Oral contraception and other factors in relation to hospital referral for fracture

Abstract

There is good evidence that estrogens and progestogens have an important effect on bone metabolism. This article explores the relationship between oral contraceptive (OC) use and fractures occurring at various sites among the 17,032 participants in the Oxford-Family Planning Association contraceptive study, which now includes information accumulated during 310,000 woman-years of observation between 1968 and 1994. In total, 1308 women suffered at least one fracture during the follow-up period, which was largely confined to premenopausal years. When all fractures were combined, there was a modest, but highly significant trend (p <0.001) of increasing risk with total duration of oral contraceptive use. In addition, there was statistically significant heterogeneity (p <0.01) when overall fracture rates were examined in relation to recency of oral contraceptive use during the premenopausal lifespan. The highest relative risk (1.3, 95% CI 1.1–1.5) was for current or recent oral contraceptive users; however, viewed as a whole, no clear pattern of risk was apparent. Examination of the data for individual fracture sites (including the lower end of the radius/ulna) did not provide any evidence of a protective effect of oral contraceptive use. These results are closely similar to those reported from the Royal College of General Practitioners Oral Contraception Study in 1993.

Introduction

Estrogens and progestogens are known to have important effects on bone metabolism.1., 2. Accordingly, it is not surprising that a considerable number of studies have been conducted seeking to find a relationship between oral contraceptive use and bone mass at different ages and at various skeletal sites. A comprehensive review published in 1993 on the epidemiology of bone mass in premenopausal women came to the conclusion that oral contraceptive studies published up to that time had given conflicting results.3 The review also stressed the numerous problems that had to be resolved in trying to produce a clear answer. A more recent review reported on eight studies showing a positive effect of oral contraceptives (OC) on bone mineral density and four studies showing no such effect.4 The author considered that the weight of the evidence suggested that premenopausal use of OC is beneficial for preserving bone mass. This issue, however, remains highly controversial.5

In 1993, the Royal College of General Practitioners (RCGP) Oral Contraception Study provided the first prospective data concerned with oral contraceptive use and fracture risk—clearly a more important outcome measure than bone mass.6 Surprisingly, the risk of fracture for all sites combined among those who had ever used OC was slightly but significantly greater than that among those who had never used OC (relative risk 1.20, 95% CI 1.08–1.34). No relationship between pill use and forearm fracture risk was detectable. The authors recognized that the study did not provide much information on older women, but nonetheless stressed that the findings were not suggestive of a beneficial effect of OC.

In view of the report from the RCGP study, it was considered worthwhile to examine the corresponding data in the Oxford-Family Planning Association (Oxford-FPA) contraceptive study. The findings are summarized below.