Use of depot medroxyprogesterone acetate and fracture risk. Oral contraception and other factors in relation to hospital referral for fracture. Findings in a large cohort study. Prior oral contraception and postmenopausal fracture: a Women's Health Initiative observational cohort study. The association between oral contraceptive use, bone mineral density and fractures in women aged 50-80 years. Oral-contraceptive use and risk of hip fracture: a case-control study. Adolescent use of the monthly contraceptive injection. Oral contraceptive pill use and fractures in women: a prospective study. The effect of previous oral contraceptive use on bone mineral density in perimenopausal women. Fracture risk in very young women using combined oral contraceptives.
Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited.
                We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk.
                We conducted a case-control analysis using the United Kingdom-based General Practice Research Database.
                Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008.
                Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders.
                We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (>2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1.
                This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures. 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. To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause.
                A prospective cohort of 93,725 postmenopausal women.
                Forty Women's Health Initiative (WHI) clinical centers across the United States.
                Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old.
                None.
                The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire.
                The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women without any postmenopausal hormone treatment, past OC use for < or =5 years led to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97-1.23) compared with never users.
                This study does not support the idea that past OC use protects against later fracture. The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial.
                A cross-sectional study of 491 women aged 50-80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry.
                Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5-10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22-0.94).
                Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.
                Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved. Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain.
                We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded.
                130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30.
                Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method. To compare weight and continuation among adolescents using monthly medroxyprogesterone acetate (MPA)/ethinyl estradiol cypionate (E2C), tri-monthly depot MPA (DMPA), and daily oral contraceptive pills (OCP).
                Medical records were reviewed for body mass index, demographics, and sexual history at baseline; and weight and continuation at 3, 6, 9, and 12 months. Bivariate analyses were performed by method, and continuation functions were compared by the log-rank and Wilcoxon tests. The effect of method on use duration was assessed by Cox regression.
                Hospital adolescent clinic.
                12- to 21-year-old patients who initiated MPA/E2C, DMPA, or OCPs in 2001.
                Weight gain and method continuation.
                MPA/E2C was initiated by 40 (18%) patients, DMPA by 63 (28%), and OCPs by 119 (54%, P < 0.001). OCP users were younger (P = 0.005) and more likely to be white, privately insured, and in school (P < 0.004) than MPA/E2C or DMPA users. Previous DMPA and OCP use, pregnancy, and sexually transmitted infections (STI) were more common among MPA/E2C than DMPA or OCP users (P < or = 0.001). Baseline BMI was lowest (P = 0.06) among DMPA users, and MPA/E2C users were most likely to be overweight (P = 0.03). There were non-significant differences in weight change. Continuation functions differed by the method only in the first three months of use (P = 0.03). Leading reasons for discontinuation were unavailability of MPA/E2C (20%), bleeding with DMPA (22%), and forgetting OCPs (17%). Duration of use was independently associated with white race (P < 0.005) and STI-never (P < 0.0001) but not with method type.
                Although MPA/E2C use was associated with overweight status and early discontinuation, it also was associated with previous use of other methods. For all methods, poor continuation at one year supports the ongoing search for effective contraceptive alternatives. It has been suggested that use of the oral contraceptive pill by women confers protection against osteoporosis later in life. However, cross-sectional studies of bone density among pill users have yielded discrepant results. We therefore investigated the relationship between pill use and subsequent occurrence of fracture in a cohort of 46,000 women enrolled in the Royal College of General Practitioners Oral Contraception Study during 482,083 person-years of follow-up. Fracture risk was lower among multiparous women, non-smokers, and those of lower socio-economic class. The risk of subsequent fractures among the women who had ever used the oral contraceptive pill was significantly greater than that among women who had never used it (relative risk 1.20, 95% confidence intervals 1.08-1.34) after adjustment for these variables. When the analysis was confined to forearm fractures, no significant effect of pill use on fracture risk was detected. Although the study only includes limited observation of older women to date, these data do not support the hypothesis that pill use protects women against the occurrence of osteoporotic fractures in later life. The bone mineral density (BMD) of the lumbar vertebrae L2-4 and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) in 3222 perimenopausal women-a random stratified sample of the population-based Kuopio Osteoporosis Study (OSTPRE). The mean age of the women was 53.4 years (range 47.9-59.6 years). Twenty-nine percent of the women were past users of oral contraceptives (OC) containing 50 micrograms or less of ethinyl estradiol and 7.4% (n = 250) of the women reported OC use for more than 6 years. There was a slight but statistically significant difference between OC users (n = 939) and non-users (n = 2283) in lumbar BMD (1.134 +/- 0.155 g/cm2 v 1.123 +/- 0.161 g/cm2, p = 0.014). A statistically significant difference was recorded also after adjustment for years since menopause, duration of hormonal replacement therapy (HRT) and present weight (p = 0.044). When the analysis was performed among women who had never used oestrogen replacement therapy (n = 1427) and among premenopausal women (n = 387), no differences in BMD were found between OC users and non-users. Similarly, femoral neck BMD did not differ between the groups. This population-based study demonstrated a slightly higher lumbar BMD among past OC users. However, OC users and non-users differed from each other in many behavioral characteristics. Thus, the differences in BMD may be accounted for more by other factors than by past OC use itself. The low-dosage estrogen OCs used today would not be expected to have any positive bone effects among future perimenopausal women. Little is known on fracture risk in young women using oral contraceptives.
                Case-control study (64,548 cases, 193,641 controls).
                Overall, no major association with risk of fracture was present. Only in a few age groups a limited increase (OR 1.1-1.5) was seen in those using low average doses (less than one tablet per day - i.e., intermittent use). Neither 20 nor >or=30 mcg per day of ethinylestradiol was associated with risk of fractures, while changing from 20 to >or=30 mcg per day or vice versa was associated with a limited increase in fracture risk (OR 1.1-1.4) in some age groups.
                In general, use of oral contraceptives in young women did not seem to be associated with an increased risk of fractures. The isolated increase seen in some strata with low average doses may be linked to factors associated with discontinuation of oral contraceptives rather than pharmacological effects.
Observational studies do not indicate an overall association between OC use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Researchers should be clear about the variables examined in multivariate analysis.