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Rapid Responses: Rapid Responses published:
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Article's recommendation is not questionable
- Margaret CP Rees (12 May 2008)
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HRT for premature menopause is not questionable
- John C Stevenson (14 May 2008)
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HRT is recommended in women with premature ovarian failure
- Timothy C Hillard DM FFSRH FRCOG (15 May 2008)
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Young women and HRT
- Kathy Abernethy, Amanda Hillard, Debra Holloway (16 May 2008)
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HRT for women with premature menopause should not be questioned
- David W Sturdee, None (17 May 2008)
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Margaret CP Rees, Reader in Reproductive Medicine, University of Oxford Women's Centre, John Radcliffe Hospital, Oxford oX3 9DU
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I strongly disagree with Martin Lewars’ conclusion about the use of hormone replacement therapy (HRT) in women with a premature menopause. He is quoting the Women’s Health Initiative which was undertaken in women over the age of 50 and do not pertain to women in their 30s or even younger with early ovarian failure. Women with untreated premature menopause are at increased risk of developing osteoporosis, cardiovascular disease, cognitive decline, dementia and parkinsonism [1-4]. Therefore, there is a need for estrogen replacement until the average age of the natural menopause which is about 52 years in the UK. This does not increase the risk of breast cancer [5]. The recommendation for HRT use by Jones et al is in accordance with national guidelines [6,7,8]. 1.Ossewaarde ME, Bots ML, Verbeek AL, et al. Age at menopause, cause- specific mortality and total life expectancy. Epidemiology 2005;16:556-62. 2.Rocca WA, Grossardt BR, de Andrade M, et al. Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol 2006;7:821-8. 3.Rocca WA, Bower JH, Maraganore DM, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074-83. 4.Rocca WA, Bower JH, Maraganore DM, et al. Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology 2008;70:200-9. 5.Ewertz M, Mellemkjaer L, Poulsen AH, Friis S, Sorensen HT, Pedersen L, McLaughlin JK, Olsen JH. Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study. Br J Cancer 2005; 92: 1293-7. 6. Committee on Safety of Medicines. Further advice on safety of HRT: risk:benefit unfavourable for first-line use in prevention of osteoporosis. CEM/CMO/2003/19. www.mhra.gov.uk 7. Clinical Knowledge Summary. Menopause. http://cks.library.nhs.uk/menopause/view_whole_topic 8. British Menopause Society Consensus Statement: Premature Menopause. http://www.thebms.org.uk/statementcontent.php?id=3 Competing interests: None declared |
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John C Stevenson, Consultant Physician and Reader in Metabolic Medicine National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, London SW3 6NP
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Randomised clinical trials compare a treatment with a placebo and use statistics to determine whether any differences found are meaningful or could be merely due to chance. It would probably have been useful for Dr Lewars to have actually read the articles on the final results of the Women’s Health Initiative (WHI) before making his comments about hormone replacement therapy (HRT). WHI did not find a significant increase in coronary heart disease (CHD) with combined HRT use [1], and indeed WHI has now concluded that women who initiated therapy closer to menopause tend to have reduced CHD risk [2]. A significantly reduced risk for a composite CHD outcome was seen with estrogen alone in those initiating therapy below 60 years of age [3]. Similarly, there were no significant differences between HRT and placebo in stroke incidence [2] in those initiating therapy below 60 years of age. When the WHI breast cancer findings with combined HRT were adjusted for confounding variables there was no significant increase in risk [4], nor was there with estrogen alone therapy where those compliant with the therapy actually showed a significantly reduced risk [5]. Had Dr Lewars read the published paper rather than the BMJ Short Cut he would have also realised that there was no significant difference in breast cancer incidence between former HRT users or placebo users in the 3-year follow-up after cessation of the WHI trial [6]. What WHI has told us is not to commence elderly women on overdoses of HRT. But not recommending long-term HRT to young women experiencing premature menopause would certainly seem contrary to good practice. 1. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523-34. 2. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465-77. 3. Hsia J, Langer RD, Manson ME, et al. Conjugated equine estrogens and coronary heart disease. Arch Intern Med 2006;166:357-65. 4. Anderson GL, Chlebowski RT, Rossouw JE, et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin. Maturitas 2006;55:103-15. 5. Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647-57. 6. Heiss G, Wallace R, Anderson GL, et al. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA 2008;299:1036-45. Competing interests: I have previously received grants from the Medical Research Council and from Pharmaceutical companies to carry out HRT research. |
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Timothy C Hillard DM FFSRH FRCOG, Chairman British Menopause Society British Menopause Society, 4-6 Eton Place, Marlow SL7 2QA
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Dr Lewars is seriously misinformed in questioning the recommendation to use HRT in young women with premature ovarian failure. Untreated these women not only often suffer severe menopausal symptoms and premature genito-urinary atrophy they are also at higher risk of osteoporosis, premature cardiovascular disease and dementia (1-3). National and international evidence based guidelines conclude that the advantages of HRT in women with a premature menopause outweigh any small risks and recommend that this group of women should continue some form of HRT at least until the age of expected natural menopause which is usually 51-52 (4-6) In the original WHI study quoted by Dr Lewars, the mean age of participants was 63 with 20% over 70 years old. In the ensuing 6 years, various reanalysis of these data by the authors themselves and others have clearly indicated that HRT in women under 60 does not increase cardiovascular risk and indeed may be associated with a reduced risk (7,8). Equally the breast cancer data quoted by Dr Lewars are selective. The Million Womens’ study was a large observational study which provided useful epidemiological information about women undergoing mammographic screening. However there have been numerous criticisms of this study both for its sensationalist headlines and the extrapolation of their results (9). It has been well documented for many years that long-term use (> 5 years)of HRT in postmenopausal women may lead to a small increase in breast cancer risk, data in women with premature menopause are relatively few. The largest meta-analysis to date did not indicate any increased risk with prolonged use of HRT under the age of 50 (10) Thus, all the available evidence suggests the balance of risks and benefits is strongly in favour of recommending HRT for these women. Women who have the misfortune to go through a premature menopause, be it genetic, iatrogenic or secondary to oncological treatments deserve far more than Dr Lewars’ sympathy, they deserve appropriate, accurate and balanced information from well informed and upto date clinicians and other health professionals. 1. Jacobsen BK, Knutsen SF, Fraser GE. Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study. J Clin Epidemiol 1999;52:303–7 2. Rocca WA, Grossardt BR, de Andrade M, et al. Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol 2006;7:821–8 3. Rocca WA, Bower JH, Maraganore DM, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074-83 4. Committee on Safety of Medicines. Further advice on safety of HRT: risk:benefit unfavourable for first-line use in prevention of osteoporosis. CEM/CMO/2003/19. www.mhra.gov.uk 5. British Menopause Society Consensus Statement: Premature Menopause. http://www.thebms.org.uk/statementcontent.php?id=3 6. International Menopause Society recommendation on postmenopausal hormone replacement therapy http://www.imsociety.org/pdf_files/ims_recommendations/ims_updated_recommendations_on_postmenopausal_hormone_therapy_27_02_07.pdf 7. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465-77. 8. Hsia J, Langer RD, Manson ME, et al. Conjugated equine estrogens and coronary heart disease. Arch Intern Med 2006;166:357-65 9. Whitehead M, Farmer R. The million women study: a critique. Endocrine 2004; 24: 187-93. 10.Anonymous. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047-59. Competing interests: I have received educational and research grants from a variety of organisations including some pharmaceutical companies who make products used in the treatment of menopausal symptoms and the prevention of postmenopausal osteoporosis. |
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Kathy Abernethy, Chair: Royal College of Nursing Menopause Group Northwick Park Hospital, Harrow HA13UJ, Amanda Hillard, Debra Holloway
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Women who experience a premature menopause are not typical menopausal women. Along side a myriad of health issues to worry about, they often report a lack of understanding from their doctors about risks and benefits of HRT in their age group. Their physical and psychological needs are immense and to withhold HRT based on studies of women in their 50s and beyond seems unethical. Based on current evidence (see previous letters), we continue to recommend HRT at least until the normal age of menopause and offer support for women who receive conflicting advice such as that given in Dr Lewar’s letter. Women themselves are confused by media reports on HRT – it appears some of our medical colleagues are too. Competing interests: The RCN Menopause Group has received educational grants from various companies and organisations, including those involved in the field of menopause. |
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David W Sturdee, Consultant Gynaecologist Solihull Hospital, B91 2JL, None
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As a gynaecologist, I strongly dispute the comments from Dr Lewars, a radiologist, about the use of hormone replacement therapy (HRT) in women experiencing a premature menopause. Such women should be advised to take HRT for the medical reasons outlined by Jones et al1 and as recommended also by the Committee on Safety of Medicines2 and the Royal College of Obstetricians and Gynaecologists3. Dr Lewars selective use of data from the Women’s Health Initiative (WHI) study ignores the later evidence that HRT given to young postmenopausal women carries minimal risk, a lower overall mortality and probably a reduced risk of cardiovascular disease4. However, it is not appropriate to extrapolate the WHI findings from women with a mean age of 63years receiving HRT to young women with premature ovarian failure being given replacement of the oestrogen that they were designed to have anyway. This should be taken at least until the normal age of the menopause, however long that may be. A situation not dissimilar to other hormone deficient conditions such as hypothyroidism or diabetes for which appropriate hormone therapy is not questioned. 1. Jones GL, Ledger W, Mitchell C. Suspected premature menopause. BMJ, 2008; 336: 833. 2. Duff G. Committee on Safety of Medicines. Use of hormone replacement therapy in the prevention of osteoporosis. 3 December 2003. [http://medicines.mhra.gov.uk] 3. Critchley H, Gebbie A, Beral V. Menopause and Hormone Replacement. RCOG Press, London, 2004. 4. Roussouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297: 1465-77. Competing interests: I have received honoraria for lecturing and research grants from several pharmaceutical companies that produce hormone products |
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