Melanie Cole, MS (Host): Welcome to Back to Health, your source for the latest in health, wellness and medical care. Keeping you informed so you can make informed healthcare choices for yourself and your whole family. Back to Health features conversations about trending health topics and medical breakthroughs from our team of world-renowned physicians at Weill Cornell Medicine.

Melanie Cole, MS: I'm Melanie Cole. And joining me today is Dr. Alexis Melnick. She's an assistant attending obstetrician gynecologist at New York Presbyterian Hospital Weill Cornell Medical Center, and an Assistant Professor of Obstetrics, Gynecology and Reproductive Medicine at Weill Cornell Medical College, Cornell University. And she's here to talk to us today about hormone replacement and fertility.

Dr. Melnick, it's a pleasure to have you join us today. Can you tell us a little bit about some of the fertility considerations that patients may have in their various age groups? As a woman ages, what are some of the most common fertility challenges that you see?

Alexis Melnick, MD: Thanks so much for having me. It's great to be here. So, the biggest challenge as women ages is unfortunately her age. Fertility declines relatively precipitously, particularly in the late 30s. Women are born with a fixed number of eggs. And that number from puberty starts to decline slowly and then the rate of decline really steepens in the later 30s. But more so what actually happens is the quality of eggs declines very quickly as women get older, and that makes reproduction much more inefficient in older women. So, women, as they get older, are less likely to get pregnant. If they do get pregnant, they're more likely to have a miscarriage or potentially have a child affected with a chromosomal issue. So, this is really the biggest effect that age has on fertility.

Melanie Cole, MS: This is such an interesting topic. And as someone who had my first baby at 36 and my second at 38, I know these challenges and I can feel this topic. Now, hormone replacement therapy, I'd like you to tell us a little bit about that and really what reasons a woman might consider hormone replacement therapies during her reproductive years. We think of it as something in post menopause and perimenopause as we lose our estrogen. But why would someone use HRT before that?

Alexis Melnick, MD: Great question. So yes, HRT we always think of as something for perimenopause or menopause. But there are definitely women of reproductive age who are on them. Typically, you would see this for a couple of reasons. One would be somebody who has gone through early menopause, either surgically, so somebody who's needed to have their ovaries removed or ovaries plus uterus; or who has gone through menopause, either from a medical condition, a genetic condition; or someone who underwent cancer treatment or some type of gonadotoxic therapy early during their reproductive years that basically rendered their ovaries incapable of functioning. So in these scenarios, we know that in women of reproductive age who lose that estrogen early, it behooves them for many, many reasons to be on hormone replacement therapy, both for bone health, for cardiac health, for cognitive health. There's a lot of data that shows really just increased overall morbidity and mortality in women who go through early menopause that don't have this estrogen replacement. So, that's one subset.

Then, you have another set of women who may have low estrogen, but still do have ovaries that are capable of functioning. And we typically would see this in women who have what's called hypothalamic amenorrhea. And this is a situation in which the brain is really not sending the proper signals to the ovaries. So, the ovaries are capable of functioning, they have a normal quantity of eggs in them, but they really just aren't working to make any estrogen because they're not getting signals from the brain. This can be from a variety of reasons. It can be idiopathic, but it can also be due to excessive exercise, excessive stress, eating disorders, really anything that leads to energy deprivation. And in these women, the concern is really, you know, again, the long-term health benefits of estrogen depletion and low estrogen levels. So, this is another subset of women of reproductive age who may be on hormonal therapy.

Melanie Cole, MS: What a great explanation, Dr. Melnick. So, how can hormone replacement therapy affect fertility? Does it depend on the type of HRT and the individual's underlying medical conditions? Tell us a little bit about how it affects the ability to get pregnant. Does it improve or affect it negatively?

Alexis Melnick, MD: Yeah. So, that's a great question. It really depends on the situation. So for somebody who's in early menopause, who's gone through what we call primary ovarian insufficiency or premature ovarian failure is what it was formerly known as, that's somebody who is really on this medication for life or until they reach the natural age of menopause, at which time we would potentially lower those dose of medication. These are women who almost always are not going to be able to conceive on their own. So in these cases, they can use, you know, fertility treatment and sort of seamlessly transition from being on the hormone replacement therapy that they're on into fertility treatment because the medications are really quite similar. We use estrogen to thicken the uterine lining. And that medication would continue, sometimes the doses are changed as you start the fertility treatment process. And then, ultimately, progesterone has started to help with implantation. And so, these are women who typically would be looking to get pregnant using either an egg donor or if they had eggs of their own that had been frozen previously. So in that group of women, they can be on that hormone replacement therapy, kind of leading into treatment. For other women, most of the time someone who's going to have hypothalamic amenorrhea and not getting periods on their own, most of those women, again, are going to need some type of help for fertility. It's usually to help induce ovulation, and there's a variety of ways that we do that. And again, in those situations, they can be on the hormonal therapy up until treatment.

The one thing that's important to note is that these therapies can mask or prevent normal ovulation from happening. So, in some women who are on, let's say a birth control pill for hormone replacement therapy, that's going to stop any natural ovulation. So in cases like that, you know, if we have a patient who needs some type of hormone therapy, but also wants to know if she's, you know, ovulatory or not be too suppressive, I would recommend something different from a birth control pill.

Melanie Cole, MS: So then, tell us a little bit about if a woman wants to get pregnant. So, you said that she would stop right before starting any kind of fertility treatments, yes?

Alexis Melnick, MD: If it's somebody who falls into that amenorrhea category where their ovaries are, you know, have the potential to function, but are just not getting the right signals, then yes, we would stop the hormone therapy and then begin whatever other treatment we wanted to do to stimulate the ovaries.

In some scenarios, if it's somebody where they'd had this issue for many years, starting in their late teens, early 20s, we might stop the therapy and just see if things sort of resume, kind of go back to normal and they start ovulating on their own because as women get older, that can happen. The access between the brain and the ovary can mature. But if it's somebody who's looking to get pregnant very quickly, we often will use medication for ovulation induction that can start pretty much immediately after the hormones are stopped.

Melanie Cole, MS: After the hormones are stopped, whatever medical condition she has, does that flare up? Is that something that you concern yourself with? And while she's going through any fertility treatments that she might be trying to do, do you manage these comorbid conditions and medical underlying situations?

Alexis Melnick, MD: The only thing that I'd expect to see in somebody who'd been on, you know, long term HRT, that then came off of it, would be the consequences of low estrogen, which can be hot flashes, vaginal dryness, mood swings, sleep disturbances. And that's why the goal is really to keep women who have low estrogen, keep the window of time that they're off estrogen as short as possible. That would really be the goal.

Melanie Cole, MS: So, what about side effects and risks of birth defects? Does HRT cause any of those if it's taken in those reproductive years?

Alexis Melnick, MD: No, there's no data to show that it causes any of those issues. HRT, you know, when I'm explaining it to women, especially if you're using it again during these reproductive years, you're looking at very similar hormone levels to what's in a conventional birth control pill. And many women who are on a birth control pill really just stop that right before they're ready to get pregnant. So, safety wise, from a birth defect standpoint, it's the safety is very, very good.

Melanie Cole, MS: Well, that's an excellent way to think about it, similar to a birth control pill. And we've always heard you just go off and then you can start trying to get pregnant and there's no residual factors left going on. So, I'd like you to summarize for us HRT considerations for patients who are considering fertility options. When they want to start a family, Dr. Melnick, give us your best advice for couples that are considering these kind of treatments. If they are on HRT for some other condition, what is it you tell them when they come to see you?

Alexis Melnick, MD: Just tell them that it's not uncommon for somebody to come in on existing hormones who then may need some other type of hormonal therapy. And that again, the goal is really to keep that no-estrogen window as short as possible, but that it's very doable to work those medications sort of into the treatment plan. It should not be something that, you know, is a cause for concern. And oftentimes, the hormones that they're on may actually be what we're going to use for some types of treatment.

Melanie Cole, MS: Isn't that so interesting? And what wonderful work you're doing. Dr. Melnick, thank you so much for joining us. And Weill Cornell Medicine continues to see our patients in person as well as through video visits, and you can be confident of the safety of your appointments at Weill Cornell Medicine.

That concludes today's episode of Back to Health. We'd like to invite our audience to download, subscribe, rate, and review Back to Health on Apple Podcasts, Spotify and Google Podcasts. And for more health tips, you can always go to weillcornell.org and search podcasts. And parents, don't forget to check out our kids HealthCast. I'm Melanie Cole. Thanks so much for joining us today.

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