The use of hormone replacement therapy for women has become a controversial topic since the publication of the Women’s Health Initiative study more than 20 years ago. As a result, some doctors are hesitant to prescribe this treatment to women due to concerns about increased risk of cancer or other health conditions, including cardiac events.
Nicole Gaulin, MD, a gynecologic oncologist, and Sheheryar Kabraji, BMBCh, Chief of Breast Medicine, both at Roswell Park Comprehensive Cancer Center, take a look at three different scenarios in which estrogen replacement therapy might be used: ovarian insufficiency, medically induced menopause and natural menopause.
“A lot of people tend to extrapolate data from the Women’s Health Initiative study published many years ago,” Dr. Gaulin says. “It is critical to note that women with primary ovarian insufficiency were not included in that trial. Some women did have adverse outcomes related to the use of hormone replacement therapy, but that did not include younger women. We have excellent data to support the use of HRT in these women.”
Dr. Kabraji adds much of the data pertaining to the use of HRT in menopausal women, especially women who are undergoing treatment for breast cancer, is “quite old and involves different doses than we’d use today. When we talk about breast cancer, primary failure or ovarian insufficiency, it’s important to think about the risk-benefit ratio and what the benefits might be,” as HRT can help reduce all-cause mortality and death from cardiac events, in addition to osteoporosis and other conditions.
Hello, my name is Nicole Gollin, and I'm a GYN oncologist. Hello, I'm Shararaji, and I'm a breast medical oncologist and the chief of breast medicine at Roswell Park Comprehensive Cancer Center. Today we're here to talk about hormone replacement therapy, uh, for women, uh, in the setting of menopause and in other situations. So I thought we'd start with a simple question to get us all on the same page. Nicole, what is hormone replacement therapy? Hormone replacement the. is the uh supplementation of estrogen and or progesterone in order to make up for lack of ovarian production. One of the places to start talking about is the use of hormone replacement therapy in the setting of primary ovarian insufficiency, which also could encompass surgical menopause prior to the age of natural menopause. Primary ovarian insufficiency is typically in women under 40 years. Old who either have increased destruction of the follicles of the ovary or decreased follicle production, uh, and increased destruction could be secondary to things like chemotherapy and radiation, other cancer treatments. This can be a debilitating condition. uh, these women suffer increased risks of cardiac death, all cause mortality, fractures, osteoporosis, and of course the. The side effects of the lack of estrogen in the vagina leading to what we call the genitourinary syndrome of menopause, which includes uh vaginal dryness, dysprurenia, or pain with intercourse, recurrent UTIs, etc. It is important to note here that a lot of people tend to extrapolate the data from the WHI or Women's Health Initiative study, which was published many years ago, initiated back in the. Mid 90s is really critical to note that women with primary ovarian insufficiency are not included in that trial and that trial did show some potential adverse outcomes related to the use of hormone replacement therapy, but again, this does not include the women who are younger who have the lower absolute risk of these events occurring and we have excellent data to support the use of hormone replacement therapy in these women. The risk of vertebral fractures and hip fractures is significantly decreased with the use of hormone therapy. Women experiencing menopause early have almost a 50% increased risk of ischemic related cardiac morbidity. This is really significant, and the use of hormone therapy can decrease those risks. If you were counseling a patient or their uh primary care provider about safe prescription of. Hormone replacement therapy for someone with primary ovarian failure. What are the routes or doses that you sort of consider and what are the typical kind of practical things that they should be thinking about? It's important to know that women with primary ovarian insufficiency, while their chance of becoming pregnant overall is low, it is still important for some of these women to have a pregnancy prevention tool that can be hormonal or non-hormonal. Combined oral contraceptives is an option for hormone replacement therapy in these women, as is hormone replacement therapy. Oral contraceptives are much higher dose than the hormone replacement therapy counterparts. In women with an intact uterus, it is important that they also have progesterone added to their hormone replacement therapy to decrease their risk of hyperplasia and cancer of the uterus. The routes that are available for hormone replacement therapy include transdermal options and. Oral options. The transdermal options do have a slightly decreased risk of venous thromboembolism because it eliminates the first pest metabolism through the liver. One of the things that as a breast oncologist, we're often faced with is that in treatment of patients with breast cancer, we're often eliminating their native estrogen production or blocking it. And this does lead to exactly the same kinds of side effects, um, where women For example, we have both the uh neurohormonal or the uh autonomic uh side effects of estrogen deprivation such as hot flashes, arthralgis, or joint pains, uh, but then also the genitourinary and other side effects. And one of the things that we know is safe to use in breast cancer patients is um intravaginal uh or topical estrogen. Nicole, can you tell us a little bit more about that? So vaginal estrogen is an incredible tool that we use very often. It is highly effective at treating the vaginal side effects of menopause, as mentioned before, vaginal dryness, dysporrenia, recurrent urinary tract infections that can become pretty significant for people suffering from them, and it is very easy to use with a small applicator and it's a small dose. Studies have shown that the circulating. serum estradiol levels in women using topical estrogen are very, very small and is only a transient increase in levels if an increase at all. So that's right, and for patients who are being treated for breast cancer in the curative setting in so-called adjuvant settings, the data are a little bit mixed depending on whether or not tamoxifen versus an aromatase inhibitor are used and the relative risk of subsequent breast cancer events when using. Estrogen replacement therapy in even vaginal estrogens, but in general that relative risk is small and because of the mixed picture, we do encourage, at least in our practice, a discussion about using topical um estrogens with between the provider and their patient because the benefits can be significant, especially when it comes to reducing the complications of estrogen deprivation on the morbidity from things like. tract infections and frequent use of antibiotics, which often go away with with the use of topical um estrogen replacement. Thinking about women who are now in natural menopause, what are the options for them? So this is where it starts to get a little bit more heated. The WHI or the Women's Health Initiative trial was initiated to determine whether the use of hormone replacement therapy was a viable. Option for the reduction of risk for coronary heart disease with the prevention of fractures, and they also wanted to look at the risk of breast cancer in women who are using different formulations. Looking at the use of both estrogen and progesterone in women with an intact uterus, this trial was actually concluded early, secondary to safety events that were seen significant increased risk of breast cancer, and they did not. Meet any of their primary endpoints in terms of reduction of risk in the other categories that were mentioned. Because of this, the use of hormone replacement therapy in the menopausal setting is a little bit more nuanced. We typically will reserve the use of this in women who are younger than 60 years old and within 10 years of menopause. The younger women in the WHI trial had more favorable outcomes compared to the older women, which is to be expected. And so we favor using hormone replacement therapy in the younger women. One of the important things that you've highlighted is that a lot of the data that drives our thinking around this subject is now actually quite old, and some of it involves preparations and types of estrogens at higher doses with more systemic exposure than we would typically recommend today. Another reason why thinking about estrogen replacement or hormone replacement in the sort of modern context becomes so critical, and that's. Why when we're talking about either breast cancer, primary ovarian failure, or insufficiency, or the postmenopausal setting, it's critical to think about that risk benefit ratio and the root of the estrogen replacement and what those benefits might be. So that concludes our discussion about homemone replacement therapy for now, but if you have more questions or need more resources, our team at Roswell Park, um, is available and ready to answer them, so, uh, please reach out.
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