COMMENTARY

NAMS' New Hormone Therapy Position Statement: Clinical Takeaways

JoAnn E. Manson, MD, DrPH; Arefa Cassoobhoy, MD, MPH

Disclosures

August 15, 2017

Arefa Cassoobhoy, MD, MPH: I am Arefa Cassoobhoy, an internist and senior medical correspondent for Medscape. Today I am excited to speak with Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston. Thank you so much for joining us. We are going to discuss what primary care providers should know about the 2017 Hormone Therapy Position Statement from the North American Menopause Society (NAMS).[1]

JoAnn E. Manson, MD, DrPH: It's great to be here.

Dr Cassoobhoy: I believe that the most reassuring point of the NAMS statement is that for healthy women younger than 60 years of age, who are within 10 years of menopause and are having bothersome hot flashes and night sweats, the benefits of hormone therapy often outweigh the risks. Could you provide more details about those benefits and risks?

Dr Manson: Overall, the key concepts of the position statement are that the decisions have to be individualized, because some women are good candidates for hormone therapy and have a very favorable benefit-risk ratio and other women are not good candidates. Some of the factors we looked at included younger age (below age 60) and closer proximity to onset of menopause (within 10 years). For women in that age group, who are closer to onset of menopause, the absolute risks of heart disease, stroke, deep venous thrombosis (DVT), and breast cancer, related to hormone therapy, are lower.

Women who are at greater risk for hot flashes and night sweats have a higher frequency of those menopausal symptoms and are more likely to derive quality-of-life benefits from hormone therapy. Thus, the benefit-risk ratio becomes much better because of the lower absolute risk and the greater likelihood of deriving quality-of-life benefits.

Dr Cassoobhoy: The NAMS statement mentions that the risk for DVT and stroke is lower with transdermal hormone therapy than with oral hormone therapy. How do you choose which type to prescribe for your patients?

Dr Manson: Transdermal hormone therapy has the advantage of avoiding first-pass liver metabolism, and therefore it's less likely to increase clotting protein or triglyceride levels and avoids some of the other concerns associated with the oral route of administration. The observational studies suggest that the risks for DVT, pulmonary embolism, and possibly even stroke are lower with the transdermal than the oral route. I do want to emphasize that we do not yet have large-scale randomized trials doing direct head-to-head comparisons.

Dr Cassoobhoy: When would you choose oral over transdermal hormone therapy?

Dr Manson: Generally, we believe that this should be an individual decision. Some women will prefer oral. They have tried the patch and found it uncomfortable—they got a rash or they had difficulty with it, and they prefer oral hormone therapy. Otherwise, the patch has the advantage of being started at a low dose; a 37-µg patch is reasonable. Some women will need to have the dose titrated up to 50 µg, but it should be titrated according to symptoms. I generally support starting lower and titrating up as needed.

Dr Cassoobhoy: The timing of hormone therapy seems to influence a woman's heart disease risk. What options do you present for older women, including women with diabetes or other cardiac risk factors such as metabolic syndrome?

Dr Manson: The risk for cardiovascular events, both heart disease and stroke, will be greater in older women. We believe that if you are going to use hormone therapy in women who are more distant from the onset of menopause or who have significant risk factors such as diabetes or hypertension, it is preferable to go with the low-dose transdermal formulation rather than oral hormone therapy.

Dr Cassoobhoy: We know that vulvovaginal atrophy and genitourinary syndrome of menopause—vaginal dryness, sexual dysfunction, recurrent urinary tract infections—are big issues for women and that they progress over time. What is your message for primary care providers about this?

Dr Manson: First, in contrast to the vasomotor symptoms (hot flashes and night sweats), the genitourinary symptoms actually progress over time. They are not going to get better and that is important to recognize. About 50% of women are seriously affected by these symptoms in terms of decreased quality of life, poor sexual health, and discomfort with sexual activity.[2] These are very important conditions and also are associated with urinary tract infections and physical health. These symptoms are undertreated and underrecognized, and clinicians should ask about them because many women are very uncomfortable bringing up the subject. If clinicians ask, very often they will be able to get a handle on whether the woman needs treatment.

Low-dose vaginal estrogen is the most effective treatment and does not increase the blood level of estrogen above the usual postmenopausal range. In terms of the evidence base and the clinical trial data, there is no evidence of an increased risk for heart disease, stroke, DVT, dementia, or breast cancer with low-dose vaginal estrogen.

Some women are not good candidates for even low-dose vaginal estrogen, particularly women who have estrogen-sensitive cancers or women with breast cancer who are taking aromatase inhibitors. For a woman with a history of cancer, we usually like to work directly with the oncologist to make decisions. But most women are good candidates.

Dr Cassoobhoy: When you start vaginal estrogen in a low dose, you can use it long-term. For oral or transdermal hormone therapy, is there a point when patients should definitely stop using it?

Dr Manson: With estrogen plus progestin, we try to avoid durations longer than 4-5 years. However, if a woman is significantly symptomatic, the benefits of continuing treatment are likely to outweigh the risks, as long as she understands the risks and benefits. For estrogen alone, treatment can easily continue to 10 years or more in a woman who is significantly symptomatic or who has an earlier onset of menopause or surgical menopause.

Dr Cassoobhoy: Could you give us a rundown of which groups of women we need to be especially cautious about with hormone therapy?

Dr Manson: Some groups of women are particularly good candidates—women with early menopause (either premature ovarian insufficiency or early surgical menopause)—who have an increased risk for heart disease, cognitive decline, bone loss, and osteoporosis. Those women can safely be treated with hormone therapy. All of the professional societies are recommending treating these women at least until the average age of natural menopause (about 51 or 52) and then making decisions based on symptoms.

For women with a history of DVT, we obviously need to be quite cautious. With a history of diabetes, we used to strongly discourage use, but low-dose transdermal hormone therapy may be an option and there may even be some glucose tolerance and insulin sensitivity benefits. In older women (over age 65), the Women's Health Initiative (WHI) found an increased risk for dementia and cognitive decline with hormone therapy. We would discourage initiating hormone therapy (using it for the first time) after age 65. Whether to continue or not, we have limited information about long-duration treatment in women who start early, because the randomized trials have generally lasted only 5-7 years.

Dr Cassoobhoy: We know that hormone therapy is going to prevent osteoporosis and reduce fractures, but once women stop taking hormone therapy, that benefit dissipates. How do you decide when it's appropriate to choose hormone therapy for osteoporosis?

Dr Manson: Different clinicians feel differently about this. Generally, for a woman who is at very high risk for osteoporosis (eg, a strong family history, or a woman with many known risk factors), it is quite appropriate to use hormone therapy for a limited time, especially if she has hot flashes and night sweats, because it provides an additional benefit. I believe that initiating hormone therapy exclusively for bone health has to be an individualized decision. In a woman who is very concerned about her bone health and who has a strong family history, the NAMS statement says hormone therapy is perfectly reasonable. Many members of the writing group believed that it was appropriate and others didn't, so there was some division of thought. It has to be an individualized decision. Hormone therapy should not be routinely started at the onset of menopause only for reducing bone loss and preventing osteoporosis, because those benefits are lost quite quickly after stopping hormone therapy. If you were going to try to prevent fractures, you would need to treat for well over 15-20 years, into those ages when the risk for fracture becomes quite substantial, and using hormone therapy in those older women would have risks.

Dr Cassoobhoy: The WHI Memory Study showed an increased risk for dementia with hormone therapy; it was small but definitely there. Where is the research going with that? How might the recommendations change?

Dr Manson: The research is going in the direction of trying to understand the effect of estrogen therapy or estrogen-plus-progestin therapy in recently menopausal women, especially when they have significant hot flashes, night sweats, interrupted sleep, and many of those distressing vasomotor symptoms. Studies are trying to understand whether those women will benefit in terms of cognition, concentration, and quality of life with the use of hormone therapy. When delving more deeply into the WHI memory study (which looked at women 65 and older), we found that women with a history of diabetes had the greatest risk for cognitive decline. We probably should be quite cautious about initiating hormone therapy at an older age in a woman with diabetes.

Dr Cassoobhoy: Could you speak to the non-hormone-related menopause treatments? There are a few drugs on the market, and one treatment that comes up in the news is bioidentical hormone therapy.

Dr Manson: It is quite important for women and clinicians to understand that there are many bioidentical forms of hormone therapy that are approved by the US Food and Drug Administration (FDA). Estradiol, in a wide range of oral and transdermal doses, and micronized progesterone are bioidentical and they are FDA-approved products. Very few women would need to go the custom compounding route to get bioidentical hormone therapy.

If a woman does not want hormone therapy or has contraindications to any form of hormonal treatment, the FDA has approved a nonhormonal low-dose paroxetine. There is also quite a bit of research on other selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine, escitalopram, and others. For women who are not good candidates for SSRIs or SNRIs, there is gabapentin, pregabalin, and those types of medications. There are many nonhormonal options. It is good news for women that many more options are available now, including low hormone therapy doses, transdermal applications, as well as nonhormonal treatments.

Dr Cassoobhoy: Thank you so much. Would you like to add anything else?

Dr Manson: It's very important for women to feel empowered to help make these decisions about their care. The best way to share in the decision-making is to become informed about their symptoms, how their bodies are changing, and what options they have. Many websites are available, including government-based websites and NAMS, which help to inform women about symptoms of menopause and many of these options. We also have a free (non-industry-supported) mobile app called MenoPro that helps women understand their options.

Dr Cassoobhoy: Thank you so much for joining us today. It was a pleasure speaking with you. This is great information for our primary care audience at Medscape.

Dr Manson: Thank you so much. It was great talking with you.

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