VIEWS AND REVIEWS
Introduction: Menopausal hormone therapy: where are we today? Marcelle I. Cedars, M.D. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, San Francisco, California
In this Views and Reviews section, the authors present the most updated information on menopausal hormone therapy (MHT) and an individualized treatment approach. Care of women through the menopausal transition and post-menopausally requires physicians to integrate multi-organ implications of MHT and understand the full-range of treatment alternatives. (Fertil SterilÒ 2014;101:885–6. Ó2014 by American Society for Reproductive Medicine.) Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/cedarsm-menopausal-hormone-therapy/
T
his issue of Views and Reviews focuses on the continued controversy regarding menopausal hormone therapy (MHT) for peri- and post-menopausal women. When the Women's Health Initiative (WHI) was halted and data presented in the summer of 2002, the pendulum swung rapidly from ‘‘estrogen treatment for all women forever’’ to refusal to prescribe even in women with primary ovarian insufficiency. As with most things in life (and medicine), the truth likely falls somewhere in the middle. Studies since the first publication of WHI results have tried to reconcile the results from observational trials and these Level I data. Obviously, there are a number of methodological problems with observational studies including confounding, selection bias, and incomplete capture of events, which is specifically why randomized trials are designed and carried out. However, there were also some potential biological explanations for
the unexpected differences. Most prominently, what has been termed the ‘‘timing hypothesis,’’ seemed to differentiate the WHI from prior observational studies. Additionally, as was the intention, the WHI evaluated hard outcomes: cardiovascular events, stroke, breast cancer, fracture, etc. and focused less on symptoms, the presenting complaint for many, particularly, younger women. So, where are we today? And most importantly, how should we counsel our patients regarding risks and benefits of MHT? It is important to realize, as physicians, we manage individual patients. As such, our care and recommendations should be individualized. This requires a thorough understanding of the literature, including risks and benefits, but also careful consultation with the individual patient regarding her primary complaints and concerns, her family and personal health history, and her own weighing of potential risks and benefits. Once this is taken into
Received February 6, 2014; accepted February 13, 2014; published online March 6, 2014. M.I.C. has received a grant from the Kronos Longevity Institute. Reprint requests: Marcelle I. Cedars, M.D., Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, 1635 Divisadero Street, Suite 601, San Francisco, California 94115 (E-mail: [email protected]). Fertility and Sterility® Vol. 101, No. 4, April 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2014.02.026 VOL. 101 NO. 4 / APRIL 2014
Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
consideration, a decision for one patient may be quite different from a decision for another. As we move into an era of personalized medicine this individualization of care should seem quite natural to us. In the following articles, the authors discuss key areas of concern for women. The first article deals with the current knowledge regarding menopause, hormones, and cardiovascular disease (CVD) risk. Women are largely unaware of their risk for CVD or, that once diagnosed, their prognosis is worse than for men. As such, improving our understanding of CVD risk and the specific implications for women's health is critical. There are unique features in women where both general aging and the loss of estrogen expose the vascular system to risk. Dr. Harman discusses the pathogenesis of atherosclerosis and impact of estrogen. Additionally, he reviews the available epidemiological data. Lastly, he focuses the results from randomized clinical trials. While this review supports that controversy remains, and no current information supports treatment with estrogen or estrogen/progestin for cardiovascular protection, guidance is given regarding those individuals who 885
VIEWS AND REVIEWS would be at most risk and those for whom potential risk may be less. Again, there is no evidence, at the current time of benefit with respect to cardiovascular protection. Drs. Al-Safi and Santoro take a broad look at menopausal symptoms. They rightly discuss the normal onset and duration of symptoms. This is critical information for patients to know as they weigh potential risks/benefits of treatment alternatives. Understanding the natural history of vasomotor symptoms is important information for patients to weigh as they make critical decisions regarding management. While MHT is the most effective treatment for vasomotor symptoms and vaginal dryness, there is a growing body of literature regarding nonhormonal and alternative treatment strategies. The detailed discussion of these agents, and available lifestyle choices, aids the development of an individual treatment strategy. Dr. Fischer and colleagues discuss the impact of aging and hormonal changes on a woman's cognitive and mental health. This too has been a controversial area about which much remains to be understood. The potential mechanisms by which estrogen impacts the brain are discussed in an attempt to address the conflicting information. Additionally, the authors address different preparations and combinations of hormones with respect to impact on the brain. A critical time period during which the impact of estrogen may be
886
positive or negative appears to hold true for the brain, as may be the case for the heart. Dr. Manson tries to put the available literature in context. For all of us as physicians, the most important decision is the individual one. Many of the randomized controlled trials were designed to specifically look at ‘‘hard’’ health outcomes (CVD, breast cancer, osteoporotic fracture, etc.), but it's important to remember that many women come to see their physician with menopausal symptoms.1 MHT remains the most effective treatment for many menopausal symptoms, but should not be prescribed long-term for prevention of the diseases associated with aging. This is one area of medicine where new information is presented on an almost daily basis. Today, all we can do as we manage our patients is hear their concerns and symptoms, and share with them the known risks and benefits of MHT and available alternatives to MHT. An individual decision should then be made with the patient. This decision should be revisited on a yearly basis as new information becomes available.
REFERENCE 1.
Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010;95(7Suppl):s1–66.
VOL. 101 NO. 4 / APRIL 2014
Introduction: Menopausal hormone therapy: where are we today? Marcelle I. Cedars, M.D. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, San Francisco, California
In this Views and Reviews section, the authors present the most updated information on menopausal hormone therapy (MHT) and an individualized treatment approach. Care of women through the menopausal transition and post-menopausally requires physicians to integrate multi-organ implications of MHT and understand the full-range of treatment alternatives. (Fertil SterilÒ 2014;101:885–6. Ó2014 by American Society for Reproductive Medicine.) Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/cedarsm-menopausal-hormone-therapy/
T
his issue of Views and Reviews focuses on the continued controversy regarding menopausal hormone therapy (MHT) for peri- and post-menopausal women. When the Women's Health Initiative (WHI) was halted and data presented in the summer of 2002, the pendulum swung rapidly from ‘‘estrogen treatment for all women forever’’ to refusal to prescribe even in women with primary ovarian insufficiency. As with most things in life (and medicine), the truth likely falls somewhere in the middle. Studies since the first publication of WHI results have tried to reconcile the results from observational trials and these Level I data. Obviously, there are a number of methodological problems with observational studies including confounding, selection bias, and incomplete capture of events, which is specifically why randomized trials are designed and carried out. However, there were also some potential biological explanations for
the unexpected differences. Most prominently, what has been termed the ‘‘timing hypothesis,’’ seemed to differentiate the WHI from prior observational studies. Additionally, as was the intention, the WHI evaluated hard outcomes: cardiovascular events, stroke, breast cancer, fracture, etc. and focused less on symptoms, the presenting complaint for many, particularly, younger women. So, where are we today? And most importantly, how should we counsel our patients regarding risks and benefits of MHT? It is important to realize, as physicians, we manage individual patients. As such, our care and recommendations should be individualized. This requires a thorough understanding of the literature, including risks and benefits, but also careful consultation with the individual patient regarding her primary complaints and concerns, her family and personal health history, and her own weighing of potential risks and benefits. Once this is taken into
Received February 6, 2014; accepted February 13, 2014; published online March 6, 2014. M.I.C. has received a grant from the Kronos Longevity Institute. Reprint requests: Marcelle I. Cedars, M.D., Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, 1635 Divisadero Street, Suite 601, San Francisco, California 94115 (E-mail: [email protected]). Fertility and Sterility® Vol. 101, No. 4, April 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2014.02.026 VOL. 101 NO. 4 / APRIL 2014
Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
consideration, a decision for one patient may be quite different from a decision for another. As we move into an era of personalized medicine this individualization of care should seem quite natural to us. In the following articles, the authors discuss key areas of concern for women. The first article deals with the current knowledge regarding menopause, hormones, and cardiovascular disease (CVD) risk. Women are largely unaware of their risk for CVD or, that once diagnosed, their prognosis is worse than for men. As such, improving our understanding of CVD risk and the specific implications for women's health is critical. There are unique features in women where both general aging and the loss of estrogen expose the vascular system to risk. Dr. Harman discusses the pathogenesis of atherosclerosis and impact of estrogen. Additionally, he reviews the available epidemiological data. Lastly, he focuses the results from randomized clinical trials. While this review supports that controversy remains, and no current information supports treatment with estrogen or estrogen/progestin for cardiovascular protection, guidance is given regarding those individuals who 885
VIEWS AND REVIEWS would be at most risk and those for whom potential risk may be less. Again, there is no evidence, at the current time of benefit with respect to cardiovascular protection. Drs. Al-Safi and Santoro take a broad look at menopausal symptoms. They rightly discuss the normal onset and duration of symptoms. This is critical information for patients to know as they weigh potential risks/benefits of treatment alternatives. Understanding the natural history of vasomotor symptoms is important information for patients to weigh as they make critical decisions regarding management. While MHT is the most effective treatment for vasomotor symptoms and vaginal dryness, there is a growing body of literature regarding nonhormonal and alternative treatment strategies. The detailed discussion of these agents, and available lifestyle choices, aids the development of an individual treatment strategy. Dr. Fischer and colleagues discuss the impact of aging and hormonal changes on a woman's cognitive and mental health. This too has been a controversial area about which much remains to be understood. The potential mechanisms by which estrogen impacts the brain are discussed in an attempt to address the conflicting information. Additionally, the authors address different preparations and combinations of hormones with respect to impact on the brain. A critical time period during which the impact of estrogen may be
886
positive or negative appears to hold true for the brain, as may be the case for the heart. Dr. Manson tries to put the available literature in context. For all of us as physicians, the most important decision is the individual one. Many of the randomized controlled trials were designed to specifically look at ‘‘hard’’ health outcomes (CVD, breast cancer, osteoporotic fracture, etc.), but it's important to remember that many women come to see their physician with menopausal symptoms.1 MHT remains the most effective treatment for many menopausal symptoms, but should not be prescribed long-term for prevention of the diseases associated with aging. This is one area of medicine where new information is presented on an almost daily basis. Today, all we can do as we manage our patients is hear their concerns and symptoms, and share with them the known risks and benefits of MHT and available alternatives to MHT. An individual decision should then be made with the patient. This decision should be revisited on a yearly basis as new information becomes available.
REFERENCE 1.
Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010;95(7Suppl):s1–66.
VOL. 101 NO. 4 / APRIL 2014
