're going to gradually, step wise, increase that estrogen, because we're not going to see a significant loss in efficacy based on the trial data, by going lower versus higher doses of estrogen, and those discontinuation rates possibly being due to loss of cycle regulation, we can increase efficacy by increasing compliance, if someone's not getting the fact they want and they're getting early cycle bleeding, we're going to do them a disservice by not changing that to a higher dose estrogen. So we increase the estrogen dose when needed to regulate the cycle better. Speaker 1 18:14 So then, as the name suggests of combined oral contraception, we must have a second agent, and that's our progesterone and kind of like with estrogen, we don't have estrogen, like the actual drug of estrogen in these products. We have, you know, estrogen derivatives. The same is true with progesterone. So you're not going to get a progesterone specific product, but you do have derivatives of progesterone. So Dr. super, what are some of the common available progesterone like drugs that would be in these combined oral contraceptives, Speaker 3 18:45 like with the difference in estrogen doses, we've not seen a major difference in efficacy with the various progestins as far as contraceptive efficacy goes. Now, there are other major differences between these these hormonal products, but the most common ones we see in practice are levonorgestrel, which is an older progestin, norethindrone, which is also an older one. And the newer generation ones are drospirenone, norgestimate, etto nor gestral. And you'll hear talk of some of these being less androgenic, because progesterones have a kind of multitude of side effects that include some androgenic effects, potential acne, hirsutism, mood changes and these, of course, can be major problems for women taking these agents. So these newer progestins that have fewer androgenic effects can be favorable in that way, especially with regard to mood and acne, which are two things that some of these agents are approved for, in fact, by the FDA. Now among the newer agents, drospirenone is one I want to draw your attention to, because it's one that's considered almost bioidentical to native progesterone. So this is why it's become one of the reasons it's become one of the more favorable ones, as well as having pure androgenic effects. So that's when you see more. More and more of and we see less and less of those older progestins because of those androgenic effects and some increase in fluid retention as well. And now I will say here, as far as drospirenone goes, which we see in yas Yas and Yasmin are ones you hear a lot about as far as brand names go, but there's 1000 of those. So drospirenone is the one of these progestins that has been noted to have a somewhat increased risk of venous thromboembolism, so possible increase in DVT/PE risk compared to the other progestins. So if you have anyone with a remote history of PE, DVT, or a family history thereof, that might favor choosing a different progestin, but there are enough options out there that you can still choosing a less androgenic progestin and mitigate that risk of VTE as well. That's a brief overview of what's available. There is like seven or eight total I probably missed, yeah, I skipped a couple. desogestrel, norgestimate, norgestrel. There's a whole host of the oh and of course, Provera hydroxy progesterone, which is also an older one. It's commonly formulated in intramuscular injection given in clinic. We think about estrogens more by doses, as far as how efficacious they are between progestins, we think more about which one you're using. The progestins change from agent to agent. So that's really where you get the when you're trying to adjust the progestin efficacy in a certain formulation, you don't so much change the progestin dose. You change the progestin you're using. Dr. Khyati Patel 21:26 That's a great point you made about based on the patient's preference, as well as some of the side effect profile of the progestins, you basically change the progestin type, and there is nothing to change about the dose itself. And then I want to pick point from a couple of things that you mentioned about the androgenic effect and stuff. That's why we have certain combined hormonal contraceptives like Astro step or tri spin type that are approved for acne. And then we also have specific ones that are indicated for the post menstrual dysphoric disorder. But the focus of the episode, we don't have time to go into details as to you know, what is the evidence behind these? However, just so you know, you are choosing the right thing for your patient, these are additional indications for some of the combined contraceptives, Speaker 2 22:17 in addition to the premenstrual dysphoric disorder, some of the oral contraceptives also have benefits in menstruation related problems, so decreased cramps, decreased in ovulation pain. They're also associated with the reduced risk of ovarian and endometrial cancer, uterine fibroids and endometriosis. This is also one of the benefits of oral contraceptives. So when we were talking about, how do you assess and choose or select a contraception for a patient? One of these additional indications, or these additional benefits may be one reason you would lean towards an oral contraceptive in a patient who is complaining of menstrual related problems or additional endometriosis or uterine fibroids. Speaker 1 23:01 From a side effect standpoint, you know, Dr. super and Dr. kinderlau, you've already mentioned some of these side effects, but we'll just kind of reiterate them. For estrogen, the most common side effect is irregular bleeding. Why is this happening? And what do we do about that? And then we'll kind of piggyback after that in terms of the non bleeding related adverse effects of estrogen containing products. So we'll start with Dr. Candelario. What's going what's going on with the bleeding? What do we do about that, if a patient experiences irregular bleeding with the estrogen component of these combined oral contraceptives? Speaker 2 23:32 This is a common complaint of women who are started on estrogen contraception, and there's a couple of things you need to evaluate. So you need to determine the time frame from the initiation of the oral contraception. So is this irregular or bleeding occurring three months after initiation, or is it occurring six to 12 months after initiation? That time frame is going to help you determine what it is that you actually want to do with it. The second thing you need to evaluate is, when is the irregular or breakthrough bleeding? Is often what we'll call it as well. In practice, when is the breakthrough bleeding occurring? So is it happening during that early cycle, that follicular phase, that first 14 days? Is it happening late in the cycle, or that luteal phase, which is later. Understanding the timeframe for this is important if the irregular bleeding is occurring before six months. So usually in that three to month range, we may leave the patient on the estrogen dose that they're currently on and reevaluate them after that three to four months, typically, if the patient is still experiencing that breakthrough bleeding after six months, then that may require a dose adjustment and will increase the estrogen component only if it's associated with early to mid cycle bleeding. So for example, if we have a patient. In clinic who is presenting with breakthrough bleeding in, you know, somewhere between days 10 and 14 of the cycle, and it's been about eight months, which is probably a longer time frame for follow up, but just to kind of exercise the point, if the patient presented eight months for follow up and was having breakthrough bleeding day 10 to 14, then we would increase that estrogen dose. And like Dr. super had discussed, we're probably starting patients on lower doses. So we're starting low and going slow, and then we can increase the estrogen dose. Speaker 1 25:34 And then Dr. super in terms of some other side effects, you'd already mentioned, nausea, that can happen, breast tenderness, headache. What are some other side effects that come to your mind in terms of the estrogen component of these oral contraceptives? And then, is there anything that you do about them? Speaker 3 25:48 Specifically, the headaches in particular, can be a tricky one, because there's such a huge overlap between menstrual irregularities and migraines, let's say so. One thing we'll do in clinic at least is we'll refer patients who are having recurrent headaches to neurology, let's say, for an evaluation, and say, Is this a contraceptive related issue, or is this CNS etiology? Otherwise, the only real recourse we have, besides reducing the estrogen dose, which then may lead us to have psycho irregularities that Dr. Candelaria alluded to, is exploring non estrogenic options, because these side effects, you know, it tends to be that when they're occurring, since we can't really change from one estrogen to another between two different contraceptives, we're not going to get any improved ADRs rates with going from 25 mics and say, a yas versus In another formulation. So if it's if it's a bothersome side effect and we can't manage it with non pharmacologic means, and we've ruled out other etiologies, then we're discussing progestin only options, possibly either pills or an IUD or implant or injections. Speaker 2 26:57 But I think it's important to mention that if a patient is experiencing what we call severe aches or A, C, H, E, S, the patient needs to immediately discontinue their oral contraceptives and aches is a simple acronym that stands for abdominal pain, chest pain, headache, eye problems and swelling, or severely, severely painful legs, all of these kind of associated with the estrogen component and the VTE risk, and so most of these are signs and symptoms and subtype of thromboembolism. So patients will present with breast tenderness or headache, fluid retention, perhaps mood changes within with increased estrogen or too high of an estrogen dose for that but including severe aches in your patient. Counseling is important to be able to differentiate between a simple headache versus a headache that may be indicative of a more problematic concern, such as stroke. Dr. Khyati Patel 28:01 So, you know, what we just talked about was just estrogen related side effects when we talked about progesterone or progestins earlier, you know, we talked about some side effects, such as maybe the headache or the depressive mood, the bloating, then the weight gain kind of follows. It increased appetite. And again, migraine or headaches are also common with them, just like the estrogen, where you know too much estrogen can give you x side effect and too little can give you y side effect. We have similar scenario going on with the progestin. So Dr. super, if you can briefly describe what is the scenario when one can have too little progestin or progesterone, and what do we do to remedy that? And what are the cases where we can identify maybe too much or higher level of progestin? And what are some of the symptoms patients can present with? Speaker 3 28:53 So progestin, when we have an excess of progestin, effects, we tend to see late cycle bleeding. So Dr. Candelaria mentioned that early to mid cycle bleeding is a sign that someone's got too little s too little estrogen. Late cycle bleeding is a sign that someone's got too little progestin. And those progestin side effects we talked about fluid retention and other mineralocorticoid effects, as well as hirsutism, acne, mood changes, these types of things are due to an excess of progestin effects. So although we don't have the luxury with progestins of changing the dose within a given product, so within many products that are combined, you can change the estrogen dose, but keep the progestin the same. We can't do the opposite. We can't change the progestin dose in a given product. It's always the same. So if someone's having, let's say, adverse progestin reactions, whether it's late cycle bleeding or ADRs to progestin with either too little or too much effect, let's assign we need to change the progestin since we can't adjust the dose itself. So we're going to try and adjust the progestin coverage in the in the hormonal system by changing the actual agent we're using. Since we can't adjust the dose itself, you. The ideal, of course, would be to just tweak that dose of the progestin. Go up or down based on whether it's if it's late cycle bleeding, you increase the dose. If it's adverse reaction, you decrease the dose. But in the real world, we can't do that those those different doses aren't available to a given product. So we just change to a different product that has the same amount of estrogen, but a different progestin. Speaker 2 30:20 I think this highlights an important reasoning for following up with our patients. So the initiation of a hormonal contraception is not a one and done, as Dr. super mentioned, there's so many on the market, and the reason is, is that we have to titrate the estrogen and the progestin dose based on how the patient is experiencing the oral contraceptive, and so follow up, then becomes so important, you know, is it that three or six month follow up, bringing them back to assess, you know, side effects? So are they experiencing any breakthrough bleeding? Are they experiencing any side effects of increased estrogen or progestin, and monitoring that and reevaluating it, and then possibly changing the contraception. Most women will discontinue their contraception because of these side effects, so we need to ensure that we're following up with them and adjusting it, and helping them to understand that the first go around, or the first dose of what we prescribe may not be where they land, or what the final dose is for them. We have so many options. So helping them to understand that, I think, will increase the patient provider relationship, and help them to understand I have to come back and let my provider know if I'm experiencing any adverse effects, so that they can tweak it, and Dr. Khyati Patel 31:35 kind of talking about possibilities. And, you know, open conversations with their provider, we add more to it by having different formulations. So these contraceptives are, again the combined ones available in monophasic, multiphasic, extended cycle and continuous cycle. And then there are some that have even shortened hormone free interval. Usually that hormone free interval is seven days. The shortened ones would have it less than seven days. So for monophasic in this particular type of formulation, we have one continuous dose of active, you know, contraceptive pills. So with containing hormones for 21 days, there'll be seven days of placebo. Sometimes the placebo is placebo. Sometimes placebo contains iron to even some folate. For that matter, the extended cycle combinations are where there is 84 days of hormone pills or active pills, and seven days of placebo. Again, there's some of these products would have in the placebo with very little estrogen. We are talking 10 microgram of estrogen as placebo. Some of the continuous cycles have no placebo at all. They're just all active. So there is no hormone free interval which will delay menstruation. And as we talked about earlier, we have the shortened hormonal free interval as well, where instead of seven days of placebo, pill will get the four days. What's more interesting, though, is the multiphasic product, as well as the extended cycles product, where we have different tiers in the multiphasic product of 21 days. So like, week one will have certain concentration of hormone. Week two will have a certain concentration. Week Three will have a different concentration. And then placebo. Is there? Dr. super An advantage of using multiphasic product over some of the other one that are just constant level of hormones. So short answer Speaker 3 33:31 is, there's an advantage to every formulation. It's just when that is an advantage and that's that's where that patient follow up becomes key. So with multiphasics, multiphasic products arise out of the concept that a woman's hormonal cycle is not static. You know, the estrogen levels kind of rise mid cycle, then come back down, and the progestin levels rise at the end of the cycle. So prior to these products being developed, back in the 80s, the notion had been steady, you know, hormonal levels throughout the whole 28 day cycle of taking the medication. So same level of progestin, same level of estrogen the whole cycle. But what you find, as we mentioned already, is you have patients who have breakthrough bleeding at various points in the cycle, and the multiphasics are a nice way of addressing some of those forms of bleeding, because with a bump up in the estrogen level mid cycle, you can address some late mid cycle bleeding, and then with an increasing progestin dose over time you can address some late cycle bleeding. So as a general rule, that's how these multiphasic works. Is week one is a fairly low estrogen low progestin dose. Week two a higher estrogen dose and a somewhat higher progestin dose. And then Week Three is again a lower estrogen and a higher progestin dose. So estrogen goes up and then back down. Progestin rises throughout the cycle. So those are the three tiers, and then your last week is again, inactive placebo, like in a like in a monophasic. So this is a really valuable option for patients who may have multiple problems. You know, taking a taking a monophasic, let's say they're taking a monophasic and they have bleeding. From days, you know, 10 to 20 and there have been 10 to bleeding days, you know, 10 plus days a month, starting mid cycle to late cycle. This is a way of adjusting their hormonal levels to control those levels of bleeding as well. And this is an option we can use when someone does develop a kind of complex suite of bleeding issues. It gives us a nice option that regard. And these are the ones you'll see. They look like a pack of candy because there's four different colored pills. Week one is that low estrogen, low progestin. Week two is a high estrogen, moderate progestin. Week three is low estrogen, high progestin. Week four, placebo, all different colors. There's no, you know, rhyme or reason to the colors they choose, other than they tend to be bright. And so that's it's it's something that we don't see. A ton of you certainly wouldn't start someone on a multiphasic unless they have a history of taking them and they know for a fact that they respond well to that kind of pattern. Speaker 1 35:53 So then Dr. super, as you mentioned, there's kind of no rhyme or reason to the colors you're going to see different pack sizes, especially for the extended cycle, you're going to have kind of a multi pack where you have, you know, all 84 days, plus the seven days of placebo and one fill for the patient. From a branding perspective, it's very common that we'll see kind of this branded generic philosophy with these, where these are generic medications that even have AB compatibility ratings with each other, but they will have a brand name associated with them. Oftentimes, these are kind of female names in terms like female first names, just kind of how it's gone from a marketing perspective. But there are a ton, an absolute monster list of potential branded generic names for these oral contraceptives as well. Speaker 3 36:41 Yeah, yeah. And you've seen a move over time from the kind of sort of scientific names, like ortho Novum was an early, early generation one, then we move on to Angelique and Nikki and Lorena and all these ones now. And you're right, there's their there are other branded generics, and a lot of times the woman won't even see the brand name. So when you pull out a pack, the pack out of the actual external package, and it just says the manufacturer's name, so you don't see Nicky or Lorena or whatever. So it's women often don't know that the formulation that the brand has actually been changed because they are AB interchangeable. No one ever knows if they're on Nicky or whatever. They may know that they're on Yaz or the equivalent of Yas, which is kind of the leading brand name, but all those other followers tend to just be known more by their their manufacturer than their brand name. Speaker 2 37:32 Educating patients on following up and continuing to have open conversations with their providers is important even small changes in the formulation can lead to side effects or adverse effects in women. So they may not have had breast tenderness with one formulation, but when changed over to another, for some reason, they are having breast tenderness. So encouraging our patients to have an open lines of communication with us, and encouraging providers to continue to ask about their oral contraceptive and how they're doing, particularly in the times of when formulations are changing, because we have had experiences where even just to switch from branded generic to branded generic can cause adverse effects in a woman, and perhaps they don't recognize them, or They don't realize that they'll discontinue their contraception, not follow up with anybody, when truly perhaps we just needed to make another switch on that oral contraceptive. Dr. Khyati Patel 38:31 The other common question we get is, you know what to do with the placebo? As we discussed earlier, some contain folate, some contain small amount of iron, or even very tiny dose of estrogen in their placebo week. What is the common practice? Dr. Candelario, Speaker 2 38:47 we used to call these sugar pills, with the thought that they were inactive and that they contained maybe sugar, the reality is that they do not take contained sugar and are just inactive that they don't have hormone. With that being said, technically, your patient doesn't have to take them because they are inactive, unless it contains iron or folate and it's introduced into those inactives, then you would certainly want your patient to take them. However, I always encourage my patients to take that last week of inactive placebo pill. Couple of reasons. I think medication adherence can be maintained when continuing that last week of inactive pills, it could be difficult for anybody to have to stop taking medication for a week and then remember to restart it again after seven days. So for most of my patients, I will encourage them to maintain consistency and to take those inactive pills in order to just make sure that they're continuing the the contraception appropriately. Speaker 1 39:50 So then kind of segueing, so you identify the formulation that you're going to start your patient on. Out of the multitude of different options, you pick whatever the option is, and kind of conjunction with the. Patient's preferences. How do you actually start it? So is it started at the beginning of the cycle? Is it started after administration is done? Where do we start this? And what is the rationale for doing it that way? Speaker 2 40:12 So there are three initiation options. We'll describe those, but there's some nuances to all of them, and I think a discussion with your patient is crucial to identifying what works for them. But in general, there are three initiation options. The first is the first day of the menstrual cycle. The second is the first day after the start of the menstrual cycle, and the third is the quick start. So the first one is the first day of the menstrual cycle. The benefit here is that this is the only method of initiation that doesn't require a backup method. When we say backup method, we know we're all talking about some type of barrier method, females or male condoms. It the first day of menstrual cycle. Initiation would not require that. So that's a nice option. The second option is the first Sunday after the start of the menstrual cycle. So for example, if the patient is presenting on a Tuesday and they're right in the middle of their menstrual cycle, they can choose to start on the Sunday after the start of that menstrual cycle. This initiation method would require a backup method for one week. The third initiation option is the quick start. So you can start on the day of receiving the oral contraceptive. With this one, you would also need to use a backup method for one week, and this can cause a delay in the menstrual cycle. So the patient would need to be aware of that the decision to initiate would be based on a conversation with the patient. So I would ask things like, what are their goals? What day are they currently in their menstrual cycle? Are they agreeable to using a backup method? I think some of the answers to those questions would help you decide which initiation method is best for patients, Quick Start may lead to a higher rate of adherence, because they're taking it the day that they're leaving you, versus having to wait until the first Sunday after their menstrual cycle, and depending where they are in their cycle, that may be two or three weeks before they initiate. So considering your patient, considering adherence, considering what their preference and their goals are, if their goals may be prevention of pregnancy versus their goals are menstruation related disorders such as cramping, perhaps a quick start. Is it necessary for them? So considering all of those things together, I think are important for deciding which is best for your patient. Speaker 1 42:36 So then, why don't we touch base with some of that, those patient education points, you know one is obviously being consistent, not missing doses taken at the same time every day, if possible. But sometimes patients do miss doses for oral contraceptives and really for any medication. Generally speaking, how Doctor super How do you typically approach a missed dose instruction when a patient is not calling you because they've missed a dose, but for them to just know if I was to miss a dose, these are the kinds of things that I think about. Speaker 3 43:07 Well, the first thing I do, and this is the case for us in the VA, and I'm not sure how easy this is to do for non VA providers, is to make sure my patients, when I consult them on missed doses, that I offer them the option of an emergency contraceptive and having one on hand. So since those do come into play here with the missed dose procedure, but the general rule more constantly a patient is, if you miss one dose, or if you're less than you know, if you're a day late on a medic on a dose, let's say take the missed dose of the late dose right away and just resume the pack where you left off. You can consider using an emergency contraceptive, but it's generally not going to be necessary if you're only missing one dose, or, you know, a day or so late on that dose. But the key information if they're more than a day late or so, it's, it's going to be when in your cycle are you, you know, how many doses have you missed, and when do you usually take it? And based on that information, there's enough. There's so many products out there that the constantly points are going to vary for points are going to vary from one person to the next and one situation Speaker 1 44:05 to the next. So Doctor super I just want to emphasize because this is actually not the typical advice that we give patients for other medications, like a blood pressure medication, for example. So if I miss my Sunday dose, and on Monday I realize, Oh, I forgot to take my Sunday dose. You're saying that the patient will take two tablets on Monday, but then if they miss more than two days worth, if they miss Sunday and Monday, it gets more complicated. Depends on a variety of different Exactly. So, Dr, super. Dr, Candelario, I wanted to thank you for your time today. This is actually the end of part one. We're going to have you on again for part two, where we're going to cover progestin only pills or pops and a variety of other hormonal contraceptive considerations, options, things like that. So I think this is a great time to take that logical break for part one. So thank you for your time. And with that, I'm Dr. Kane Dr. Khyati Patel 44:57 and I'm Dr. Patel. Thank you to our guests. And as always, your audience. Study hard. Narrator - Dr. Abel 45:03 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 45:14 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.