Maggie McKay (Host): Welcome to BayCare HealthChat and part two of our episode focusing on perimenopause with obstetrician and gynecologist, Dr. Irene Wahba. In this episode, we'll be focusing on perimenopause treatments and hormone replacement therapy.  Thank you so much for being here today, Dr. Wahba.  

Dr. Irene Wahba: Thank you so much. I'm happy to be here. 

Host: To start off with, dealing with perimenopause, I mean, of course, you have to talk to your doctor about what treatment options are best for you, but what about hormonal versus non-hormonal treatments? What's the difference? What's the pros and cons? 

Dr. Irene Wahba: So, there are so many studies on this. Arguably not enough studies because, as you probably know, women's health studies are really limited in comparison to men's over these many years of scientific research. So, there's an organization called the North American Menopause Society. Every five years, they sort of give an updated position statement. And the most recent one in 2022 talks about benefits of hormone replacement therapy. I'll get to that in a second, but this year they published what non-hormonal options are proven to be beneficial or not beneficial. And this was very interesting to me because so many of the things you hear about, the herbal supplements and diet and exercise approaches, so many of them are not really well established or proven.

Now, the limit of what I'm quoting is going to be what is useful for treating vasomotor symptoms. You'll hear the term VMS or vasomotor symptoms frequently when people talk about menopause. So, a lot of the studies, because that is sort of the obvious, you're definitely having menopausal symptoms because nothing else really causes hot flashes, night sweats, where you wake up in a puddle of sweat in the middle of the night. Nothing really causes that as much as menopause. So, you will hear about various non-hormonal options to treat VMS, and many of them are unproven.

So, some herbal remedies that have been proposed are soy products or phytoestrogens. there are yams, dong quai, black cohosh is a popular one. Interestingly, one of the big problems is that most of the studies that you'll hear clinically proven to improve this, you'll hear that a lot in commercials for herbal products. And some of the clinical trials are 90 patients or 50 patients. So, they really don't give us great data. Interestingly, specifically with yam creams or yam products, they say that a lot of them are contaminated with other things. So, a lot of them don't have any yam in them whatsoever. And then, they'll have contaminants like estrogen or Prozac or other things that give little small amounts in some studies, so a lot of contaminants in the herbal products. So, you don't always know what you're getting. And even if you are getting what you're purported to get, that doesn't mean that there's a clinical correlation that's very satisfying.

There is something called ammonium succinate, and I don't want to use the brand name. But there are some studies that suggest improvement in estradiol levels, or kind of a bump up in your natural production of estrogen. So, that's kind of an interesting angle. And that product, it's not scientifically proven, but the data is a little better than some of the other herbal remedies.

And similarly, there's a proprietary extract made from flower pollen that has been found to significantly reduce vasomotor symptoms. Again, small studies, but still some data that shows promising outcomes. Those are two that I might put in a different category from some of the other over-the-counter things.

Black cohosh is really renowned for use for treating vasomotor symptoms. One of the big limitations, however, is that it can cause some liver toxicity. So theoretically, it's not something you should be on long term, so short term use, little pulses of it may help a little bit, but you have to be careful with your liver function. 

Host: So when it comes to non-hormonal treatments, which you've been talking about, which symptoms can be treated with those? 

Dr. Irene Wahba: The ones I've mentioned so far are really specific to hot flashes and night sweats. Maybe insomnia, a little touch on insomnia, especially because night sweats are really what's causing the insomnia a lot of the times. 

Host: And what symptoms work better with hormones or hormonal medicine? 

Dr. Irene Wahba: So, hormones are more effective for all of those symptoms. And hormones definitely treat, hot flashes, night sweats, and basically anywhere estrogen receptors are functional in the body. So, not everybody's aware of how expansive the impact of estrogen is, but it has an impact on your cardiovascular system, that includes blood vessels, that includes clotting risks, how your blood clots. It includes the sinoatrial nodes, so it can affect the regulation of your heart rate, you can have palpitations if your estrogen levels are dropping. There are estrogen receptors on your bones, which affect your osteoporosis risk, which we'll get to in a moment. It can affect your joints, your genitourinary system has many estrogen receptors. So, your bladder function, your urethra, your vagina, elasticity thereof, and the lubrication are both significantly affected by estrogen. Your brain has estrogen receptors. Your skin has estrogen receptors, and even your gut. So, men digest food and have a different gut biome than women do. And postmenopausal women can actually have more intestinal tendencies or digestive tendencies, similar to men, where they may not have it. It can be a drastic change for women as they approach menopause or pass it. 

Host: Dr. Wahba, what are the pros and cons of hormone replacement therapy? Because it got bad press from one study decades ago, right? 

Dr. Irene Wahba: Correct. So, the Women's Health Initiative study, which I referenced a few minutes ago, was published in 2002. And the aim of that study was to determine whether hormone replacement therapy can reduce the risk of cardiovascular disease and Alzheimer's. But nobody really knows that because what happened was that they found a significant increase in the risk of breast cancer in the women who had not had a hysterectomy and who were taking estrogen with progestin. And basically, when that hit the press, nobody wanted to hear anything more. That was it. That was all that they needed to know. 

Dr, Irene WahbaSo, there were some flaws in that study. One issue was the type of hormone used that's been proposed as one of the issues. Probably the bigger issue was the average age of patients was mid-60s. So here were patients that maybe had not seen hormones in a decade or so, and now they were being exposed to hormone replacement therapy. And so, what happens when you've had this gap in treatment, and then you start using hormones, is really suspected to be the problem.

So, the North American Menopause Society that I mentioned earlier, their recent position statement, in analyzing all the current data, all of the research that's happened in 20 years, so this represented a 20-year interval between the initial study and their statement, what we know to be true now is that hormone replacement therapy improves quality of life in many women. So, it'll reduce hot flashes, night sweats, insomnia, vaginal dryness, sexual dysfunction and, importantly, it will reduce the progression or slow the progression of coronary artery disease. If you recall, I just said that was one of the intended endpoints of the initial study, but it wasn't established at the time when the study was ended early. Since then, we've been able to prove that as primary prevention of coronary artery disease, hormone replacement therapy is effective.

Interestingly, it's also contraindicated if you already have coronary artery disease or if you have a significant risk for that, like clotting disorders that run in families, or if you've had significant heart disease in the past. The risk of breast cancer is still found to be increased. But even in that initial study, the risk was one in a thousand increase in the hormone group over the non-hormone group. But breast cancer patients actively being treated for breast cancer should definitely not use hormone replacement therapy. That's a clear contraindication.

The other benefits are there's a reduction in risk of osteoporosis and colon cancer in hormone users. Those are really big things for later in life. A little caveat to that is if you're taking hormone replacement therapy at 50 and then you're pretty fit and healthy and you can walk well, your stability is good, your muscles are strong, then you stop hormones, your bones will rapidly decline, and so it may not be protective if you later have a hip fracture at age 80. So, you may lose the benefit of it if you use hormones only temporarily, which is sort of where we're at as far as recommendations now, the standard of care.

The official position statement of the North American Menopause Society though was in women less than 10 years out from menopause and under the age of 60, the benefits of hormones for somebody who's an appropriate candidate outweigh the risks. 

Host: Okay. What are the risks? 

Dr. Irene Wahba: The risks are blood clotting events, such as a blood clot to your legs or your lungs and breast cancer risk, again an increase in about one in a thousand in hormone users versus non-hormone users. And abnormal bleeding, basically you would never use hormones in somebody who has undiagnosed abnormal vaginal bleeding, because we do have to be concerned with cancers that can be stimulated by estrogen. 

Host: So just to wrap up, are there any new treatment options? 

Dr.Irene Wahba: Yes. So, other than hormone replacement therapy, there are several other medications that have been proven to have some effectiveness. So, selective serotonin reuptake inhibitors, you may know some brand names like Paxil, or paroxetine is the generic name for that, or serotonin norepinephrine reuptake inhibitors, like venlafaxine, those have been proven to be helpful. There's also a medicine called gabapentin, or Neurontin, that is used for helping with hot flashes and night sweats. But more recently, fezolinetant is a newer medication that targets the hypothalamus of the brain, and it seems to be very effective in reducing hot flashes and night sweats and quickly actually. So within about a week, women will notice an improvement in symptoms. I think it's classically effective for women who can't otherwise use hormone replacement therapy or who are just reluctant to use it. But overall, a reduction in symptoms about 63% is noted. So, it's pretty significant. 

Host: Well, that's encouraging. How do you feel about women who are just take the natural approach and like, "You know what? I can live through a few night sweats and all the other things, and I'm just not going to take anything." Is that okay? 

Dr. Irene Wahba: That is perfectly fine. It's respectable and everybody should be entitled to make her own decision. I think what's missing often in the doctor-patient interaction is just this informed decision. So, what I'm saying is that you can certainly opt that way, and you can certainly go in that direction, and that may work well for you. But you should also know the long term risks and benefits. So if you're talking to somebody who has a significant risk of osteoporosis, already has osteoporosis in her early 50s, I think I'm going to talk to you a little bit differently than if you don't have any risk factors or if you have fewer risk factors.

But you should know that there are risks to taking hormones and there are definitely risks to not taking hormones. And I feel like the dialogue should go in that direction now. And what should never happen is that I should not tell you, you need to take hormones or you need to not take hormones because I think they're good or they're bad. This should really be informed decisions on both parts. I should give you the information and you should make the decision that makes you comfortable. 

Host: Well, thank you so much for sharing your expertise about perimenopause. This has been very educational. 

Dr. Irene Wahba: My pleasure. Thank you. 

Host: Again, that's Dr. Irene Wahba. This was part 2 in our series on perimenopause. If you’d like to listen to part 1 please visit BayCareHealthChat.org. That wraps up this episode of BayCare HealthChat. Head on over to our website at  BayCare.org for more information and to get connected with one of our providers.