Vitamin D deficiency and age at menarche: a prospective study.
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ABSTRACT: Background
Early menarche is a risk factor for cardiometabolic disease and cancer. Latitude, which influences sun exposure, is inversely related to age at menarche. This association might be related to vitamin D, but to our knowledge it has not been investigated in prospective epidemiologic studies.Objective
We studied the association between vitamin D status and the occurrence of menarche in a prospective study in girls from Bogota, Colombia.Design
We measured plasma 25-hydroxyvitamin D [25(OH)D] concentrations in a random sample of 242 girls (mean ± SD age: 8.8 ± 1.6 y) and followed them for a median of 30 mo. Girls were asked periodically about the occurrence and date of menarche. Baseline 25(OH)D concentrations were categorized as <50 nmol/L (deficient), ≥50 and <75 nmol/L, or ≥75 nmol/L (sufficient). The incidence of menarche was compared between groups by using time-to-event analyses.Results
A total of 57% of girls in the vitamin D-deficient group reached menarche during follow-up compared with 23% of girls in the vitamin D-sufficient group (P-trend = 0.0004). The estimated mean (±SE) ages at menarche in the same groups were 11.8 ± 0.2 y and 12.6 ± 0.2 y, respectively (P = 0.0009). After adjustment for baseline age and BMI-for-age z score in a Cox proportional hazards model, the probability of menarche was twice as high in vitamin D-deficient girls than in girls who were vitamin D-sufficient (HR: 2.05; 95% CI: 1.03, 4.07; P = 0.04). Similar results were obtained in girls aged ≥9 y at baseline (HR: 2.39; 95% CI: 1.14, 5.00; P = 0.02).Conclusion
Vitamin D deficiency is associated with earlier menarche.
SUBMITTER: Villamor E
PROVIDER: S-EPMC3360555 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Study questionIs sugar-sweetened beverage (SSB) consumption associated with age at menarche?Summary answerMore frequent SSB consumption was associated with earlier menarche in a population of US girls.What is known alreadySSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated.Study design, size, durationThe Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche.Participants/materials, setting, methodsCumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression.Main results and the role of chanceMore frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ?2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ?2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche.Limitations, reasons for cautionAlthough we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure.Wider implications of the findingsMore frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption.Study funding/competing interestsThe Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare.
| S-EPMC4325672 | biostudies-literature
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| S-EPMC5860078 | biostudies-literature
Project description:ObjectiveTo examine the association between age at menarche and risk of gestational diabetes mellitus (GDM).Research design and methodsA prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health Study II.ResultsThe adjusted risk ratios for GDM across the age at menarche categories (?11, 12, 13, and ?14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI.ConclusionsThese findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity.
| S-EPMC4764040 | biostudies-literature
Project description:PURPOSE:Traditional epidemiological studies suggest that there is an association between age at menarche (years) (AAM) and bone mineral density (BMD) at the sites of the femoral neck and lumbar spine (FNK and LS BMD), indicating a potentially important relationship between AAM and the development of osteoporosis (OP). However, these findings may be influenced by unmeasured confounding factors that can obscure the true relationship between the phenotypic traits. Therefore, we performed Mendelian randomization (MR) analyses to determine whether there is a causal relationship between AAM and BMD (FNK and LS BMD), where late AAM may increase the risk of developing OP. METHODS:Adopting a two-sample MR approach we incorporated genome-wide association (GWAS) summary statistics from the Reproductive Genetics (ReproGen) Consortium (n?=?182,416) (females only) and the GEnetic Factors for OSteoporosis (GEFOS) Consortium (n?=?53,236) (both males and females). RESULTS:Using this MR approach we discovered that each additional year in AAM is associated with a modest reduction in FNK BMD (??=?-0.072 se?=?0.022, 95% CI (-0.115, -0.030), p?=?0.001) and LS BMD ((??=?-0.072, se?=?0.025, 95% CI (-0.121, -0.023), p?=?0.004), and therefore influences OP susceptibility. CONCLUSIONS:This study demonstrates that AAM in females may play a causal role in OP etiology and provides novel insights into the pathophysiology of bone related diseases like osteoporosis, osteopenia and fracture. SUMMARY:Our study demonstrates that AAM in females may play a causal role in OP etiology and provides novel insights into the pathophysiology of bone related diseases like osteoporosis, osteopenia and fracture. By adopting Mendelian Randomization approaches, our study was not susceptible to bias from unmeasured confounders or reverse causation.
| S-EPMC6346741 | biostudies-literature
Project description:Evidence between age at menarche and endometrial cancer risk have been controversial. Therefore, we conducted a meta-analysis of prospective studies to analyze the aforementioned association. Relevant studies were identified by searching PubMed and EMBASE databases until the end of June 2015. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between menarcheal age and endometrial cancer risk. Our meta-analysis included eight prospective studies involving 4553 subjects with endometrial cancer. The summarized RRs of endometrial cancer for menarcheal age were 0.68 (95%CI = 0.58-0.81, I(2) = 41.9%, P = 0.099, n = 8) when comparing women with oldest category of menarcheal age with women with youngest category of menarcheal age. Notably, there was an 4% reduction in risk for per 2 years delay in menarcheal age (summarized RR = 0.96; 95%CI = 0.94-0.98, I(2) = 45.7%, P = 0.101, n = 6). Additionally, significant inverse associations were consistent within all stratified analyses. There was no evidence of publication bias or significant heterogeneity between subgroups detected by meta-regression analyses. Our findings support the hypothesis that late menarcheal age is inversely associated with endometrial cancer risk. Further larger prospective or pooled studies are warranted to fully adjust for potential confounders and distinguish whether the associations differ by histological subtypes of endometrial cancer.
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Project description:A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8-47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2-69.9; p = 0.001). In adolescent girls we found an opposite effect (-56.5 mL; -108.3 to -4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).
| S-EPMC5591357 | biostudies-literature
Project description:Younger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.Mean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m2 lower adult BMI. Women in the earliest menarche quintile (8-11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49-1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18-1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.Women with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
| S-EPMC3816901 | biostudies-other
Project description:ObjectiveThis study aimed to examine the association between age at menarche and a range of cardiovascular disease (CVD) risk factors at 17 and 20 years of age, and whether this was influenced by childhood body mass index (BMI).MethodsOf the 1413 girls born in the Western Australian Pregnancy Cohort (Raine) Study, 846 had age at menarche recorded. Subsequently 557 underwent metabolic assessment at 17 years and 541 at 20 years. Associations between age at menarche and cardiovascular risk factors, and being in a high-risk metabolic cluster at 17 and 20 years, or having the metabolic syndrome at 20 years, were investigated by linear mixed effects and logistic regressions, respectively.ResultsEach year later of onset of menarche was associated with a 0.75 kg/m2 reduction in BMI (coefficient -0.75 [95%CI -1.06, -0.44]), and an approximate 30% reduction in the odds of being in the high-risk metabolic cluster at 17 years (OR = 0.73 [95%CI 0.57, 0.94]) and 20 years of age (OR = 0.68 [95%CI 0.52, 0.87]), and a 40% reduction in the odds of having the metabolic syndrome at 20 years (OR = 0.60 [95% CI 0.41, 0.88]). These data show earlier age at menarche was associated with increased BMI and odds of being in the high-risk metabolic cluster at 17 and 20 years, and increased odds of having the metabolic syndrome at 20 years. However, these associations were no longer statistically significant after adjustment for BMI at age 8 years. Current smoking, alcohol consumption, physical activity, socio-economic status, or hormonal contraceptives use did not affect these associations.ConclusionsEarlier age at menarche may be indicative of a higher risk profile for CVD in young adulthood. Our findings suggest that targeted interventions to reduce BMI in girls who experience menarche at younger age may reduce CVD risk in the future.
| S-EPMC6303033 | biostudies-literature
Project description:BackgroundHip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population.ObjectiveThis study aims to determine whether 25-hydroxyvitamin D [25(OH)D] concentration or the Geriatric Nutritional Risk Index (GNRI) is associated with mortality or rates of walking in a patient cohort after hip fracture surgery.MethodsPatients undergoing hip fracture repair from a multisite study in North America were included. Mortality and mobility were assessed at 30 and 60 d after surgery. Serum albumin, 25(OH)D, and intact parathyroid hormone were measured. Patients were characterized according to 25(OH)D <12 ng/mL, 12 to <20 ng/mL, 20 to <30 ng/mL, or ≥30 ng/mL. GNRI was categorized into major/moderate nutritional risk (<92), some risk (92 to <98), or in good nutritional status (≥98).ResultsOf the 290 patients [aged 82 ± 7 y, BMI (kg/m2): 25 ± 5], 73% were women. Compared with patients with <12 ng/mL, those with higher 25(OH)D concentrations had higher rates of walking at 30 d (P = 0.031): 12 to <20 ng/mL (adjusted OR: 2.61; 95% CI: 1.13, 5.99); 20 to <30 ng/mL (3.48; 1.53, 7.95); ≥30 ng/mL (2.84; 1.12, 7.20). In addition, there was also greater mobility at 60 d (P = 0.028) in patients with higher 25(OH)D compared with the reference group (<12 ng/mL). Poor nutritional status (GNRI <92) showed an overall trend to reduce mobility (unadjusted P = 0.044 and adjusted P = 0.056) at 30 but not at 60 d. There was no association of vitamin D or GNRI with mortality at either time.ConclusionsVitamin D deficiency (<12 ng/mL) is associated with reduced ambulation after hip fracture surgery, whereas GNRI also contributes to immobility but is a less reliable predictor. Mechanisms that can explain why vitamin D deficiency is associated with mobility should be addressed in future studies.
| S-EPMC7458775 | biostudies-literature
Project description:ObjectiveTo determine whether maternal vitamin D deficiency during pregnancy is associated with small for gestational age (SGA).MethodsA comprehensive literature search of PubMed, the Cochrane Library, Embase, and the Elsevier ScienceDirect library was conducted to identify relevant articles reporting prospective cohort studies in English, with the last report included published in February 2017. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to evaluate the correlation in a random effects model.ResultsA total of 13 cohort studies were included in this meta-analysis with a sample of 28?285 individuals from seven countries. The pooled overall OR for babies born SGA was 1.588 (95% CI 1.138 to 2.216; p<0.01) for women with vitamin D deficiency. The prevalence of vitamin D deficiency during pregnancy varied from 13.2% to 77.3%. Subgroup analyses identified no significant differences in the association between vitamin D deficiency and SGA based on study quality, gestational week during which blood sampling was performed, cut-off vitamin D levels, sample size, adjustment for critical confounders and method for measuring vitamin D.ConclusionThis meta-analysis suggests that vitamin D deficiency is associated with an increased risk of SGA.
| S-EPMC5629738 | biostudies-literature