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Early Life Body Fatness, Serum Anti-Mullerian Hormone, and Breast Density in Young Adult Women.

ABSTRACT: BACKGROUND:Emerging evidence suggests positive associations between serum anti-Müllerian hormone (AMH), a marker of ovarian function, and breast cancer risk. Body size at young ages may influence AMH levels, but few studies have examined this. Also, no studies have examined the relation of AMH levels with breast density, a strong predictor of breast cancer risk. METHODS:We examined associations of early life body fatness, AMH concentrations, and breast density among 172 women in the Dietary Intervention Study in Children (DISC). Height and weight were measured at baseline (ages 8-10) and throughout adolescence. Serum AMH concentrations and breast density were assessed at ages 25-29 at the DISC 2006 Follow-up visit. We used linear mixed effects models to quantify associations of AMH (dependent variable) with quartiles of age-specific youth body mass index (BMI) Z-scores (independent variable). We assessed cross-sectional associations of breast density (dependent variable) with AMH concentration (independent variable). RESULTS:Neither early life BMI nor current adult BMI was associated with AMH concentrations. There were no associations between AMH and percent or absolute dense breast volume. In contrast, women with higher AMH concentrations had significantly lower absolute nondense breast volume (Ptrend < 0.01). CONCLUSIONS:We found no evidence that current or early life BMI influences AMH concentrations in later life. Women with higher concentrations of AMH had similar percent and absolute dense breast volume, but lower nondense volume. IMPACT:These results suggest that AMH may be associated with lower absolute nondense breast volume; however, future prospective studies are needed to establish temporality. Cancer Epidemiol Biomarkers Prev; 25(7); 1151-7. ©2016 AACR.

SUBMITTER: Bertrand KA

PROVIDER: S-EPMC4930720 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Early Life Body Fatness, Serum Anti-Müllerian Hormone, and Breast Density in Young Adult Women.

Bertrand Kimberly A KA Baer Heather J HJ Orav E John EJ Klifa Catherine C Kumar Ajay A Hylton Nola M NM LeBlanc Erin S ES Snetselaar Linda G LG Van Horn Linda L Dorgan Joanne F JF

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20160509 7

<h4>Background</h4>Emerging evidence suggests positive associations between serum anti-Müllerian hormone (AMH), a marker of ovarian function, and breast cancer risk. Body size at young ages may influence AMH levels, but few studies have examined this. Also, no studies have examined the relation of AMH levels with breast density, a strong predictor of breast cancer risk.<h4>Methods</h4>We examined associations of early life body fatness, AMH concentrations, and breast density among 172 women in t ...[more]

PMID: 27197299

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Project description:INTRODUCTION:Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk, independent of adult body mass index (BMI). These associations may be mediated through breast density. METHODS:We prospectively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children (DISC) who were ages 25-29 at follow-up. Height, weight, and other factors were measured at baseline (ages 8-10) and annual clinic visits through adolescence. We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25-29 with quartiles of age-specific youth body mass index (BMI) Z-scores, adjusting for clinic, treatment group, current adult BMI, and other well-established risk factors for breast cancer and predictors of breast density. RESULTS:We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density, adjusting for current adult BMI and other covariates (all p values <0.01). Women whose baseline BMI Z-scores (at ages 8-10 years) were in the top quartile had significantly lower adult breast density, after adjusting for current adult BMI and other covariates [least squares mean (LSM): 23.4 %; 95 % confidence interval (CI): 18.0 %, 28.8 %] compared to those in the bottom quartile (LSM: 31.8 %; 95 % CI: 25.2 %, 38.4 %) (p trend <0.01). Significant inverse associations were also observed for absolute dense breast volume (all p values <0.01), whereas there were no clear associations with non-dense breast volume. CONCLUSIONS:These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density, independent of current BMI, and further suggest direct or indirect influences on absolute dense breast volume. CLINICAL TRIALS REGISTRATION NUMBER:NCT00458588 ; April 9, 2007.

Project description:BackgroundTo determine the effects of age and the serum anti-Müllerian hormone (AMH) level on in vitro fertilization (IVF) outcomes, especially among young women with low serum AMH levels and older women with high AMH levels.MethodsThis study was a cohort study in which a total of 9431 women aged 20-51?years who were undergoing their first IVF cycles were recruited. Ovarian response parameters included the number of retrieved oocytes, the number of 2 pronuclear zygotes (2PN), and the frequency of good-quality embryos (GQE). Pregnancy outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage rate (MR), and cumulative CPR and LBR (CCPR and CLBR).ResultsAmong women under 35?years of age, the ovarian response, CPR, CCPR, LBR and CLBR (p?<?0.01) were significantly lower in the low-AMH group than in the average-AMH and high-AMH groups. In women above 35?years of age, the ovarian response, CPR, CCPR and CLBR (p?<?0.01) were significantly higher in the average-AMH and low-AMH groups. The LBR in the older high-AMH group was significantly higher (37.45% vs 20.34%, p?<?0.01) than that in the older low-AMH group, but there was no difference (37.45% vs 32.46%, p?=?0.11) compared with the older average-AMH group. When there was a discrepancy between age and the AMH level, the young low-AMH group showed a poorer ovarian response but a better CPR (58.01% vs 49.44%, p?<?0.01) and LBR (48.52% vs 37.45%, p?<?0.01) than the older high-AMH group. However, the CCPR (65.37% vs 66.11%, p?=?0.75) and CLBR (56.35% vs 52.89%, p?=?0.15) between the two groups were comparable. The conservative CLBR in the two discrepancy groups increased until the third embryo transfer and reached a plateau thereafter.Conclusion(s)Even with a relatively low AMH level, young women still had better pregnancy outcomes following IVF than older women. However, increasing the AMH level improves the cumulative outcomes of the older group to a comparable level through a notable and superior ovarian response.

Project description:BackgroundObesity is a state of excess body fat accumulation, and appears to be closely associated with polycystic ovary syndrome (PCOS). Notably, plausible biological pathways through which obesity can regulate anti-Müllerian hormone (AMH) production have been proposed, and women with PCOS characteristically have an increased AMH level. Body fat accumulation can be described by body fat percentage (BFP). However, the relationship between BFP and AMH still remains unclear.Materials and methodsA total of 87 controls and 156 PCOS patients were divided into lean and overweight/obese groups, and the PCOS patients were further divided into hyper-AMH and normal-AMH subgroups. Univariate regression was used to assess the unadjusted relationship between AMH and outcome variables, multivariable regression analysis was performed to test whether and how serum AMH levels were associated with BFP after adjusting for other co-variables. Receiver-operating characteristic (ROC) curve analyses were used to test the utility of BFP for the diagnosis of PCOS.ResultsBFP was higher in PCOS patients compared with controls, regardless of obesity. Serum AMH levels were negatively associated with BFP in the PCOS group (r = -0.371; P < 0.001) but not in the control group (r = -0.095; P = 0.385). Multivariable logistic regression analysis showed that elevated BFP was associated with a high risk of PCOS (odds ratio, 1.290; 95% confidence interval, 1.084-1.534, P = 0.004). Furthermore, the combination of BFP and serum AMH into a multivariate model gave an improved area under the curve (AUC) of 88.5%, with a sensitivity of 72.4% and specificity of 87.4%; the positive and negative predictive values were 91.2% and 63.9%, respectively. One limitation of this study is all the conclusion reported was based on small sample size.ConclusionsHerein, we described the negative correlation between BFP and serum AMH levels for the first time, and the present results highlight the importance of further investigation into the role of BFP, especially in body fat-related AMH change as it relates to the underlying pathogenesis of PCOS.

Project description:BackgroundChildhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density.MethodsLongitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation.ResultsOf the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV.ConclusionsAdditional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.

Dataset Information

Early Life Body Fatness, Serum Anti-Mullerian Hormone, and Breast Density in Young Adult Women.

Publications

Early Life Body Fatness, Serum Anti-Müllerian Hormone, and Breast Density in Young Adult Women.

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