In this study, hysterectomy was not associated with an increased long term risk of death from any cause, cardiovascular disease, or cancer.
Information on hysterectomy and potential confounding variables was provided prospectively by doctors participating in the oral contraception study. Information bias would therefore have occurred if they reported information differently on the basis of a woman's hysterectomy status. Such bias is, however, unlikely as the purpose of the oral contraception study is to examine the effects of oral contraception rather than those of hysterectomy. Information about cause of death was mainly based on information from death certificates, often without post mortem. This may have affected cause specific analyses, although many certificates were based on recent illness before death, and any inaccuracies are likely to be non-differential between the groups. The mean length of follow-up was more than 20 years, enabling us to investigate medium to long term risks of mortality associated with hysterectomy, based on a substantial number of deaths.
Some women in the original oral contraception study cohort were not flagged, mainly because they left the study before flagging occurred. We have shown previously that the large losses to general practitioner follow-up incurred by the main study have not substantially biased the results for overall mortality.21
The previous analysis also showed that women in the oral contraception study tend to be healthier than the general population.21
Thus, although comparisons within the group are valid, caution should be exercised when extrapolating the results to all women who have had a hysterectomy. Other studies are needed to confirm or refute our findings.
Our results may have been affected by residual confounding, partly from the imprecise ascertainment of some factors. For example, social class was evaluated in three broad categories, and at one point in time—possibly when effects were not most influential. Furthermore, some factors were not measured at all—for example, use of hormone replacement therapy after hysterectomy, which may affect the risk of subsequent mortality. Information about use of hormone replacement therapy after hysterectomy was not available for women who left the main oral contraception study after the operation. Current understanding, however, is that hormone replacement therapy may be associated with a balance of higher risk of serious disease (such as breast cancer, stroke, and pulmonary embolism) than benefits (such as reduced risk of colorectal cancer and fractures of the neck of the femur).22
More women who have had a hysterectomy than those who have not use hormone replacement therapy.23
It is unlikely, therefore that the reduced risk of all cause mortality among the hysterectomy group was due to confounding from subsequent use of hormone replacement therapy.
Smoking status was based on information obtained at recruitment to the oral contraception study. The status of many women is likely to have changed. Assuming a pattern similar to national trends24
(that is, substantially more middle aged women stopping smoking than starting), the prevalence of smoking among the cohort will have fallen. This was the case in a subset of women in the oral contraception study who participated in a health survey in the mid-1990s.25
The effects of smoking, therefore, are likely to be underestimated. Since we found no significant relation between smoking and hysterectomy, however, our measurement of smoking is unlikely to have affected the risk estimates between hysterectomy and subsequent mortality.
The finding of a lower risk of death among ever users of oral contraceptives in women who were older when they had their hysterectomy (but not younger) was unexpected, and is not readily explained. It may be a chance finding.
We have been able to find only one study that looked at the long term risk of all cause mortality after hysterectomy, and that found no overall effect.7
In our study, hysterectomy was not associated with a significantly altered risk of death due to cardiovascular disease. Other studies have examined non-fatal cardiovascular outcomes, with conflicting results.8,10
Some studies have considered the effects of oophorectomy with hysterectomy. We do not know how many of the women in our study with hysterectomy had a concurrent unilateral or bilateral oophorectomy. If hysterectomy with oophorectomy has different effects from hysterectomy without oophorectomy, the effects of different combinations will have been masked. Even if this information was available, it is often difficult to know how many women become menopausal soon after hysterectomy. We were therefore unable to carry out separate analyses using menopausal status.
Previous studies have looked at risk of specific cancers such as ovarian and breast cancer after hysterectomy, rather than all cancer mortality. The reduced risk of ovarian cancer after hysterectomy found in one study26
may have been due to a screening effect, as surgery provides an opportunity to detect abnormal ovaries. Such effects would persist for as long as it takes visible premalignant abnormalities to produce symptoms of cancer.26
This bias could have occurred in our study, although it is not clear how long such a protective effect might have influenced our risk estimates of all cancer mortality.
Most women in our study had a hysterectomy for non-malignant reasons. They would no longer be at risk of endometrial, cervical, or ovarian cancer if they also had bilateral oophorectomy. Cancers comprise more than a third of deaths in middle aged women, with many at gynaecological sites. The observed lower risk of death (although not statistically significant) from all causes and from cancer among young women who had a hysterectomy was therefore unsurprising. Our results ignore any non-fatal, physical, psychological, and social costs to the individual after hysterectomy. The results should therefore not be used to argue that hysterectomy be used as a public health measure to reduce women's risk of death later in life. Instead, patients should be reassured that hysterectomy will not put their lives at risk later in life.
What is already known on this topic
Hysterectomy is a common operation
Little is known about the long term effects of hysterectomy
What this study adds
Hysterectomy did not significantly increase a woman's risk of mortality from all causes, cardiovascular disease, and cancer