LIVE from LA: Hormones, Menopause, Cancer Prevention, and Women’s Health Research with USC Gynecologic Oncologist Dr Lynda Roman

Editor’s note: This transcript has been edited for readability, cohesion, and sequence while preserving the substance and language of the original conversation. This is an edited transcript of a live conversation and should not be read as personal medical advice. Readers should discuss individual decisions with their own clinicians.

Why Lynne Cohen Foundation preventive care clinics exist

Amy Cohen Epstein: The reason we set up our clinics in LA at USC Norris and LA General in the way that we have from the beginning is because, honestly, that’s how my mom would have wanted it.

She would have wanted every woman who has a history of cancer in their family, who’s potentially at increased risk for cancer, to have access to literally the highest levels of preventive care. When you come through our clinic and you see a doctor like Dr. Roman, who on a normal day you wouldn’t even know how to get in touch with— that’s how the world works. And we wanted all women to be able to have a mammogram, a gynecologic visit, access to genetic counseling and genetic testing.

All women should be able to have that if they have any sort of fear that there’s cancer coming to them because of their family history, because they have had cancer, or because they’re Ashkenazi Jews, which puts us at increased risk. That’s why we did it. And Dr. Roman spearheaded it all really from the beginning, which has been amazing.

Menopause, Hormone Therapy, and Preventive Care

Amy Cohen Epstein: The topic of conversation today is what we all talk about on the phone with our friends and at lunch and complain about to ourselves in the shower, which is this time of life where perimenopause and menopause have taken over your brain. And the topic of conversation is hormone replacement therapy.

Are there other things I can do to feel better, to have energy, to be living what I felt was normal? ...Is there a way to deal with my all of a sudden crying and I don’t know why?

I hate my children, but I really don’t. I want to punch my husband in the throat more often than I used to - all these things that you’re feeling that feel very out of control. But I want to talk about that through your eyes. So I think hearing about it through your eyes, and the lens of cancer prevention and preventive care, is a different twist on the conversation than most of us have.

Dr. Lynda Roman: I think in the world of social media and all this noise out there, there’s a lot of confusion and misinformation. I think the best way to do this is get back to the basics. What exactly happens at menopause? What causes the problems? And why is there some confusion? Then we can delve into the cancer impact of all that.

The Basics: What Happens at Menopause

[Dr. Roman asks for a show of hands from the room before beginning with the physiology.]

Dr. Lynda Roman: Basically, in the female ovary, two hormones are made as part of normal function. Estrogen, and the role of estrogen is basically to prepare the uterus and make it able to accept implantation by an embryo. It has the impact of building the uterus up, making the lining thick. It’s secreted primarily in the first half of the cycle.

After ovulation, a second hormone comes in called progesterone that then stabilizes the uterus so that it is ready for an embryo to implant. These two hormones have to work together. Their entire function is reproduction and pregnancy. That’s what they’re there for. And they have to work in balance. If they don’t work in balance, when you’re young, you can end up with irregular periods, heavy bleeding, and all kinds of issues. For the uterus to be healthy, these hormones have to be in balance.

As a woman ages and gets into her 40s - and the 40s are the years of perimenopause - the ovaries start getting lazy. The brain is going, okay, make another egg, start making estrogen. And the ovary is like, well, maybe. I’m trying, but I’m getting tired.

What happens, and it’s different in every woman, is that as one gets into the 40s, the ovary’s not doing such a good job anymore. It may start the job, but it may never actually ovulate. What will commonly happen, usually in the late 40s, is that people’s periods start to space out, or bleeding becomes irregular, because ovulation is no longer happening monthly in a clockwork fashion. In some women, that doesn’t happen, and they have regular periods up until they stop.

But generally, for most women, there’s this prodrome when the hormones are changing and women are aware: I’ve lived my life with monthly periods for how long, and all of a sudden, I’m off. Something feels funny. This isn’t my usual cyclicity. Ultimately, the ovary says, I’m done. No more. When that happens, the estrogen levels drop dramatically. There’s no more ovulation, obviously, and no more chance to get pregnant. In this country, the average age is now in the low 50s.

Symptoms: Hot Flashes, Sleep, Mood, and the Body’s Rhythm

Dr. Lynda Roman: When the ovaries stop working and estrogen levels drop, the classic effects of menopause are primarily due to the loss of estrogen: bone loss and vasomotor symptoms, the classic hot flashes.

Classic hot flashes are usually a flush that starts in the chest and goes up the neck to the face, and you just break out in a sweat. The cheeks are often flaming, which is awful if you’re in a profession like mine, giving talks. And for professional women, this is not good. Of course, a lot of people know exactly what’s going on, which makes it even worse.

The other problem with hot flashes is that they love to happen at night. They are most predominant at night. You wake up thinking, I’m so hot, throwing off the covers. Your husband goes, I’m freezing, what are you doing? And you’re like, I’m going to burn up, open the windows. Then, of course, it reverses and all of a sudden you’re cold.

The body has a biorhythm, and for some reason this loss of temperature control often shows up at night. The other thing that happens at night a lot is peaks of anxiety. Many times when people are anxious, 2 a.m. is the absolute time where it’s going to be worse. Maybe it’s because you’re not distracted, who knows. But anxiety also peaks at night.

So what happens? You don’t sleep. The depression and the grumpiness and taking your husband’s head off and hating the world and the crying is really a lot about disturbed sleep patterns. I have had fights with some of the breast cancer male doctors who are like, eh, it’s not a big deal. And I’m like, you try this. You try to come to work after you’ve been up all night - sleeping an hour, waking up; sleeping an hour and a half, waking up.

It is a big deal when it happens. It doesn’t happen to everyone. There are definitely women who glide through menopause and feel absolutely nothing. And then there are some where these hot flashes, if they don’t do anything, can go on 10-plus years. On average, hot flashes tend to die out over about a year. But it’s enormously variable. One certainly cannot judge what’s happening to someone else based on their experience.

Why Menopause Matters Now

Dr. Lynda Roman: Historically, women either died before menopause or lived a very small part of their life in menopause. But in the last 100 years, the lifespan has increased dramatically. Now, on average, women are living a good third of their life in menopause. And that has caused problems.

Other than hot flashes and bone loss, what else happens? Increased risk of atherosclerosis - plaques in the arteries - and vaginal dryness. Estrogen is good for vascular health. We’ve long known that women in the premenopausal years have a much lower rate of heart attack compared to men of the same age.

The vagina loses not just moisture, but it becomes rigid. It can’t expand. So intercourse becomes painful. And I’ll be honest with you, you’re going to laugh, but the introduction of Viagra was one of the worst things that happened to older women. [Laughter.]

Amy Cohen Epstein: My husband was just at a talk a couple weeks ago where a doctor was there for men and said that one of the things he prescribes to his patients is microdosing Cialis. And my husband thought, that’s what I’m going to start doing. I’m like, are you fucking kidding me? Thanks a lot.

Dr. Lynda Roman: These things really are the main effects of menopause. For a long time menopause was something women just didn’t talk about. It was silent. When I was young and in residency, it was the era of awakening around the needs of women - Lamaze classes, menstrual symptoms, menopause - and it started to be okay to talk about these things.

Hormone Replacement Therapy and the WHI Study

Dr. Lynda Roman: Hormone replacement therapy, which back then was given orally, became a thing. It became clear that it did wonders for hot flashes, which is why it was introduced. All the initial studies suggested there were fewer heart attacks, there was clear bone protection, and vaginal health was much better. People got on board. It became popular.

One of the big challenges with hormone replacement therapy is that if you have a uterus in place, you can’t just go on estrogen. You have to go on estrogen and progesterone to keep the uterus in balance, or else the risk of uterine cancer is extremely high. Bleeding is one of the challenges, because nature does it better than we do, and it is not easy for every woman to find the hormone balance she needs. If you don’t have a uterus, it’s much easier: estrogen alone. Obviously bleeding is not an issue, and that makes it easier.

Amy Cohen Epstein: Can I ask you a question about that? For people who don’t have a uterus, why wouldn’t they use progesterone, too? I find that it’s so calming to the body, and there are so many other benefits to it.

Dr. Lynda Roman: Progesterone has a lot of harm as well. That’s the problem. Progesterone is not good for your vascular circulation. And the combination of estrogen and progesterone increases the risk of breast cancer.

Amy Cohen Epstein: I’m sorry, what?

Dr. Lynda Roman: It increases the risk of breast cancer. The combo. When you put the two together.

Progesterone is also the hormone that gives PMS, by the way. The second half of the cycle is a progesterone-dominant part of the cycle, so PMS and bloating that tend to happen in the second half of the cycle are primarily due to progesterone. Every woman responds to hormones differently. It’s like pregnancy: one woman says, I never felt better in my life; another says, I never felt worse in my life. It’s very individual.

But from the point of view of being good for your body, progesterone for most people is not particularly a beneficial hormone once pregnancy is out of the picture. How you do hormone replacement therapy differs depending on whether there is a uterus or not.

Dr. Lynda Roman: People ask, well, what are the normal levels? In menopause, the normal hormone levels are low. You’re not supposed to have hormones in menopause. So normal is low. But now that women are in menopause so long, the question is: is it really such a good idea to let all this happen if there’s an alternative to prevent it?

There was a huge study called the WHI study that was done in the 90s that threw an entire wrench into this whole thing. It was a badly done study... They meant well, but the interpretation was problematic. Not on purpose, not a big pharma thing - people just err sometimes.

The WHI study took a bunch of menopausal women. There was a group with a uterus and a group without a uterus. One group got estrogen alone. The group with a uterus got estrogen and progesterone. Back then, it was given by mouth. And I just want you to remember something: the ovary, when it makes hormones, puts them directly into the blood circulation. When you put something in your mouth, it gets shunted to your liver. Your liver processes it, and you will have a different effect.

Some of you might remember when the birth control pill came out in the 60s. I was a kid in elementary school, granted, but my sixth grade teacher had a stroke from the birth control pill. Why? They were using very high doses of oral hormones. And what happens when you put a high dose of estrogen into the liver? It increases your clotting factors. It helps the cholesterol profile, but it increases your clotting factors.

Dr. Lynda Roman: The WHI study was randomized: one group got hormones, the other group didn’t. Generally, hormones are started at menopause. But in this study, you could go on at 50, you could go on at 60, you could be older. You could have been in menopause for 10 years and started because the thinking was: we’re going to decrease heart attacks, we’re going to decrease strokes, we should offer it to everybody.

But when estrogen goes away around 50, the risk of atherosclerosis starts to rise. How does atherosclerosis cause a heart attack or a stroke? You have this irregular part of the blood vessel wall. If a blood clot forms on it, it obstructs the blood vessel. The oxygen cannot get to the heart or to the brain, and you have an event. Anything that increases clotting factors and increases the risk of a blood clot is a bad idea as one ages.

The WHI study, to everyone’s shock, showed an increased risk of heart attacks in the estrogen and progesterone arm. There was also an increased risk of breast cancer. It was small... but the bottom line is, after four years of use, the risk of breast cancer in combination hormones began to slowly rise. Theoretically, if you kept going longer, it would rise more. That is the feeling.

So they stopped the study early and said, this is harmful. Black box warning. No more. Women who were on hormones were stopping them. Doctors were suddenly saying, if you have terrible menopausal symptoms, we’ll give it to you for a few months or a year to calm you down, but then you’re coming off.

The estrogen-only arm did not show an increase in breast cancer risk. There wasn’t an increase in heart attack risk, but there seemed to be a slight increased risk in stroke. That was also nerve-wracking. And it was totally contradictory to the studies where hormones were started at menopause. But WHI was considered a landmark randomized study, and that was it. Black box warning. Over.

Bio-identical Hormones and Routes of Delivery

Dr. Lynda Roman: At USC at the time, there was a huge division of reproductive endocrinology. The chair’s whole focus was hormones and what they do to the body. And I remember him saying, this isn’t the estrogen. This is when they started it and the fact that they gave it by mouth.

Introduce the current way of giving estrogen, which is a patch. This is the bioidentical way to give estrogen: a patch.

Amy Cohen Epstein: Will you explain the difference between bioidentical and synthetic?

Dr. Lynda Roman: Unfortunately, all estrogen is manufactured. We can’t take it from the ovary. But what bioidentical means is that you’re giving exactly what the ovary is giving. You’re replicating what the natural body would do.

The ovary secretes the active part of estrogen, called estradiol, right into your blood. The patch is estradiol. It is synthetic, but you absorb it through the skin and it goes right into your blood. It replicates what the ovary does.

Amy Cohen Epstein: And the birth control pill?

Dr. Lynda Roman: Does not. That is an entirely different hormone and it goes through your liver.

Amy Cohen Epstein: What about the Femring?

Dr. Lynda Roman: Femring is absorbed through the vaginal mucosa. Yes, this is a natural way of absorbing estrogen. It is all about whether you put it through your mouth, where it goes through the GI tract, or absorb it another way.

Dr. Lynda Roman: Right now progesterone is mostly used by mouth. There have been estrogen/progesterone combination patches that are available, though there has been concern that progesterone absorption is not as reliable. If you take a progesterone patch, you are also replicating the way the ovary puts progesterone into the system. But progesterone by mouth has much less impact in the liver than estrogen does.

Some drugs, when you put them in the liver, get the liver going. Others are more of a bypass effect. Estrogen has a big impact on the liver. Progesterone has much less. So it is less of a concern how you take progesterone as far as impact on your body. It is the estrogen that matters.

Dr. Lynda Roman: The minute transdermal estrogen became available, it became clear: whole different ball game. There is benefit as far as vascular health and vascular events. But it didn’t solve the issue of breast cancer, because breast cancer has nothing to do with what the liver does. The breasts are a very hormone-sensitive organ. It seems like the longer one is on hormones, the risk of breast cancer - especially with the two together - goes up a little bit.

What is frustrating is that after all these years, we still don’t have the data. We know it goes up at four years. What happens if you’re on it for 10 years? What happens if you’re on it for 15 years? What exactly is the risk? Does it matter what formulation of progesterone you use? Is it all the same? Does it matter if it’s a patch rather than an estrogen pill?

Twenty-something years later, we still don’t know. You can talk to the breast cancer specialists. You can talk to the reproductive endocrinologists. They all go: we don’t know. We should know, but women’s health in this country and the research is a problem. And it remains a problem.

The Current Standard: Risk, Benefit, and Quality of Life

Amy Cohen Epstein: So what’s the standard of care today, then? What would you offer?

Dr. Lynda Roman: This is what I tell people: most people who do what I do end up on hormone replacement therapy. I think in our heart, we all feel there’s benefit, as long as there’s no major contraindication. The biggest contraindication tends to be a history of breast cancer or some kind of cancer that has hormone receptors and is activated by female hormones. That’s a different story.

Audience Member: What about gynecologic conditions?

Dr. Lynda Roman: Most of them are okay, but there are a few exceptions. There are a few gynecologic cancers that are hormone-sensitive: certain kinds of uterine cancer, low-grade serous ovarian cancer, certain stromal tumors. But most of them are actually okay. Breast cancer is the big one.

There are a few absolute contraindications, but if you do not have one of those, obviously it’s a personal decision. The black box warning finally got removed... and all of a sudden I have 70-year-olds walking in going, can I have hormones?

Amy Cohen Epstein: Because they want to feel better or because they want the benefits?

Dr. Lynda Roman: They feel like they will feel better and they want the benefits.

To answer the question about what to do nowadays, people have definite ideas about putting things into their body and playing with nature. Because it isn’t natural, right? It’s not meant to be.

Amy Cohen Epstein: You’re shaving off nature.

Dr. Lynda Roman: You’re trying to say evolution hasn’t caught up yet, so I’m going to take action. That’s how I look at it.

But I think the first decision is: how symptomatic are you? If you’re miserable, you have to do something. You don’t have to, but you should consider it. If you’re not miserable and you’re feeling nothing, then it is more a decision of: do I want to undertake this for the potential benefits? That is a personal decision. I don’t think anyone can say it is medically demanded or absolutely you have to do it. It’s a choice. All of this is a choice.

You are never going to replicate in menopause exactly what the ovary did. Women are far more complicated than men. There is no Cialis for women. Hormonal function in women is finely tuned, with peaks and troughs that make ovulation and menstruation happen. Libido is also tied up in those fluctuations. We probably should be able to replicate it in menopause, but nobody has.

So you’re not going to reliably replicate what happened before menopause, but you can stave off some of the more damaging effects. There are benefits here. There’s a detriment to the pocketbook. The breast cancer issue is something to remember.

Dr. Lynda Roman: There is a progesterone-containing IUD that can be put in the uterus, where it really sits in the uterus and hardly gets into the body at all. By doing that, that small increased risk in breast cancer may go way down. That is called the Mirena, or there’s a Kyleena IUD. So that is an option.

A person can go on hormones, try it the normal way, and say, I really like this and I want to stay on this for years and years. If you plan to use hormones for years, it is worth considering a progesterone IUD because we do not really know what the long-term progesterone risk is.

But far more important than what may happen 15 years from now is how you feel today. I don’t think quality of life should be underestimated. When one goes on hormones, how do you feel? Do you like it or not? Is it worth it? You have to decide how you feel, your lifestyle, your pocketbook, and whether it is worth it.

Amy Cohen Epstein: If you’ve gone through menopause and you miss a patch, will you bleed?

Dr. Lynda Roman: Everyone’s different, but yes. Generally, if you forget to put it on, the bleeding comes from the hormone levels dropping off. You definitely might bleed.

Amy Cohen Epstein: So if you went through menopause and were doing an estradiol patch and taking progesterone for four years, and then you said, I don’t want to do this anymore, I want to see what my body’s like - will you start getting periods, or start bleeding?

Dr. Lynda Roman: You will not start getting periods. When you stop, you may have a bleed. Then it should stop and you should be done with it. That’s expected when you stop. A period comes from hormone withdrawal. If you’re on hormone replacement therapy, it’s a good idea not to muck around with those pills because you may end up bleeding unexpectedly and that’s a hassle.

So it is, first of all, a quality of life issue. How do you feel? Some people think they feel great. It does not convert the face into a 20-year-old face, but it can convert the vagina into the vagina of a young woman, for sure, as far as sexual function and comfort.

Vaginal Health and Local Estrogen

Dr. Lynda Roman: Lubricants cannot overcome a menopausal vagina, because the vagina has to expand to have a baby and to have sex comfortably. It has to be able to stretch without hurting. A post-menopausal vagina doesn’t want to stretch, and it tears. That causes pain. It can also be very hard to have a Pap smear, pelvic exam, and speculum insertion.

From a health point of view, with how women are living nowadays, the use of estrogen matters. Not progesterone so much - progesterone is needed for the uterus - but estrogen is the key hormone as far as health.

Dr. Lynda Roman: I will also tell you that many reproductive endocrinologists offer women forms of testosterone to help with bone loss and muscle mass. Again, we should have this data. It’s ridiculous we don’t, but we don’t. Theoretically, it’s a benefit. When you ask the breast cancer doctors, is this bad for the breasts? Their answer is: I don’t know.

It’s important to understand that we have data on estrogen and progesterone. We are missing data on testosterone, DHEA-S, and exactly what good it does and what harm it may do. This is a big business. There are boutiques out there saying, we’ll check levels and make you feel like you’re 20 again. Not exactly. You’re not going to be 20 again. And do you want to be 20 again? I don’t think I do, honestly. But you want to keep it in context.

Amy Cohen Epstein: Let’s go on and ask questions.

Dr. Lynda Roman: Most people ask, do I have to stop? I intend to stay on estrogen. I think it’s good for me. So no, you don’t have to stop. What I do think you can do as you age is try to lower it. There is no normal level of estrogen as you age; a lot of it has to do with how you feel. And I’m always a believer that more is not always better.

As you age, I think you could try to come down a little bit on the hormone dose. I don’t know that we really know if you take estrogen for 25 years, does breast cancer risk start to go up a little bit? Maybe. So what I’ve done is crept down a little bit. The standard postmenopausal dose is 0.05. As people age, you could probably get away with 0.0375 or 0.025. And if you feel fine, good enough. But I don’t think you need to feel you have to stop.

Audience Member: I’m scared to go back to that.

Dr. Lynda Roman: You may not. Many people go on hormones, come off, and do not have symptoms. When it happened to me the first time, I got into a knock-down, drag-out fight with a breast medical oncologist because I was very grumpy and tired, and he said the wrong thing to me at the wrong time... But the second time, I’d gone on hormones and I came off and had no symptoms at all. I’ve heard that from a lot of people.

If you want to try, you don’t do cold turkey. You lower and lower and lower. And if nothing happens, you lower further.

Amy Cohen Epstein: You don’t just tear the patch up.

Dr. Lynda Roman: Women are much more complicated than men when it comes to sexual function and libido. I hate to say men are much more programmed and mechanical, but they are. With women, a lot of it is what’s in the head, to be quite honest with you. And that is a hard thing.

[Audience discussion follows about vaginal estrogen and localized treatment options.]

Dr. Lynda Roman: If a woman either does not want to take hormones that go into the body, or there’s a contraindication, there is an option to at least treat the vaginal effects of lack of estrogen. That is a hormone cream. There’s Premarin cream and Estrace cream. I like Estrace cream because Premarin cream comes from horse’s urine, and I’m like, why torture a horse when there’s a synthetic form?

It comes with an applicator, and you’re supposed to put it all the way up in the vagina, usually before you go to bed. We usually start it two times a week, sometimes three, to get the vagina built up and then back off. You pee, put it in right before bed, and lie down. If you put it in and run around, it’ll drip out. It’s a little messy, but it works.

In the breast cancer realm, there was a fair amount of pushback against it. There has been some recent data suggesting that even in women with a history of breast cancer, this is safe, because very little gets absorbed into the body. This will not help hot flashes. This is not going to help the bones. This is really for vaginal health. But for women who either choose against hormones or cannot take hormones, there’s at least something they can do to protect the vagina. It is very effective.

There are also tablets. The tablets are not as strong. There is a tablet that absorbs much slower, so you don’t have the messiness. It’s not as potent in my experience, but it’s better than nothing. So there are options for vaginal health.

Testing, Metabolism, and Listening to the Body

[Audience question about the DUTCH test and whether it can show how an individual metabolizes estrogen.]

Audience Member: It’s a urine test. The idea is that it shows pathways of how estrogen is used by your body, but there is no data that the DUTCH test can prognostically say whether estrogen is more likely to cause cancer in one person versus another. It might show whether one person is metabolizing estrogen at a faster or slower rate.

Dr. Lynda Roman: That, for sure. People metabolize hormones differently, 100%. The question is: is that harmful?

Estrogen alone, in a healthy individual, is not the issue as long as there’s no uterus. I would never use this test to say, I’ve got a uterus and I’m going to take estrogen by itself. The risk of uterine cancer is hugely high if you have unopposed estrogen for long periods of time. I would really want to see the data in a large cohort before saying that’s safe.

The million-dollar question is whether, if you metabolize estrogen differently, you need a lower dose. How we usually tell what’s an adequate dose is: listen to your body. How do you feel? Are you getting vaginal health? Are you not getting hot flashes? Estrogen is more about maintaining bone than building bone. So what are your end effects, and how do you feel?

In some women, estrogen causes breast tenderness. So we titrate the dose. How are you feeling? Rather than a blood level, it’s more like: what is your body telling us is happening inside?

Amy Cohen Epstein: That’s kind of the best clue.

Brain Health, Heart Health, and Bone Health

Dr. Lynda Roman: The brain health issue, to my knowledge, has been harder to pin down. The brain is such a complex organ, and obviously quality of sleep plays a role. It has been harder to pin down than the cardiovascular benefit.

Obviously, if you have better vascular health, your risk of stroke should be less and you have more blood flow to the brain. But women are so differently impacted by hormones. If you are one of those people where you take estrogen and your brain clears, obviously in you there’s something going on. It may not mean your stroke risk is less, but your brain function has changed. Not everyone experiences this.

One very common thing that happens in menopause is that women often lose some of that ability to do five things at once. I was very good at doing five things at once, and then I couldn’t do that anymore. The keys ended up in the refrigerator. I realized it wasn’t working, and I had to pull back. I have not found estrogen made the slightest bit of difference to that for me, but I have heard many women say their brain feels clear on estrogen. Listening to your body is extremely important. Hormones are not for everyone. Not everyone likes the way they feel on hormones. If you don’t, don’t do it.

[Audience question: If someone has contraindications and cannot take hormones, are there other ways to build bone health and heart health?]

Dr. Lynda Roman: Medicine has come a long way as far as options for heart health and bone health. For heart health, there are statins and many other drugs for cholesterol control. Despite what you might think, cholesterol levels - the good and the bad - have more to do with genetics than diet. I’m not saying diet doesn’t have an impact; it does. But there is a lot of genetics.

Statins definitely impact the cholesterol ratio, and there is very good data regarding long-term decreased vascular events with statins. Not smoking, blood sugar control, exercise - all these other things are obviously beneficial as well. But statins have been a game changer.

For bone health, adequate vitamin D levels are very important in menopause. Vitamin D, more than calcium, is important for bone health. Despite the fact that we live in a sunny climate, maybe because we use sunscreen, most of the time when you do vitamin D levels in women, they’re low without supplementation. Weight-bearing exercise is important. Bone loss is also very much related to genetics.

For people experiencing bone loss, there are all kinds of things they can do. The most common are the bisphosphonates, which can be given orally or via injection, or denosumab, which is called Prolia. Reclast is the IV bisphosphonate form; it is once a year for three years. Prolia is every six months. These drugs can definitely build bone and decrease fracture risk. There is also Evenity.

[A clinician in the room adds details on anabolic agents and bone-building medications.]

Clinician in Audience: The anabolic agents, the ones that are really efficacious for building bone, are Evenity and recombinant PTH. Evenity is a once-a-month medication that you take for a year with a bisphosphonate to consolidate the impact of it. But we don’t use it in patients who have had a heart attack or stroke.

Dr. Lynda Roman: With Evenity, there’s a cardiovascular risk concern, right? What about people with a high coronary artery calcium score, for example?

Clinician in Audience: That’s up for debate. If somebody has a high coronary artery calcium score, it’s a tough one. We think of a more risky score as being above 100, but women very rarely are above 100. One of the thoughts is that women build more soft plaque than hard plaque, and soft plaque is harder to detect in those kinds of tests. They’re using CT angiograms to look at the vessels in a different way. If you’re doing good risk-factor modification with a high-risk score, you still could be a candidate for something like Evenity, but I would probably go with one of the other ones.

Dr. Lynda Roman: They all have their pros and cons. The endocrinologists are the experts in this, and it’s constantly changing. I’ve noticed at USC that the endocrinologists hate Prolia because once you’re on, you can’t come off.

Clinician in Audience: Prolia is challenging because if you miss a dose or delay it by a couple of months, you’re going to lose bone. It’s not just bone loss; you can get rebound fractures of the spine.

Dr. Lynda Roman: Reclast would be my choice because you do it for three years and get a break. But in all honesty, it happened to me: I felt awful for two weeks. Chills, exhaustion, body aches, kidney function was off... The endocrinologist said it will be easier the next time, and I’m trying to get my guts up to do it again.

Clinician in Audience: That is the very rare side of it. About 25% of people have symptoms, usually gone within two days. Two weeks is unusual, but it happens. Sometimes it’s more severe if your calcium is on the lower side going into the infusion. We always tell people to hydrate and take Tylenol.

Dr. Lynda Roman: The point is, there are a lot of options. None of them come without a potential price. Sometimes it’s a very small price. Sometimes it’s a bigger price. You have to weigh it: what are you gaining versus what might you be losing? And it’s a decision between you and your doctor.

It freaks me out how people blow off bone health. There has been a lot of negative publicity about these drugs. The thing that freaks everyone out is that some of these drugs can cause necrosis of the jaw. It is extremely rare, but when it happens, it is miserable. I’ve had it happen in one cancer patient, and I’ve used a lot of these drugs. I’ve seen it once, but it’s miserable when it happens.

There is also concern about atypical fractures. Nothing is perfect, but the overall fracture rate is clearly less.

Clinician in Audience: The decision-making is the same as it is with hormones. We’re always looking at what your risks are without doing anything versus the risks of something happening when you take the drug. Part of it is making sure you have someone with their eye on the ball, someone who is really looking at you as the patient.

Dr. Lynda Roman: I really feel the endocrinologists are the experts. People ask why I don’t prescribe it to them, and I say: I’ll prescribe your hormones, but these decisions are complicated and the data is changing.

Peptides, GLP-1s, and the Limits of What We Know

Amy Cohen Epstein: Linda, I know this isn’t really your expertise, but one last topic that we all think about a lot and hear about and try: can you talk at all about peptides, from your lens?

Dr. Lynda Roman: I don’t have any experience. I’ve met a lot of people who’ve used peptides who feel it has made a big difference, but I don’t have any experience.

Amy Cohen Epstein: I have a feeling I’m going to give the same answer you are, which is that we just don’t know enough yet. I’m never going to tell somebody sitting in front of me and telling me they feel so much better with what they’re doing that it’s not making a difference, but I also can’t tell somebody...

Dr. Lynda Roman: That it’s not doing harm. That’s what worries me.

This has become very relevant with the GLP-1 drugs, the Ozempic class of drugs. The GLP-1 drugs were really for morbid obesity and weight loss, especially for diabetics. We have a massive obesity epidemic in the United States, and we are seeing the medical effects of that. They have definitely had a huge impact on weight loss.

The psychology of eating affects the reward center, which has a lot to do with overeating. We evolved lean. For most of our history, there was not enough food. Somewhere after World War II, processed foods came into play. We went from a bunch of malnourished underweight people to a bunch of malnourished overweight people, which is worse. It’s not how our bodies evolved to be healthy.

These GLP-1s have been a game changer, not for everybody, but for a lot of people who are obese. It’s not just about weight loss and diabetes control and cholesterol levels lowering. Impulsive behavior seems to be less. Inflammatory conditions seem to be less. The obsessiveness about food - thinking all day long, what am I going to eat? - seems to be less.

It will be interesting to see where it goes. In my heart, I have a feeling it’s going to be the next statin. I feel this is going to be a good thing for a lot of people. But I think it’s premature to say that taking it to lose 15 pounds so you can wear a bikini this summer is a good idea. When you stop it, it seems like the effects go away. So you’re talking about ongoing use, and we have no idea what the long-term effects are going to be.

If you are already at big risk because of what’s happening to you, okay. But it’s a little nerve-wracking when you’re taking it because you want to get into a dress for a wedding. Let’s be a little careful.

Dr. Lynda Roman: It’s one of these things where the train has left the station. We can compare it to medicine more broadly, even the COVID vaccine. We don’t know the long-term effects of mRNA vaccines. We know we were in a crisis. We know we had to do something, and we know the vaccination caused hospitalization rates to plummet.

Hopefully there are no terrible long-term effects, because this technology is staying. It’s going to become important in cancer therapy. mRNA technology is here to stay and is probably going to have a huge role in cancer. Time will tell. We’ll see the data when it comes out.

Cancer Trends: Ovarian, Uterine, Colon, and Cervical Cancer

Amy Cohen Epstein: I have one last question that is specific to your area of expertise. Is it just because we know so many more people, or because they all tell me personally: are more younger women getting ovarian cancer?

Dr. Lynda Roman: Uterine cancer. Uterine cancer for sure. The other big one is colon. Colon cancer is definitely going up. Don’t I wish I knew why.

The uterine cancer question is easy. Uterine cancer is related to obesity. Most of the time, in women who are very overweight, fatty tissue - adipose tissue - can make weak, low levels of estrogen. So you have chronic estrogen production, and it screws up ovulation. They don’t ovulate properly. They don’t make progesterone. Their body just sees estrogen. The uterus begins to overgrow and overgrow, and it finally becomes atypical and cancerous.

We have in our clinic 18-, 20-, 21-, 22-year-olds with endometrial cancer, almost certainly from obesity and anovulation. This has been one of the unfortunate impacts of our obesity crisis. Uterine cancer is the only one of the gynecologic cancers that is rising in incidence.

Ovarian cancer is actually going down. The feeling is that we have discovered that the bad type of ovarian cancer doesn’t start in the ovary; it starts in the fallopian tube. Now the practice is that if you ever operate on somebody for anything in the pelvis and they’re done having kids, remove the fallopian tubes and leave the ovary. A lot of people who decide they want a tubal ligation instead go for removal of the fallopian tubes. It probably is having an impact.

Long-term use of the birth control pill also reduces the risk of ovarian cancer. So we are seeing less ovarian cancer with time, and less cervical cancer because of the Gardasil vaccine and HPV testing in this country. But endometrial cancer is very much going up, unfortunately.

Dr. Lynda Roman: Does obesity have to do with colon cancer? The gastroenterologists feel it does. But you know what my gastroenterologist said? Plastic. Microplastics. And I looked at her and said, how do you know that? I know it’s the buzzword. How do we know this? And she said, I just have a feeling. And I’m like, not good enough.

I suspect it is dietary. A lot of us are alarmed that it has to do with what we’re eating. Lifestyle does matter. In this country, I feel like we have kind of lost control of our lifestyle. Not everybody, but in general. Even if you have access to good food, the amount of stuff used in our foods and the degree of pesticides is nerve-wracking. Somehow we’ve lost control.

Tapering Estrogen and the Missing Data

[Audience question from a person who has had uterus and ovaries removed and is using an estrogen patch without progesterone.]

Audience Member: Why do you need to lower the patch over time?

Dr. Lynda Roman: You don’t have to. Data regarding long-term use of estrogen and breast cancer is not available. So theoretically, if you don’t need the higher dose and you feel just as good with the lower dose, maybe you should think about it.

Audience Member: But if you feel very good with the higher dose?

Dr. Lynda Roman: Then go with the higher. I don’t think I can tell you it’s dangerous. Sadly, we should know. Are there great studies out there? No. We all support women’s health, and we encourage other people to do so. Is that a decent answer?

Dr. Lynda Roman: You would be shocked how little interest there is in this area. Women’s health is still very understudied in general. When women share diseases with men - lung cancer, colon cancer - those are studied. With gynecologic cancers, I will be honest: because pharma can benefit from treating women’s cancers, there have been more studies in the female cancers. It has gotten better. But national funding for the gynecologic cancers is rock bottom when you look at the funding-to-lethality ratio: how many people die versus the amount of funding per person.

[Audience discussion follows about brain, heart, and hormonal research programs, including the loss of specialized programs and the challenge of long-term studies.]

Dr. Lynda Roman: These studies are not easy to do. You need a large number of people studied over a long period of time. It’s a big investment. You’re not going to get the answer in a year.

In the gynecology world, this was classically the bailiwick of reproductive endocrinologists. When I was younger, they were brilliant at this. When I was at USC in my early years, they had an amazing department for hormones, hormone replacement therapy, birth control, reproductive endocrinology. And then IVF hit. Where’s the money? IVF.

I keep saying, what about the endocrinology part? Isn’t that part of your job? It’s upsetting. Even PCOS is a common problem, and it’s miserable, and nobody knows what to do about it other than go on the birth control pill. It’s an endocrine abnormality, and I’m like, can’t we figure out what to do about this already? There have to be answers here.

Dr. Lynda Roman: The point is, women’s health is very much understudied. How do we fix it? Advocacy. I’ve thought about this a long time because in my position I’ve pushed women’s health very hard. At USC there are research programs having to do with women’s cancers, including early detection, because there’s a team of people who are extremely interested in this.

But there has been a pushback against women in our country, very clearly. It comes out in many ways: women’s rights, women’s reproductive rights. I never thought we would get here, but we’re here. I am at a loss other than vote, honestly. But we do have a problem.

Why Philanthropy Matters

[A question from the room shifts the conversation toward advocacy, philanthropy, and how private funding can move research forward.]

Dr. Lynda Roman: Things like what you’re doing through education and advocacy - that is tremendous. And donors who are supporting groups and physicians at academic universities have the opportunity to make a huge impact. A lot of places can start a research project that way rather than through the traditional channels of federal funding. I don’t want to say it’s all bleak, but it takes people being really proactive.

Amy Cohen Epstein: I’ll tell you something. In 1995, my mom was in her second year of cancer, and she switched doctors from a doctor at Cedars to a doctor who has since passed, who was head of gynecologic oncology at USC, a research doctor. She was just flummoxed that he had no money.

He wanted to do something. It was either bring in a fellow or have some funding for a project. I think at that time it was platinums, which are now standard practice in ovarian cancer, and at that time it wasn’t. My mom was not an advocate for herself, and she wasn’t an advocate for ovarian cancer when she had it. She didn’t really want to be that person. But she was so overwhelmed by the idea that these doctors - the most brilliant people on our planet, in this room right now - didn’t have the funds to do what they wanted to do, that they knew would make a difference, that they knew would help women, that they knew would push into a new realm.

I guess I inherited that bug from her.

Amy Cohen Epstein: It’s not just the lack of government funding or the idea that private funding is helpful. It’s that doctors and research institutions and the leaders of institutions are much more open and excited to receive it. It may be less oversight, I don’t know, but I also think it’s targeted and directed. That makes a really big difference.

When you work in partnership with really smart people in a research-based academic institution, and you listen to them about what the needs are, it’s not so big. It’s not so overwhelming. It’s not, I need a billion dollars. It’s: no, I need this amount to do this, and then we’ll come back when we need more. It’s very tangible.

When we started this foundation, I was so young. I think that was the overwhelming part until I realized that you can do a lot of really important work by giving to people who are doing really important work and know exactly what’s happening.

People have asked me for years: why aren’t you bigger? Don’t you want to have clinics all over? Shouldn’t you be Susan G. Komen at this point? My answer was always no, because I want to be able to know the people we’re working with and what they need. The advocacy part comes along with that. It’s really finding those people you can work with and trust, and then support them.

Dr. Lynda Roman: I began by saying there is an enormous amount of good. There has classically always been work that the government is interested in, but there are also simple studies with potentially very impactful answers that the government has never been interested in. Foundations can make a huge difference.

With the Lynne Cohen Foundation, it was literally putting together a clinic for women from different strata, including underserved populations, focusing on women who carry mutations, bringing them in to see the doctors on both the breast side and the GYN side at once. We discuss the patient so the breast doctor doesn’t say, you cannot use hormones, and the GYN doctor says, you must use hormones. We don’t cause confusion. We’re all on the same page. We stay up on the data.

We also establish a clinic in underserved populations so that we try not just to treat the patients who show up because they’ve had a cancer, but their relatives. This all happened because of philanthropy. And the impact was huge.

Dr. Lynda Roman: As we do this, we are collecting blood specimens and tissue specimens on women who are having risk-reducing surgeries. So now, for example, there’s a PhD at USC who has developed a blood test that seems to be incredibly effective at diagnosing high-grade serous ovarian cancer. We are partnering with other institutions to see if that blood test is positive in people with the earliest forms of ovarian cancer that we can sometimes find when we preventively remove fallopian tubes from people with the BRCA mutation.

This is how an early detection test is going to happen. This whole thing is privately funded. Rather than aiming for the stars to answer questions that may take 30 years, there are things that can be done on the ground. It is about getting together and strategizing. Any support of women’s cancers is gold, and you use it well.

Breaking Silos

[Audience question: How do we break down silos and improve coordination among researchers and institutions?]

Dr. Lynda Roman: How do you break the silos? From my point of view, I just want the progress. I don’t give a hoot who does it. I have no ego in the game. It’s just: can we help the patients, please?

Amy doesn’t know this, but we had a meeting literally two weeks ago - UCLA, Cedars, USC, Stanford, remotely - to talk about the early detection piece, what we’re all doing, and how to share resources. Can we do a California consortium? Every single MD there was on board.

People were floored to hear about the Lynne Cohen clinic, going: what? You have blood? You have tissue? Part of the problem is that you don’t have that many doctors who have no ego in the game. In my experience, I’ve met a handful of them. Many do have ego, and it’s a huge piece.

Audience Member: Ego is a big part.

Dr. Lynda Roman: That’s the game changer. It takes an advocate finding those doctors who don’t have an ego in the game and are just about progress, and working to find ways to get them together. I’m happy to do it. I’m in.

The piece is saying: I want to spend X percentage of my time on a cause that matters to me, and I’m going to find the people doing the work who don’t care about their name being the person who founded this. They just want to help, and they want to make a difference for the people in front of them. In my opinion, that’s how you do it.

Closing

Amy Cohen Epstein: One of the wonderful things about doing these events, and having a host like Marina, is that she asked me, who should I invite? I said, just the people you think are your friends, and also interesting and different, and the conversation will be really robust. And it was today, so thank you for contributing.

The idea that we can collaborate and talk and say, I don’t know, that’s not my specialty, you’re an endocrinologist, Stephanie, you talk about it - that is wonderful. Thank you to Marina. Thank you for coming.

This is what we do. Christine and I made a decision that we don’t really want to spend the insane amount of time putting together huge benefit events, which we do once in a while, but it’s just not time well served, in our opinion. We really love these kinds of things.

I hope you’ll be supportive by coming, by figuring out how to be an advocate first and foremost for yourself, and secondly for a cause that matters. And support the work that we do, because I promise you it’s really important. We are looking at the women in front of us, and I think we can all do that.

I hope when you leave today, you know a little bit more about something you didn’t know so much about when you got here. And then anyone in your life who has that question, instead of saying, I don’t know, you at least know where to start. I think that’s the goal. I hope that we’ve pushed your starting line a little bit farther forward.

Marina, thank you so much for hosting. Thank you for bringing together such a wonderful group of women. This was a wonderful conversation, and until next time. Thank you.