The 2017 Hormone Therapy Position Statement of the North American Menopause Society (NAMS)Citation1 allows the conversation about hormone therapy for menopausal women to be individualized for a specific woman. Instead of the recommendation of ‘lowest dose for the shortest period of time’, the NAMS Hormone Therapy Position Statement Advisory Panel’s review of the literature on hormone therapy suggests that women are better served using evidence-based information to determine the most appropriate type, dose, formulation, route of administration, and duration of use of hormone therapy. Decisions about hormone therapy should be based on the unique health risks of the woman, age or time from menopause and goals of therapy.
The evidence suggests that, for menopausal women aged younger than 60 years or within 10 years of menopause onset, without contraindications, systemic hormone therapy benefits outweigh risks for relief of menopausal hot flashes, sleep disturbances, and prevention of bone loss for those at elevated risk. This finding is in agreement with the 2016 Revised Global Consensus Statement on Menopausal Hormone TherapyCitation2.
When the initial results of the Women’s Health Initiative (WHI)Citation3,Citation4 were released, there was widespread panic and concern among women taking hormone therapy and providers who prescribed it because of the risks identified for increased heart disease, breast cancer, venous thromboembolic events (VTE) and stroke, and dementia. However, in the 15 years since the initial results were released, additional results and analysis of the WHI have occurred, with publication of longer-term follow-up of up to 13 yearsCitation5 as well as newer randomized trials and observational data.
The 23 experts who served on the Advisory Panel (national and international experts) reviewed all the key published data on hormone therapy for menopausal women. The review was not limited to one study, findings from one country or one product. Data were reviewed on the effect of hormone therapy on cardiovascular disease (CVD) and diabetes; cancers including breast, endometrial, lung, colon and ovary; osteoporosis and fracture prevention; mood and cognition; vasomotor symptoms (VMS); quality-of-life and economic issues; liver and gallbladder; musculoskeletal and joints; special senses (skin, eyes, ears); and genitourinary issues. Special populations evaluated included women with early menopause, whether natural, induced or surgical, those having BRCA genes with risk-reducing early oophorectomy, and those who request extended duration because of persistent hot flashes, bone loss or quality-of-life concerns. The Advisory Panel and the 2016–2017 NAMS Board of Trustees graded the level of evidence, provided key points, and identified areas of scientific uncertainty for which more research is needed before clear recommendations can be givenCitation1.
The NAMS 2017 Hormone Therapy Position StatementCitation1 is approximately 10 000 words long, published ahead of print and in print in July 2017. In addition to the comprehensive review and key points in each section, research priorities are identified, and clinical recommendations are provided at the end. It is the hope of NAMS that this Hormone Therapy Position Statement will allow conversations about initiating, continuing or stopping hormone therapy to be evidence-based, and not fear-based, and occur with a provider who is knowledgeable about all the available literature. The full Scientific Background Report for the Position Statement is more than 40 000 words long and is available for review on the NAMS website (https://www.menopause.org).
The NAMS Advisory Panel and NAMS Board of Trustees recognize that the WHI is the largest and longest randomized, blinded trial ever performed, but the findings cannot be translated to women with early menopause initiating hormone therapy. The participants in the WHI were aged on average 63 years and were 13 years from menopause onsetCitation6, and there was limited enrollment of women with bothersome VMS.
The WHI and the 13-year cumulative follow-up provide very important information about using standard-dose conjugated equine estrogen (CEE) combined with a potent synthetic progestin. However, for an individual woman, shared decision-making based on published reviewed literature should allow evaluation of unique health risks and goals of treatment and include potential benefits and risks from starting or continuing hormone therapy. The recent US Preventive Services Task Force draft evidence reviewCitation7, giving hormone therapy a 'D' recommendation grade for prevention of chronic disease, misses the need for VMS relief in women with persistent bothersome symptoms, the efficacy of hormone therapy for prevention of osteoporosis and fracture, the improved quality of life seen by many women on hormone therapy, and the use of low-dose vaginal estrogen for treatment of genitourinary symptoms associated with estrogen loss.
There is 'no one size fits all' when it comes to deciding about hormone therapy. There are many different types of hormone therapy formulations, with recognition that lower doses appear safer with fewer adverse events. In addition, the observational data showing fewer VTEs and strokes with transdermal therapy provideCitation8 options for women who wish to continue hormone therapy as they age. Women with a uterus who need protection against endometrial cancer if estrogen is being considered have options of micronized progesterone (shown in the E3N studyCitation9 to have less effect on breast cancer risk) and the new tissue-selective estrogen complex, CEE plus bazedoxifeneCitation10, which is a progestogen-free combination protecting the uterus, providing relief of hot flashes and sleep disturbances, prevention of bone loss, and relief of vaginal symptoms without the adverse events of bleeding or breast tenderness seen with traditional estrogen/progestin combinations.
NAMS hopes that the recommendations from the Hormone Therapy Position Statement will remove fear from the conversation to allow shared decision-making on the basis of evidence-based information to determine what is best for a woman at any point in time. With longer duration of use, there is a need for continued evaluation and reassessment. Lowered doses or transdermal therapies may provide more benefits than risks for the individual woman.
Major findings from the 2017 Hormone Therapy Position Statement of the North American Menopause Society
Hormone therapy is the most effective treatment for VMS and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture.
The clearest benefit of hormone therapy is for the treatment of VMS and prevention of bone loss for those at elevated risk aged younger than 60 years or within 10 years of menopause onset, if there are no contraindications.
Age and time from menopause onset at initiation of hormone therapy are important determinants of the benefit–risk ratio.
In addition to a woman’s health risks, risks of hormone therapy may differ for women depending on type, dose, duration, route of administration, and timing of initiation and whether a progestogen is needed.
Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic re-evaluation about benefits and risks of continuing or discontinuing hormone therapy.
Compounded hormone therapies, despite celebrity hype, lack safety and efficacy data, are not monitored or regulated by the government, and have unique risks associated with compounding itself, including concerns about sterility; impurities; over- or under-dosing, which could increase cancer risk; and lack of a label providing warnings about potential risks.
For women who initiate hormone therapy aged older than 60 years, certainly aged older than 70 years, or those who are more than 10 or 20 years from menopause onset, the use of hormone therapy has a less favorable benefit–risk ratio because of greater absolute risks of heart disease, stroke, VTE, and dementia as women age.
The effects of hormone therapy on coronary heart disease (CHD) may vary depending on when hormone therapy is initiated in relation to a woman’s age and/or time since menopause onset, with data suggesting reduced risk of CHDCitation11 in women who initiate hormone therapy aged younger than 60 years and/or within 10 years of menopause onset. However, for women who initiate hormone therapy more than 10 years or clearly by 20 years from menopause onset, risk of CHD appears increasedCitation12.
A significant reduction in all-cause mortalityCitation11 has been found in meta-analysis for women who initiate hormone therapy aged younger than 60 years and/or within 10 years from menopause onset. However, no protective effect was found in women with initiation more than 10 years from menopause onset.
Clinical scenarios
Extended use of hormone therapy
There is no evidence to support routine discontinuation of hormone therapy after age 65. Decisions about longer durations of therapy should be individualized and considered for indications such as persistent VMS or bone loss, with shared decision-making, documentation and periodic re-evaluation.
Longer duration of use appears more favorable for estrogen therapy than for estrogen/progestin therapy, based on the WHI randomized, controlled trials.
Risks can be minimized with use of lower doses of both estrogen and progestogens, transdermal therapies to avoid the hepatic first-pass effect, and the combination of CEE paired with the tissue-selective estrogen receptor modulator bazedoxifene, which provides endometrial protection without the need for a progestogen.
Women with only vaginal symptoms
For bothersome vulvovaginal or urinary symptoms not relieved with over-the-counter therapies and without indications for use of systemic hormone therapy, low-dose vaginal estrogen therapy or other therapies (ospemifene or intravaginal dehydroepiandrosterone) are recommended and can be continued as long as indicated. There is minimal absorption of low-dose vaginal estrogen, with levels within normal postmenopausal levels. Based on 1-year safety studies, progestogen is not needed with low-dose vaginal estrogenCitation13.
Special populations of women
Early menopause
For women with hypoestrogenism, primary ovarian insufficiency, or early menopause, whether natural, surgical or induced, and without contraindications, hormone therapy is recommended until at least the median age of menopause (52 years) because observational dataCitation14 suggest that benefits exceed the risks for effects on prevention of osteoporosis and fracture, CVD, cognition and mood concerns, genitourinary syndrome of menopause, sexual function, and Parkinson’s disease.
Family history of breast cancer
Observational studies suggest that use of hormone therapy does not further alter the risk for breast cancer in women with a family history of breast cancer, although family history should be assessed when counseling about hormone therapy.
Women who are BRCA-positive but who have not had breast cancer
For BRCA-positive women who have undergone risk-reducing bilateral salpingoophorectomy, observational dataCitation15 suggest that systemic hormone therapy to the median age of menopause to decrease health risks associated with premature loss of estrogen does not increase breast cancer risk, with decisions considered on an individual basis.
Survivors of endometrial and breast cancer with bothersome VMS
For women with prior estrogen-sensitive cancers, the use of hormone therapy is usually not recommended. Tested and effective non-hormone or complementary therapies should be used. If unsuccessful and systemic estrogen is considered for persistent symptoms, decisions should be made for compelling reasons after detailed counseling and in conjunction with their oncologists.
Prior early-stage endometrial or breast cancer with bothersome genitourinary symptoms
On the basis of limited observational data, there appears to be minimal to no demonstrated risk for recurrence of early-stage endometrial or breast cancer using low-dose vaginal estrogen, but decisions should be made in conjunction with an oncologist after failure of non-hormone optionsCitation16.
Potential risks of hormone therapy
Potential risks for women aged younger than 60 years or within 10 years of menopause onset include the rare risk of breast cancer seen with combination estrogen/progestin therapy, endometrial hyperplasia or cancer if the estrogen effect is inadequately opposed, VTE, and biliary issues. Additional risks across ages include myocardial infarction, stroke and dementiaCitation12.
Summary
In the recently published 2017 Hormone Therapy Position Statement of the North American Menopause Society and guidelines on hormone therapy, NAMS reaffirms the safety and efficacy of hormone therapy for menopausal women with bothersome vasomotor symptoms, or for those at high risk of bone loss, particularly for those aged younger than 60 years or within 10 years of menopause onset. NAMS encourages practitioners to find the appropriate type, dose, duration, formulation, and duration of hormone therapy, with individualized shared decision-making on the basis of evidence-based information, the unique health risks of the individual woman and with ongoing surveillance and periodic reassessment.
References
- The 2017 Hormone Therapy Position Statement of The North American Menopause Society. Menopause 2017;24:728–53. Epub ahead of print June 20, 2017
- de Villiers TJ, Hall JE, Pinkerton JV, et al. Revised Global Consensus Statement on Menopausal Hormone Therapy. Climacteric 2016;19:313–15
- Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. Jama 2002;288:321–33
- Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. Jama 2004;291:1701–12
- Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. Jama 2013;310:1353–68
- Barnabei VM, Cochrane BB, Aragaki AK, Women's Health Initiative Investigators, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol 2005;105:1063–73
- Gartlehner G, Patel SV, Viswanatha M, et al. Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: An Evidence Review for the US Preventive Services Task Force. AHRQ Publication No. 15-05227-EF-1. Rockville, Maryland. May 2017
- Canonico M, Scarabin PY. Oral versus transdermal estrogens and venous thromboembolism in postmenopausal women: what is new since 2003? Menopause 2016;23:587–8
- Fournier A, Mesrine S, Dossus L, Boutron-Ruault MC, Clavel-Chapelon F, Chabbert-Buffet N. Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Res Treat 2014;145:535–43
- Pinkerton JV, Komm BS, Mirkin S. Tissue selective estrogen complex combinations with bazedoxifene/conjugated estrogens as a model. Climacteric 2013;16:618–28
- Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015;3:CD002229
- Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2017;1:CD004143
- Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015;18:483–91
- Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2016;8:CD001500
- Gabriel CA, Tigges-Cardwell J, Stopfer J, Erlichman J, Nathanson K, Domchek SM. Use of total abdominal hysterectomy and hormone replacement therapy in BRCA1 and BRCA2 mutation carriers undergoing risk-reducing salpingo-oophorectomy. Fam Cancer 2009;8:23–8
- American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice, Farrell R. ACOG Committee Opinion No. 659 summary: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Obstet Gynecol 2016;127:618–19