How Breast Cancer Treatment Can Impact Menopause and Fertility

In an interview with CURE, Dr. Elizabeth Sakatch, a breast medical oncologist at the Winship Cancer Institute of Emory University, explained how breast cancer treatment can affect ovarian function and trigger early menopause. Chemotherapy carries the highest risk, especially for women over 40, while radiation typically does not. Hormone therapies don’t usually cause menopause but can lead to symptoms like hot flashes, mood changes, sleep issues, cognitive difficulties and weight gain.

She also discussed fertility considerations for younger patients. Egg preservation is the most reliable option, and some ovarian protection strategies may help, though they are not guaranteed. Importantly, Sakatch highlighted research showing many women can safely pause hormone therapy to conceive and later return to treatment without raising their risk of recurrence.

CURE: How do different cancer treatments, such as chemotherapy, radiation or hormone therapy impact ovarian function and potentially trigger early menopause?

Sakatch: Of those therapies, chemotherapy has the most significant impact on ovarian function and can cause early menopause in many women, especially over the age of 40. Radiation does not have an impact, luckily, and endocrine therapy, we don’t find hastens menopause or has women go into early menopause, but certainly it causes menopausal symptoms.

What are the most common signs and symptoms of treatment-induced menopause that patients should be aware of?

So this can unfortunately be confusing for many women, as many of the same signs and symptoms of menopause can be experienced by women just because of undergoing this diagnosis of breast cancer and emotionally processing this huge life change and the stress and anxiety that come with that. But nonetheless, there can be mood changes for many women that are undergoing treatment-induced menopause. These would be significant anxiety and depression that’s out of proportion to what these patients have experienced in the past. Hot flashes are very common, sleep disturbances, cognitive changes such as difficulty focusing or word-finding difficulty. Women will report sexual dysfunction, so vaginal dryness, decreased or absent libido, and weight gain or trouble losing weight. And this is really significant for women — greater than 95% of women actually gain weight on chemotherapy, which is surprising to many of these women — and then it can be really difficult to lose that weight or maintain their weight once we’re also doing the extended periods of endocrine therapy.

Are there ways to reduce the risk of premature menopause during cancer treatment, such as fertility preservation or ovarian suppression strategies?

So unfortunately, much of the risk of premature menopause from these treatments is based on biology and age. The risk of having premature menopause is greater in women that are older than 40 at the time that they receive chemotherapy, whereas women that are younger than 30 do not experience chemotherapy-induced amenorrhea — or the lack of periods or early menopause — as often. Ovarian function often returns in women that are younger than 40, maybe like 50% of the time, but the majority of women over 40 will not have return of ovarian function once they’ve had chemotherapy, and that’s a large proportion of our patients. And so certainly we use ovarian function suppression or GnRH agonists — Lupron (leuprolide) is one of the examples — and give this in partnership with the chemotherapy in patients who are premenopausal and hoping to have return of ovarian function or fertility preservation. But the data behind this approach is mixed, and so we definitely caution our patients that it’s not a sure-fire approach, and it doesn’t guarantee that they’ll have return of ovarian function.

How does treatment-induced menopause affect long-term health, including bone density, heart health and cognitive function?

This is a super important question for our patients, and truthfully, an area of unmet need. We know that treatment-induced menopause affects each of those areas significantly, and we’re really working to develop robust survivorship clinics for our patients to address these issues, because many patients are surviving their cancer now, but we have to ensure that they’re doing well for years after their treatment. So bone density is tremendously impacted by estrogen deprivation — our bones like all the estrogen in our body to be happy and healthy. And so women that have really high-risk disease, they need more estrogen deprivation, unfortunately, to reduce their risk of recurrence, and they have a significant risk of developing osteoporosis. So those are the women that are on the maximum amount of endocrine therapy, which is an aromatase inhibitor and ovarian function suppression. It causes these women to be in a menopausal state. And we actually don’t recommend that they take this for more than five years because of the risk of osteoporosis, and we switch them to tamoxifen to complete 10 after those first five. And we monitor them very closely with bone-density scans and encourage weight-bearing exercise — which is super important — and appropriate vitamin D and calcium intake.

And then the question about heart health and cognitive function — those are both also impacted. We know that women have an increased risk of cardiovascular disease if they’re in an early menopausal state. This would be in the form of increased risk of heart attacks and heart failure, and we really think this is because of increased levels of cholesterol or hyperlipidemia, and unfortunately, that’s what many of our therapies are also causing for these women. It’s important to know that tamoxifen, which many premenopausal women are on, actually can improve your lipid profile, so it doesn’t run that risk, but it’s still a continued area of unmet need. We aren’t really sure how to best monitor these patients, but education is an important start to be talking with patients about this risk. And then we’re not entirely clear what the cognitive impact is of endocrine therapy. We know that patients that undergo early menopause because of removing their ovaries before natural menopause have an increased risk of dementia and cognitive impairment, but there’s mixed data about the impact of endocrine therapy.

For younger patients concerned about fertility and future pregnancies, what guidance can you provide before, during and after cancer treatment?

If patients are about to begin cancer therapy, especially with chemo, it’s really important to have open and honest communication with their provider about their desire to have children and family planning. It’s really important to meet with a reproductive endocrinologist or fertility specialist early on in their treatment planning and to have these conversations. The gold standard is to pursue egg preservation or egg harvesting, and unfortunately that can be really cost prohibitive for many women, and also time-consuming. So there are conflicting bodies of evidence about this, but certainly we support women with these GnRH agonists through ovarian function suppression while they undergo chemo as an alternative method. It calms the ovaries, so that, in theory, you’re protecting the ovaries from having as much exposure to the chemo. And there’s evidence that this is helpful, but we’re not sure that it entirely preserves fertility. So the gold standard, again, would be egg preservation.

And then, most importantly, there is a really significant trial that’s helpful for our patients to finally counsel them with some evidence of what their risk is about trying to conceive while they’re on endocrine therapy. It’s called the POSITIVE trial, and women have been asking for this answer for years. And we finally have this study that enrolled about 500 patients that had early-stage hormone-positive breast cancer. They took their endocrine therapy for about two to three years before pausing to conceive. And the majority of these women — around 75% — successfully conceived during their break from endocrine therapy and gave birth to healthy babies. They stayed off for up to a year to breastfeed if desired, and got back on their endocrine therapy, and this did not reflect an increased risk of recurrence of their breast cancer, which is really incredible data to have for these women and their families.

Transcript has been edited for clarity and conciseness.

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