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ObjectiveThe effect of oral contraceptive (OC) use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, we conducted a population-based case-control study in a Pacific Northwest HMO, Group Health Cooperative.MethodsFor the January 2008 to March 2013 interval, 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women were enrolled. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs).ResultsParticipation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases versus controls for OC use in the 10 years before menopause (OR 0.90, 95% CI 0.74, 1.11); for OC use after age 38 (OR 0.94, 95% CI 0.78, 1.14); for duration of use, or for other OC exposures.ConclusionsThe current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38. For women considering OC use at these times, fracture risk does not seem to be either reduced or-reassuringly-increased.

PurposeOral contraceptive (OC) use can occur throughout a woman's reproductive life span with the potential for long-term impacts on health. To assess potential measurement error in prior OC use, this study compared level of agreement between self-reported prior OC use and pharmacy dispensing data in perimenopausal and/or early postmenopausal women.MethodsThe study's 1399 women (ages, 45-59 years) were participants in a population-based case-control study of the association between OC use and fracture risk. Episodes of lifetime self-reported OC use (in months) were collected, by telephone interview, for January 1, 2008 through November 25, 2012. Pharmacy fills, back to 1980, were collected from automated data. Agreement was measured using the prevalence-adjusted and bias-adjusted kappa index.ResultsThe number of women with OC pharmacy fills was 11% to 45% higher than those who reported OC use during each time period. Between-measures agreement was better for more recent use. Prevalence-adjusted and bias-adjusted kappa index values ranged from 0.88 (95% confidence interval, 0.85-0.90) within 5 years from the reference date to 0.65 (95% confidence interval, 0.59-0.71) within 15 to 20 years.ConclusionsFor studies designed to assess the long-term effects of OC use, the current results are reassuring in noting moderate agreement between self-reported OC use and pharmacy data for up to 15 to 20 years before the interview.

ContextOral contraceptive (OC) use is common, but bone changes associated with use of contemporary OC remain unclear.ObjectiveThe objective of the study was to compare bone mineral density (BMD) change in adolescent and young adult OC users and discontinuers of two estrogen doses, relative to nonusers.Design and settingThis was a prospective cohort study, Group Health Cooperative.ParticipantsParticipants included 606 women aged 14-30 yr (50% adolescents aged 14-18 yr): 389 OC users [62% 30-35 μg ethinyl estradiol (EE)] and 217 age-similar nonusers; there were 172 OC discontinuers. The 24-month retention was 78%.Main outcome measureThe main outcome measure was BMD measured at 6-month intervals for 24-36 months.ResultsAfter 24 months, adolescents using 30-35 μg EE OCs, but not those using lower-dose OCs, had significantly smaller adjusted mean percentage BMD gains than nonusers at the spine [group means (95% confidence interval for between group differences) 1.32 vs. 2.26% (-1.89, -0.13%)] and whole body [1.45 vs. 2.03% (-1.29%, -0.13%)]. Adolescents who discontinued 30-35 μg EE OC showed significantly smaller gains than nonusers at the spine after 12 months [0.51 vs. 1.72% (-2.38%, -0.30%)]. Young adult OC users did not differ from nonusers. However, OC discontinuers of both doses differed significantly from nonusers at the spine 12 months after discontinuation [-1.32% < 30 μg EE, -0.92% 30-35 μg EE vs. +0.27% nonusers (-2.48, -0.54, and -1.94%, -0.55%, respectively)]. Results were similar for mean absolute BMD change (grams per square centimeter).ConclusionsBoth OC use and discontinuation were associated with BMD losses/smaller gains relative to nonusers (differences < 2% after 12-24 months for all skeletal sites). The clinical significance of these results regarding future fracture risk is unknown. Study of longer-term trends after discontinuation is needed.

BackgroundThe range of protein intakes for optimizing bone health among premenopausal women is unclear. Protein is a major constituent of bone, but acidic amino acids may promote bone resorption.ObjectiveThe objective was to examine cross-sectional and longitudinal associations between baseline dietary protein and bone mineral density (BMD) among 560 females aged 14-40 y at baseline enrolled in a Pacific Northwest managed-care organization. The role of protein source (animal or vegetable) and participant characteristics were considered.DesignDietary protein intake was assessed by using a semiquantitative food-frequency questionnaire in participants enrolled in a study investigating associations between hormonal contraceptive use and bone health. Annual changes in hip, spine, and whole-body BMD were measured by using dual-energy X-ray absorptiometry. Cross-sectional and longitudinal associations between baseline protein intake (% of energy) and BMD were examined by using linear regression analysis and generalized estimating equations adjusted for confounders.ResultsThe mean (+/-SD) protein intake at baseline was 15.5 +/- 3.2%. After multivariable adjustment, the mean BMD was similar across each tertile of protein intake. In cross-sectional analyses, low vegetable protein intake was associated with a lower BMD (P = 0.03 for hip, P = 0.10 for spine, and P = 0.04 for whole body). For every percentage increase in the percentage of energy from protein, no significant longitudinal changes in BMD were observed at any anatomic site over the follow-up period.ConclusionsData from this longitudinal study suggest that a higher protein intake does not have an adverse effect on bone in premenopausal women. Cross-sectional analyses suggest that low vegetable protein intake is associated with lower BMD.

BackgroundMost of the millions of oral contraceptive (OC) users are under 30 years of age and in the critical period for bone mass accrual.Study designThis cross-sectional study of 606 women aged 14-30 years examined both OC duration and estrogen dose and their association with bone mineral density (BMD) at the hip, spine, and whole body (dual-energy X-ray absorptiometry).ResultsOf 389 OC users and 217 nonusers enrolled, 50% were adolescents (14-18 years). Of OC users, 38% used "low-dose" OCs [12 months of low-dose OCs for the hip, spine and whole body (p=.02, .003 and .002, respectively).ConclusionsProlonged use of today's OCs, particularly

Non-removable navel jewelry can increase the measured bone density of the underlying vertebra. We measured lumbar spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) in an observational study of 727 adolescents and young women aged 14-30 yr. We evaluated several methods of correcting BMD: manually erasing a small area, eliminating 1 or 2 vertebrae, estimating the BMD from 1 or 2 vertebrae using data from remaining vertebrae, and estimating the BMD using T-scores of the remaining vertebrae. Ten percent (n=71) of the subjects were wearing navel jewelry. The areal BMD by DXA of L1 and L2 was similar in those with jewels as in controls without jewels, but L3-L4 showed higher bone density in those with jewelry, and the spine BMD of L1-L4 was significantly higher in the bejeweled women (1.043+/-0.011 vs 1.006+/-0.004 g/cm2, p=0.01). The estimated errors in accuracy (g/cm2) were 0.034 due to the jewels; 0.005 from erasing a small area; 0.019 from eliminating L4; 0.044 from eliminating both L3 and L4; 0.016 from predicting BMD using L1-L3; and 0.028 using L1-L2. The T-scores using the Hologic database were progressively lower in the caudal vertebrae, even in 96 local women aged 30-35 yr, whose average T-score was 0.35 at L1 but -0.26 at L4. Thus, we found significant errors due to intravertebral variability. We suggest the optimal method of correcting for small artifacts is to erase the area under the artifact.

ObjectivesTo evaluate the association between chronic kidney disease and incident hip fracture using serum cystatin-C as a biomarker of renal function calculated without reference to muscle mass.DesignCase-control study nested within a prospective study.SettingThe Women's Health Initiative Observational Study conducted at 40 U.S. clinical centers.ParticipantsFrom 93,676 women aged 50 to 79 followed for an average of 7 years, 397 incident hip fracture cases and 397 matched controls were studied.MeasurementsCystatin-C levels were measured on baseline serum using a particle-enhanced immunonepholometric assay. Estimated glomerular filtration rates (eGFR(cys-c)) were calculated using a validated equation and categorized into three groups (>or=90.0 mL/min per 1.73 m(2), 60.0-89.9 mL/min per 1.73 m(2), and

BackgroundSeveral studies report an association between depot medroxyprogesterone acetate (DMPA) injectable contraception and decreased bone mineral density. Adolescents, who are still gaining bone, may be particularly affected, but there has been little study of the association in adolescent users and none following discontinuation.ObjectiveTo evaluate bone mineral density changes in adolescents using and discontinuing use of DMPA contraception.DesignA population-based prospective cohort study.ParticipantsOne hundred seventy adolescent women, aged 14 to 18 years; 80 baseline DMPA users and 90 age-similar, unexposed comparison women. Sixty-one participants discontinued DMPA use during follow-up.Main outcome measureBone mineral density, measured every 6 months for 24 to 36 months at the hip, spine, and whole body, comparing mean bone mineral density changes in DMPA users and discontinuers with nonusers.ResultsAmong DMPA users, bone mineral density declined significantly relative to nonusers at the hip and spine but not the whole body. Annualized mean percentage changes, adjusted for covariates, were hip, -1.81% vs -0.19%; P

Although adolescent women are actively acquiring bone, there has been little study of the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception use on bone density in adolescents. We conducted a cross-sectional evaluation of the association between DMPA use and bone mineral density in adolescent women, ages 14-18 years. Of 174 study participants, 81 were DMPA users (range, 1-13 injections, median = 3) and 93 were not. Mean bone density at all anatomic sites (hip, spine and whole body) was lower for DMPA users than nonusers, but differences were not statistically significant (e.g., hip, 0.940 vs. 0.970 g/cm2, p = 0.10; spine, 0.970 vs. 0.992 g/cm2, p = 0.19). Duration of DMPA use showed a trend toward lower spine bone density (p-value for trend = 0.06). This study did not find a strong association between DMPA use and bone density. Further prospective evaluation of bone density changes with DMPA use and after DMPA discontinuation are needed in this age group.

The primary aim of this 36-month prospective cohort study was to evaluate the association between use of oral contraceptives (OCs) and bone mineral density in reproductive-age women. The 36-month bone density (g/cm2) at the spine, hip and whole body and percent change from baseline (measured at 6-month intervals) were evaluated among 245 women 18-39 years of age; 89 were using OCs (median duration: 3.7 years at study entry) and 156 were not using any hormonal contraception. Before and after adjustment for covariates (baseline bone density, age, race, ever pregnant, exercise, body mass and calcium intake), women using OCs did not differ significantly from comparison women in percent change in bone density over 36 months or in absolute bone density at 36 months. All p-values for between-group differences were >0.55. In conclusion, within the limitations of this study, OCs did not appear to impact bone density over time in this cohort of reproductive-age women.

OBJECTIVES:To determine the effects of low doses of hydrochlorothiazide (HCTZ) on plasma lipids in healthy older men and women. DESIGN:Randomized, double-blind, placebo-controlled clinical trial for 3 years followed by a 1 year extension without medication. SETTING:Research clinic of a nonprofit health maintenance organization. PARTICIPANTS:Two hundred five women and 115 men aged 60 to 79 with normal blood pressure, bone density within two standard deviations of mean for age, and low-density lipoprotein cholesterol (LDL-C) levels less than 190 mg/dL. INTERVENTION:Placebo or HCTZ 12.5 or 25 mg/d. MEASUREMENTS:Plasma cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides. RESULTS:There were no significant differences in the change in the plasma lipids between placebo and either group. The mean changes +/- standard deviation in LDL-C after 3 years in men were -5.2 +/- 3.9 mg/dL (placebo), -4.6 +/- 3.7 (12.5 mg), and 1.1 +/- 3.8 (25 mg) and in women were 1.3 +/- 2.8 (placebo), -1.1 +/- 2.8 (12.5 mg), and -6.8 +/- 2.8 (25 mg). No significant differences were seen when analysis was done only for subjects who adhered to study medication. CONCLUSION:This study provides evidence that low doses of thiazide diuretics have minimal effects on cholesterol metabolism in healthy older adults. Therefore, effects on lipid levels need not limit use of thiazides for prevention of osteoporotic fractures.

To evaluate the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception on depressive symptoms, we conducted a population-based prospective study with women aged 18-39 years old enrolled at a health maintenance organization. At baseline, 183 women used DMPA and 274 were non-users. Data on depressive symptoms and on factors potentially related to DMPA use and depression were collected by questionnaire at 6-month intervals for up to 3 years. In multivariate longitudinal analysis, we found an increased likelihood of reporting depressive symptoms among continuous DMPA users (OR = 1.44; 95% CI = 1.00-2.07) and discontinuers (OR = 1.60; 95% CI = 1.03-2.48) when compared to non-users. Women who discontinued DMPA use had elevated depressive symptoms prior to discontinuation (OR = 2.30; 95% CI = 1.42-3.70) and immediately following discontinuation (OR = 2.46; 95% CI = 1. 46-4.14), and depressive symptoms subsided at subsequent visits relative to non-users. Our prospective analyses found an association between DMPA use and depressive symptoms but further research is needed to determine whether the relationship is causal.