Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Psychosocial stress and bone loss among postmenopausal women: results from the Women's Health Initiative.

BACKGROUND: Bone loss is a major public health concern with large proportions of older women experiencing osteoporotic fractures. Previous research has established a relationship between psychosocial stressors and fractures. However, few studies have investigated bone loss as an intermediary in this relationship. This study investigates whether social stress is associated with bone loss during a 6-year period in postmenopausal women. METHODS: Data from 11 020 postmenopausal women from the USA was used to examine self-reported psychosocial stress in relation to change in bone mineral density (BMD) measured at the femoral neck, lumbar spine and total hip. Linear regression models were used to examine associations between social measures of psychosocial stress (social strain, social functioning and social support) and per cent change in BMD over 6 years. RESULTS: High social stress was associated with decreased BMD over 6 years. After adjustment for confounders, each point higher in social strain was associated with 0.082% greater loss of femoral neck BMD, 0.108% greater loss of total hip BMD and 0.069% greater loss of lumbar spine BMD (p<0.05). Low social functioning and low social support were associated with greater decreases in femoral neck BMD, and low social functioning was associated with greater decreases in total hip BMD. CONCLUSION: The findings provide evidence for an association between high social stress and greater bone loss over 6 years of follow-up. In agreement with the prior literature, the findings for social strain and social functioning suggest that poor quality of social relationships may be associated with bone loss in postmenopausal women.

Cost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan.

We constructed a Markov microsimulation model among hypothetical cohorts of community-dwelling elderly osteoporotic Japanese women without prior hip or vertebral fractures over a lifetime horizon. Compared with weekly oral alendronate for 5 years, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold. INTRODUCTION: The objective of the study was to examine the cost-effectiveness of subcutaneous denosumab every 6 months for 5 years compared with weekly oral alendronate for 5 years in Japan. METHODS: We calculated incremental cost-effectiveness ratios [ICERs] (2016 US dollars [$] per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling osteoporotic Japanese women without prior hip or vertebral fractures at various ages of therapy initiation (65, 70, 75, and 80 years) over a lifetime horizon from three perspectives: societal, healthcare sector, and government. RESULTS: Denosumab was cost-saving compared with alendronate at ages 75 and 80 years from any of the three perspectives. The ICERs of denosumab compared with alendronate were $25,700 and $5000 per QALY at ages 65 and 70 years from a societal perspective and did not exceed a willingness-to-pay of $50,000 per QALY from the other two perspectives. In deterministic sensitivity analyses, results were sensitive to changes in the effectiveness of denosumab for reducing hip fracture and clinical vertebral fracture and the rate ratio of non-persistence with denosumab compared to alendronate. In probabilistic sensitivity analyses, the probabilities of denosumab being cost-effective compared with alendronate were 89-100% at a willingness-to-pay of $50,000 per QALY. CONCLUSIONS: Among community-dwelling elderly osteoporotic women in Japan, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold of willingness-to-pay at all ages examined, compared with weekly alendronate for 5 years. This study provides insight to clinicians and policymakers regarding the relative economic value of osteoporosis treatments in elderly women.

Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. INTRODUCTION: The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. METHODS: We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. RESULTS: At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. CONCLUSIONS: Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment options to reduce fracture risk.

Adult bone strength of children from single-parent families: the Midlife in the United States Study.

UNLABELLED: Bone health may be negatively impacted by childhood socio-environmental circumstances. We examined the independent associations of single-parent childhood and parental death or divorce in childhood with adult bone strength indices. Longer exposure to a single-parent household in childhood was associated with lower bone strength in adulthood. INTRODUCTION: Because peak bone mass is acquired during childhood, bone health may be negatively impacted by childhood socio-environmental disadvantage. The goal of this study was to determine whether being raised in a single-parent household is associated with lower bone strength in adulthood. METHODS: Using dual-energy X-ray absorptiometry data from 708 participants (mean age 57 years) in the Midlife in the United States Biomarker Project, we examined the independent associations of composite indices of femoral neck bone strength relative to load (in three failure modes: compression, bending, and impact) in adulthood with the experience of single-parent childhood and parental death or divorce in childhood. RESULTS: After adjustment for gender, race, menopause transition stage, age, and body mass index, each additional year of single-parent childhood was associated with 0.02 to 0.03 SD lower indices of adult femoral neck strength. In those with 9-16 years of single-parent childhood, the compression strength index was 0.41 SD lower, bending strength index was 0.31 SD lower, and impact strength index was 0.25 SD lower (all p values < 0.05). In contrast, parental death or divorce during childhood was not by itself independently associated with adult bone strength indices. The magnitudes of these associations were unaltered by additional adjustment for lifestyle factors and socioeconomic status in childhood and adulthood. CONCLUSIONS: Independent of parental death or divorce, growing up in a single-parent household is associated with lower femoral neck bone strength in adulthood, and this association is not entirely explained by childhood or adult socioeconomic conditions or lifestyle choices.

Socioeconomic status in relation to incident fracture risk in the Study of Women's Health Across the Nation.

UNLABELLED: We examined baseline and annual follow-up data (through annual follow-up visit 9) from a cohort of 2,234 women aged 42 to 52 years at baseline. Independent of financial status, higher educational level was associated with lower fracture incidence among non-Caucasian women but not among Caucasian women. INTRODUCTION: This study was conducted to determine the associations of education and income with fracture incidence among midlife women over 9 years of follow-up. METHODS: We examined baseline and annual follow-up data (through annual follow-up visit 9) from 2,234 participants of the Study of Women's Health Across the Nation, a cohort of women aged 42 to 52 years at baseline. We used Cox proportional hazards regression models to examine the associations of socioeconomic predictors (education, family-adjusted poverty-to-income ratio, and difficulty paying for basics) with time to first incident nontraumatic, nondigital, noncraniofacial fracture. RESULTS: Independent of family-adjusted poverty-to-income ratio, higher educational level was associated with decreased time to first incident fracture among non-Caucasian women but not among Caucasian women (p(interaction) 0.02). Compared with non-Caucasian women who completed no more than high school education, non-Caucasian women who attained at least some postgraduate education had 87% lower rates of incident nontraumatic fracture (adjusted hazard ratio 0.13, 95% confidence interval [CI] 0.03-0.60). Among non-Caucasian women, each additional year of education was associated with a 16% lower odds of nontraumatic fracture (adjusted odds ratio 0.84, 95% CI 0.73-0.97). Income, family-adjusted poverty-to-income ratio, and degree of difficulty paying for basic needs were not associated with time to first fracture in Caucasian or non-Caucasian women. CONCLUSIONS: Among non-Caucasian midlife women, higher education, but not higher income, was associated with lower fracture incidence. Elucidation of the mechanisms underlying the possible protective effects of higher educational level on nontraumatic fracture incidence may allow us to better target individuals at risk of future fracture.

Marital histories, marital support, and bone density: findings from the Midlife in the United States Study.

UNLABELLED: We examined the association between marital life history and bone mineral density (BMD) in a national sample from the US. In men, being stably married was independently associated with better lumbar spine BMD, and in women, more spousal support was associated with better lumbar spine BMD. INTRODUCTION: Adult bone mass may be influenced by stressors over the life course. We examined the association between marital life history and bone mineral density (BMD) net socioeconomic and behavioral factors known to influence bone mass. We sought evidence for a gender difference in the association between marital history and adult BMD. METHODS: We used data from 632 adult participants in the Midlife in the United States Study to examine associations between marital history and BMD, stratified by gender, and adjusted for age, weight, menopausal stage, medication use, childhood socioeconomic advantage, adult financial status, education, physical activity, smoking, and alcohol consumption. RESULTS: Compared to stably married men, men who were currently divorced, widowed, or separated, men who were currently married but previously divorced, widowed, or separated, and never married men had 0.33 (95% CI: 0.01, 0.65), 0.36 (95% CI: 0.10, 0.83), and 0.53 (95% CI: 0.23, 0.83) standard deviations lower lumbar spine BMD, respectively. Among men married at least once, every year decrement in age at first marriage (under age 25) was associated with 0.07 SD decrement in lumbar spine BMD (95% CI: 0.002, 0.13). In women, greater support from the spouse was associated with higher lumbar spine BMD. CONCLUSIONS: Our findings suggest that marriage before age 25 and marital disruptions are deleterious to bone health in men, and that marital quality is associated with better bone health in women.

Physical activity as determinant of femoral neck strength relative to load in adult women: findings from the hip strength across the menopause transition study.

UNLABELLED: Our objective was to examine associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Greater physical activity in each of the domains of sport, active living, home, and work was associated with higher peak femoral neck strength relative to load. INTRODUCTION: Our objective was to examine the associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Composite indices of femoral neck strength integrate body size with femoral neck size and bone mineral density to gauge bone strength relative to load during a fall, and are inversely associated with incident fracture risk. METHODS: Participants were 1,919 pre- and early perimenopausal women from the Study of Women's Health Across the Nation. Composite indices of femoral neck strength relative to load in three failure modes (compression, bending, and impact) were created from hip dual-energy X-ray absorption scans and body size. Usual physical activity within the past year was assessed with the Kaiser Physical Activity Survey in four domains: sport, home, active living, and work. We used multiple linear regression to examine the associations. RESULTS: Greater physical activity in each of the four domains was independently associated with higher composite indices, adjusted for age, menopausal transition stage, race/ethnicity, Study of Women's Health Across the Nation study site, smoking status, smoking pack-years, alcohol consumption level, current use of supplementary calcium, current use of supplementary vitamin D, current use of bone-adverse medications, prior use of any sex steroid hormone pills or patch, prior use of depo-provera injections, history of hyperthyroidism, history of previous adult fracture, and employment status: standardized effect sizes ranged from 0.04 (p < 0.05) to 0.20 (p < 0.0001). CONCLUSIONS: Physical activity in each domain examined was associated with higher peak femoral neck strength relative to load in pre- and early perimenopausal women.

Trajectories of femoral neck strength in relation to the final menstrual period in a multi-ethnic cohort.

UNLABELLED: The purpose of this study was to describe the evolution of femoral neck strength relative to load across the menopause transition. It declined significantly over the 10 years bracketing the final menstrual period, and the rate of decline was modified by body mass index, race/ethnicity, and smoking status. INTRODUCTION: Composite indices of femoral neck strength, which integrate dual energy X-ray absorptiometry (DXA)-derived bone mineral density and bone size with body size, are inversely associated with hip fracture risk. Our objective was to describe longitudinal trajectories of the strength indices across the menopausal transition. METHODS: Data came from the Study of Women's Health Across the Nation; participants were pre- or early peri-menopausal, ages 42-53 at baseline, and were followed up for 9.1 ± 1.8 years. Composite indices of femoral neck strength in different failure modes (compression, bending, and impact) were created in 921 women who had three or more hip DXA scans and had definable final menstrual period (FMP) dates. We used mixed effects models to fit piecewise linear growth curves to the baseline-normalized strength indices as a function of time to/after the FMP. RESULTS: Compression and impact strength indices did not decline until 1 year prior to the FMP, and declined rapidly thereafter, with some slowing of decline 1 year after the FMP. Bending strength index increased slightly until 2 years prior to the FMP, then plateaued, and began to decline at the FMP. Mean decline in strength indices over 10 years was 6.9 % (compression), 2.5 % (bending), and 6.8 % (impact). Women with higher body mass index had larger declines in two of the three indices. Other major modifiers of rates of decline were race/ethnicity and smoking status. CONCLUSIONS: Femoral neck strength relative to load declines significantly during the menopausal transition, with declines commencing 1 to 2 years prior to the FMP.

Socioeconomic status, race, and bone turnover in the Midlife in the US Study.

UNLABELLED: Among a group of 940 US adults, economic adversity and minority race status were associated with higher serum levels of markers of bone turnover. These results suggest that higher levels of social stress may increase bone turnover. INTRODUCTION: To determine socioeconomic status (SES) and race differences in levels of bone turnover. METHODS: Using data from the Biomarker Substudy of the Midlife in the US (MIDUS) study (491 men, 449 women), we examined cross-sectional associations of SES and race with serum levels of bone turnover markers (bone-specific alkaline phosphatase [BSAP], procollagen type I N-terminal propeptide [PINP], and N-telopeptide [Ntx]) separately in men and women. Linear multivariable regression was used to control for body weight, menopausal transition stage, and age. RESULTS: Among men, low family poverty-to-income ratio (FPIR) was associated with higher turnover, but neither education nor race was associated with turnover. Men with FPIR <3 had 1.808 nM BCE higher Ntx (P = 0.05), 3.366 U/L higher BSAP (P = 0.02), and 7.066 higher PINP (P = 0.02). Among women, neither education nor FPIR was associated with bone turnover, but Black women had 3.688 nM BCE higher Ntx (P = 0.001), 5.267 U/L higher BSAP (P = 0.005), and 11.906 µg/L higher PINP (P = 0.008) compared with non-Black women. CONCLUSIONS: Economic adversity was associated with higher bone turnover in men, and minority race status was associated with higher bone turnover in women, consistent with the hypothesis that higher levels of social stresses cause increased bone turnover. The magnitude of these associations was comparable to the effects of some osteoporosis medications on levels of turnover.

Menopausal bone changes and incident fractures in diabetic women: a cohort study.

SUMMARY: The purpose of this study was to evaluate the rate of bone loss and incident fractures in women with diabetes mellitus (DM) across menopause. During menopause, DM women experienced bone mineral density (BMD) loss that was faster at hip and slower at spine and had a higher risk of fractures, perhaps because of their earlier menopause. The increasing DM epidemic will contribute to higher fracture burden. INTRODUCTION: Women with DM have a higher risk of fractures independent of age, body mass index (BMI), and BMD. Our objective is to evaluate if women with DM experience greater bone loss and more fractures across menopause. METHODS: Two thousand one hundred seventy one women, aged 42 to 52 years at baseline (1996), enrolled in the Study of Women's Health Across the Nation (SWAN), a prospective study, with 8 years of annual follow up. One thousand three hundred forty six (62%) completed annual visit 7 (2004). Women with baseline fasting blood glucose level of ≥126 mg/dl and those being treated for diabetes were designated as DM. Annual assessment of menopausal stage, BMD, and urinary N-telopeptide (NTx) were carried out. Rate of change in BMD across menopause and annual self-report data for risk of incident fractures by DM status were determined. RESULTS: Despite higher baseline BMD at hip (p = <0.001), and lumbar spine (p = <0.001), rate of decline in BMD was faster at hip (ß = -0.45 vs. -0.11 gm/cm(2)/year, p = <0.001) for DM women, compared to non-DM. However, lumbar spine bone loss was slower in women with DM as compared to non-DM women (ß = 0.04 vs. -0.25 gm/cm(2)/year, p = 0.004). DM women experienced menopause 3 years earlier than non-DM women (p = 0.002), and age adjusted incident fractures were two fold higher in women with DM compared to non-DM (RR = 2.20, 95% CI: 1.26-3.85, p = <0.006). CONCLUSIONS: BMD loss is greater in hip and slower at spine in DM women during menopausal transition. Women with DM have a higher risk of fractures, perhaps because of their earlier menopause.

Menopausal symptoms within a Hispanic cohort: SWAN, the Study of Women's Health Across the Nation.

INTRODUCTION: Since the designation of people as Hispanic involves the amalgamation of a number of different cultures and languages, we sought to test the hypothesis that menopausal symptoms would differ among Hispanic women, based upon country of origin and degree of acculturation. METHODS: A total of 419 women, aged 42-52 years at baseline, were categorized as: Central American (CA, n = 29) or South American (SA, n = 106), Puerto Rican (PR, n = 56), Dominican (D, n = 42), Cuban (Cu, n = 44) and non-Hispanic Caucasian (n = 142). We assessed vasomotor symptoms, vaginal dryness and trouble in sleeping. Hispanics and non-Hispanic Caucasians were compared using the chi(2) test, t test or non-parametric alternatives; ANOVA or Kruskal-Wallis testing examined differences among the five Hispanic sub-groups. Multivariable regression models used PR women as the reference group. RESULTS: Hispanic women were overall less educated, less acculturated (p < 0.001 for both) than non-Hispanic Caucasians and more of them reported vasomotor symptoms (34.1-72.4% vs. 38.3% among non-Hispanic Caucasians; p = 0.0293) and vaginal dryness (17.9-58.6% vs. 21.1% among non-Hispanic Caucasians, p = 0.0287). Among Hispanics, more CA women reported vasomotor symptoms than D, Cu, SA, or PR women (72.4% vs. 45.2%, 34.1%, 50.9%, and 51.8%, respectively). More CA (58.6%) and D women (38.1%) reported vaginal dryness than PR (17.9%), Cu (25.0%) and SA (31.4%) women. More PR and D women reported trouble in sleeping (66.1 and 64.3%, respectively) compared to CA (51.7%), Cu (36.4%), and SA (45.3%) women. CONCLUSION: Symptoms associated with menopause among Hispanic women differed by country of origin but not acculturation. Central American women appear to be at greatest risk for both vasomotor symptoms and vaginal dryness.

Estrogen replacement therapy and colon cancer: a clinical review.

Colorectal cancer is the third leading cause of cancer death in women. Studies on the potential protective effect of postmenopausal hormone replacement on the incidence of colon cancer have been contradictory. To attempt to clarify the potential protective effect of hormone replacement therapy (HRT), an English-language key word (KW) search of MEDLINE, up to August 1999, was performed for KW colon cancer or colorectal adenoma or colon adenoma or adenomatous polyp and KW estrogen replacement or hormone replacement. Additional references were obtained from reading of the reference lists. Thirty-five studies, including 3 meta-analyses, were found. Of these, 23 suggested any degree of protective effect of HRT, 11 reported neutral results, and 1 reported negative impact of hormone replacement. The single prospective randomized controlled trial included small numbers of inpatients taking high-dose estrogen. However, studies did not uniformly specify hormone type, dose, duration, and potential differential effects on right and left colon. Estrogen and progesterone effects were not often considered separately. Many studies had inadequate control of confounders, for example, family history of colon cancer or indication for endoscopy. Therefore, although the majority of studies, especially more rigorously designed recent studies, support the conclusion that postmenopausal estrogen replacement therapy (ERT) has a protective effect against colon adenomas and colon cancer, methodological limitations preclude practical application of study results at present. Prospective studies are needed to confirm the existence and degree of protective effect, as well as to specify the mechanism of protection.

Stress effects on the nonverbal behavior of repressors and sensitizers.

Differences between repressors and sensitizers in nonverbal behavior were found in two studies of male and female undergraduates which manipulated the amount of stress present during an interaction between an S and a confederate (C). In Study I (N = 72), sensitizers used less eye contact and more personal space than measures of personal space and eye contact, intensified the stress manipulation, and added two distinct types of stressors (interpersonal and situational). Significant differences in the same direction as in Study I were again observed between repressors and sensitizers in the use of personal space. Level of eye contact for repression-sensitization was significantly different in the second half of the interaction, though opposite in direction to found in Study I. The reversal was explained by focusing on the information-gathering versus the emotional-communication functions of eye contact. Only interpersonal stress produced significant differences in the amount of eye contact used as well as interacting significantly with stress and repression-sensitization.