G Model MAT-6154; No. of Pages 2
ARTICLE IN PRESS Maturitas xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Guest Editorial
Hot flushes and the menopause: How long should they be expected to last?
Keywords: Menopause Hot flushes Duration
Relief for hot flushes, the predominant symptom of menopause, is among the most common reasons for gynecological visits of mid-life women. Hormone therapy (HT) continues to be the primary treatment and is arguably the most effective treatment for menopausal hot flushes, but its identified risks have led many experts to limit the duration of its use to the lowest effective dose “for the shortest period of time” (“not to exceed 3–5 years”) [1]. This was predicated on widely accepted observations that hot flushes persisted for about 6 months to 2 years for most women, and could therefore be ameliorated in this time period. However, empirical evidence for the duration of menopausal hot flushes was lacking, and only in recent years have well-designed studies with longer follow-up periods suggested that many women may experience hot flushes considerably beyond the 3–5 years recommended for HT. Recent studies of the duration of hot flushes indicate that women can expect hot flushes to continue, on average, for nearly 5 years after the final menstrual period (FMP), while more than onethird of women who experience moderate/severe hot flushes will continue to have them for more than 10 years after the FMP [2]. This duration was reported in a population-based cohort of healthy women who were not using HT and were observed to reach natural menopause in a 16-year follow-up. Another study in the same cohort showed that the majority of women experienced the onset of hot flushes well before the FMP. When the duration of hot flushes was estimated over its natural course from onset to endpoint, regardless of the FMP, the total median duration of moderate/severe hot flushes was 10.2 years from initial onset to observed endpoint. Including women with mild hot flushes in the estimates increased the median duration of hot flushes to 11.6 years, from onset to observed endpoint [3]. While the proportion of women with hot flushes peaked in the first 2 years after the FMP, the prevalence decreased slowly after menopause. The prevalence did not return to premenopausal levels until 9 years after the FMP, when the prevalence of moderate/severe hot flushes was 32%, the same prevalence as that in the year before the FMP [2]. Again, these women were in general good
health and without other serious medical problems, yet reported natural durations of moderate/severe hot flushes that considerably exceeded the time frame of several years that is generally accepted in clinical practice. These studies were preceded by several investigations that also suggested the duration of menopausal hot flushes was considerably longer than a few years. In a meta-analysis of 10 primarily crosssectional studies, nearly half of the women reported hot flushes 4 years after the FMP, and 10% reported symptoms 10 years after the FMP [4]. In a study of Australian women, the mean duration of hot flushes from symptom onset to study endpoint was 5.3 years [5], although the duration in relation to the FMP, which is a key marker for medical management, was not identified. A survey of more than 8000 Latin-American women indicated that over 60% reported vasomotor symptoms 12 years after menopause [6]. Overall, the data suggested that the duration of hot flushes extended beyond 2–3 years for many women. Predictors of women who might have a short duration versus a long duration of hot flushes have not been clearly identified. Significant predictors of the overall duration of hot flushes include age (the younger the age at onset, the longer the duration), race (African American women had a longer duration than white women), and a complex association of body mass index (BMI), where African American women (both obese and non-obese) and obese white women have the greatest risk of moderate/severe hot flushes and non-obese white women the lowest risk [2,3]. Higher anxiety levels have been identified as a strong risk factor in multiple studies, but it is not known whether anxiety amplifies hot flushes or is primarily a predictor. The natural course and duration of hot flushes is essential information for individualizing treatment of menopausal symptoms. HT is considered appropriate for the management of moderate/severe hot flushes in early menopause, but clinical judgment is needed in determining the duration of treatment that is consistent with the woman’s needs [7]. Data support “several years” of HT, but this duration may not be sufficient for many women, based on the increasing data-based evidence. In addition to the long natural duration of hot flushes for many women, hot flushes often reappear after cessation of HT: 87% reported return of symptoms, regardless of duration of use up to 5 years [8]. Other women have contraindications for estrogen use (e.g., cardiovascular events, breast cancer) or do not wish to use hormones. A growing body of evidence supports reasonable alternatives to HT for the clinical management
http://dx.doi.org/10.1016/j.maturitas.2014.04.010 0378-5122/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Freeman EW. Hot flushes and the menopause: How long should they be expected to last? Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.04.010
G Model MAT-6154; No. of Pages 2
ARTICLE IN PRESS Guest Editorial / Maturitas xxx (2014) xxx–xxx
2
of hot flushes: for example, serotonergic antidepressants (e.g., escitalopram, venlafaxine, desvenlafaxine, low-dose paroxetine), tissue-selective estrogens (estrogen/bazodoxifene), low-dose gabapentin and tibolone effectively reduce the frequency and severity of hot flushes with known safety profiles for women who seek options other than HT. Our understanding of the physiology of hot flushes and their treatments remains incomplete. Studies are needed to determine whether the frequent return of hot flushes after cessation of HT reflects their natural duration that had not run its course; and head-to-head trials of non-hormonal therapies with currently prescribed dosages of HT are needed to clarify the extent to which these treatments reduce hot flushes is similar. In the meantime, recognition that the natural course of hot flushes extends over a number of years, with a duration of 5 to more than 10 years for many healthy women, is important information for planning individualized treatment for those who seek relief from this symptom of menopause.
References [1] The North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012;19:257–71. [2] Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause January 2014;21(9) [Epub ahead of print]. [3] Freeman EW, Sammel MD, Lin H, Liu A, Gracia CR. Duration of menopausal hot flushes and associated risk factors. Obstet Gynecol 2011;117(5): 1095–104. [4] Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Intern Med 2008;23(9):1507–13. [5] Col NF, Guthrie JR, Politi M, Dennerstein L. Duration of vasomotor symptoms in middle-aged women: a longitudinal study. Menopause 2009;16:453–7. [6] Blumel JE, Chedraui P, Baron G, et al. A large multinational study of vasomotor symptom prevalence, duration and impact on quality of life in middle-aged women. Menopause 2011;18(7):778–85. [7] Manson JE. Current recommendations: what is the clinician to do? Fertil Steril 2014;101(4):916–21. [8] Lindh-Astrand L, Brynhildsen J, Hoffman M, Hammar M. Vasomotor symptoms usually reappear after cessation of postmenopausal hormone therapy: a Swedish population-based study. Menopause 2009;16(6):1213–7.
Contributors a
Ellen Freeman is the sole author. Competing interest None declared. Funding None.
Ellen W. Freeman (PhD) a,b,∗ Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States b Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States ∗ Correspondence
to: 3701 Market Street, Suite 820, Philadelphia, PA 19104, United States. Tel.: +1 215 662 3628; fax: +1 215 349 5521. E-mail address: [email protected]
Provenance and peer review Commissioned, not externally peer reviewed.
10 April 2014 Available online xxx
Please cite this article in press as: Freeman EW. Hot flushes and the menopause: How long should they be expected to last? Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.04.010
ARTICLE IN PRESS Maturitas xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Guest Editorial
Hot flushes and the menopause: How long should they be expected to last?
Keywords: Menopause Hot flushes Duration
Relief for hot flushes, the predominant symptom of menopause, is among the most common reasons for gynecological visits of mid-life women. Hormone therapy (HT) continues to be the primary treatment and is arguably the most effective treatment for menopausal hot flushes, but its identified risks have led many experts to limit the duration of its use to the lowest effective dose “for the shortest period of time” (“not to exceed 3–5 years”) [1]. This was predicated on widely accepted observations that hot flushes persisted for about 6 months to 2 years for most women, and could therefore be ameliorated in this time period. However, empirical evidence for the duration of menopausal hot flushes was lacking, and only in recent years have well-designed studies with longer follow-up periods suggested that many women may experience hot flushes considerably beyond the 3–5 years recommended for HT. Recent studies of the duration of hot flushes indicate that women can expect hot flushes to continue, on average, for nearly 5 years after the final menstrual period (FMP), while more than onethird of women who experience moderate/severe hot flushes will continue to have them for more than 10 years after the FMP [2]. This duration was reported in a population-based cohort of healthy women who were not using HT and were observed to reach natural menopause in a 16-year follow-up. Another study in the same cohort showed that the majority of women experienced the onset of hot flushes well before the FMP. When the duration of hot flushes was estimated over its natural course from onset to endpoint, regardless of the FMP, the total median duration of moderate/severe hot flushes was 10.2 years from initial onset to observed endpoint. Including women with mild hot flushes in the estimates increased the median duration of hot flushes to 11.6 years, from onset to observed endpoint [3]. While the proportion of women with hot flushes peaked in the first 2 years after the FMP, the prevalence decreased slowly after menopause. The prevalence did not return to premenopausal levels until 9 years after the FMP, when the prevalence of moderate/severe hot flushes was 32%, the same prevalence as that in the year before the FMP [2]. Again, these women were in general good
health and without other serious medical problems, yet reported natural durations of moderate/severe hot flushes that considerably exceeded the time frame of several years that is generally accepted in clinical practice. These studies were preceded by several investigations that also suggested the duration of menopausal hot flushes was considerably longer than a few years. In a meta-analysis of 10 primarily crosssectional studies, nearly half of the women reported hot flushes 4 years after the FMP, and 10% reported symptoms 10 years after the FMP [4]. In a study of Australian women, the mean duration of hot flushes from symptom onset to study endpoint was 5.3 years [5], although the duration in relation to the FMP, which is a key marker for medical management, was not identified. A survey of more than 8000 Latin-American women indicated that over 60% reported vasomotor symptoms 12 years after menopause [6]. Overall, the data suggested that the duration of hot flushes extended beyond 2–3 years for many women. Predictors of women who might have a short duration versus a long duration of hot flushes have not been clearly identified. Significant predictors of the overall duration of hot flushes include age (the younger the age at onset, the longer the duration), race (African American women had a longer duration than white women), and a complex association of body mass index (BMI), where African American women (both obese and non-obese) and obese white women have the greatest risk of moderate/severe hot flushes and non-obese white women the lowest risk [2,3]. Higher anxiety levels have been identified as a strong risk factor in multiple studies, but it is not known whether anxiety amplifies hot flushes or is primarily a predictor. The natural course and duration of hot flushes is essential information for individualizing treatment of menopausal symptoms. HT is considered appropriate for the management of moderate/severe hot flushes in early menopause, but clinical judgment is needed in determining the duration of treatment that is consistent with the woman’s needs [7]. Data support “several years” of HT, but this duration may not be sufficient for many women, based on the increasing data-based evidence. In addition to the long natural duration of hot flushes for many women, hot flushes often reappear after cessation of HT: 87% reported return of symptoms, regardless of duration of use up to 5 years [8]. Other women have contraindications for estrogen use (e.g., cardiovascular events, breast cancer) or do not wish to use hormones. A growing body of evidence supports reasonable alternatives to HT for the clinical management
http://dx.doi.org/10.1016/j.maturitas.2014.04.010 0378-5122/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Freeman EW. Hot flushes and the menopause: How long should they be expected to last? Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.04.010
G Model MAT-6154; No. of Pages 2
ARTICLE IN PRESS Guest Editorial / Maturitas xxx (2014) xxx–xxx
2
of hot flushes: for example, serotonergic antidepressants (e.g., escitalopram, venlafaxine, desvenlafaxine, low-dose paroxetine), tissue-selective estrogens (estrogen/bazodoxifene), low-dose gabapentin and tibolone effectively reduce the frequency and severity of hot flushes with known safety profiles for women who seek options other than HT. Our understanding of the physiology of hot flushes and their treatments remains incomplete. Studies are needed to determine whether the frequent return of hot flushes after cessation of HT reflects their natural duration that had not run its course; and head-to-head trials of non-hormonal therapies with currently prescribed dosages of HT are needed to clarify the extent to which these treatments reduce hot flushes is similar. In the meantime, recognition that the natural course of hot flushes extends over a number of years, with a duration of 5 to more than 10 years for many healthy women, is important information for planning individualized treatment for those who seek relief from this symptom of menopause.
References [1] The North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012;19:257–71. [2] Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause January 2014;21(9) [Epub ahead of print]. [3] Freeman EW, Sammel MD, Lin H, Liu A, Gracia CR. Duration of menopausal hot flushes and associated risk factors. Obstet Gynecol 2011;117(5): 1095–104. [4] Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Intern Med 2008;23(9):1507–13. [5] Col NF, Guthrie JR, Politi M, Dennerstein L. Duration of vasomotor symptoms in middle-aged women: a longitudinal study. Menopause 2009;16:453–7. [6] Blumel JE, Chedraui P, Baron G, et al. A large multinational study of vasomotor symptom prevalence, duration and impact on quality of life in middle-aged women. Menopause 2011;18(7):778–85. [7] Manson JE. Current recommendations: what is the clinician to do? Fertil Steril 2014;101(4):916–21. [8] Lindh-Astrand L, Brynhildsen J, Hoffman M, Hammar M. Vasomotor symptoms usually reappear after cessation of postmenopausal hormone therapy: a Swedish population-based study. Menopause 2009;16(6):1213–7.
Contributors a
Ellen Freeman is the sole author. Competing interest None declared. Funding None.
Ellen W. Freeman (PhD) a,b,∗ Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States b Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States ∗ Correspondence
to: 3701 Market Street, Suite 820, Philadelphia, PA 19104, United States. Tel.: +1 215 662 3628; fax: +1 215 349 5521. E-mail address: [email protected]
Provenance and peer review Commissioned, not externally peer reviewed.
10 April 2014 Available online xxx
Please cite this article in press as: Freeman EW. Hot flushes and the menopause: How long should they be expected to last? Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.04.010
