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Quality of life improved by menopausal hormones?
- Martina Dören (22 August 2008)
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No minimal benefits of HRT can justify increasing cancers and numerous serious illnesses
- Ellen CG Grant (26 August 2008)
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Martina Dören, Profesor of Women´s Health Charité-Universitätsmedizin Berlin, 12167 Berlin, Germany
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It is certainly an achievement to obtain data on quality of life (QoL) of postmenopausal women in the context of a large randomized placebo -controlled trial (1). However, according to previous, yet unmentioned extensive systematic reviews, QoL not necessarily improves in women with flushes taking menopausal hormones (2-6). These sources also reflect how diverse concepts are to determine what constitutes QoL and what measures are apppropriate to capture QoL and its potential changes. "Background literature and guidelines" (quote from reference 1) on QoL are of limited value, as these references (7, 8) are not data driven to conclude that women with debilitating menopause symptoms benefit the most from MHT. Furthermore,it is at least questionable whether the risk profile for combined MHT, also used in this study (1) is more favourable in younger women (9, 10), due to methodological shortcomings of these reviews (11). Thus, it remains challenging to define what QoL actually means for menopausal women, and to develop measures to capture this construct and its potential changes. References 1. Welton AJ, Vickers MR, Kim J et al. Health related quality of life after combined hormone replacement therapy: randomised controled trial. BMJ 2008;337; doi:10.1136/BMJ.a1190 2. Nelson HD, Haney E, Humphrey L et al. Management of Menopause-Related Symptoms. Evidence Report/Technology Assessment No. 120. AHRQ Publication No. 05-E016-2. Rockville, MD: Agency for Healthcare Research and Quality. March 2005; http://www.ahrq.gov/downloads/pub/evidence/pdf/menopause/menopaus.pdf 3. Farquhar CM, Marjoribanks J, Lethaby A et al. and the Cochrane HT Study Group. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD004143. 4.MacLennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD002978. 5. Haines CJ, Fan Yim S, Chung TKH et al. A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being and quality of life in postmenopausal Chinsese women. Maturitas 2003;44:207–14. 6. Bech P, Munk-Jensen N, Obel EB et al. Combined versus sequential hormone replacement therapy: a double blind placebo-controlled study on quality of life-related measures. Psychotherapy and Psychosomatics 1998;67:259–65 7. Zethraeus N, Johannesson M, Henriksson P et al. The impact of hormone replacement therapy on quality of life and willingness to pay. Br Obstet Gynaecol 1997;104:1191-1195 8. Pines A, Sturdee DW, Birkhauser MH et al. Climacteric 2007;10:181-194 9. Salpeter SR, Walsh JME, Greyber E et al. Mortality associated with hormone replacement therapy in younger and older women. J Gen Intern Med 2004;19:791-804 10. Salpeter SR, Walsh JME, Greyber E et al. Brief report: Coronary heart disease events associated with hormone therapy in younger and older women: a meta-analysis. J Gen Int Med 2006;21:363-366 11. Dören M, Greiser EG. Menopause 2008;15:204-205 (Letter to the Editor) Competing interests: None declared |
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Ellen CG Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU
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In the WISDOM HRT trial, overall health related quality of life measures were reduced at 4 and 14 weeks of HRT use rather than increased (Table 3).1 Data was unavailable for 2 out of 3 women when the trial was terminated at a year but there were 6 deaths in HRT users compared with 2 in placebo takers. Twice as many HRT takers had stopped by 40 weeks, mostly because of large increases in endometrial bleeding (hazard ratio 13.4) and breast tenderness. The authors already reported about a seven- fold increase in major cardiovascular and venous thromboembolic events.2 Even so, they now want the current HRT guidelines revisited.1 In the light of these results, it would be irresponsible to think that any use of HRT is justifiable. How can minor improvements in a few symptoms such as flushing compare with the continued use of highest level carcinogens? There have been huge increases in breast and other cancers as hormone use has increased over the last 60 years.3,4 There were no differences in most of the 28 symptoms listed at one year because most of the women with troublesome side effects had already stopped. A much vaunted reduction in hot flushes, night sweats, insomnia and aches and pains was presumably due to HRT steroid suppression of vasomotor activity in the remaining women. The authors do not distinguish between the effects of different dose combinations on symptoms. Conjugated equine oestrogens given as a 0.625 mg dose plus 2.5 mg of medroxyprogesterone acetate reduced vaginal dryness but increased vaginal discharge and endometrial bleeding. 38% of HRT takers were unblinded because of bleeding compared with 4% of placebo takers. The progestogen dose was increased to 5 mg to reduce the oestrogen balance and bleeding but the risk of vaginal dryness and depression would increase. Basic physiological hormonal mechanisms do not alter however data is manipulated in epidemiological studies.5 We reported in 1968 that oestrogens tend to elevate mood and sexual interest while progestogens can cause depression and loss of libido. These effects coincide with lower and higher monoamine oxidase (MAO) activities in normal and treated cycles.6 More oestrogenic progestogen-dominant combinations could induce sudden changes in sexual thoughts including violence and aggression, especially in the combinations with marked endometrial vascular changes. Increases in suicides and violent deaths have been shown in HRT users.7 Such mental changes are not a sign of improved sexual health. Vasomotor symptoms such as flushing have many causes including adverse reactions to tobacco, alcohol and coffee, toxic metal sensitivities, and food and chemical allergies which are increased by nutritional deficiencies (the latter may be associated with the Pill, HRT and hormonal fertility treatments). They are warning symptoms and can be more safely treated by avoidance of precipitants and by monitored nutritional supplementation than by taking immunosuppressive, carcinogenic, thrombogenic and psychoactive steroids. It is irresponsible to continue to promote HRT or to expect that a single pill can solve complicated medical problems. 1 Welton AJ, Vickers MR, Kim J et al. Health related quality of life after combined hormone replacement therapy: randomized controlled trial. BMJ 2008;337:a1190 2 Vickers MR, MacLennan AH, Lawton B, et al. Main morbidities recorded in the women’s international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ 2007;335:239. 3 IARC. Combined estrogen-progestogen contraceptives and combined estrogen-progestogen menopausal therapy. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 2007; Volume 91 4 Grant ECG. Increases in breast cancer incidence http://bmj.com/cgi/eletters/328/7445/921#55298, 1 Apr 2004. 5 Grant ECG. Hormone balance of oral contraceptives. J Obstet Gynaecol Br Commonw 1967;74:908-18. 6 Grant ECG, Pryce-Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. BMJ 1968 28; 3:777-780. 7 Price EH. Increased risk of mental illness and suicide in oral contracrptive and hormone replacement therapy studies. J Nutr Environ Med 1998;8:121-128. Competing interests: None declared |
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