Rumor vs Truth

Hormone Replacement Therapy for Menopause

• TRC Healthcare • Season 2 • Episode 1

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Hot flashes or cool facts… are menopause and hormone replacement therapy (HRT) in the middle of the rumors? In this episode, Don and Steve turn up the heat on common claims about estrogen therapy and menopause management. Joined by guest expert Sara Klockars, PharmD, BCPS, they separate fact from fiction and share practical tips for clinicians.

🔥 Is HRT the go-to for every patient with hot flashes?
💊 Are bioidentical hormones truly better… or just better marketed?
🩹 Is topical estrogen safer than oral therapy?
🎗 Does hormone therapy raise breast cancer risk… or is the evidence more nuanced?

Bust the hype, and uncover the facts behind these hot-button hormone claims:

  • All patients with low estrogen levels should use HRT
  • Bioidentical estrogens are more effective than other estrogens
  • Topical estrogen is safer than oral options  
  • Hormone replacement therapy causes breast cancer

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TRC Healthcare Editor Hosts: 

  • Stephen Small, PharmD, BCPS, BCPPS, BCCCP, CNSC 
  • Don Weinberger, PharmD, PMSP

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Guest: 

  • Sara Klockars, PharmD, BCPS (TRC Healthcare Editor)

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CE Information:

None of the speakers have anything to disclose. 

TRC Healthcare offers CE credit for this podcast for subscribers at our platinum level or higher. Log in to your Pharmacist’s Letter, Pharmacy Technician’s Letter,or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.

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The clinical resources mentioned during the podcast are part of a subscription to Pharmacist’s Letter, Pharmacy Technician’s Letter, and Prescriber Insights: 

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Narrator:

Welcome to Rumor vs Truth, your trusted source for facts, where we dissect the evidence behind risky rumors and reveal clinical truths. Today, we're exploring heated claims around hormone replacement therapy for menopause.

Steve Small:

So, Don, when I got the memo, we were talking about hormone replacement therapy today. I thought, didn't we just do a testosterone episode?

Don Weinberger:

Yeah, yeah. You know, we sure did, Steve. But that episode led to several listeners, you know, they're asking us to talk about another major hormone, which is estrogen.

Steve Small:

Yeah. Oh, so a spinoff. Okay. I I like that idea.

Don Weinberger:

Okay. So before I hog all the credit here, uh hello everyone. I'm Don the pharmacist.

Steve Small:

And I'm Steve the pharmacist.

Don Weinberger:

And you could probably tell by now in this episode, we're going to take a pause so we can learn about menopause and look at claims about hormone replacement therapy, focusing mostly on estrogen.

Steve Small:

Yeah, timely topic for sure. And speaking of time, it's always a good time to get CE. This podcast offers continuing education credit for pharmacists, pharmacy technicians, prescribers, and nurses.

Don Weinberger:

All right. So just log into your Pharmacist's Letter, pharmacy technicians letter, or Prescriber Insights account, and look for the title of this podcast in the list of available CE courses.

Steve Small:

And for the purposes of disclosure today, none of the speakers have anything to disclose.

Don Weinberger:

That's right. So we've got a lot of questions about hormone replacement therapy, a commonly abbreviated HRT or HT for hormone therapy lately, especially with FDA's recent change in boxed warnings around these products for menopause.

Steve Small:

Yep. And there's lots of talk out there on the internet, TV, social media, you name it. And it's important that we have the facts to really help our patients on this.

Don Weinberger:

And speaking of facts, stick around. Also answer our listeners' question about GLP1 side effects from our last episode.

Steve Small:

And you know, I don't think we do this topic justice on our own, Don. So for this episode, we've enlisted the help of one of our editors again, Sara Klockars, PharmD, BCPS, to help us tackle these claims. And she's done a lot of research on this topic. So welcome, Sara.

Don Weinberger:

Yes, welcome, Sara. And before we kind of put your feet to the fire here and uncover the facts about hormones replacement therapy, can you give us a rundown about menopause and where estrogen actually plays a role?

Sara Klockars:

Sure. Thanks for having me. Um menopause is a normal part of aging in all women. Essentially, it's where menstrual cycles stop permanently for at least 12 consecutive months. And most women can expect this to occur between age 45 and 55. And this occurs because of that declining hormone production by the ovaries. And that also includes a drastic decrease in estrogen, which can have many effects on the body, not just stopping periods.

Steve Small:

Yeah. So many effects. Can you tell us about those?

Sara Klockars:

Sure. So many women experience symptoms for several years before menopause. And that perimenopause transition phase sometimes persists for years. And symptoms can persist for years after as well, into menopause. Patients can experience vasomotor symptoms during this time, and those are those hot flashes or night sweats. And it can also lead to genitourinary symptoms such as vaginal dryness, burning, itching, and urinary symptoms such as frequency and urgency. Patients can also have migraines, mood changes such as irritability, depression. You hear about brain fog and loss of concentration. And really the list goes on and on.

Don Weinberger:

And since low estrogen is a cause of these symptoms, you know, it does make sense that getting estrogen replacement is one way to treat these patients, right?

Steve Small:

Yeah, putting those uh pieces together in terms of menopause, and that's a really good review. So going into claim number one here, uh, knowing estrogen's role in menopause symptoms, it leads to the question uh or this claim that all patients with low estrogen levels should use HRT. What is your take on this, Sara?

Sara Klockars:

Well, generally lab tests are not required for the diagnosis of menopause. So we don't know if someone necessarily has low estrogen levels. But the diagnosis is made clinically based on the patient's age, menstrual changes, and irregularity, and then those symptoms like the hot flashes are what I personally try to think of as power surges.

Don Weinberger:

Okay, so power surges. So how common are these?

Sara Klockars:

Well, up to 80% of menopausal patients report bothersome vasomotor symptoms. And other patients may not have problems at all. So, but for the majority, menopause is a real challenge when it impacts your sleep, your personal relationships, your emotional well-being. And that's when we would consider treatment rather than relying on lab tests alone.

Steve Small:

Yeah, and you know, thinking about lab tests here, I did look up recommendations from the menopause society for this episode. And they note that, quote, salivary and urine hormone testing to determine dosing are unreliable and not recommended. Uh, serum hormone testing is rarely needed. So interesting point there.

Sara Klockars:

Exactly, Steve. So those hormone concentrations fluctuate greatly during that perimenopause phase, especially with those irregular cycles where you may be going months without a cycle. And they they don't really stabilize until up to six years after that final menstrual period. Um, the American College of Obstetricians and Gynecologists, or ACOG, also support the recommendation that hormone testing isn't recommended during perimenopause or before starting hormone therapy for most patients, since levels aren't likely to offer useful info. However, there are certain cases that levels are helpful, but they're not always needed.

Steve Small:

Yeah, good caveat there. So when it comes to this claim that all patients with low estrogen levels should use HRT, the verdict is... Rumor. So the decision to start HRT really comes down to whether patients feel they have bothersome menopause symptoms affecting their life rather than relying on estrogen levels.

Don Weinberger:

Yeah, not to mention weighing benefits and risks of therapy. Some patients may have contraindications for use, right? Uh, I agree levels don't appear to correlate very well with symptoms here. So it's difficult to use them for treatment decisions. Um, and if you think about all the added costs with healthcare labs, do you add up to it, right?

Steve Small:

Yeah, good thoughts there. And if a patient qualifies for therapy, we have a helpful FAQ chart managing vasomotor menopause symptoms that gives a helpful rundown on various options, including estrogens and non-hormonal therapies.

Don Weinberger:

Yeah, good call-out. And remember, just like many things in medicine, we need to treat the patient and not the numbers, right?

Steve Small:

Nice.

Don Weinberger:

And speaking of numbers, let's move on to our claim number two here. And it is bioidentical estrogens are more effective than other estrogens. So, Sara, glad you're here again. Spell this out for us. What makes something a bioidentical estrogen?

Sara Klockars:

Yeah, so bioidentical estrogens are estrogens with the identical chemical structure as those produced by the ovaries. So, as an example, estradiol is a naturally occurring hormone the body makes, meaning it's bioidentical. Uh, another example of ethanol estradiol that is not bioidentical since we don't make this chemical structure or hormone in our bodies.

Don Weinberger:

Right. That's a good common distinction that we kind of see in pharmacy, right? And I've heard some healthcare professionals differentiate between formulations, uh, referring to compounded formulations as bioidentical, while calling the commercial available FDA-approved formulations body identical. You know, very there's a nuance there, right? But uh it sounds like they mean the same thing. And perhaps it comes down to marketing.

Sara Klockars:

Right. So there are both commercially available and compounded bioidentical hormones. Um, another estrogen we'll chat about more is conjugated equine estrogens. And these are extracted from pregnant mare's urine and are not considered bioidentical to human hormones since they're from horses, obviously.

Steve Small:

Yeah, and premarin is the brand name of that kind of product example. And it's named since it's extracted from pregnant, so P-R-E, pregnant, mare, M-A-R, uh, urine. The premarin, it all makes sense. So clever naming there. So then are bioidentical versions more effective?

Sara Klockars:

Good question. Based on the evidence, all forms of systemic estrogen appear to help with those vasomotor symptoms when compared to placebo. We can't say necessarily that bioidentical estrogens are more effective since we don't have many head-to-head trials. Um, some would say that would be putting the cart before the horse.

Steve Small:

Horsing around with some puns now, okay.

Sara Klockars:

It's also important to note that compounded bioidentical hormones have less data. And there are so many different formulations and combinations out there, and they're not evaluated by the FDA, just to note that.

Don Weinberger:

Okay, good. Thank you for kind of bringing that in there. So let's go ahead and go back to that claim, which is bioidentical estrogens are more effective than other estrogens. And the verdict is... Rumor. So it looks like we might be naysayers on this one. We don't really have enough evidence to say one way or another. Uh, it's important to think about the route and tailoring the choice to the patient. Uh, for example, you know, I have had some patients prefer a compounded product to get a customized dosage.

Steve Small:

Yeah, good point. And a good reminder that patients should use a US licensed pharmacy, ideally accredited in compounding, to really help ensure safety and quality with this.

Don Weinberger:

Yeah, good point. And while there's so many options out there, we can use our menopausal hormone therapies chart to help you compare product, dosage forms, strengths, and more. We have a column in there to identify which hormones are bioidentical.

Steve Small:

Yeah, that's super handy. And take a look at the show notes or description since we've linked directly to that resource in Pharmacist's Letter, Pharmacy Technician's Letter, and Prescriber Insights, as well as our managing vasomotor menopause symptoms chart we talked about earlier.

Don Weinberger:

Yeah, and if you aren't a subscriber, don't miss out on these resources. Sign up today to stay ahead with trusted and topical insights and tools.

Steve Small:

Good segue, Don. Topical indeed. Uh, because that's our next claim that topical estrogen is safer than oral options. Again, Sara, over to you.

Sara Klockars:

Well, this is a bit nuanced and complex due to some limited robust safety data. But just to take a step back and clarify, topical estrogens can include transdermal patches or sprays. For example, those products you put on your skin and also vaginal products such as the creams, rings, or tablets.

Steve Small:

Good to point that out. And you know, since drug absorption and levels in the body aren't necessarily the same with all of these, right?

Sara Klockars:

Right. So yeah, we rely on transdermal options to provide systemic levels. And that's where there's enough to get absorbed into the bloodstream to treat those vasomotor symptoms as an alternative to oral therapies. When it comes to vaginal products, there are different amounts absorbed depending on the product. So we have a low-dose vaginal option that only helps with those local symptoms, those genitourinary symptoms. And there's a higher dose estradiol acetate ring, Femring, and that provides systemic levels to treat those vasomotor and vaginal symptoms. Um, just one little tidbit is keep the vaginal ring straight with this phrase. Um, a ring, so thinking Femring is bigger than a string. Think Estring. So Femring provides that higher dose for systemic effects, and Estring is that lower dose for local effects.

Don Weinberger:

Right. I mean, we do love our mnemonics here, right? That's for sure. So what is the evidence around safety then?

Sara Klockars:

Yeah, so let's start with the orals. Um, most of the well-designed hormone therapy studies and menopause are with oral conjugated equine estrogens, that premerin, um, with or without medroxyprogesterone acetate, another synthetic progestin. So these options may increase risk of blood clots and stroke, especially for patients who are older than 60 or more than 10 or 20 years from menopause onset when starting it. So we we also have observational studies that suggest a lower clot risk with estradiol compared to oral conjugated equine estrogens.

Steve Small:

Okay. And based on that, where might this thought then come from that transdermal products are safer?

Sara Klockars:

Yeah. So when it comes to transdermal preps, which are still systemic, so they're being absorbed like those orals, um, but they are associated with a lower clot risk than oral estrogens, since the transdermal preps avoid that absorption in the stomach and the metabolism in the liver. So they're not getting broken down in the liver, and they have less of an impact on the clotting factors. And then this is thought to also apply to Femring, which has likely a more favorable safety profile than oral estrogen as well. Um, I do want to note we do even have a safer option. So we have those low-dose vaginal estrogen products that have minimal absorption. So we'd anticipate fewer risks as well. Um, we have some observational data that suggests these options are not linked to blood clots and they can be used at any age, um, and even in patients with a higher risk of um blood clots.

Steve Small:

Yeah, that data seems reassuring then.

Sara Klockars:

Yes, yes, it does. Um, and even though we're relying mostly on observational data, these meds have been around for quite some time. Um, but overall, robust evidence uh of various estrogen products, different estrogen doses, different formulations, and even different progestin, progesterone options in there. Um and in other younger populations, that those that evidence is just really missing from this whole picture. Um, so that makes it hard to draw some good conclusions for most other safety outcomes, such as you know, cardiovascular events or fractures.

Steve Small:

Yeah, I can see where that's tricky to really sort it out. So, so when it comes to this claim that topical estrogen is safer than oral options, the verdict is... True with conditions. Based on that, it's a good practice to look at personal and familial risk of things like cardiovascular disease, stroke, and blood clots before a patient starts hormone therapy. And let's not forget smoking, since that really impacts risks too.

Don Weinberger:

All right, glad you mentioned the smoking. And transdermal options may have a lower clot risk. It's important to think about those non-hormonal options, including paroxetine, uh fezolinentant, or elinzanetant. Said those right, for patients with a history of heart attack, stroke, or blood clots, or at a high risk uh thrombotic disease.

Steve Small:

Yeah. And that reminds me of our great article about elinzanetant in the January issue of Pharmacist's Letter, Pharmacy Technician's Letter, and Prescriber Insights. And we also have more answers to questions about transdermal and vaginal estrogens in our managing genitourinary menopausal symptoms chart.

Don Weinberger:

Oh, that reminds me, Steve. Uh you know, looking back at our audience questions, I remember we got some about some talking about this really. I think cut the estradiol patches in half to lower the dose.

Steve Small:

Yeah, we kind of talked about the yeah, we talked about the dosage and what that kind of effect can have. And really, when it comes to patches, a lot of this can depend on the product. Many estrogen patch products are adhesive matrix patches where that drug is kind of uh spread out throughout the adhesive layer. And those might be okay to cut since the drug is evenly dispersed in there, but it's always important to check each product individually carefully to make sure.

Don Weinberger:

Yeah, open those package, those huge package inserts and take a look, or you can look at them online and kind of figure that out too. So to help you out, another clinical resource we have our characteristics of transdermal patches chart that reviews various estrogen patches and administration tips.

Steve Small:

Yeah, very helpful chart there. And before we get into our last claim here,

Don Weinberger:

If this episode is helping you cut through the noise. Here's something to make your professional life easier.

Steve Small:

Yeah, already a subscriber. Don't forget to claim CE credit for this episode.

Don Weinberger:

And not subscribed yet or thinking about upgrading, access more trusted clinical insights and save 10% with our exclusive listener promo code RVT1026 at checkout.

Steve Small:

Yeah, and details and links are in the show notes, so don't miss out.

Don Weinberger:

Okay, so for our last claim here, we're saving the controversial one for last. For you, Sara. It's been talked about for a long time and has recently been in the news. So the claim is hormonal replacement therapy causes breast cancer. Over to you, Sara.

Sara Klockars:

Well, I can piggyback off the prior discussion in terms of evidence using that conjugated equine estrogens with medroxyprogesterone acetate study. Um, the women's health initiative went on for about five years. In women, it was stopped early. Um it was the average age, uh mean age of around 63 years, but it was stopped early because it was linked to one more breast cancer case per a thousand patients per year. So that's what sparked a lot of the um controversy with breast cancer.

Steve Small:

Yeah. And when you said, you know, 63 years, to me, that's quite an older patient population. Uh since the average age of menopause, we were kind of talking about is around 50, like 51, 52 years. And that risk also can sound kind of low.

Sara Klockars:

Yeah, great points there, exactly, Steve. Uh, and to put the risk in perspective, uh, it's slightly less than having two glasses of wine daily. And it's similar to the cancer risk from obesity or a sedentary lifestyle. Um, the other thing with that study, there's another side to this. Um, the use of estrogen alone. So those patients who'd had a prior hysterectomy was actually associated with a reduced breast cancer risk. Uh, there's also other evidence to suggest estrogen alone has little to no increase in risk of breast cancer. So there's definitely a more complex interplay here between estrogens and progestogens than initially thought. And the latest is, you know, the progestogens might actually be the driver of the increased breast cancer risk. So um, there might be a lower risk of breast cancer in patients taking micronized progestin compared to those taking the synthetic progestin, such as medroxyprogesterone acetate.

Don Weinberger:

Right. That's a good kind of point to bring up. And that I could bring in that FDA's announcement that happened in November to 2025 that it removed the box warnings about breast cancer risk from hormone replacement therapy products. But that kind of leaves that set subset of population who has a history of breast cancer, right? So since some of these cancers rely on a supply of estrogen, what's what's the thoughts there?

Sara Klockars:

Yeah, so there's definitely more of a risk there, although evidence is limited and conflicting. But to be on the safe side, systemic hormone therapy is generally not advised for women who have a history of breast cancer, especially if they're hormone receptor positive. But I do think it's safer than we initially thought when that 2003 Women's Health Initiative study um stopped early. Um and it may be used in select severe cases after you know weighing risks and benefits and having that discussion with the provider. Um the bottom line is as we kind of alluded to earlier, that low dose vaginal estrogen is a better option for these patients if needed.

Don Weinberger:

Great wrap-up. Thank you. So let's go ahead and head back to that claim, which is hormone replacement therapy causes breast cancer. And the verdict is... Evidence is mixed.

Steve Small:

Yeah, I'd agree with uh Don. Breast cancer risk is low and may depend on which hormones are being used or what age we're talking about, and hence the recent boxed warning changes for these products. But extra care is needed in patients with a past history of breast cancer or other estrogen-dependent cancers. And typically, systemic therapy is avoided here, while vaginal estrogens may be an alternative.

Don Weinberger:

Yep. And also remember there are non-hormological therapies such as oxybutynin, and gabapentin, that may help patients. We cover these in our managing vasomotor menopause symptoms chart to help sort out options when estrogens may not actually be ideal.

Steve Small:

Yes, a very handy chart there. And thank you so much, Sara, for helping us clear the air once again on a timely topic. You've helped us cover acne, GLP1 side effects, and now menopause in our episodes. Quite the spread. And we could not do it without you. So thank you.

Sara Klockars:

Happy to help. Thanks for having me. It's been fun covering this hot topic with you guys.

Steve Small:

All right. And as Sara is leaving, uh, when it comes to this bottom line truth for today's episode, menopause symptoms can be bothersome for many women. And healthcare professionals can help patients sort through treatment options, benefits, and risks that we talked about. Right.

Don Weinberger:

And it's important to listen at patients' concerns and offer options, especially when menopause is generally undertreated.

Steve Small:

Yeah, I didn't realize how undertreated it is. So don't let treating menopause make you sweat too. We have several tools for Pharmacist's Letter, and Prescriber Insights subscribers to help guide decision making.

Don Weinberger:

Sure, and speaking of decision making, I've decided it's time for the Rumor vs Truth mailbag. And we have an audience question from last episode about GLP-1 agonist side effects that came through our send a text link in the podcast show notes. Uh, you might recall our last episode was all about GLP-1 agonist side effects. And that one listener asked, Do GLP-1s cause chronic cough?

Steve Small:

Yeah, well, that's a good question because looking into this, Don, I did find a recent observational study back in November 2025 that looked at over 400,000 patients taking GLP-1 agonists such as semaglutide to see if they had a higher risk of the side effect. And they found that patients did have a higher risk of chronic cough compared to patients who were using other diabetes medications, things like glipizide or canagliflozin. Uh, this was after controlling for existing gastroesophageal reflux disease, or what we know as GERD, um, that we also know can cause coughing. Uh, but keep in mind that this was only an observational study. It was not a randomized controlled trial that can say that GLP-1s can cause chronic cough. So keep that in mind.

Don Weinberger:

Right. So, you know, kind of want to know any thoughts on why that can actually happen.

Steve Small:

Yeah, this really is not intuitive. I kind of struggled at first to think this through. Um, but there is a thought that this is due to GLP-1 agonists causing GERD, uh, since we know that GLP-1 agonists slowed down stomach emptying, causing food to maybe potentially back up into the esophagus and cause that irritation and coughing symptoms and reflux symptoms we associate with GERD. But um, another theory is that GLP-1 agonists may stimulate the vagus nerve, a special nerve in our body that has an important pathway that impacts our breathing. But this is all very theoretical at this point. That study was not designed to figure out a cause, but it is something worth watching out for. Uh, so if a patient maybe uh has this issue, consider whether symptoms are possible, GERD, or potentially whether it's worth switching to a different med, if it really does become more bothersome. And we'll have to wait for more data, to be honest. But really interesting question.

Don Weinberger:

Right, yeah. Yeah, so thank you addressing the why there. Um, at least, at least in the theoretical sense, it's it kind of gives a kind of gives the more the nerds in us kind of the background.

Steve Small:

Or reason.

Don Weinberger:

Yeah, yeah. So you you retain it longer, right? That's what I keep telling myself. My daughter asked me why 10 different times. So when she has to do something. So I won't hold my breath on you know the the reasons why. If you'd like to if you'd like to have your questions about this episode answered next month, send us a message.

Steve Small:

Yeah, we also use your suggestions to plan our episodes, just like this one. You guys suggested we should do menopause. So email us at rumorvstruth@trchealthcare.com or send us a text right from the podcast show notes.

Don Weinberger:

Before you go, claim CE credit and access evidence-based resources from Pharmacist Letter, Pharmacy Technician's Letter, and Prescriber Insights.

Steve Small:

And if you're not yet a subscriber or want to upgrade, you can save 10% with our exclusive listener code RVT1026 at checkout. It's an easy link in the show notes.

Don Weinberger:

All right, already a subscriber? Tap the claim credit link in the show notes or search or CE organizer for this episode.

Steve Small:

And join us next time where we'll get to the root of the claims around hair loss.

Don Weinberger:

So thank you for joining us on Rumor vs Truth, your trusted source for facts, where we dissect the evidence, bind risky rumors, and reveal clinical truths. See you next time.

Narrator:

Want to put faces to these voices? Catch the video version on YouTube. Just search TRC Healthcare or click the link in our show notes. While you're there, check out our other TRC podcasts like Medication Talk and Clinical Capsules.

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Don Weinberger, PharmD, PMSP

Co-host
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Stephen Small, PharmD, BCPS, BCPPS, BCCCP, CNSC

Co-host
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Sara Klockars, PharmD, BCPS

Guest

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