Menopause: The Journal of The North American Menopause Society Vol. 20, No. 12, pp. 1234/1235 DOI: 10.1097/gme.0000000000000124 * 2013 by The North American Menopause Society

EDITORIAL Unfinished business!

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he article BQuality of life and hypertension after hormone therapy withdrawal in New York City[ in this issue of Menopause1 illustrates many of the challenges faced by clinicians, scientists, perimenopausal women, and postmenopausal women as they try to sort through available data to guide their decisions about hormone therapy (HT). The investigators took advantage of the Bexperiment of nature,[ which was a consequence of the unanticipated results of the Women’s Health Initiative (WHI) published in 2002. Many HT and estrogen therapy (ET) users stopped simultaneously. In this article, 310 community women aged 57 to 73 years who had been on long-term hormone therapy (95 y) were interviewed about hormone use and quality of life, while some of their health parameters were recorded. Those who had discontinued HT/ET were compared with those who stayed on therapy and those who resumed therapy after a hiatus. The authors argue that their data demonstrates that women who stay on HT have less hypertension and more professional satisfaction. This is an interesting notion but seems speculative and borders on wishful thinking. The investigators started with the hypothesis that Bpatients stopping HT would be at greater risk for developing chronic disease compared to the cohort continuing.[ However, by the same token, it seems clear that women at risk for chronic disease might be more likely to stop HT in the first place, especially after the publicity surrounding the WHI in 2002. In 2002, HT was thought by many to go from heart healthy to heart unhealthy overnight. Although the authors stated that Bno patients discontinued HT/ET because of hypertension,[ cardiovascular disease was an explicit adverse outcome in the WHI, and this could have been a factor in the decision making of clinicians and women who decided to stop. The authors compared women who continued HT/ET with those who quit on several cardiac risk factors: body mass index, weight-tohip ratio, lipids, diabetes, age, and self-report of health scale. The only significant difference in the groups was age, whichValthough a clear correlate of hypertension2Vthe investigators controlled for. However, the authors did not indicate when the women developed hypertension and did not drill down enough on why the women quit HT/ET to settle the issue of whether that was somehow responsible for the differences that they reported. The authors stating that the Bodds of being on blood pressure medicine is 2.289[ without discussing confidence intervals was also a deficit of this article. This article reported higher quality of life in hormone users compared with those who quit, as measured by the Utian Quality of Life Scale. Causation seems a stretch, however.

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The women who quit were older, and the quality-of-life differences in the groups with respect to organizational satisfaction disappeared when corrected for age and employment. There was no comment about overall score and age. Again, we do not know what made women quit hormones (their concerns and influences), nor do we know why they started HT/ET in the first place. Utian and Woods3 recently published a comprehensive discussion of the effects of HT/ET on quality of life. They concluded that, BA review of the present literature shows that HT provides a significant benefit on menopause specific quality of life (MSQOL) in midlife women, mainly through relief of symptoms, but treatment effects on a global increase in women’s sense of well-being (global quality of lifeVGQOL) need to be evaluated in additional studies.[ Although the study reported a difference in quality of life among those on HT/ET, there is a need for more knowledge before conclusions should be drawn. This article had some additional interesting data. It was notableValthough not statistically significantVthat 26.1% of women who stayed on HT/ET were on antidepressants compared with 17.9% of women who quit. This was not only a reverse of the 27.4% of women on antihypertensives who discontinued HT/ET compared with the 16.5% of women on HT/ET but also a contrast to what has been found in other studies. Citarella et al4 recently published in this journal a large study in Sweden, where the likelihood that women would start antidepressants after discontinuing HT was 24% higher than for other women their age. Furthermore, it is remarkable, in the first place, that so many of the women in this study were on antidepressants. If the use of antidepressants can be used as a marker for depression, then this cohort is not entirely typical of a general population of similarly aged women where the prevalence of depressive symptoms is 10%.5 That these women were thin, educated, and healthy also indicates that this population is not typical. The distribution of hormone preparations documented in this study begs the question of how dose and delivery method affect outcome. Their Table 2 displayed oral versus transdermal HT/ET. The numbers did not add up, and there was no explanation for this (eg, for those who discontinued HT/ET in group 3, the total percentage of different types added up to 134.4%). That said, the patterns noted are interesting and reflect another trend in current menopause practice. An American College of Obstetricians and Gynecologists committee opinion released last spring supported the use of transdermal therapy over oral therapy: BWhen prescribing estrogen therapy, the gynecologist should take into consideration the possible

Menopause, Vol. 20, No. 12, 2013

Copyright © 2013 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.

EDITORIAL

thrombosis-sparing properties of transdermal forms of estrogen therapy.[6 The study data suggests that participating clinicians are on board with up-to-date delivery routes. Data on overall estrogen dose or progestogens in HT users were not provided. There are multiple opportunities for further editorializing about this article. Scrutinizing it mostly raises all the questions faced by hormone prescribers. What are the benefits and harms of HT beyond symptom relief ? What are the on-the-ground determinants of starting and stopping HT/ET in particular groups of women? This article raises many questions and, sadly, answers none. Financial disclosure/conflicts of interest: None reported.

Marcie K. Richardson, MD Harvard Vanguard Medical Associates Boston, Massachusetts

REFERENCES 1. Warren MP, Richardson O, Chaudhry S, et al. Quality of life and hypertension after hormone therapy withdrawal in New York City. Menopause 2013;20:1255-1263. 2. Wolf-Maier K, Cooper RS, Banegas JR, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA 2003;289:2363-2369. 3. Utian WH, Woods NF. Impact of hormone therapy on quality of life after menopause. Menopause 2013;20:1098-1105. 4. Citarella A, Andersen M, Sundstro¨m A, Bardage C, Hultman CM, Kieler H. Initiating therapy with antidepressants after discontinuation of hormone therapy. Menopause 2013;20:146-151. 5. Joffe H. Antidepressant use after discontinuation of hormone therapy: what can one infer about postYhormone therapy depression? Menopause 2013;20:123-125. 6. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 556: postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet Gynecol 2013; 121:887-890.

Menopause, Vol. 20, No. 12, 2013

Copyright © 2013 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.

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Unfinished business!

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