Today we talk about a hormone that thinks is doing you a favor but might be sabotaging your fertility plan. Prolactin. I'm Dr. Mark Amols, and this is Taco about Fertility Tuesday. If you ever wondered why did the fertility doctors ask you if you have nipple discharge when you're trying to get pregnant? Well, this is that episode. See, prolactin is a normal hormone. its primary role is to initiate and maintain lactation in the postpartum, but it also contributes to immune modulation and osmoregulation. Now, under non pregnant conditions, prolactin secretion is kept in check by a hormone called dopamine that is released from the hypothalamus. Now, in a minute, you understand why this is important. A lot of the hormones are released from what's called the anterior pituitary, but the way they're released is from a messenger that comes down the hypophysile portal system. An example would be trh. Thyroid releasing hormone would be released to cause TSH to be released from the anterior pituitary. Now, what makes prolactin a little bit different is that dopamine is actually sent to stop it from being released. So the on off is a little bit different. All the other hormones in the anterior pituitary get a signal telling it to release something. But when it comes to prolactin, your body will just keep making it unless the dopamine is blocking it. We call this negative control. And why this is important is even a modest disturbance in dopamine signaling, whether it's from medication or due to maybe a lesion, can produce significant prolactin elevations. Now, if you've ever been pregnant before, one of the things you'll know is that after you have your baby, you start getting milk letdown and your breasts will gorge and you will release milk. But what's also interesting is, is that you'll stop gain your period. And the reason you stop g your period is because of this prolactin. What's interesting is prolactin inhibits the release of gnrh. It does this by inhibiting kispttin neurons that are, required upstream to stimulate gnrh neurons. Just so you know, gnrh is good naturrop and releasing hormone. So it's the signal to make you release FSH and lh. So when prolactin is elevated, gnrh pulse frequency in amplitude will decline. The pituitary then responds with reducing the secretion of FSH and lh, which then prevents you from making follicles, which prevents you from getting a period because you never ovulate. And then that will also lead to low estrogen and low progesterone because you're not ovulating anymore. And that prevents you from getting pregnant. And as you suspect and men, the same thing would happen. So if a guy had hyperollactinemia, he also might get some discharge from his nipples, but he will also have a reduction in those gnadropins, which will then lead to low testosterone and impair spermatogenesis. So, as you can see, having elevated prolactin can have an effect on many things, specifically your fertility, because if can't ovulate, it's pretty hard to get pregnant. But what's interesting about this one is that, again, it's the inhibitory of dopamine that stops prolactinamine and elevate. So if you're taking a medication or something that causes dopamine to go down, your prolactin level will go up. The same thing is when you have a mass we call a pituitary adenoma, the adenoma itself doesn't have to be creating the prolactin. It could actually just have a mass effect. And by pushing on the hypophasale portal system, it can block the dopamine from getting to the anterior pituitary, causing the prolactin levels to elevate, Meaning it's not producing it because of the mass. The mass is blocking the signal to tell it to not keep making it. What this means for you is there are multiple things that can cause your prolactin levels go up. There are even physiological things such as pregnancy, lactating, even sleep disturbances can cause prolactin levels to go up. Intense exercise can also cause it to go up. Even nipple stimulation can cause it to go up. As a matter of fact, it's one of the reasons we tell people to not stimulate their nipples when they get their blood drawn in case it's elevated the first time, to make sure it wasn't caused by that. Now, when it comes to pathological reasons, it could be due to a prolactinoma, which, again, could be an small adenoma, which just means like a tumor in the pituitary or in the area around the pituitary, it can be due to hypothyroidism. So trh, that hormone I was telling you about that is, sent down and release tsh, can also cause prolactin levels to increase. So you always have to look at both of Those chronic renal failure can also do it because that can reduce the clearance of the prolactin and then also chest wall injury. So if you've had injury to the chest wall, it's possible that it could be stimulating those nerves, are causing them to prolactin to be released more. Now, the other area we look at are pharmacological, and there are medications, especially dopamamine antagonists, such as antipsychotics and SSRIs, that can cause an elevation in prolactin. Now, regardless of the situation where that's causing to be raised, it's still a problem. And that problem is it's stopping you from ovulating. But more so than that, it could even be stopping you from benefiting from some of the medications. So, for example, let's say you're taking lectrozole and you're trying to get to make you ovulate. Well, the problem is if your fssh'in LH very low because you shut down the hypothalamic pituitary ovarian access, then it's not going to benefit you to take lrool, because the prolactin is too high in shutting down the system. You have to first fix the system before those medications will work. Now, yeah, you could give think ofatotropins to say, well, can't we just bypass it and give me a bunch of hormones? You can, but it's going to take more hormones now. So now have to spend more money, take more injections to get the same response. So the question then is, how do we diagnoseis? Well, the first thing we do is we do a prolactin level. Now, usually we don't do this fasting because most times it's going to be normal. But if it is elevated, then we do recommend doing the next blood draw with it fasting. Now, if you're only drawing a prolactin and it's elevated, then you want to check the thyroid as well as we talked about. Now, if that number comes back and it's over, let's say 25 to 30, but not over 60. Usually we just worry about maybe transient elevations and we recheck it again and then again. Like I mentioned, we'll do it fasting, no breast stimulation, and also make sure that there aren't any other causes. Now, when it's above 60, we start getting worried about things like pituitary adenomas. Especially if it's above 100. It's above 100. You're going to be getting an MRI because again, we want to look for that pituitary adenoma that could be there. Re causing a mass effect causing prolactin levels to rise. The reason why we're checking the MRI isn't so much because we're just trying to see if you have a microadeenoma. We're actually making sure you't have a macro adenoma. A macroadeenoma is a large, greater than centimeter tumor that can actually cause you then to lose eyesight and cause other problems if it's too big and those actually need to be treated surgically. If it's a microadeenoma, then it at least explains the prolactin levels. And then what we do is we treat it. And then what that will do is cause that tumor to start shrinking. But because it's very small, we don't get as worried, and we just watch for signs and symptoms of it growing. So if yours is above 60, but not above 100, your doctor may watch and wait, and that's reasonable. Now, above 100, most people are going to go get the MRI. Below 60, they might just watch and wait. One really interesting area is what's called macroprollactin. Macroprollactin is a high molecular weight complex that can falsely elevate prolactin levels, not because it's prolactin, but it falsely elevates it because it thinks it's prolactin. And then what they have to do is do a certain test where they basically dilute it so they can separate the real prolactin from the macrop prolactin. And then that way they can find out that it's really not causing harm. Macroprollactin may look like prolactin from the test, but it actually doesn't cause any of the symptoms of having elevated prolactin. So then when it comes to treatment, what's first line? Well, we call them dopamine agonist, which is a fancy way of saying something that causes the dopamine receptors to fire. There are two main therapies, bromocryptine and coberalline. Now, bromocryptine has more side effects, and for that reason, a lot of people will use conuralline as first line treatment because it has a much longer half life. You don't have to take it as much, and it's tolerated much better. These drugs will cause your prolactin levels to decrease significantly, and it will also cause the adenoma to decrease by about 90% if it's a microateenoma and about 70% if it's a macroadeenoma. Now with microadeenomas you don't have to repeat the MRI right away because it's already low risk. As long as the prolactin level goes down, you know that the microateenoma has shrunk. However, with macroanomas you do need to verify that it is shrinking. And so usually you repeat the MRI in about six months versus with a microadeenoma you might wait a couple years. In extremely rare cases. Sometimes surgery is needed, but usually those are refractory cases. Usually those are rare refractory cases and sometimes they even do radiotherapy to burn the area. But again those are very uncommon. So don't be worried about those. The good news is it's very treatable. So once you normalize the prolactin, you'll start ovulating again. Matter of fact, within like a cycle or two. Now you can go back to using the cheap drugs such as Clomid or Letrazole. You don't have to use as many injections when it comes to ivf. You're going to end up with more eggs because now you're going to spawn a little bit better. And you're also going to reduce the risk of having a luteal phase defect because now you're able to ovulate and produce the hormones that support the pregnancy. Now it's important to keep in mind if your prolactin level isn't that high, it's not as concerning. So your doctor is not doing anything wrong by having you still go through IVF with a prolactin level of, let's say 40. But if you're using, let's say an antagonist cycle or if you're using a cycle where you're adding fem Clomid, then you're not getting the full benefit. And so it would be worth treating the prolactin first. In the end, most clinicss just test everyone. Now technically you can sit and say, well maybe there patients with irre regular cycles or people who have breast discharge. In reality most people will just check everyone and that's what we do. Once it's found, then the question is why? And that's when you check the other hormones we talked about and start looking at imaging. Once you've found the cause, then you start the dopathine agonist, which will be very effective and will get you back to your normal fertility. So a couple interesting things not Every time that you have elevator prolactin, will you have rest discharge? Matter of fact, to be able to let milk out, you actually have to have some estrogen. And for some people that estrogen level can be so low because of the prolactineemia that you won't even have the breast discharge. The real concern on the physical exam is trying to make sure there isn't another reason for causing the discharge. And then the other thing you're looking for is to make sure there isn't signs of a macro prolactinoma because again, you don't want someone to lose their eyesight in the peripheral vision. And so one of the things we'll do is we'll test your peripheral vision to make sure that there isn't like a large macro adenoma there. In the end, many doctors don't do these exams anymore. A lot of times they just send you for the mri, which makes it a little bit easier. So the point is, if your prolactin level is elevated, obviously it needs to be treated. We talked about certain situations. You can watch and wait, but if you're wanting to get forward with treatment, you might want to treat it sooner. If your cycles are irregular, then you definitely wouldn't be checking prolactin. It is not always polycystic ovarian syndrome. There might be another reason for it. And next time your fertility doctor asks you if you're having a nipple discharge, your doctor'not a weirdo. They're just checking to make sure you'have hyperylactinemia. Sometimes nipple discharge is the only symptom that shows up. As always, I hope this episode was helpful to you. Maybe you have a friend who's going through this or a friend who has nipple discharge and said, hey, I think I know what's going on here. If you like this show where you find this information useful, please share the show with a friend. Leave us a five star rating on your favorite media but most of all keep coming back. If you have any questions feel free to send them tobftirectionferttility uh.com where ill definitely create a show about it. And if you also want to ask questions to me even live yougo can always come on our Sperm meetats egg show that is every other Wednesday at 6pm Mountain Standard Time where we do a live show and you can ask questions. I look forward to talking to you guys again next week on talko About Fertility Tuesday.