2- Puberty (Part 1): Normal puberty

Camille Imbo, MD PGY6 and Susan Kaufman, MD talk about normal puberty, the many axes involved, the milestones, and expected timing of each.

References:

• Essentials of Pediatric and Adolescent Gynecology: Chapter 5

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Pediatric and Adolescent Gynecology is a subspecialty of OBGYN (2 year fellowship) focusing on reproductive healthcare for children and young adults. It fills the overlap between general gynecologists and pediatricians. It is a multi-disciplinary field involving work with pediatric endocrinology, dermatology, hematology, surgery, ect. Go to NASPAG.org for more PAG educational resources.

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Transcript

Camille: [00:00:00] A nine year old girl comes into your clinic with her mom who's noticed breast development starting just this past month. Mom's worried because she didn't go through puberty until she was 12. So she asks you, is this normal? 

Susan: Welcome to PAG OVER pastry. This is a 20 to 30 minute review podcast of all things pediatric and adolescent gynecology.

Susan: I'm Susan Kauffman and attending at Virtua Hospital and a pediatric and adolescent gynecologist. 

Camille: And I'm Camille Imbo, a second year pediatric and adolescent gynecology fellow at Phoenix Children's Hospital. So today we'll be talking about puberty. It'll be a two part series where we'll first cover normal puberty and then listen to the next podcast to hear about abnormal puberty.

Camille: References today are chapter five, normal puberty written by Hannah Cantor and Megan Jacobs. And. Essentials of Pediatric and Adolescent Gynecology, released by NASPAC. 

Susan: And [00:01:00] Camille, what's your favorite pastry? 

Camille: I know last time I said the bear claw, which still is up there, but I also love a strawberry tart.

Camille: How about you? 

Susan: I'm gonna go with a chocolate chip cookie. A really big chocolate chip cookie with lots 

Camille:  I love  those.  Alright, let's get  started.

Susan: So, what is puberty and why do we care about it? 

Camille: Yes. So if you're listening to this podcast, you've probably gone through puberty. It's a critical stage of growth and development. Of course, I want to acknowledge that we're specifically going to be discussing puberty in assigned female at birth, but it's important for clinicians to be aware of pubertal changes, not just what they are, but also when they are supposed to happen.

Camille: Gynecologists are not the only ones that would catch this as well as pediatricians. There's [00:02:00] anyone who sees young adults and teenagers should be aware of what's normal and not normal. So today we'll talk about the many axis that occur in puberty, the hormonal changes, as well as the physical milestones.

Camille: So talking about axes, the first one is the HPG axis. What is that? 

Susan: So that's the hypothalamic pituitary ovarian. axis. And this is the process that starts ovarian function. And once ovarian function starts producing estrogen and testosterone, these are two of the main hormones that start pubertal development.

Susan: There's always a lot of questions about what actually Begins puberty. And some recent research suggests that leptin, which is a hormone that comes from adipose tissue, stimulates certain cells in the hypothalamus to produce septin. And kisspeptin is another hormone that [00:03:00] actually changes the secretion of GN Rh.

Susan: So before Kisspeptin is stimulated, the hypothalamus produces GNRH in a constant fashion. It's when the hypothalamus begins to produce GnRH in a pulsatile fashion that then the pituitary is stimulated to produce FSH and LH, which then stimulates the ovary. Once the ovary is producing estrogen and testosterone, then we see the changes begin that we then define as puberty.

Susan: What are these effects? What do we see estrogen and testosterone doing? 

Camille: So that's what we call the pubertal milestones. So thelarche is usually first, um, kind of at the same time as adrenarche. Sometimes they can switch places, but thalarky is breast budding and can happen. Anywhere between 8. 8 to 10 years has been shown.

Camille: This might be affected by race and ethnicity, [00:04:00] but we'll talk about this a little bit more later. To what degree that affects things next or as I mentioned, it could come first as anarchy happens at a similar time. And that's the onset of pubic hair around the mons as well as in the axillary. And then next you have your height spurt, which starts around nine and a half years and peaks at eleven and a half years.

Camille: It's important to note that once you reach menarche, you stop growing about two years afterwards. Really, you usually have about two inches left. That's important to note because we always get patients who come in years after their period for concern of short height and asking what can we do to help prolong their growth.

Camille: But if they've had their period for a while now, there's nothing left to do at that point. And then lastly is menarche, which the average age is 12 and a half years. And of course, it's important to remember, these are all average ages, right? So you can expect some to be a little bit [00:05:00] earlier, some to be a little bit later.

Susan: I just want to add one comment to the average age of all of these landmarks. We are seeing more young ladies starting periods at 9 and 10, and some even at 8, and really not considering it to be abnormal any longer, as long as the timing and the tempo seem to be appropriate. 

Camille: So let's break these down a little bit more.  So first, when it comes to thalarche and we talk about Tanner staging, which is how we look at each of these changes, what is the Tanner staging for breast development? 

Susan: Well, we used to just call it Tanner staging. Now we're calling it sexual maturation rating scale, but it really is exactly the same thing.

Susan: So we have five stages, whether we call them Tanner stages or SMR stages. The first stage is just elevation of the nipple above the areola, and this is a prepubertal stage. In [00:06:00] stage two, we start to have the development of breast tissue, and this breast tissue forms a little mound, and that mound can be hard.

Susan: It can also be tender, and It is important to educate parents about this stage because sometimes it is misinterpreted as something abnormal and, um, causes a whole cascade of evaluation, which is completely unnecessary. In Tanner 3, we start to see more development of the areola and more growth of breast tissue, but basically the areola and breast tissue remain one unit.

Susan: In Tanner 4, we see elevation of the areola and further elevation of the breast tissue, so it almost becomes like mound on mound, where the areola is somewhat separate from the breast tissue. And then Tanner 5, which we consider the adult breast, uh, the areola tends to flatten out. And now the breast, the areola, all becomes one unit [00:07:00] and with the nipple on the surface.

Susan: It's often at Tanner four or five where we will see beginning of menses. 

Camille: I don't know about you, but Tanner staging for breast development was one of the hardest things for me in residency. And when I started fellowship, because that's Three to four range really is hard to differentiate, and especially as childhood obesity keeps increasing, some people can look further and staging than they are.  do you have any tips for that? 

Susan: Well, that's absolutely, and we'll have lots of parents bringing their daughters in. saying that they actually have breast development or referrals from pediatricians thinking that they have breast development. And I think the key to telling the difference is the actual exam and how the tissue feels.

Susan: So if it's possible, and if the young lady is comfortable, I will first examine her sitting up and I will check under her axilla. I will look at the tissue that I'm [00:08:00] seeing and see whether it. fits into any of these landmarks that I just addressed and then lay her back down and actually feel the tissue because adipose tissue feels very different from breast tissue.

Susan: Breast tissue tends to be denser and less compressible even at Tanner three than adipose tissue is. That's really a good tip. And what about genital changes? What kind of genital changes do we see? 

Camille: Yeah. So unlike, , breast staging, there's not technically a Tanner stage for the genitalia itself. , we'll talk later about the  pubic hair. But when it comes to the genitalia, you can expect a little bit of growth in the clitoris and the labia. This is especially important when thinking about things like labial hypertrophy. I don't know why we've had a huge amount of patients come in for labial hypertrophy lately. And especially if they're under 18, we remind them that a, we don't recommend surgery in general, for the most part, [00:09:00] because of the possible repercussions, but even if they are someone who may potentially need surgery that we try to wait until their labia are fully grown because if you know they get surgery too early they are still going to grow as they progress through puberty.

Camille: Other changes are kind of how the estrogen exposure changes the color of the vagina, so When they're younger, you'll see kind of a redder, drier aspect to their mucosa. And then as they get older, the estrogen exposure decreases that erythema. And then you also start to get your discharge or physiologic leukaemia, which usually precedes menarche by six to 12 months.

Camille: So. As you mentioned, that's another common thing that parents may bring their daughters in, wondering if they're having a bacterial infection. And while you should still do a workup to make sure that it's not an infection, knowing what age they are and, you know, if they've had breast development in the last couple of years may give you a hint [00:10:00] of knowing, oh, they're probably just about to go through menarche.

Susan: And also speaking about the color changes, often in children, the red or erythematous appearance of the entroitis can be easily mistaken either by a clinical provider or by the parent as a sign of infection. So it's important to realize and be able to explain to them that this is due to the lack of estrogen.

Susan: Right. Also the labia minora can take on different shapes as well as different sizes and different colors too. So they could be brown, they could be pink. And it's our job to be able to reassure folks that this is all normal. 

Camille: Yes, absolutely. In our clinic, we have a book with pictures of different labia minora and showing it to patients because sometimes it's even their moms being like, Oh, hers don't look like mine.

Camille: It must be abnormal. And it's a there's puberty, but also be everyone's different and that that's completely okay. So yeah, absolutely agree. 

Susan: Is that [00:11:00] the pedals book. 

Camille: Yes, yes, that's the one. I couldn't remember the name, but yes, that's exactly it. Great book. So we talked about the hypothalamus, pituitary, gonadal, or ovarian axis.

Camille: What about the HPA axis? 

Susan: So while we don't have grading for genital changes, we do have grading or staging for pubic hair. Again, we have five stages and stage one is just very light, soft hair that may appear on the mons. And depending on somebody's ethnic background, they may have more or less hair on the mons, even as a child.

Susan: And again, this can be mistaken for the onset of puberty or precocious adenarchy. Um, but based on the location of the hair, and the um, softness or thickness of the hair that clues us into whether this is normal or abnormal. In stage two, the hair starts to get longer, [00:12:00] a little bit coarser, and we start to see it appear on the labia majora.

Susan: In stage three, the amount of hair increases, and again it changes. It might be Changes in color, coarseness, and starts to become curlier instead of straight. In stage four, we see it spreading out over the labia majora. So now we'll have hair on the mons, we'll have hair on the labia majora, and by the time somebody reaches stage five, the hair spreads out onto the upper medial thighs.

Susan: And stage four is considered mature adult hair distribution. 

Camille: Yeah, and my way of kind of remembering that is memorizing what stage three looks like because that's where you have a fair amount of hair more than you could count individually, but it's not a lot. quite thick yet. So a little bit less than that is two, a little bit more than that is four.

Camille: But then if it's spread to the thighs, it's five. And of course, if there's nothing at all, it's [00:13:00] one. So that's kind of how I've broken that up. And it's important to note that this starts at age eight on average, and it's from the adrenal glands producing their androgen. So DHEA, DHEAS, and Androstenedione, which I can never pronounce on my first try, um, and DHEAS is converted in the apricot and sebaceous glands leading to odor and acne.

Camille: But we have yet another axis, which is the HPS axis. Can you tell us about that one? 

Susan: So that's the hypothalamic pituitary somatotropic axis, and this is related to linear growth and the development of bone density and soft tissue. This is controlled by growth hormone, and growth hormone is controlled by what we call insulin, growth factor hormone and estrogen and testosterone.

Susan: So growth hormone [00:14:00] is released in a pulsatile fashion from the hypothalamus under the stimulation of the insulin growth hormone factor. And then this causes linear growth and The increase in bone density and soft tissue. So, linear growth, as we said before, will occur between ages 8 12 up to 10 or 11, or 10 or stage 2 or 3.

Susan: Peak growth can be measured at 8. 3 cm per year. There's also an equation that we can use if parents or girls want to calculate their maximum height, and that involves looking at Mid parental height, so between the father and the mother. It's a little bit of a complicated equation, not something I use very often.

Susan: I basically look at what's mom's height, what's dad's height, what's the rest of the height in the family, and then kind of guess at what I think this child's height might end up [00:15:00] being. But we can also calculate it if necessary. 

Camille: Yeah, I usually see the endocrinologist notes have it, but I like it. It's useful because sometimes parents will bring in their child for short stature, but then you look at them and you're like, well, your kid's probably not going to be significantly taller than you are, or that their siblings were.

Camille: So that's always a good thing to remind parents about. 

Susan: And, uh, you know, linear growth is controlled by estrogen. So when the growth plates close, Linear growth will stop, but bone density continues to accumulate, uh, throughout the teenage years, the twenties, up until the thirties, uh, when somebody will accumulate most of their bone density, it then should stay stable after that.

Susan: And when somebody reaches perimenopause and menopause, they're likely to start losing bone density. And knowing this is so important when we talk about abnormal puberty. Because if somebody's [00:16:00] either starting puberty too young and at risk of closing their growth plates too young or starting puberty too late, then they're at risk of not building enough bone density.

Susan: Right. We're going to talk about more about when we go into abnormal puberty. Yes. Yes. No spoilers. So what about What starts puberty? Which is the question always everybody asks. Well, what's going to make puberty begin? Why is it start? And you 

Camille: mentioned chemicals behind it and some of the research that's been done.

Camille: Officially, as of right now, the answer in consensus is it's still unknown. We know genetics affect a good majority of it. So just like how we talked about the mid parental height. So asking parents, moms, especially when did you go through your period? When did you start having breast budding or when the siblings did is a good way to assess that, but really it comes down to, like you mentioned earlier, the switch of GNRH continuous [00:17:00] secretion to the pulsatile secretion, which is activated by Kispeptin, Neurokinin B, Dynorphin, which if you want extra credit on your exams is produced by neurons in the GNRH.

Camille: Arcuate nucleus of the hypothalamus. But it's also important to know that there's a lot of differentiating factors, not only between individuals, but also between communities. So it's been shown that developed nations go through puberty younger. Feller key up to one year earlier and menarche up to four months earlier.

Camille: There's been research about whether that's due to our diet or. certain chemicals that we're exposed to. There's actually a really great table in the book, which I was surprised to see breaks down different chemicals, microplastics, and so on, and how that has affected puberty. So not to make everyone.

Camille: hyper aware of every tiny little thing that's in our food and environment, but those things do affect our puberty. Um, and that's important [00:18:00] because earlier menarche leads to shorter height, as you mentioned, but it also leads to heavier weight. It can be up to five and a half kilograms heavier, which is about 11 pounds, a possible increased risk in breast cancer, because, you know, the more times you're ovulating, the higher your risk.

Camille: of breast cancer. There's questions about racial differences as well. The consensus from that perspective in our clinical judgment and treatment to not use race as the reason that we don't treat someone. So even though there's some literature that African Americans and Latina girls can reach puberty a little bit earlier, I think it's important to not let that be a factor as to delay in care.

Camille: Missing. uh, precocious puberty or delayed puberty is worse than the other way around. 

Susan: I was just going to say if we're using racial factors it really creates a racial disparity because like you said [00:19:00] it may be a reason not to evaluate an eight year old or seven year old and and attribute this to her race and that is wrong and we should not be doing that.

Camille: Absolutely. Absolutely. Um, so social economic status can affect things as well. Poor health, chronic health diseases can affect things, um, increased weight, which increases the leptin hormone. And as you mentioned earlier, that's one of the main hormones that stimulates GnRH. So the short answer is yes. A lot.

Susan: I think the short answer is that we look at everybody exactly the same, apply the same criteria to evaluating everyone and look for underlying causes for whatever the concern or question is, regardless of what community somebody comes from. 

Camille: Absolutely, and piggybacking off of that, so if someone does come in and they have concerns, what exams should be done?

Susan: First, I just want to [00:20:00] talk about history. We, as you mentioned, we need to take an in depth history of the maternal history, um, and actually the paternal history. What age did people go through certain developmental landmarks? What age did periods start on both the mother's and father's side? And what are their growth curves?

Susan: Then we need to do a complete physical exam head to toe, and this becomes important when we're looking for markers for abnormal puberty, but also for normal puberty. Are we seeing the normal developmental landmarks that we should see? And then we are going to look at hormone levels. and imaging. So if we're assessing somebody's hormone levels, we're going to order the ultra sensitive LH, FSH, and estradiol, uh, free and total testosterone, uh, often a prolactin level, thyroid testing, and DHEAS.

Camille: And I want to highlight what you just mentioned there about the ultra sensitive, um, LH and FSH. That's [00:21:00] actually something I didn't realize until several months ago that ordering just the generic LH and FSH has been shown to not be as accurate in the pediatric population, right? 

Susan: Right. But sometimes that's hard to order.

Susan: I know in our EPIC, we don't have those orders, and I've been trying to get IT to put them in because of how important it is to order the right test. So you can interpret it correctly, 

Camille: right? The book does mention two situations about reassurance or that may be more conversations. So one is they're coming in like, Oh, I'm worried that my period's too early.

Camille: When you gather history, it's appropriate within their timeline, appropriate with their age. So that might be where education is more helpful. And then another one, which I'll admit is one of my Probably my least favorite chief complaint is, is my daughter a virgin? Can you check? The answer is absolutely not.

Camille: Virginity is not an anatomical concept. It's a social [00:22:00] concept. Um, this is important to note if there is a situation where we do need to do an internal exam, whether that's like placing an ID or doing a swab, I'll have. Parents ask, oh, are you taking her virginity? And it's like, nope, that's not how that works.

Camille: The hymen is, can be there, cannot be there. And virginity has nothing to do with that. So with all that being said, going back to our case. So it was a nine year old girl who came in because her mom noticed breast development starting just this past month. Mom was worried because she personally didn't go through puberty until she was 12.

Camille: And she asked, is this normal? So is it? 

Susan: In this day and age, it is absolutely normal, but it's also, you know, when mom says she didn't go through puberty until she was 12, we need to find out what she means by that actually. Does that mean her period started at 12 or her breast development started at 12?

Susan: If her breast development started at 12, then she was actually a little delayed by the criteria that we generally [00:23:00] use. But if we get a history that in the father's side of the family, His sister or his mother started periods young, then that would be acceptable and right on target with where this young lady is.

Camille: So that's about it for our talk on normal puberty. As we've hinted at many times, this only just segues very easily into our upcoming talk about abnormal puberty. But for more information or the tables that we reference from the chapter in the book, visit the Pag over Pastries page on the NASPAG website.

Camille: It'll include a transcript of all the podcasts, links to the references or emails, and anything else that you may need. 

Susan: I hope this is helpful. Provides good information for our residents and reminds them about all these things they learned in medical school and hopefully our reviewing in residency. And we'll see you shortly for the next podcast.

Camille: Thank you for listening to [00:24:00] PAG over pastries.