This study shows that of the factors considered here, the main determinants of the incidence of hip fracture are age and menopausal status. At around the time of menopause, when women are aged 50–54 y, the incidence of hip fracture was significantly higher in postmenopausal than in premenopausal women. There are too few premenopausal women aged 55 y and older to permit valid comparison. Previous publications directly observing the relationship between hip fracture risk in relation to menopause generally involve older, postmenopausal women 
, and we were unable to locate any publications comparing hip fracture rates between premenopausal and postmenopausal women of a similar age. The rapid and substantial impact of menopause on the risk of hip fracture is likely to relate to the large reductions in bone mineral density that occur in the first few years after the menopause 
, which follow the rapid reductions in circulating levels of estradiol and related hormones occurring at that time. This finding is in keeping with the established protective effect of both endogenous 
and exogenous estrogens on fracture incidence 
In postmenopausal women the incidence of hip fracture increases rapidly with age, with incidence rates in women aged 70–74 y being about seven times higher than at 50–54 (). The fact that hip fracture incidence increases rapidly with age in middle-aged and older women is well established 
Our finding of no significant difference in hip fracture incidence between postmenopausal women whose menopause resulted from a bilateral oophorectomy compared to a natural menopause, after adjusting for age and other relevant factors, is consistent with the published findings from other studies 
, however the relatively wide CI means that a small effect on risk remains possible.
We found that women's age at menopause had, at most, a weak effect on the risk of hip fracture in postmenopausal women of a given age. Women who had a menopause before age 45 differ from those with a later menopause in many important respects; they are more likely to have a history of various illnesses as well as being more likely to smoke and to come from the lower socioeconomic groups. Statistical adjustment for medical history, as well as smoking and socioeconomic group, substantially reduced the RR estimates for a menopause before age 45 versus at age 50 or older that were adjusted by age and region only (from 1.5 to 1.2), suggesting that these are important confounding factors. Our findings are in keeping with previous studies that have shown that the vast majority of hip fractures are the result of a fall 
. No information was collected on some other risk factors for hip fracture, including previous falls and sensory impairment and there was limited information on previous fractures. This lack of information and the fact that the variables that were adjusted for are measured with some error makes it likely that there is residual confounding in the adjusted estimate.
Despite the widespread belief that early menopause is a long term risk factor for osteoporosis and fracture 
, the published evidence is in keeping with our finding of little, if any, effect of age at menopause on the risk of hip fracture in postmenopausal women, over and above the strong effect of women's actual age. We reviewed published results from studies with relevant information on age at menopause and the risk of hip fracture. Eligible studies that included at least 50 cases were identified through PubMed and the Web of Science, using search terms incorporating “menopause” and “fracture,” through searches for articles citing a well known article on menopause and hip fracture 
, and through hand searches of reference lists of identified articles. Results were collated and, where possible, were summarised as the adjusted RR and 95% CI for hip fracture in women aged <45 y at menopause, compared to women aged 45 y or older at menopause. A total of 12 eligible studies were identified, varying in size from 56 
to 2,086 
hip fracture cases 
. Studies differed in their adjustment for age, socioeconomic factors, use of hormone replacement therapy, smoking, reproductive factors, body mass index, physical activity, and mental status, and only two studies adjusted for comorbidity 
. Among the studies with relevant information, the estimated RR for hip fracture in women with menopause aged <45 y versus 45 y or older ranged from 1.02 to 1.30 
, with no studies reporting a significant difference. These point estimates are consistent with the findings of the current study.
Data on bone mineral density suggest that once women are postmenopausal, the age at which they become postmenopausal has only a small effect, which is in keeping with our and other findings regarding the effect of age at menopause and hip fracture incidence. Previous studies have shown that bone mineral density falls most rapidly in the immediate perimenopausal period and less rapidly postmenopausally 
, with the rate of bone loss declining within around 3 y after menopause 
. In general it appears that bone mineral density may be reduced in women with early versus late menopause only in the years immediately following menopause 
, but that any difference diminishes with increasing age and is nonexistent or small after the age of 65 y 
. Our findings on the incidence of hip fracture in relation to menopause are generally in line with the observed effects of menopause on bone mineral density, as we found about a 2-fold difference in hip fracture incidence between premenopausal and postmenopausal women aged 50–54 y (and there are large differences in bone mineral density between such women), but little or no effect of age at menopause on hip fracture risk in postmenopausal women (and age at menopause appears to have only a weak effect, if any, on long-term bone mineral density in postmenopausal women).
Virtually all hip fractures lead to hospitalisation and occurrences of a first hip fracture in a defined time period are captured well using NHS hospital admission data 
. Furthermore, the limited data available indicate a relatively high level of accuracy of ICD coding of hip fractures or related diagnoses from hospital discharge data 
. All participants are registered with the NHS and were recruited from NHS screening services. Users of such services are likely to use other NHS health services, including NHS hospitals. Use of private hospitals in the UK is limited 
, and many of these admissions are also included in the NHS hospital admission data. Ascertainment of hip fractures occurring in Million Women Study participants using routine NHS hospital data should therefore be virtually complete.
This study has a number of strengths. It is the only study to date, to our knowledge, to combine prospectively gathered data on menopause, including data on premenopausal and perimenopausal women, with complete follow-up for incident hip fractures and adjustment for a wide range of potential confounding factors, including smoking, parity, and comorbidity. Analyses were restricted to women who had never used hormone replacement therapy, to avoid biases resulting from the close relationships between hormone replacement therapy, menopausal status 
, age at menopause 
, and hip fracture 
. Since serum measures relating to menopausal status, such as serum follicle-stimulating hormone, were not available for study participants, classification of menopausal status relied on self-reported information. Women were considered perimenopausal if they reported irregular menses attributed to menopause, which means that a proportion of women who had regular periods right up until menopause will have been classified as premenopausal during this time. However, the follow-up data on perimenopausal women indicate that such misclassification is likely to be minimal. The inclusion of a small number of perimenopausal women in with premenopausal women may have diluted the effect of menopausal status on hip fracture, yielding more conservative results. Data on other aspects of menopause and potential confounding factors in this study are also self reported. Since all exposure data are prospective, any misclassification should not be biased by the outcome but would tend to dilute the magnitude of any effect. Although Million Women Study participants have been shown to be similar to the general population 
, they are sampled from women attending breast cancer screening in the UK and this should be borne in mind when interpreting study results. While some subgroup comparisons had small numbers of events in each category (), this is still one of the largest prospective studies to investigate this issue.
What are the clinical implications of these findings? The findings suggest that reduced estrogen around the time of menopause leads to decreased bone mineral density, which in turn increases the risk of hip fracture, relative to premenopausal women. However, hip fracture is rare at the age when most women go through the menopause and increases about 7-fold from age 50–54 to age 70–74. Our findings show that age is far more important than factors relating to menopause in determining the risk of hip fracture. Hence, clinical decisions around hip fracture prevention should be based on age, and age-related factors, such as frailty, low body-mass-index, sensory impairment, and comorbidity, rather than on age at menopause. Factors which increase the risk of falling are particularly important 
. The evidence suggests that, later in life, women with an early menopause can be reassured that their risk of hip fracture does not differ markedly from that of comparable peers experiencing a later menopause.
Hip fracture becomes an important health issue as women age and is a significant cause of morbidity and mortality from around the age of 70 y onwards—almost one in every 100 never-users of hormone replacement therapy aged 70–74 y in this cohort were admitted to hospital with a hip fracture over a 5-y period; whereas the figure is about seven times lower in women aged 50–54 y. Our findings show that at around the time of menopause, when hip fractures are relatively uncommon, postmenopausal women have a higher incidence of such fractures than premenopausal women. However, after the menopause the incidence of hip fracture increases rapidly with age and fracture rates are determined far more by women's actual ages than by factors relating to the menopause, including the type of menopause and women's ages at menopause.