Long term effects of hysterectomy on mortality: nested cohort study
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《英国医生杂志》
1 Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre, Aberdeen AB25 2AY
Correspondence to: L Iversen l.iversen@abdn.ac.uk
Objectives To investigate the long term risk (mean > 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy.
Design Nested cohort study.
Setting Royal College of General Practitioners' oral contraception study.
Participants 7410 women (3705 flagged at the NHS central registries for cancer and death who had a hysterectomy during the oral contraception study and 3705 who were flagged but did not have the operation).
Main outcome measures Mortality from all causes, cardiovascular disease, and cancer.
Results 623 (8.4%) women had died by the end of follow-up (308 in the hysterectomy group and 315 in the non-hysterectomy group). Older women who had had a hysterectomy had a 6% reduced risk of death compared with women of a similar age who did not have the operation (adjusted hazard ratio 0.94, 95% confidence interval 0.75 to 1.18). Compared with young women who did not have a hysterectomy those who were younger at hysterectomy had an adjusted hazard ratio for all cause mortality of 0.82 (0.65 to 1.03). Hysterectomy was not associated with a significantly altered risk of mortality from cardiovascular disease or cancer regardless of age.
Conclusion Hysterectomy did not increase the risk of death in the medium to long term.
Several new technologies may reduce the need for hysterectomy,1 yet the procedure remains common in many countries. For example, about 600 000 hysterectomies are carried out in the United States annually,2 with more than 25% of women having the operation by age 60.3 Although the number of hysterectomies carried out by the NHS in England and Scotland has fallen by 25% since 1998,4 5 around 47 500 women still had the procedure in 2002. Around 20% of women in the United Kingdom have a hysterectomy by age 55.6 Any long term effects of hysterectomy are therefore important, particularly on all cause mortality and on cardiovascular disease and cancer, the most common causes of death.
The only study to date to examine all cause mortality found no evidence of an association with hysterectomy. But the study may have misclassified hysterectomy status, and follow up was short (5.6 years).7
Studies of cardiovascular sequelae have produced conflicting evidence. One study found that hysterectomy with preservation of both ovaries was weakly associated with an increased risk of non-fatal myocardial infarction.8 Another study found that after hysterectomy with or without preservation of the ovaries, women had an increased 10 year risk of myocardial infarction or coronary death (according to the Framingham score) than women with an intact uterus and ovaries.9 Conversely, another study found no excess risk of myocardial infarction in premenopausal women after hysterectomy or after unilateral oophorectomy, although it did find an increased risk in post-menopausal women after hysterectomy with or without unilateral oophorectomy.10
Another study found an increased risk of non-genital (mainly rectal and thyroid) cancer among women after hysterectomy compared with those with an intact uterus, although the authors concluded that hysterectomy was not associated with a substantial effect on cancers in general.11 Several studies have found a reduced risk of ovarian cancer after hysterectomy without bilateral oophorectomy12 13 and a decreased risk of breast cancer after hysterectomy (with or without oophorectomy).14 15 Conversely, a study found that renal cell carcinoma was significantly more common among women who had had a hysterectomy compared with those who did not have the operation.16
Using data from the Royal College of General Practitioners' oral contraception study, we examined the long term risk of hysterectomy on mortality.
Methods
The oral contraception study
During a 14 month period starting in May 1968, 1400 general practitioners throughout the United Kingdom recruited 23 000 women who were using oral contraceptives, and a similar number of age matched women who had never done so.17 The participants' average age at recruitment was 29 years, all were married or living as married, and most (98%) were white. Baseline information collected included details of any previous use of oral contraceptives, social class (as determined by husband's occupation),18 smoking, parity, and important medical history. Every six months the doctors provided details of any hormonal preparations prescribed, pregnancies and their outcome, surgery, new episodes of illness, and deaths.
During the mid-1970s, 75% of the cohort was flagged at the NHS central registries for future deaths or cancer registrations. The other women could not be flagged because they or their doctor had left the study. The doctors stopped their observations in 1996, but the study continues to be notified of deaths and cancer registrations.
Nested cohort
We identified 3706 women with an intact uterus at recruitment to the oral contraception study who were flagged at the NHS central registries and who subsequently had a hysterectomy (surgical operations and procedures19 code R690-6, excluding R695) during the oral contraception study. These women constituted the exposed group. From the remaining 31 481 non-exposed women, we randomly identified for each woman who had a hysterectomy a woman who was born within one year of the exposed woman, had a different recruiting doctor, and was in the oral contraception study at the time of operation. Each non-exposed woman was assigned a false date for operation (pseudo-operation) of the same month and year as the hysterectomy carried out on her matched exposed woman.
For the newly assembled cohort we extracted data on social class and cigarette consumption at recruitment, parity, use of oral contraceptives and hormone replacement therapy, history of uterine fibroma (international classification of diseases, eighth revision; code 2180),20 gynaecological malignancy (1800, 1820, 1829-31, 1839, 2340, 2341, 2349), other malignancy (1400-1991, 2000-90, excluding 1800, 1820, 1829-31, and 1839), cardiovascular disease (3900-80, 4100-39, 4200-69, 4300-89, 4400-29, 4439-49, 4500, 4511, 4520, 4531, 4539, 4270-99), and hypertension (4000-40). These data were all up to and including the date of operation or pseudo-operation, except for use of hormone replacement therapy, which was up to the month before the operation or pseudo-operation. When appropriate we also extracted information on the date and cause of death. Follow-up was to 31 December 2003.
Statistical analysis
We analysed the data using SPSS version 11.5.1. When appropriate we transformed continuous variables into categorical variables. Social class was categorised as non-manual (I-IIIa), manual (IIIb-V), or other (husbands recorded as students or in the armed forces). We compared differences in characteristics between the groups using the 2 test for categorical variables, independent two sample t tests for continuous normally distributed variables, and Mann-Whitney tests for non-normally distributed variables.
For each group we generated Kaplan-Meier survival curves comparing the probability of survival from any cause, cardiovascular disease, or cancer to end of follow-up. We applied the log rank test. We examined survival curves for each of the potential confounding variables, and survival time for deviation from the proportional hazards assumption.
We carried out separate analyses for those aged below or equal to the median age at hysterectomy and those aged above. This was done because age at operation may alter the effect of hysterectomy on outcome, as young women often have hysterectomy for menstrual problems, whereas older women are more likely to have the operation for precancerous or cancerous conditions.
We then used forward conditional stepwise Cox regression to examine the relation between hysterectomy and survival time after adjustment for potential confounding. Into the initial model we entered social class, smoking, age, parity, use of oral contraceptives and hormone replacement therapy, history of malignancy, uterine fibroma, hypertension, or cardiovascular disease, and we retained variables in a stepwise manner if they hadaPvalue of 0.05 (and removed them if they hadaPvalue of 0.10).
Results
One woman died from a Mullerian tumour more than 26 years after hysterectomy. We found no further information on the death certificate or in the oral contraception study's database to explain the anomaly. We excluded this woman and her matched non-exposed comparator from the cohort, leaving 7410 women for analysis.
Hysterectomy not elsewhere classified (code R696) was the most common type of hysterectomy recorded (2526 women, 68.2%). Both groups had similar characteristics at baseline (table 1). The median age of the cohort at time of operation was 43.7 years (interquartile range 38.9-48.1 years). The hysterectomy group had a significantly higher mean parity than that of the non-hysterectomy group (2.55 (SD 1.3) versus 2.47 (SD 1.3) births, P = 0.01).
Table 1 Characteristics of hysterectomy and non-hysterectomy groups* Values are numbers (percentages) unless stated otherwise
Both groups were followed-up for a mean length of 250.3 (SD 87.1) months. By the end of follow-up, 623 (8.4%) women had died; 233 from cancer, 160 from cardiovascular disease, and 230 from other causes.
None of the Kaplan-Meier plots for survival from all cause mortality and mortality due to cardiovascular disease or cancer showed significant differences between groups (plots not shown). We found no obvious deviations from the proportional hazards assumption in the Kaplan-Meier plots for each potential confounding factor. For each of our outcomes we present hazard ratios only for variables identified important for the final model.
After stepwise adjustment, women who were younger at hysterectomy had a non-significant 18% reduction in risk of all cause mortality, compared with young women who did not have a hysterectomy (table 2). Smoking and a history of hypertension or non-gynaecological cancer were each independently associated with all cause mortality in younger women. Women who were older when they had a hysterectomy had an adjusted 6% reduced risk of all cause mortality compared with older women not having the procedure. In older women, smoking and a history of hypertension, cardiovascular disease, gynaecological cancer, or non-gynaecological cancer was independently associated with death from any cause. All cause mortality was significantly reduced among older women who had used oral contraceptives.
Table 2 Factors associated with all cause mortality in women who had or had not had hysterectomy in relation to median age*
Hysterectomy was not associated with a significantly altered risk of mortality due to cardiovascular disease regardless of age (table 3). Smoking and a history of cardiovascular disease or non-gynaecological cancer among younger women was associated with future death from cardiovascular disease. Among older women, smoking and a history of hypertension or cardiovascular disease was associated with an increased risk of death from cardiovascular disease. The risk of death from cardiovascular disease was 40% lower among older women who had ever used oral contraceptives compared with never users (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.92).
Table 3 Factors associated with death from cardiovascular disease in women who had or had not had hysterectomy in relation to median age*
Women who were younger at operation had a non-significant reduced risk of death from cancer than similarly aged women who did not have a hysterectomy (adjusted hazard ratio 0.81, 0.55 to 1.19; table 4). A history of non-gynaecological cancer, however, was associated with a significantly increased risk of death from cancer. In contrast, women who were older when they had their hysterectomy had almost the same risk of death from cancer as similarly aged women not having the procedure (adjusted hazard ratio 1.02, 0.69 to 1.49). In the older group, death from cancer was significantly more likely among women who smoked or had a history of gynaecological or non-gynaecological cancer, and was lower in previous users of oral contraception.
Table 4 Factors associated with death from cancer in women who had or not had hysterectomy in relation to median age*
Discussion
Bongers MY, Mol BW, Br?lmann HA. Current treatment of dysfunctional uterine bleeding. Maturitas 2004;47: 159-74.
Keshavarz H, Hillis SD, Kieke BA, Marchbanks PA. Hysterectomy surveillance—United States, 1994-1999. In: CDC surveillance summaries (Jul 12). MMWR 2002;51(SS-5): 1-8.
Lepine LA, Hillis SD, Marchbanks PA, Koonin LM, Morrow B, Kieke BA, et al. Hysterectomy surveillance—United States, 1980-1993. In: CDC surveillance summaries (Aug 8). MMWR 1997;46(SS-4): 1-15.
Department of Health. Table 4. Main operations summary (for years 1998-99 through 2002-03). In: Hospital episode statistics. www.dh.gov.uk/PublicationsAndStatistics/HospitalEpisodeStatistics/fs/en (accessed 4 Jul 2004).
ISD Scotland. Hospital operations/procedures. Hysterectomy. www.isdscotland.org/acute_activity/surgical.asp (accessed 21 Aug 2004).
Vessey MP, Villard-Mackintosh L, McPherson K, Coulter A, Yeates D. The epidemiology of hysterectomy: findings in a large cohort study. Br J Obstet Gynaecol 1992;99: 402-7.
Bush TL, Cowan LD, Barrett-Connor E, Criqui MH, Karon JM, Wallace RB, et al. Estrogen use and all-cause mortality. Preliminary results from the lipid research clinics program follow-up study. JAMA 1983;249: 903-6.
Rosenberg L, Hennekens CH, Rosner B, Belanger C, Rothman KJ, Speizer FE. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol 1981;139: 47-51.
Hsia J, Barad D, Margolis K, Rodabough R, McGovern PG, Limacher MC, et al. Usefulness of prior hysterectomy as an independent predictor of Framingham risk score (the women's health initiative). Am J Cardiol 2003;92: 264-9.
Falkeborn M, Schairer C, Naessén T, Persson I. Risk of myocardial infarction after oophorectomy and hysterectomy. J Clin Epidemiol 2000;53: 832-7.
Luoto R, Auvinen A, Pukkala E, Hakama M. Hysterectomy and subsequent risk of cancer. Int J Epidemiol 1997;26: 476-83.
Green A, Purdie D, Bain C, Siskind V, Russell P, Quinn M, et al. Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Int J Cancer 1997;7: 948-51.
Riman T, Persson I, Nilsson S. Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence. Clin Endocrinol 1998;49: 695-707.
Kreiger N, Sloan M, Cotterchio M, Kirsh V. The risk of breast cancer following reproductive surgery. Eur J Cancer 1999;35: 97-101.
Parazzini F, Braga C, La Vecchia C, Negri E, Acerboni S, Franceschi S. Hysterectomy, oophorectomy in premenopause and risk of breast cancer. Obstet Gynecol 1997;90: 453-6.
Gago-Dominguez M, Castelao JE, Yuan J-M, Ross RK, Yu MC. Increased risk of renal cell carcinoma subsequent to hysterectomy. Cancer Epidemiol Biomark Prevent 1999;8: 999-1003.
Royal College of General Practitioners. Oral contraceptives and health. Tunbridge Wells: Pitman Medical, 1974.
General Registrar Office. Classification of occupations. London: HMSO, 1966.
General Register Office. Classification of surgical operations, 2nd revision. London: GRO, 1969.
World Health Organization. International classification of diseases, injuries and causes of death, 8th revision. Geneva: WHO, 1967.
Beral V, Hermon C, Kay C, Hannaford PC, Darby S, Reeves G. Mortality in relation to method of follow-up in the Royal College of General Practitioners' oral contraception study. In: Hannaford PC, Webb AMC, eds. Evidence-guided prescribing of the pill. Lancashire: Parthenon; 1996: 327-39.
Beral V, Banks E, Reeves G. Evidence from randomised trials on the long-term effects of hormone replacement therapy. Lancet 2002;360: 942-4.
Moorhead T, Hannaford P, Warskyj M. Prevalence and characteristics associated with use of hormone replacement therapy in Britain. Br J Obstet Gynaecol 1997;104: 290-7.
Office for National Statistics. Smoking. In: Living in Britain. The 2002 general household survey. www.statistics.gov.uk/lib2002/downloads/smoking.pdf (accessed 25 Aug 2004).
Owen-Smith V, Hannaford PC, Warskyj M, Ferry S, Kay CR. Effects of changes in smoking status on risk estimates for myocardial infarction among women recruited for the Royal College of General Practitioners' oral contraception study in the UK. J Epidemiol Community Health 1998;52: 420-4.
Irwin KL, Weiss NS, Lee NC, Peterson HB. Tubal sterilisation, hysterectomy, and the subsequent occurrence of epithelial ovarian cancer. Am J Epidemiol 1991;134: 362-9.(Lisa Iversen, research fellow1, Philip C)
Correspondence to: L Iversen l.iversen@abdn.ac.uk
Objectives To investigate the long term risk (mean > 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy.
Design Nested cohort study.
Setting Royal College of General Practitioners' oral contraception study.
Participants 7410 women (3705 flagged at the NHS central registries for cancer and death who had a hysterectomy during the oral contraception study and 3705 who were flagged but did not have the operation).
Main outcome measures Mortality from all causes, cardiovascular disease, and cancer.
Results 623 (8.4%) women had died by the end of follow-up (308 in the hysterectomy group and 315 in the non-hysterectomy group). Older women who had had a hysterectomy had a 6% reduced risk of death compared with women of a similar age who did not have the operation (adjusted hazard ratio 0.94, 95% confidence interval 0.75 to 1.18). Compared with young women who did not have a hysterectomy those who were younger at hysterectomy had an adjusted hazard ratio for all cause mortality of 0.82 (0.65 to 1.03). Hysterectomy was not associated with a significantly altered risk of mortality from cardiovascular disease or cancer regardless of age.
Conclusion Hysterectomy did not increase the risk of death in the medium to long term.
Several new technologies may reduce the need for hysterectomy,1 yet the procedure remains common in many countries. For example, about 600 000 hysterectomies are carried out in the United States annually,2 with more than 25% of women having the operation by age 60.3 Although the number of hysterectomies carried out by the NHS in England and Scotland has fallen by 25% since 1998,4 5 around 47 500 women still had the procedure in 2002. Around 20% of women in the United Kingdom have a hysterectomy by age 55.6 Any long term effects of hysterectomy are therefore important, particularly on all cause mortality and on cardiovascular disease and cancer, the most common causes of death.
The only study to date to examine all cause mortality found no evidence of an association with hysterectomy. But the study may have misclassified hysterectomy status, and follow up was short (5.6 years).7
Studies of cardiovascular sequelae have produced conflicting evidence. One study found that hysterectomy with preservation of both ovaries was weakly associated with an increased risk of non-fatal myocardial infarction.8 Another study found that after hysterectomy with or without preservation of the ovaries, women had an increased 10 year risk of myocardial infarction or coronary death (according to the Framingham score) than women with an intact uterus and ovaries.9 Conversely, another study found no excess risk of myocardial infarction in premenopausal women after hysterectomy or after unilateral oophorectomy, although it did find an increased risk in post-menopausal women after hysterectomy with or without unilateral oophorectomy.10
Another study found an increased risk of non-genital (mainly rectal and thyroid) cancer among women after hysterectomy compared with those with an intact uterus, although the authors concluded that hysterectomy was not associated with a substantial effect on cancers in general.11 Several studies have found a reduced risk of ovarian cancer after hysterectomy without bilateral oophorectomy12 13 and a decreased risk of breast cancer after hysterectomy (with or without oophorectomy).14 15 Conversely, a study found that renal cell carcinoma was significantly more common among women who had had a hysterectomy compared with those who did not have the operation.16
Using data from the Royal College of General Practitioners' oral contraception study, we examined the long term risk of hysterectomy on mortality.
Methods
The oral contraception study
During a 14 month period starting in May 1968, 1400 general practitioners throughout the United Kingdom recruited 23 000 women who were using oral contraceptives, and a similar number of age matched women who had never done so.17 The participants' average age at recruitment was 29 years, all were married or living as married, and most (98%) were white. Baseline information collected included details of any previous use of oral contraceptives, social class (as determined by husband's occupation),18 smoking, parity, and important medical history. Every six months the doctors provided details of any hormonal preparations prescribed, pregnancies and their outcome, surgery, new episodes of illness, and deaths.
During the mid-1970s, 75% of the cohort was flagged at the NHS central registries for future deaths or cancer registrations. The other women could not be flagged because they or their doctor had left the study. The doctors stopped their observations in 1996, but the study continues to be notified of deaths and cancer registrations.
Nested cohort
We identified 3706 women with an intact uterus at recruitment to the oral contraception study who were flagged at the NHS central registries and who subsequently had a hysterectomy (surgical operations and procedures19 code R690-6, excluding R695) during the oral contraception study. These women constituted the exposed group. From the remaining 31 481 non-exposed women, we randomly identified for each woman who had a hysterectomy a woman who was born within one year of the exposed woman, had a different recruiting doctor, and was in the oral contraception study at the time of operation. Each non-exposed woman was assigned a false date for operation (pseudo-operation) of the same month and year as the hysterectomy carried out on her matched exposed woman.
For the newly assembled cohort we extracted data on social class and cigarette consumption at recruitment, parity, use of oral contraceptives and hormone replacement therapy, history of uterine fibroma (international classification of diseases, eighth revision; code 2180),20 gynaecological malignancy (1800, 1820, 1829-31, 1839, 2340, 2341, 2349), other malignancy (1400-1991, 2000-90, excluding 1800, 1820, 1829-31, and 1839), cardiovascular disease (3900-80, 4100-39, 4200-69, 4300-89, 4400-29, 4439-49, 4500, 4511, 4520, 4531, 4539, 4270-99), and hypertension (4000-40). These data were all up to and including the date of operation or pseudo-operation, except for use of hormone replacement therapy, which was up to the month before the operation or pseudo-operation. When appropriate we also extracted information on the date and cause of death. Follow-up was to 31 December 2003.
Statistical analysis
We analysed the data using SPSS version 11.5.1. When appropriate we transformed continuous variables into categorical variables. Social class was categorised as non-manual (I-IIIa), manual (IIIb-V), or other (husbands recorded as students or in the armed forces). We compared differences in characteristics between the groups using the 2 test for categorical variables, independent two sample t tests for continuous normally distributed variables, and Mann-Whitney tests for non-normally distributed variables.
For each group we generated Kaplan-Meier survival curves comparing the probability of survival from any cause, cardiovascular disease, or cancer to end of follow-up. We applied the log rank test. We examined survival curves for each of the potential confounding variables, and survival time for deviation from the proportional hazards assumption.
We carried out separate analyses for those aged below or equal to the median age at hysterectomy and those aged above. This was done because age at operation may alter the effect of hysterectomy on outcome, as young women often have hysterectomy for menstrual problems, whereas older women are more likely to have the operation for precancerous or cancerous conditions.
We then used forward conditional stepwise Cox regression to examine the relation between hysterectomy and survival time after adjustment for potential confounding. Into the initial model we entered social class, smoking, age, parity, use of oral contraceptives and hormone replacement therapy, history of malignancy, uterine fibroma, hypertension, or cardiovascular disease, and we retained variables in a stepwise manner if they hadaPvalue of 0.05 (and removed them if they hadaPvalue of 0.10).
Results
One woman died from a Mullerian tumour more than 26 years after hysterectomy. We found no further information on the death certificate or in the oral contraception study's database to explain the anomaly. We excluded this woman and her matched non-exposed comparator from the cohort, leaving 7410 women for analysis.
Hysterectomy not elsewhere classified (code R696) was the most common type of hysterectomy recorded (2526 women, 68.2%). Both groups had similar characteristics at baseline (table 1). The median age of the cohort at time of operation was 43.7 years (interquartile range 38.9-48.1 years). The hysterectomy group had a significantly higher mean parity than that of the non-hysterectomy group (2.55 (SD 1.3) versus 2.47 (SD 1.3) births, P = 0.01).
Table 1 Characteristics of hysterectomy and non-hysterectomy groups* Values are numbers (percentages) unless stated otherwise
Both groups were followed-up for a mean length of 250.3 (SD 87.1) months. By the end of follow-up, 623 (8.4%) women had died; 233 from cancer, 160 from cardiovascular disease, and 230 from other causes.
None of the Kaplan-Meier plots for survival from all cause mortality and mortality due to cardiovascular disease or cancer showed significant differences between groups (plots not shown). We found no obvious deviations from the proportional hazards assumption in the Kaplan-Meier plots for each potential confounding factor. For each of our outcomes we present hazard ratios only for variables identified important for the final model.
After stepwise adjustment, women who were younger at hysterectomy had a non-significant 18% reduction in risk of all cause mortality, compared with young women who did not have a hysterectomy (table 2). Smoking and a history of hypertension or non-gynaecological cancer were each independently associated with all cause mortality in younger women. Women who were older when they had a hysterectomy had an adjusted 6% reduced risk of all cause mortality compared with older women not having the procedure. In older women, smoking and a history of hypertension, cardiovascular disease, gynaecological cancer, or non-gynaecological cancer was independently associated with death from any cause. All cause mortality was significantly reduced among older women who had used oral contraceptives.
Table 2 Factors associated with all cause mortality in women who had or had not had hysterectomy in relation to median age*
Hysterectomy was not associated with a significantly altered risk of mortality due to cardiovascular disease regardless of age (table 3). Smoking and a history of cardiovascular disease or non-gynaecological cancer among younger women was associated with future death from cardiovascular disease. Among older women, smoking and a history of hypertension or cardiovascular disease was associated with an increased risk of death from cardiovascular disease. The risk of death from cardiovascular disease was 40% lower among older women who had ever used oral contraceptives compared with never users (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.92).
Table 3 Factors associated with death from cardiovascular disease in women who had or had not had hysterectomy in relation to median age*
Women who were younger at operation had a non-significant reduced risk of death from cancer than similarly aged women who did not have a hysterectomy (adjusted hazard ratio 0.81, 0.55 to 1.19; table 4). A history of non-gynaecological cancer, however, was associated with a significantly increased risk of death from cancer. In contrast, women who were older when they had their hysterectomy had almost the same risk of death from cancer as similarly aged women not having the procedure (adjusted hazard ratio 1.02, 0.69 to 1.49). In the older group, death from cancer was significantly more likely among women who smoked or had a history of gynaecological or non-gynaecological cancer, and was lower in previous users of oral contraception.
Table 4 Factors associated with death from cancer in women who had or not had hysterectomy in relation to median age*
Discussion
Bongers MY, Mol BW, Br?lmann HA. Current treatment of dysfunctional uterine bleeding. Maturitas 2004;47: 159-74.
Keshavarz H, Hillis SD, Kieke BA, Marchbanks PA. Hysterectomy surveillance—United States, 1994-1999. In: CDC surveillance summaries (Jul 12). MMWR 2002;51(SS-5): 1-8.
Lepine LA, Hillis SD, Marchbanks PA, Koonin LM, Morrow B, Kieke BA, et al. Hysterectomy surveillance—United States, 1980-1993. In: CDC surveillance summaries (Aug 8). MMWR 1997;46(SS-4): 1-15.
Department of Health. Table 4. Main operations summary (for years 1998-99 through 2002-03). In: Hospital episode statistics. www.dh.gov.uk/PublicationsAndStatistics/HospitalEpisodeStatistics/fs/en (accessed 4 Jul 2004).
ISD Scotland. Hospital operations/procedures. Hysterectomy. www.isdscotland.org/acute_activity/surgical.asp (accessed 21 Aug 2004).
Vessey MP, Villard-Mackintosh L, McPherson K, Coulter A, Yeates D. The epidemiology of hysterectomy: findings in a large cohort study. Br J Obstet Gynaecol 1992;99: 402-7.
Bush TL, Cowan LD, Barrett-Connor E, Criqui MH, Karon JM, Wallace RB, et al. Estrogen use and all-cause mortality. Preliminary results from the lipid research clinics program follow-up study. JAMA 1983;249: 903-6.
Rosenberg L, Hennekens CH, Rosner B, Belanger C, Rothman KJ, Speizer FE. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol 1981;139: 47-51.
Hsia J, Barad D, Margolis K, Rodabough R, McGovern PG, Limacher MC, et al. Usefulness of prior hysterectomy as an independent predictor of Framingham risk score (the women's health initiative). Am J Cardiol 2003;92: 264-9.
Falkeborn M, Schairer C, Naessén T, Persson I. Risk of myocardial infarction after oophorectomy and hysterectomy. J Clin Epidemiol 2000;53: 832-7.
Luoto R, Auvinen A, Pukkala E, Hakama M. Hysterectomy and subsequent risk of cancer. Int J Epidemiol 1997;26: 476-83.
Green A, Purdie D, Bain C, Siskind V, Russell P, Quinn M, et al. Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Int J Cancer 1997;7: 948-51.
Riman T, Persson I, Nilsson S. Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence. Clin Endocrinol 1998;49: 695-707.
Kreiger N, Sloan M, Cotterchio M, Kirsh V. The risk of breast cancer following reproductive surgery. Eur J Cancer 1999;35: 97-101.
Parazzini F, Braga C, La Vecchia C, Negri E, Acerboni S, Franceschi S. Hysterectomy, oophorectomy in premenopause and risk of breast cancer. Obstet Gynecol 1997;90: 453-6.
Gago-Dominguez M, Castelao JE, Yuan J-M, Ross RK, Yu MC. Increased risk of renal cell carcinoma subsequent to hysterectomy. Cancer Epidemiol Biomark Prevent 1999;8: 999-1003.
Royal College of General Practitioners. Oral contraceptives and health. Tunbridge Wells: Pitman Medical, 1974.
General Registrar Office. Classification of occupations. London: HMSO, 1966.
General Register Office. Classification of surgical operations, 2nd revision. London: GRO, 1969.
World Health Organization. International classification of diseases, injuries and causes of death, 8th revision. Geneva: WHO, 1967.
Beral V, Hermon C, Kay C, Hannaford PC, Darby S, Reeves G. Mortality in relation to method of follow-up in the Royal College of General Practitioners' oral contraception study. In: Hannaford PC, Webb AMC, eds. Evidence-guided prescribing of the pill. Lancashire: Parthenon; 1996: 327-39.
Beral V, Banks E, Reeves G. Evidence from randomised trials on the long-term effects of hormone replacement therapy. Lancet 2002;360: 942-4.
Moorhead T, Hannaford P, Warskyj M. Prevalence and characteristics associated with use of hormone replacement therapy in Britain. Br J Obstet Gynaecol 1997;104: 290-7.
Office for National Statistics. Smoking. In: Living in Britain. The 2002 general household survey. www.statistics.gov.uk/lib2002/downloads/smoking.pdf (accessed 25 Aug 2004).
Owen-Smith V, Hannaford PC, Warskyj M, Ferry S, Kay CR. Effects of changes in smoking status on risk estimates for myocardial infarction among women recruited for the Royal College of General Practitioners' oral contraception study in the UK. J Epidemiol Community Health 1998;52: 420-4.
Irwin KL, Weiss NS, Lee NC, Peterson HB. Tubal sterilisation, hysterectomy, and the subsequent occurrence of epithelial ovarian cancer. Am J Epidemiol 1991;134: 362-9.(Lisa Iversen, research fellow1, Philip C)