WEBVTT 1 00:00:00.400 --> 00:00:02.879 All right, so let's talk about polycystic overy syndrome before 2 00:00:02.879 --> 00:00:05.040 we get started. As always, thank you so much for 3 00:00:05.080 --> 00:00:07.440 the support, Thank you, thank you so much. All Right, 4 00:00:07.480 --> 00:00:10.839 let's talk about polycystic ovary syndrome or p COS as 5 00:00:10.839 --> 00:00:13.000 I like to call it, So polycystic overy syndrome. The 6 00:00:13.160 --> 00:00:16.320 name quite literally means a syndrome of many cysts of 7 00:00:16.359 --> 00:00:18.440 the ovaries. So you might think that that's all this is, 8 00:00:18.480 --> 00:00:21.199 but in actuality, you don't even need to have polycystic 9 00:00:21.199 --> 00:00:23.760 overies to be diagnosed, and the fluid filled structures in 10 00:00:23.800 --> 00:00:25.879 the ovaries they're not even true cysts, but we'll talk 11 00:00:25.920 --> 00:00:28.160 more about that later. So PCOS is one of the 12 00:00:28.199 --> 00:00:31.519 most common endochronopothies in women of reproductive age. It effects 13 00:00:31.559 --> 00:00:34.280 between six point five and ten percent of all women 14 00:00:34.280 --> 00:00:36.520 of reproductive age. Let's go ahead and get started with 15 00:00:36.520 --> 00:00:40.240 the patho first. So the patho is pretty complex, multifactorial, 16 00:00:40.280 --> 00:00:42.159 there's a lot going on, so we'll keep it focused 17 00:00:42.200 --> 00:00:44.280 on what you need to know. Some key concepts or 18 00:00:44.320 --> 00:00:47.119 trends that we typically see in patients with piacos. So 19 00:00:47.119 --> 00:00:50.759 starting with your LH levels. So PACOS patients have altered 20 00:00:50.880 --> 00:00:55.799 LH levels with relatively higher serum lutinizing hormone concentrations relative 21 00:00:55.840 --> 00:00:59.159 to FSH concentrations. This is just a small component of 22 00:00:59.159 --> 00:01:02.159 the whole picture, but I think is important to understand. 23 00:01:02.399 --> 00:01:04.640 So let's do a quick review of a normal functioning 24 00:01:04.719 --> 00:01:08.840 hypothalamic pituitary ovariant axis. In a normal HPO axis, the 25 00:01:08.920 --> 00:01:13.439 hypothalamus releases GnRH in a pulsatile manner, stimulating the anterior 26 00:01:13.480 --> 00:01:17.159 pituitary to secrete LH and FSH. LH goes down and 27 00:01:17.200 --> 00:01:20.359 acts on the thika cells in the ovary, promoting androgen 28 00:01:20.400 --> 00:01:25.400 production primarily androstendon, while FSH stimulates granulosa cells to produce aromatase. 29 00:01:25.519 --> 00:01:28.879 Romatase is an enzyme that converts these androgens into estrogen, 30 00:01:29.280 --> 00:01:33.120 specifically estradil. So as this process goes on, a dominant 31 00:01:33.200 --> 00:01:37.079 follicle develops. F SH stimulates the follicle to develop. Rising 32 00:01:37.200 --> 00:01:40.439 estrogen levels trigger positive feedback on the pituitary, leading to 33 00:01:40.480 --> 00:01:43.519 a surge in LH, which induces ovulation. Most of this 34 00:01:43.599 --> 00:01:47.519 you probably already know. After ovulation, progesterone from the corpus 35 00:01:47.599 --> 00:01:52.680 lutium provides negative feedback, slowing down GnRH pulses, reducing LH 36 00:01:52.719 --> 00:01:55.640 and FSH secretion to complete the cycle. It's a lot, 37 00:01:55.640 --> 00:01:57.079 but here's the part that you need to know and 38 00:01:57.159 --> 00:01:59.879 p cosse. This balance is disrupted due in part two, 39 00:01:59.879 --> 00:02:03.400 a higher pulsatile frequency of g n rh which LH 40 00:02:03.519 --> 00:02:06.480 is more responsive to, leaving us with excessive amounts of 41 00:02:06.640 --> 00:02:09.800 LH relative to f SH levels. So it means those 42 00:02:09.840 --> 00:02:12.879 thikas cells which are stimulated by LH are now producing 43 00:02:12.919 --> 00:02:16.520 too many androgens and FSH can't keep up to convert them. 44 00:02:16.840 --> 00:02:20.400 These elevated androgen levels, along with the relatively lower f 45 00:02:20.479 --> 00:02:25.879 SH levels, which normally stimulate follicular development, impair normal follicle maturation, 46 00:02:26.159 --> 00:02:30.280 resulting in anovulation and in accumulation of these immature follicles 47 00:02:30.280 --> 00:02:32.759 in the ovary, which lead to the classic appearance we'll 48 00:02:32.800 --> 00:02:36.039 see on ultrasound in some patients. Okay, so remember the 49 00:02:36.120 --> 00:02:39.039 increased LH to FSH ratio. One other part of the 50 00:02:39.039 --> 00:02:41.639 pathway I feel is important to understand is how insulin 51 00:02:41.680 --> 00:02:44.439 resistance plays a role. So fifty to seventy percent of 52 00:02:44.439 --> 00:02:48.919 females with p costs demonstrate clinically measurable insulin resistance, So 53 00:02:48.960 --> 00:02:53.080 we have insulin resistance which leads to compensatory hyper insulinemia. 54 00:02:53.360 --> 00:02:55.719 So high levels of insulin in the body. But what 55 00:02:55.800 --> 00:02:58.319 do high levels of insulin have to do with androgen 56 00:02:58.400 --> 00:03:01.840 excess and ovulatory to spunction. Well more than you'd think, 57 00:03:01.919 --> 00:03:04.680 So besides the obvious regulation of glucose that comes to 58 00:03:04.719 --> 00:03:07.039 mind when thinking of insulin, it does something else when 59 00:03:07.039 --> 00:03:09.479 in high levels, and that is to stimulate the THIKA 60 00:03:09.560 --> 00:03:12.759 cells of the ovaries to produce more androgens. So kind 61 00:03:12.759 --> 00:03:14.360 of like what we were talking about before with the 62 00:03:14.360 --> 00:03:18.479 effect of LH on the ovaries, insulin can stimulate steroidogenesis, 63 00:03:18.520 --> 00:03:21.639 causing those THECA cells to crank out more androgens. And 64 00:03:21.719 --> 00:03:25.039 these increased levels of insulin also inhibit production of something 65 00:03:25.120 --> 00:03:29.360 known as SHBG, sex hormone binding globulin. This is a 66 00:03:29.439 --> 00:03:32.960 transport protein that binds to hormones like testosterone as well 67 00:03:33.000 --> 00:03:35.719 as others, and it regulates their access to certain tissues. 68 00:03:35.919 --> 00:03:39.560 When hormones like testosterone are bound to SHBG, though, and 69 00:03:39.599 --> 00:03:42.240 this is the important part, these hormones are rendered inactive, 70 00:03:42.360 --> 00:03:44.719 meaning they can't do anything. So the fact that these 71 00:03:44.800 --> 00:03:48.520 high insulin levels inhibit production of SHBG means we have 72 00:03:48.680 --> 00:03:51.319 more of those androgens hanging out free in the bloodstream 73 00:03:51.639 --> 00:03:55.000 in their active state, able to unleash their hyper androgenic effects. 74 00:03:55.080 --> 00:03:57.919 High insulin levels even seem to override the ovara's natural 75 00:03:57.960 --> 00:04:02.960 resistance to LH, making them hyperresponsive, driving even more androgen production, 76 00:04:03.360 --> 00:04:05.479 all of which lead to some of the clinical manifestations 77 00:04:05.479 --> 00:04:07.439 will go over all. Right, So that's a lot of info. 78 00:04:07.719 --> 00:04:11.599 May take away. Excess LH relative to FSH, excess insulin 79 00:04:11.639 --> 00:04:14.319 from insulin resistance. Remember those and let's move on to 80 00:04:14.360 --> 00:04:17.639 the clinical manifestations next. So this is a syndrome, so 81 00:04:17.680 --> 00:04:20.439 the clinical presentation can vary from person to person, and 82 00:04:20.480 --> 00:04:26.240 there's many potential clinical manifestations irregular menstrual cycles, hersutism, acne, obesity, 83 00:04:26.319 --> 00:04:30.839 mood disorders, metabolic issues, cardiovascular issues, diabetes. But the two, 84 00:04:31.040 --> 00:04:33.000 the two I want you to remember that are also 85 00:04:33.079 --> 00:04:35.920 part of the diagnostic criteria will go over shortly is 86 00:04:35.959 --> 00:04:40.920 as follows. The first is menstrual dysfunction oligomenareea amenareea. So 87 00:04:41.000 --> 00:04:44.600 women with PA costs will have infrequent or absent menstrual cycles, 88 00:04:44.639 --> 00:04:48.639 which is caused by infrequent or absent ovulation. As a result. 89 00:04:48.720 --> 00:04:52.480 Infertility is a common consequence of these menstrual regularities and 90 00:04:52.600 --> 00:04:55.000 is frequently one of the reasons women with pea costs 91 00:04:55.040 --> 00:04:58.839 will seek medical attention. So remember oligomenarea or amenarea and 92 00:04:58.879 --> 00:05:04.600 the potential for infertil Next, hyper androgenism, hersaitism, acne, female 93 00:05:04.639 --> 00:05:07.639 pattern hair loss. So these are the repercussions of those 94 00:05:07.720 --> 00:05:11.800 excess androgens like testosterone we mentioned earlier. So hersaitism which 95 00:05:11.839 --> 00:05:14.879 is a thick or pigmented body hair also known as 96 00:05:14.959 --> 00:05:17.720 terminal hair and a male distribution pattern. So we can 97 00:05:17.759 --> 00:05:19.839 see dark hair growth on the upper lip, the chin, 98 00:05:19.920 --> 00:05:23.120 around the nipples, the perieriolar surface, as well as the 99 00:05:23.160 --> 00:05:27.079 lower abdomen. The linear alba acne is common as well. 100 00:05:27.120 --> 00:05:29.199 This can be on the face, back, chest as well 101 00:05:29.240 --> 00:05:31.639 as other areas of the body. And then finally, female 102 00:05:31.639 --> 00:05:34.000 pattern hair loss, so these women may start to have 103 00:05:34.079 --> 00:05:37.959 thinning of the hair on their head. This diffuse alopecia. Okay, 104 00:05:38.040 --> 00:05:42.079 So menstrual dysfunction, oligo or a menorrhea, and hyper androgenism. 105 00:05:42.120 --> 00:05:43.839 Now these are the two I want you to focus on, 106 00:05:44.040 --> 00:05:46.399 but of course be aware there are other potential clinical 107 00:05:46.480 --> 00:05:51.120 manifestations metabolic issues like obesity, insulin resistance, but focus on 108 00:05:51.160 --> 00:05:55.279 the menstrual dysfunction, infertility and hyper androgenic features. Let's talk 109 00:05:55.319 --> 00:05:58.639 about diagnosis next. So when we're talking about the diagnosis 110 00:05:58.680 --> 00:06:01.439 of PECOS, there is no no single lab or imaging 111 00:06:01.439 --> 00:06:04.600 study you can do to definitively diagnose this syndrome. So 112 00:06:04.600 --> 00:06:06.800 what we do to make the diagnosis is by using 113 00:06:06.839 --> 00:06:10.000 something known as the Rotterdam criteria. There are a few 114 00:06:10.040 --> 00:06:13.000 different criteria out there, but the Rotterdam criteria is the 115 00:06:13.000 --> 00:06:15.759 one most expert groups use and therefore it's the one 116 00:06:15.800 --> 00:06:18.040 you need to know. So what does the criteria entail? 117 00:06:18.360 --> 00:06:20.240 So to make the diagnosis of PA costs, you need 118 00:06:20.279 --> 00:06:22.040 to have two out of the three based on the 119 00:06:22.079 --> 00:06:26.839 Rotterdam criteria. The first is oligoovulation or anovulation, which will 120 00:06:26.839 --> 00:06:30.199 generally manifest with menstrual regularity like we talked about before, 121 00:06:30.279 --> 00:06:34.160 so infrequent or absent menstrual cycles. The next is clinical 122 00:06:34.240 --> 00:06:38.000 and or biochemical signs of hyper androgenism. So this means 123 00:06:38.079 --> 00:06:42.360 either the patient has clinical signs of hyperandrogenism so hersitism, 124 00:06:42.399 --> 00:06:45.720 actne et cetera. Or they have biochemical signs of hyper 125 00:06:45.800 --> 00:06:49.680 androgenism so you obtain labs and they have elevated testosterone levels. 126 00:06:49.839 --> 00:06:52.079 And then finally, the last criteria, which we haven't talked 127 00:06:52.079 --> 00:06:54.920 too much about yet is the ultrasound defindings. So the 128 00:06:55.079 --> 00:06:59.240 last criteria is polycystic ovaries by ultrasound. So let's talk 129 00:06:59.279 --> 00:07:02.519 about the ultra findings. Like I mentioned before, the fluid 130 00:07:02.519 --> 00:07:04.720 filled structures in the ovary that we see in some 131 00:07:04.800 --> 00:07:07.839 women with PA costs are not cists, but rather these 132 00:07:07.879 --> 00:07:11.519 immature follicles that never developed during those failed ovulation events. 133 00:07:11.639 --> 00:07:14.480 So an ultrasound will see abnormally high numbers of small 134 00:07:14.519 --> 00:07:19.040 follicles within these enlarged sclerotic ovaries. The small follicles are 135 00:07:19.079 --> 00:07:22.120 often located on the periphery of the ovary and sometimes 136 00:07:22.120 --> 00:07:25.079 they'll resemble a string of pearls and you'll sometimes hear 137 00:07:25.120 --> 00:07:28.120 them being referred to as that string of pearl sign 138 00:07:28.160 --> 00:07:31.800 when describing p COS ultrasound findings. So the Rotterdam criteria 139 00:07:31.839 --> 00:07:34.720 states a positive finding on ultrasound is twelve or more 140 00:07:34.759 --> 00:07:37.839 of these small follicles and either ovary measuring two to 141 00:07:37.959 --> 00:07:41.560 nine millimeters in diameter and or increased ovarian volume over 142 00:07:41.639 --> 00:07:44.839 ten mL. Now, there are some groups that suggest revising 143 00:07:44.879 --> 00:07:47.639 this increasing to twenty or more follicles per ovary because 144 00:07:47.639 --> 00:07:51.079 of the improvements and resolution of pelvic ultrasound and the 145 00:07:51.120 --> 00:07:53.720 fact that a percentage of normal cycling women met the 146 00:07:53.759 --> 00:07:56.879 threshold without having PA costs. What that means to you is, 147 00:07:57.079 --> 00:07:59.519 don't memorize these numbers. If they can't agree on the 148 00:07:59.519 --> 00:08:02.279 criteria for the specifics here, they can't expect you to 149 00:08:02.519 --> 00:08:05.160 remember them or memorize that for an exam. So don't 150 00:08:05.160 --> 00:08:07.759 worry so much about the specific number. But keep in mind, 151 00:08:07.759 --> 00:08:11.040 if the question is describing numerous small follicles and a 152 00:08:11.040 --> 00:08:14.319 big old plump ovary, they're probably describing pea cos all right. 153 00:08:14.319 --> 00:08:17.279 So that's the Rotterdam criteria. That's what you need to know. 154 00:08:17.480 --> 00:08:21.879 Irregular ovulation, hyper androgenism, and polycystic ovaries on ultrasound you 155 00:08:21.959 --> 00:08:23.879 need two out of a three, meaning if you have 156 00:08:23.920 --> 00:08:27.199 a patient with irregular mensis and hyper androgenic symptoms, you 157 00:08:27.240 --> 00:08:29.879 don't even need an ultrasound to diagnose. But there is 158 00:08:29.959 --> 00:08:33.000 one last part we're missing, one very important component. Before 159 00:08:33.039 --> 00:08:36.480 you make the diagnosis based on the Rotterdam criteria, you 160 00:08:36.600 --> 00:08:40.799 absolutely have to rule out your differentials. Rotterdam criteria also 161 00:08:40.879 --> 00:08:44.399 require exclusion of other conditions that mimic pea costs, So 162 00:08:45.200 --> 00:08:48.840 peacos has some very sneaky impostors conditions that have many 163 00:08:49.000 --> 00:08:51.720 of the same or in some cases exactly the same 164 00:08:51.720 --> 00:08:54.759 clinical findings. So once you establish a patient fits the 165 00:08:54.879 --> 00:08:57.519 Rotterdam criteria, the next step is to rule out your 166 00:08:57.639 --> 00:09:00.919 very important differentials. Now, there are a number of differentials. 167 00:09:00.960 --> 00:09:03.200 I'm not going to cover every single one, but the 168 00:09:03.200 --> 00:09:04.919 ones you need to know and the ones that will 169 00:09:05.000 --> 00:09:07.879 likely be tested on can all be found in your apartment. 170 00:09:08.279 --> 00:09:11.039 Your apartment as an APT what does that mean? Apartment 171 00:09:11.120 --> 00:09:15.159 APT stands for three important areas and those are adrenal, pituitary, 172 00:09:15.440 --> 00:09:17.799 and thyroid. So these are the differentials to roll out 173 00:09:17.840 --> 00:09:20.200 before making your diagnosis, and they can all be found 174 00:09:20.240 --> 00:09:22.879 in your apartment. So starting with adrenal, the letter A, 175 00:09:23.120 --> 00:09:25.399 what I'm going to cover right now is the most 176 00:09:25.480 --> 00:09:28.639 important differential you need to know, and if they're going 177 00:09:28.639 --> 00:09:30.519 to give you a differential on an exam, it will 178 00:09:30.639 --> 00:09:34.519 very likely be this one. This is known as NCCAH 179 00:09:34.720 --> 00:09:38.240 non classic congenital adrenal hyperplasia. If you want to forget 180 00:09:38.279 --> 00:09:40.279 all of the other differentials, I'm going to go over 181 00:09:40.360 --> 00:09:42.879 and just remember one. This is it. A patient with 182 00:09:43.039 --> 00:09:46.960 NCCAH can present with almost identical signs and symptoms as 183 00:09:46.960 --> 00:09:51.600 those with PECOS hyperindrogenism, olligo, manaia, polycystic overies, So you 184 00:09:51.679 --> 00:09:53.720 don't want to miss this. So to screen for this, 185 00:09:53.960 --> 00:09:57.840 you obtain a serum seventeen hydroxy progesterone, which is also 186 00:09:57.879 --> 00:10:00.480 super high heal to know, I sometimes remember the as 187 00:10:00.519 --> 00:10:04.000 apartment seventeen just to help me remember this screening test 188 00:10:04.039 --> 00:10:06.799 because it's just so popular to be tested on, and 189 00:10:06.840 --> 00:10:09.000 I definitely got a question on this in school, So 190 00:10:09.120 --> 00:10:11.879 please remember this one and then the other. Adrenal differential 191 00:10:11.960 --> 00:10:14.360 is an adrenal tumor, so a patient with an adrenal 192 00:10:14.399 --> 00:10:18.519 androgen secreting tumor or an adrenal cortical carcinoma. These patients 193 00:10:18.559 --> 00:10:22.720 can have clinical and biochemical manifestations of hyper androgenism like 194 00:10:22.799 --> 00:10:26.000 pa COS, but generally more severe. These patients usually have 195 00:10:26.120 --> 00:10:31.320 significant elevation of testosterone and or DHVAS levels way higher 196 00:10:31.360 --> 00:10:34.679 than PECOS patients, and usually will exhibit more severe signs 197 00:10:34.720 --> 00:10:38.559 of hersitism and even signs of virilization things like cliteromegaly, 198 00:10:38.840 --> 00:10:41.720 increased muscle mass, and deepening of the voice, which we 199 00:10:41.759 --> 00:10:44.440 typically don't see in pea COS. Okay, so that's the 200 00:10:44.480 --> 00:10:48.919 a for apartment. Adrenal main takeaway, don't forget NCCAH screened 201 00:10:48.919 --> 00:10:53.120 with the seventeen hydroxy progesterone. Remember your apartment seventeen. Next 202 00:10:53.159 --> 00:10:56.559 letter in the apartment is P which stands for pituitary. Specifically, 203 00:10:56.639 --> 00:11:00.399 we're talking about hyper prolactinemia. So hyperperlactinemia, which is an 204 00:11:00.440 --> 00:11:04.240 elevation of prolactin levels from the pituitary, can lead to infertility, 205 00:11:04.320 --> 00:11:07.159 oligomenarea or a menareea, so this needs to be in 206 00:11:07.200 --> 00:11:09.799 your workup. And then finally, the T stands for thyroid, 207 00:11:10.039 --> 00:11:13.759 so both hypo and hyperthiroidism can also lead to oligomenarea, 208 00:11:13.919 --> 00:11:16.320 so check a TSH as well. There are, of course 209 00:11:16.360 --> 00:11:21.720 other differentials Cushing syndrome, primary ovarian insufficiency, ovarian hyperthiicosis, pregnancy 210 00:11:21.759 --> 00:11:24.480 of course a very important cause of a menarea. But 211 00:11:24.519 --> 00:11:26.720 the ones I highlighted in your apartment those are the 212 00:11:26.759 --> 00:11:29.159 ones to remember as those will likely be tested on again. 213 00:11:29.240 --> 00:11:33.200 Highlighting non classic congenital adrenal hyperplasia, which you screen for 214 00:11:33.279 --> 00:11:36.480 with a seventeen hydroxy progesterone. All right, next, let's talk 215 00:11:36.480 --> 00:11:39.879 about treatment. So treatment for PCOS is targeted at a 216 00:11:39.960 --> 00:11:42.679 number of different areas because of all of the complications 217 00:11:42.720 --> 00:11:48.159 associated with this condition. Remember we have oligomanarea, hyperindrogenism and fertilities, obesity, 218 00:11:48.159 --> 00:11:51.200 insulin resistance, dyslibidemia. So I'm breaking this down to highlight 219 00:11:51.279 --> 00:11:53.799 the essentials. Let's start with what is considered the first 220 00:11:53.840 --> 00:11:56.679 line intervention for many women with peacos, and that is 221 00:11:56.720 --> 00:12:01.480 lifestyle changes diet exercise, weight reduction. Specifically in our overweight 222 00:12:01.600 --> 00:12:04.440 or obese patients with p costs, Diet, exercise and weight 223 00:12:04.480 --> 00:12:08.120 loss are very effective for improving insulin resistance, decreasing the 224 00:12:08.200 --> 00:12:11.399 hyperandrogenic symptoms, and some studies have found that modest weight 225 00:12:11.440 --> 00:12:14.080 loss five to ten percent reduction in body weight may 226 00:12:14.120 --> 00:12:17.799 restore normal ovulatory cycles and improve pregnancy rates. Of course, 227 00:12:17.799 --> 00:12:21.399 this is also beneficial for managing the underlying metabolic abnormalities 228 00:12:21.399 --> 00:12:25.440 we talked about cardiovascular disease, type two diabetes, etc. So 229 00:12:25.480 --> 00:12:27.840 this should be the first step for all overweight and 230 00:12:27.840 --> 00:12:30.440 obese women with PA costs. The next step for treatment 231 00:12:30.480 --> 00:12:33.559 we're going to talk about. Our medications are pharmacologic therapy. 232 00:12:33.679 --> 00:12:36.320 We're going to break this down into two categories, women 233 00:12:36.360 --> 00:12:39.600 pursuing pregnancy and those who are not pursuing pregnancy. So 234 00:12:39.600 --> 00:12:42.399 starting first with women not pursuing pregnancy, a patient who 235 00:12:42.399 --> 00:12:45.200 does not want to get pregnant, who has menstrual dysfunction 236 00:12:45.399 --> 00:12:48.799 and or androgen excess, which medication can we use? So 237 00:12:48.879 --> 00:12:51.519 the first line pharmacotherapy for most women will be with 238 00:12:51.679 --> 00:12:55.159 a combined oral contraceptive or a COC, which is a 239 00:12:55.159 --> 00:12:58.639 combination of estrogen and progestin. So the coeocs have a 240 00:12:58.720 --> 00:13:02.159 number of benefit for women with PCOS. First, they suppress 241 00:13:02.159 --> 00:13:06.799 ovarian androgens, decreasing the hyper androgenic features. Obviously, provide contraception 242 00:13:06.960 --> 00:13:10.840 because even women with oligomenarrhea may still ovulate intermittently lead 243 00:13:10.919 --> 00:13:13.679 to unwanted pregnancy. And then finally, something that we may 244 00:13:13.679 --> 00:13:16.720 not be thinking about, but patients with chronic annovulation like 245 00:13:16.759 --> 00:13:19.639 in PECOS. These patients are at higher risk for endometril 246 00:13:19.720 --> 00:13:23.360 hyperplasia and even endometrial cancer. And that's because we have 247 00:13:23.440 --> 00:13:27.720 this chronic anovulatory state causing the endometrium to be exposed 248 00:13:27.759 --> 00:13:31.000 to estrogen without the balancing effect of progesterone. We call 249 00:13:31.039 --> 00:13:35.000 this unopposed estrogen, and combined oral contraceptives help prevent this 250 00:13:35.080 --> 00:13:38.279 by providing daily progestin, which is a synthetic form of 251 00:13:38.320 --> 00:13:42.399 progesterone which counteracts the proliferative effects of estrogen on the 252 00:13:42.480 --> 00:13:45.799 endometrium and the second part of the combined oral contraceptive, 253 00:13:45.879 --> 00:13:52.000 the estrogen component reduces serum androgen concentrations by increasing SHBG concentration. 254 00:13:52.360 --> 00:13:55.320 Remember SHBG the guy who gives testosterone a big hug 255 00:13:55.360 --> 00:13:57.600 and doesn't let go. So this in turn reduces the 256 00:13:57.639 --> 00:14:01.000 symptoms of acne or hersitism. Binding these in a CEOC 257 00:14:01.120 --> 00:14:04.759 helps you manage both hyper androgenism and menstrual dysfunction, and 258 00:14:04.759 --> 00:14:08.120 that's why these are generally considered first line pharmacologic treatment. Now, 259 00:14:08.120 --> 00:14:10.759 what about a patient with hyperandrogenic symptoms who's been on 260 00:14:10.799 --> 00:14:13.720 a COEC for many months with no improvement. What other 261 00:14:13.759 --> 00:14:16.679 medication do we have in our arsenal specifically for these 262 00:14:16.679 --> 00:14:21.039 persistent hyperandrogenic symptoms. Well, the one you should know is spirinolactone. 263 00:14:21.159 --> 00:14:25.039 Spiralactone is a minerali cordiicoid receptor antagonist, and it is 264 00:14:25.080 --> 00:14:28.600 an effective treatment option for androgen excess as it blocks 265 00:14:28.639 --> 00:14:33.279 androgen receptors and also decreases testosterone production. And spirinalactone falls 266 00:14:33.360 --> 00:14:36.440 under the women not pursuing pregnancy category because you do 267 00:14:36.480 --> 00:14:39.000 not want to get pregnant while taking this medication as 268 00:14:39.039 --> 00:14:43.039 it can actually feminize male fetuses, preventing development of their genitalia, 269 00:14:43.120 --> 00:14:45.320 so the patient needs to also be on a contraceptive 270 00:14:45.360 --> 00:14:48.200 while taking this medication. There are some other options out there, 271 00:14:48.240 --> 00:14:51.080 such as finess, dride fluta, mind, but spirinalactone is the 272 00:14:51.120 --> 00:14:53.720 preferred agent compared to the other available options due to 273 00:14:53.759 --> 00:14:56.080 its efficacy. All right, next, let's talk about women who 274 00:14:56.120 --> 00:15:00.000 are pursuing pregnancy who are experiencing infertility and require treatment. 275 00:15:00.360 --> 00:15:03.120 So before we go over our meds and ovulatory women 276 00:15:03.159 --> 00:15:05.799 with peacos who are overweight oral beats should attempt to 277 00:15:05.799 --> 00:15:09.639 weight loss prior to initiating ovulation induction therapy. In most cases, 278 00:15:09.919 --> 00:15:12.879 some older women or women whose testing shows diminished ovarian 279 00:15:12.919 --> 00:15:15.519 reserve sometimes they'll go straight to meds, but in general 280 00:15:15.720 --> 00:15:18.799 weight loss for navulatory women who are overweight oral beese 281 00:15:18.879 --> 00:15:22.399 weight loss is recommended first. If lifestyle changes and weight 282 00:15:22.399 --> 00:15:25.279 loss are not effective and medication is needed, the one 283 00:15:25.320 --> 00:15:27.600 you should know is in romatase inhibitor by the name 284 00:15:27.600 --> 00:15:30.840 of lectrisol. Lectrosols should be first line treatment for ovulation 285 00:15:30.960 --> 00:15:34.600 induction in infertile analvieslory women with peacos. Now this has 286 00:15:34.600 --> 00:15:36.960 shifted over the years, as clomaphene used to be first 287 00:15:37.000 --> 00:15:39.240 line by per up to date and the twenty eighteen 288 00:15:39.279 --> 00:15:42.840 International evidence based guidelines, lectrosol is now the first line 289 00:15:42.879 --> 00:15:46.600 treatment option for ovulation induction in women with peacos, Like 290 00:15:46.639 --> 00:15:48.840 a number of pea cost treatments. It's still not FDA 291 00:15:48.840 --> 00:15:51.000 approved for the syndication, so your patients need to be 292 00:15:51.039 --> 00:15:54.200 aware of that, And there are some alternatives clomaphene met foreman, 293 00:15:54.360 --> 00:15:56.639 although both of those are less effective for live birth 294 00:15:56.679 --> 00:15:59.360 rates compared to lectrozol, so I would just focus on 295 00:15:59.440 --> 00:16:02.480 lectrosol after weight loss in women pursuing pregnancy. So how 296 00:16:02.519 --> 00:16:05.440 does letrozol work for ovulation induction? While letrozol is in 297 00:16:05.519 --> 00:16:09.320 aromatase inhibitor. Romatase, as we briefly discussed earlier during the 298 00:16:09.320 --> 00:16:12.960 path or review, is an enzyme that converts androgens into estrogen. 299 00:16:13.200 --> 00:16:16.399 So if we inhibit aromatase, less endrogens are converted to 300 00:16:16.559 --> 00:16:19.039 estrogen and we have much less estrogen in the body. 301 00:16:19.200 --> 00:16:21.919 When we have less estrogen in the body, the hypothalamus 302 00:16:21.960 --> 00:16:24.720 and pituitary sense this say oh, crap we need to 303 00:16:24.720 --> 00:16:27.519 help out, and they produce more FSH, that hormone we 304 00:16:27.559 --> 00:16:30.039 have been lacking because LH took over the show, and 305 00:16:30.080 --> 00:16:33.519 with more FSH we have improved follicular development and improved 306 00:16:33.519 --> 00:16:36.120 ovulatory rates. Those are the mens I think you should know. 307 00:16:36.159 --> 00:16:38.200 There's plenty of others, but the ones I went over 308 00:16:38.279 --> 00:16:40.360 are the most commonly used and the ones you'll likely 309 00:16:40.399 --> 00:16:42.720 get tested on. All right, so that is p COS. 310 00:16:42.759 --> 00:16:44.960 It's a lot, so you probably need a mnemonic. Now, 311 00:16:45.039 --> 00:16:46.720 before I tell you what the mnemonic is, I first 312 00:16:46.759 --> 00:16:48.639 want to be clear. This is just a memory tool. 313 00:16:48.679 --> 00:16:50.759 It's just a way to remember what you need to 314 00:16:50.799 --> 00:16:53.039 know about pa cos. In no way do I intend 315 00:16:53.039 --> 00:16:55.440 for this to be offensive to anyone with PCUS. It's 316 00:16:55.440 --> 00:16:58.080 just a simple little visualization that helped me remember. So 317 00:16:58.159 --> 00:17:00.240 PCUS or pa COS I used to remember in Seat 318 00:17:00.240 --> 00:17:03.600 of Peacos as pea clause. Piacos is pea clause as 319 00:17:03.600 --> 00:17:06.119 in Santa Claus, and Santa Claus contains all of the 320 00:17:06.200 --> 00:17:08.759 high old things you need to know about peacos, including 321 00:17:08.759 --> 00:17:11.960 a Rotterdam criteria and the most important meds. So again, 322 00:17:12.039 --> 00:17:15.240 PACs is now pea clause as in Santa Claus. So 323 00:17:15.319 --> 00:17:17.759 when we visualize our Pea cos Santa Claus, you'll notice 324 00:17:17.799 --> 00:17:20.039 a few things about this version of him. First, in 325 00:17:20.039 --> 00:17:22.240 his right hand, he's holding a ball of lettuce, a 326 00:17:22.319 --> 00:17:24.359 lettuce ball. His left hand, he's holding a bottle of 327 00:17:24.359 --> 00:17:26.559 Coca Cola. On his forehead is a big old pimple 328 00:17:26.559 --> 00:17:29.039 being popped with a spear. He's wearing a pearl necklace 329 00:17:29.240 --> 00:17:31.759 on the wall as a calendar with December twenty fifth circle, 330 00:17:32.039 --> 00:17:34.440 and of course has expected he has a big white beard, 331 00:17:34.480 --> 00:17:36.160 as we've all come to know him for now, what 332 00:17:36.200 --> 00:17:38.920 do all these things represent when it comes to Peacas. First, 333 00:17:38.960 --> 00:17:41.160 that ball of lettuce in his right hand, That lettuce 334 00:17:41.160 --> 00:17:44.319 ball helps remember the first line pharmacologic therapy for patients 335 00:17:44.359 --> 00:17:48.200 pursuing pregnancy letrasol lettuce ball letrasol. And his left hand 336 00:17:48.200 --> 00:17:50.319 holds the clue for first line treatment for women not 337 00:17:50.400 --> 00:17:54.400 pursuing pregnancy, COC's or combined oral contraceptives with the first 338 00:17:54.400 --> 00:17:57.519 three letyers of Coca Cola highlighted coc What about the 339 00:17:57.519 --> 00:17:59.640 big pimple on his forehead being popped by a spear. 340 00:18:00.119 --> 00:18:03.640 Pimple represents your hyper androgenic symptoms like acne and the 341 00:18:03.720 --> 00:18:05.759 spear popping it helps you remember how you treat it 342 00:18:05.799 --> 00:18:10.720 speir in a lactone, spear rhonolacton, speierronolactone. The anti androgen 343 00:18:10.799 --> 00:18:15.480 we used for patients with persistent hyperandrogenic symptoms despite coc monotherapy, 344 00:18:15.799 --> 00:18:17.920 is why beard helps you remember the hersaitism we can 345 00:18:17.920 --> 00:18:20.440 see in patients with peacos. The pearl necklace helps you 346 00:18:20.480 --> 00:18:23.559 remember the string of pearl sign remember those numerous follicles 347 00:18:23.559 --> 00:18:25.960 on the periphery of the ovary. And then the calendar 348 00:18:26.000 --> 00:18:29.119 on the wall shows December twenty fifth circled, symbolizing infrequent 349 00:18:29.160 --> 00:18:31.279 or aps in periods like Sanna who only shows up 350 00:18:31.359 --> 00:18:33.160 once a year in his red suit. So there's a 351 00:18:33.200 --> 00:18:34.960 lot to remember in peacos. But I feel like if 352 00:18:34.960 --> 00:18:38.200 you can just remember Sanna and Apartment seventeen cement this 353 00:18:38.400 --> 00:18:40.720 crazy image in your brain, you should be just fine. 354 00:18:40.880 --> 00:18:42.519 Now that we have our mnemonic, let's do a few 355 00:18:42.559 --> 00:18:45.920 quick questions to test your knowledge. Question one, a twenty 356 00:18:46.039 --> 00:18:48.720 nine year old woman presents to the office complaining of 357 00:18:48.759 --> 00:18:52.000 excessive hair growth on her upper lip, chin, lower abdomen, 358 00:18:52.039 --> 00:18:54.920 as well as irregular menstrual cycles. The patient is five 359 00:18:54.960 --> 00:18:57.640 feet five inches tall, weighs one hundred and thirty two pounds, 360 00:18:57.720 --> 00:19:00.440 and has a BMI of twenty two. On physical examination, 361 00:19:00.519 --> 00:19:02.480 there is terminal hair noted on the face and along 362 00:19:02.519 --> 00:19:05.200 the line alba of the lower abdomen. She's not currently 363 00:19:05.200 --> 00:19:08.480 taking any medications, denies any known medical conditions, and is 364 00:19:08.480 --> 00:19:10.720 not planning on pregnancy at any point in the near future. 365 00:19:11.000 --> 00:19:13.920 She's interested in starting a medication to address the persistent 366 00:19:13.960 --> 00:19:16.200 hair growth on her face and abdomen and the absence 367 00:19:16.200 --> 00:19:18.920 of contraindications. Which of the following would be the most 368 00:19:18.920 --> 00:19:22.240 appropriate next step in management for the likely diagnosis A 369 00:19:22.559 --> 00:19:28.720 letrazol B spirriinalactone C met foreman D combined oral contraceptive 370 00:19:29.119 --> 00:19:38.480 or E lifestyle changes, diet, exercise, weight reduction. So the 371 00:19:38.519 --> 00:19:42.240 correct answer is D combined oral contraceptive. So why is 372 00:19:42.240 --> 00:19:44.079 that the correct answer? So we have a twenty nine 373 00:19:44.119 --> 00:19:47.480 year old female presenting with hersaitism or regular metro cycles 374 00:19:47.720 --> 00:19:50.599 based on the Rotterdam criteria. She has pics. Of course, 375 00:19:50.640 --> 00:19:52.960 to definitively say that full work up to roll out 376 00:19:53.000 --> 00:19:55.119 your differentials would be needed, but that's not what this 377 00:19:55.200 --> 00:19:58.160 question is asking. It's asking based on the likely diagnosis 378 00:19:58.200 --> 00:20:00.599 which treatment are you going to recommend to her hyper 379 00:20:00.640 --> 00:20:03.160 androgenic symptoms? So we know the medication we're going to 380 00:20:03.200 --> 00:20:06.519 prescribe as a coc or combined oral contraceptive. Remember that 381 00:20:06.559 --> 00:20:08.920 bottle of Coca Cola and Santa's left hand. Now, what 382 00:20:08.960 --> 00:20:11.720 about the other options? While letrozol would not be appropriate, 383 00:20:11.799 --> 00:20:15.240 this medication is used for ovulation induction in women pursuing pregnancy. 384 00:20:15.480 --> 00:20:18.599 Spirinalactone could be used as an adjunct therapy for persistent 385 00:20:18.640 --> 00:20:22.400 hyperandrogenic symptoms, but it's generally not first line met foreman 386 00:20:22.480 --> 00:20:24.880 which at one time was used pretty frequently for peacs, 387 00:20:25.240 --> 00:20:27.880 is no longer recommended for hersaitism per the twenty eighteen 388 00:20:27.960 --> 00:20:30.680 Endercin Society guidelines, as it has been found to provide 389 00:20:30.680 --> 00:20:33.359 little or no benefit. And then finally, lifestyle would have 390 00:20:33.400 --> 00:20:36.000 been appropriate if this patient was overweight or obese, but 391 00:20:36.119 --> 00:20:39.240 this patient as a normal BMI of twenty two. Question two. 392 00:20:39.440 --> 00:20:41.480 A twenty six year old woman presents to the clinic 393 00:20:41.519 --> 00:20:44.759 with concerns about difficulty becoming pregnant. She and her partner 394 00:20:44.839 --> 00:20:47.720 have been trying to conceive for several months without success. 395 00:20:48.000 --> 00:20:50.279 She reports only one to two menstrual cycles over the 396 00:20:50.319 --> 00:20:53.039 past year. It's not on any medications and has no 397 00:20:53.119 --> 00:20:57.119 significant past medical history. Physical examination reveals hersatism on the 398 00:20:57.160 --> 00:20:59.960 upper lip and lower abdomen. Her height is five foot four, 399 00:21:00.079 --> 00:21:03.000 weight is two hundred pounds BMI thirty four point three. 400 00:21:03.319 --> 00:21:07.240 A transvaginal ultrasound reveals enlarged ovaries with multiple small follicles 401 00:21:07.319 --> 00:21:10.440