Zero to GP - GP Revision Podcast

Hormone Replacement Therapy (HRT) - Essential GP Revision

• Thomas Watchman • Season 1 • Episode 8

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SPEAKER_00

Hi, this is Tom, and in this episode, I'm going to be going through hormone replacement therapy, covering the key things you need to know for your GP AKT exam. As always, the format of these episodes is I'm going to present a case, ask you questions. Your job is to ideally write down your answer, if not say it out loud, try and commit to an answer if you can, and then we're going to go through the explanation. If you want more resources like this, I recommend heading over to zero to finalshop.com where you can now get the AKT revision book, the Zero to GP AKT revision book, which covers all the key content you need for the AKT exam. So it's a great foundation to build your knowledge, and it's much better than just using a question bank or just one kind of self-testing resource. Use this book in combination, and you'll definitely improve your AKT mark. There's also the AKT revision flashcards, and these are very much in limited uh quantities. So once they sell out, I'm not planning to make any more of these AKT revision flashcards. There's also zero2gp.com where you can find short answer questions and an ANCI-like fact trainer tool for doing space repetitions of the key facts for your AKT exam, as well as multiple choice questions, more like a traditional question bank, and digital flashcards. But for now, let's get straight into this episode on hormone replacement therapy. So our first case is a 48-year-old woman, and she has where she presents to you with symptoms of brain fog, hot flushes, and sweating. Particularly, she says she has night sweats where she's really hot and sweaty at night time. She's experiencing irregular, lighter periods. So her periods are stretching out, there's a longer time between periods, and the periods are lighter. Her last period was four months ago. So the first question is what's your suspected diagnosis here? We could call this perimenopause. So she's experiencing symptoms as she approaches the menopause. The second question is, when would you classify or when does postmenopause start? At what point would you describe her as post-menopause? Someone is post-menopause 12 months after their last menopause, last menstrual period. So when you have your last period, um, the last period before bleeding stops altogether and you never have bleeding again for the rest of your life, at that point that's menopause. But you can't say somebody has reached menopause until 12 months after their last period, because it's kind of a retrospective diagnosis to say that was the last period. She had her last period four months ago. So at this point, you would kind of call her perimenopause. It may be that she never has a period ever again, in which case she's reached the menopause, but we don't know that until 12 months since her last period, at which point she would be postmenopause. Hopefully that makes sense.

SPEAKER_01

The next question is what hormonal change is causing her symptoms?

SPEAKER_00

Low estrogen. And estrogen is the essential hormone that keeps uh women feeling feeling well and themselves, and as estrogen drops towards the menopause, that's what causes these symptoms such as brain fog, hot flashes, joint aches, fatigue, mood changes, and so on. So it's estrogen is the key here, the drop in estrogen. The next question is what's the normal source of estrogen? Where does where do women get estrogen from before the menopause? Now, for the answer to this question, I'm not going to accept just the ovaries, that's too vague. It comes from the granulosa cells of the developing follicles. So each month, one or more follicles develop in the ovaries, and there's granulosa cells within those follicles that are developing that release estrogen. The next question is: what's the source of progesterone premenopause? Progesterone comes from the corpus luteum. So let's go back and review some physiology, some basic physiology of the menstrual cycle. It may be a while since you've recapped this, but it is very helpful for understanding menopause, the estrogen and progesterone, and then HRT regimes as well. So here we have the illustration of the menstrual cycle. You'll see day zero of the menstrual cycle is when bleeding starts, and a typical menstrual cycle is around 28 days long. Halfway or 14 days before the end of the menstrual cycle, you have ovulation, so somewhere in the middle. So on the left-hand side, you can see the developing follicle, and within that developing follicle is the granulosa cells. As the follicle is developing during the first half of the menstrual cycle, the follicular phase, those granulosa cells are releasing estrogen. So you can see the estrogen level is building up through that follicular phase. Then around day 14 or 14 days before the end of the menstrual cycle, there's a spike in LH or luteinizing hormone, and this triggers ovulation. So the ovum is released from that follicle. That follicle has released the ovum, so the egg is gone, but that that follicle then becomes the corpus luteum, which is this yellowish thing you can see on the right hand side of the screen. The corpus luteum, after ovulation, releases progesterone. And so progesterone builds in the second half of the menstrual cycle, the luteal phase. The corpus luteum also releases some estrogen. So what happens is you have the follicular phase, there's plenty of estrogen in the system, and this estrogen builds up the endometrium. It causes proliferation and building up of the endometrium. Estrogen stimulates the endometrium to proliferate. Then progesterone is released in the second half of the menstrual cycle, and progesterone kind of stabilizes and maintains the endometrium. So it stops the estrogen effect of proliferating it, it just maintains it at the healthy, nice level. So that's the effect of progesterone. Estrogen without progesterone will cause proliferation of the endometrium, but if you have progesterone, that stabilizes it and keeps it nice and stable. And then as estrogen and progesterone drop at the end of the menstrual cycle, if there's no fertilization, then with these drop in these hormones, the endometrium breaks down and bleeding occurs, which is a period. Okay, so back to this case, we've got a 48-year-old woman, she has brain fog, hot flushes, and sweating, irregular lighter periods, and her last period was four months ago. So the next question is what hormone can we give this woman to help with her symptoms?

SPEAKER_01

If we want to help her symptoms, we need to give her back estrogen.

SPEAKER_00

So it's not progesterone. Sometimes people think giving you give estrogen and progesterone in HRT, but the progesterone has no effect on the symptoms. The only thing we give to help with symptoms is the estrogen. So the next question is what options do we have for giving her estrogen?

SPEAKER_01

So we can give estrogen in several ways.

SPEAKER_00

She could take oral estrogen in the form of tablets, so she she could take estrogen tablets, or transdermal estrogen, where estrogen is absorbed through the skin, and that could be given as patches, which he puts on and changes twice a week, or gels, which he squirts on the skin and rubs in and it gets absorbed. So the next question is why would we give progesterone? We're giving estrogen for the symptoms.

SPEAKER_01

What's the point of giving progesterone?

SPEAKER_00

As we explored with the menstrual cycle, progesterone is there to stabilize the endometrium. So if we gave estrogen on its own, the endometrium would just carry on proliferating and proliferating and proliferating, and this creates a risk of endometrial hyperplasia and endometrial cancer. So we give progesterone alongside estrogen to stabilize the endometrium and prevent that proliferation, hyperplasia, and cancer, or reduce the risk.

SPEAKER_01

Next question is what options do we have for giving progesterone to her?

SPEAKER_00

There's a few options. We've already explored we can give tablets or patches for estrogen, for progesterone, which we need to give alongside the estrogen to protect the endometrium. The best option is probably to give the intra u intrauterine system, IUS, specifically something like the Myrena coil. So this is giving a little device, a coil, into the endom into the uterus, and it sits there and constantly releases progesterone. And that protects the endometrium from the estrogen. And the great thing about, for example, the myrina coil, you put it in and then it protects the endometrium for five years after you put it in. And then you can just give estrogen either through tablets or patches, and you know the endometrium is protected. Other options are you can give progesterone orally, for example, with utergest and tablets, or transdermally, for example, combined patches that contain both estrogen and progesterone. So the patch contains both hormones. Okay, on to the next the next question. Again, the same case, 48-year-old woman, brain fog light, hot flushes and sweating, irregular light periods, and her last period was four months ago. So the next question for this patient is what regime options do we have for HRT to give to this patient? So the two options really are to give an intrauterine system like the Myrena coil plus estrogen in the form of tablets or patches or gels. The other option is to give sequential combined HRT. So what do we mean by sequential combined HRT? This means you give continuous estrogen, because that's what helps with the symptoms, and sequential progesterone. So the estrogen is continuous, but we give progesterone for part of the month. So for example, two weeks of progesterone on and then two weeks off progesterone. Remember, this kind of matches the normal menstrual cycle, where you have estrogen most of the time, and then you have two weeks in the luteal phase where the corpus luteum is producing progesterone. So it's kind of similar to what happens in a normal menstrual cycle. And then with sequential combined HRT, the patient will have a withdrawal bleed like a period after the progesterone section finishes. So they have two weeks on of the progesterone, then they stop the progesterone, and they'll have similar to a period like a withdrawal bleed, and then after two weeks off the progesterone, they'll restart the progesterone. So two weeks on, two weeks off kind of thing. And they'll have controlled withdrawal bleeds. So let's go through some example regimes of sequential combined HRT. So the options are estrogen gel. So there's various ways you can do sequential combined HRT. One option is to use estrogen gel that they put on every day and use it continuously, plus cyclical uterjeston tablets. So 200 milligrams of utragestin, two weeks on, two weeks off, two weeks on, two weeks off, and so on. Another option is cyclical combined patches. So you can get formulations that a box will contain patches where they take two weeks of patches that contain both hormones, then two weeks of patches where they contain just the estrogen, and do that back and forwards. Or cyclical combined tablets, where the box of tablets had or the tablets for two weeks contain both hormones, then one week uh two weeks contain just the estrogen. So these are the example possible regimes. Okay, on to the next question. Again, we have the same case. The next question is what are the risks of HRT? What risks are you going to counsel this patient about? But there's various risks with HRT to mention to patients, and these risks depend a bit on the formulation. So the first risk to talk about is breast cancer, and this is a risk with combined HRT. So if you have a woman who doesn't have a uterus, she's had a hysterectomy, um therefore she doesn't need progesterone to protect her endometrium because she doesn't have an endometrium. So she can just have estrogen-only HRT. In that scenario, with estrogen-only HRT, the risk of breast cancer doesn't increase. But if you have somebody on combined HRT, they're having oestrogen and progesterone, then it does increase the risk of breast cancer. The next risk is endometrial cancer. And endometrial cancer, the risk goes up with sequential HRT, but not with continuous combined HRT. So if you have somebody who's taking HRT two weeks on, two weeks off of the progesterone, during those two weeks off, there is some unopposed estrogen which causes some proliferation of the endometrium. And so there is a slight increased risk of endometrial cancer with sequential, but not with continuous HRT. The next risk is ovarian cancer, although this is a very slight increased risk, and particularly with people on HRT for a long time. The next risk is venous thromboembolism. So things like deep vein thrombosis and pulmonary embolism. And the risk of uh venous thromboembolism is primarily with oral HRT. So people taking transdermal HRT, like patches or gels, the risk doesn't seem to increase nearly as much of venous thromboembolism. And the final risk is a risk of stroke. And this is really with people taking oral HRT, particularly in patients who are older. So younger patients taking transdermal HRT don't need to worry about this risk of stroke.

SPEAKER_01

Okay, on to the next question, which is what are the primary benefits of HRT?

SPEAKER_00

Number one benefit of HRT is that it controls the symptoms. So that's really why we use HRT. There is a slight uh side benefit of taking HRT, which is it seems to reduce the risk of fragility fractures. So the estrogen helps to keep the bones healthy and lower the risk of fragility fractures from osteoporosis. The next question is what kind of estrogen side effects could you warn patients about or could they expect? The next question is what progesterone predominant side effects might the woman experience? Some progesterone side effects are things like mood swings, it can make them feel depressed or kind of premenstrual type of symptoms, fluid retention, acne, and again other things like headaches. Okay, on to the next scenario. We've got again a 48-year-old woman, and this time she's starting HRT. Her last menstrual period was four months ago. So the next question is does she require contraception?

SPEAKER_01

The answer is yes.

SPEAKER_00

HRT does not provide contraception. So if somebody's starting HRT, they need additional contraception because the HRT won't cover them for contraception, they can still get pregnant. So the next question is what contraception options are there in somebody starting HRT? So we've got a few options here. Maybe the best solution is the Myrena coil, which covers you for HRT and contraception. It's licensed for both indications. So if you put in the Myrena coil, plus give additional estrogen HRT like patches or gels or tablets, that will cover her for both the endometrial protection, the estrogen will provide symptom control for her menopausal symptoms, and she'll be covered for contraception. Another option is that she takes HRT, for example, gel and tablets, for example, plus progestogen-only methods of contraception. So the progestogen-only pill, for example. The progestogen-only pill or progestogen-only methods of contraception, like the injection, these won't uh these won't cover her for endometrial protection. Although the progestogen-only pill contains progesterone, that won't give her the endometrial protection she needs for the HRT. So she might take the progestrogen-only pill plus uh progestrogen for the HRT regime and the estrogen for the HRT regime. So progestogen-only pill plus the full HRT regime. And another option in patients under 50 is to take the combined contraceptive pill. And the combined contraceptive pill is obviously a contraception, but it will also help manage the symptoms of the permenopause and menopausal period. But that's for people under 50. So they could use the combined pill mainly for contraception, but also it will help with their menopausal symptoms instead of HRT. The next question is how long would you consider her to be fertile for? So in Women around this period of the menopause, how long at what point would you say they're no longer fertile? So you can tell women that they're no longer fertile after if it's two years after their last menstrual period and they're under aged 50. So let's say they're 49, it's been two years since their last period, at that point they've become they're no longer fertile, they don't need contraception. One year after their last menstrual period, if they're above the age of 50, and everybody at age 55, you would then consider them not to be fertile anymore. So everyone who reaches 55, at that point you can say it's very, very unlikely that you're fertile, will consider you no longer fertile, you don't need contraception anymore. So let's look at an interesting scenario. Let's say there's a woman who's taking the progestogen-only pill, which often stops the period altogether, and she's over 50 years of age, and she's not had any periods for the past however many years. So we don't know if her periods have stopped because she's past the menopause or because she's taking the progestogen-only pill. So at this point, what can we tell her about whether to stop taking the progestogen-only pill? What can we do to see whether she's still fertile? So either she can carry on taking it, or if we want to know whether she can stop taking it, we can check her FSH level, follicle stimulating hormone, and you need to check two FSH levels six weeks apart. So one today, and then check it again in six weeks' time. And if both FSH levels are above 30 IU per liter, then she can stop taking the progester the POP after one more year. So both levels are above 30, she still needs to wait one more year and then she can stop taking it. Okay, onto a completely new case. You've got a 51-year-old woman, and she's been taking sequential combined HRT. And this has given her predictable withdrawal bleeds. She's been taking it for three years, so she started at aged 48, and she's been taking sequential, so two weeks on, two weeks off, and getting the regular withdrawal bleeds as expected. And the question at this point is why would you want to switch to continuous combined HRT as opposed to carrying on with sequential combined HRT?

SPEAKER_01

So why switch?

SPEAKER_00

You want to switch because continuous combined HRT has a lower risk of endometrial cancer compared with sequential combined HRT. And then as a general rule, they say switch within five years, five years at the latest, of taking sequential combined HRT if the patient starts after age 45, and or at the latest, you want to switch before the age of 54 years. So at this point, it's reasonable to consider switching over to continuous. The next question is what would be the risk of switching? What's the risk of something happening when you switch her to continuous combined HRT? The risk is that she gets an irregular bleeding pattern. So she gets kind of breakthrough bleeding on continuous combined HRT. Now the risk of having irregular bleeding is actually higher on sequential or abnormal bleeding is higher on sequential combined HRT. However, because we don't know whether she's still got some follicular activity going on in her ovaries, producing its own hormone uh hormone cycle, if there's ongoing follicular activity in the ovaries, this can cause some irregular bleeding on continuous combined HRT. If she's postmenopausal and she no longer has follicular activity in the ovaries, the ovaries are essentially postmenopause, then she shouldn't have any abnormal bleeding on continuous combined HRT. So it'd be fine to switch. This bleeding uh is is problematic and can cause trouble in managing it and lead to concerns about could there be something like endometrial cancer? Um, so it can be problematic, but actually it's safer to be on continuous combined HRT than sequential combined HRT. So uh the next question is what regime options do you have for continuous combined HRT? So this is what you would use in somebody who's switching over to continuous combined HRT, or in somebody who's starting HRT having not had any periods for at least 12 months. What regime options do you have? So the options are just like with sequential or somebody who's less than 12 months uh since their last period, you always have this option of inserting an intrauterine system like the Myrena and giving continuous estrogen. That's the best kind of option in all scenarios with the lowest risk. Um so that's an option. The other option is continuous combined HRT. And example regimes for continuous combined HRT is that you give estrogen gel every day plus utragest and tablets continuously. So one tablet or 100 milligrams at night continuously. The reason you give it at night is it can cause some drowsiness. Another option is continuous combined patches. So patches that she just changes twice a week, and all the patches in her pack contain both hormones, or continuous combined tablets. So these continuous combined tablets, she just takes them every day and they contain both hormones. So just as a brief summary of how you would choose a HRT regime, if you've got somebody who's not got a uterus, they've had a hysterectomy, they just take estrogen only. That's all they need. They don't need progesterone. Progesterone's just there to protect the endometrium. If they do have an endometrium and it's less than 12 months since their last period, then they should go on sequential combined HRT. And if it's more than 12 months since their last period, they go on continuous combined HRT. So I hope that video was helpful. Um, don't forget to check out the Zero to GP AKT revision book that contains notes on HRT, menopause, other gyney, uh obs and gyney stuff, um, and everything else you need for your AKT exam. The link is in the description, it's at zero to finalshop.com. And I'll see you in the next video, which will be in about a week's time.