Taller Adult Height Research Articles

Association Between Early-Life and Premorbid Measurements of Body Composition and Risk of Motor Neuron Disease: A Prospective Cohort Study in the UK Biobank.

The objective of this study was to investigate the association between developmental and premorbid body composition measurements and the risk of motor neuron disease (MND). We performed a cohort study in the UK Biobank to assess the association of developmental body metrics and premorbid body composition measures (using 28 measurements and 7 patterns of body composition) with the risk of MND. Among participants with longitudinal measures, we compared the changes in body composition over time between individuals who later developed MND and those who remained free of MND. Among the 412,691 individuals included in this study, 549 people received an MND diagnosis during the follow-up visit. Higher birth weight was associated with an increased risk of MND among individuals born over 4 kg (hazard ratio [HR] per kg increase = 2.21, 95% confidence interval [CI] = 1.38-3.55), and taller adult height was associated with an increased risk of MND (HR per 5 cm increase = 1.10, 95% CI = 1.03-1.17). We observed that measures of elevated fat mass were associated with a lower risk of MND more than 5 years before diagnosis. A higher "leg-dominant fat distribution" pattern was associated with an increased risk whereas higher "muscle strength" was associated with a reduced risk of MND 5 years before diagnosis. Longitudinal analyses indicated a faster decline in measures of fat mass and muscle strength, as well as a shift in fat distribution from arm to leg dominant, among individuals who later developed MND, compared with others. Body composition at early and middle age may be indicative of the risk of MND development. ANN NEUROL 2024.

Mendelian randomization analysis on the impacts of age at menarche on adult height: A Taiwanese population study

BackgroundsAmple evidence supports potential influence of age at menarche (AM) on adult height (AH), but multiple confounders may affect causal estimates. To address this issue, the Mendelian randomization (MR) analysis was used to explore the causal impacts of AM on AH. MethodsUsing data (n = 57,349) from the publicly accessible Taiwan Biobank and randomly splitting them into 2 equal-size subsets, we identified single nucleotide polymorphisms (SNPs) significantly associated with AM in the exploration subset and used these SNPs as instrumental variables to estimate the effects of instruments on AH in the validation subset based on two stage least squares (2SLS) regression. In addition, three more summary statistics-based approaches, namely inverse variance weighted (IVW), MR-Egger, and weighted median (WM) analyses, were used to verify the findings. We also performed heterogeneity and sensitivity analyses to evaluate the robustness of the results. ResultsWe identified 4 leading SNPs associated with AM at the genome-wide significant level, whereas rs9409082 may exert some pleiotropic effects on AH. After eliminating rs9409082, the 2SLS analysis indicated that one year delay in genetically determined AM predicted 1.5 cm height gain in adulthood (β = 1.508, 95% confidence interval [0.852, 2.163]). The causal relationship was also supported by WM (β = 1.183, [0.329, 2.038]) and IVW (β = 1.493, [0.523, 2.463]) methods. ConclusionsEvidence from the present MR study supports a causal relationship between later AM and taller AH.

Abstract 2204: Evaluating ovarian cancer risk factors in the Mexican Teachers′ Cohort

Abstract Purpose: Ovarian cancer is the most lethal gynecologic cancer in North America, yet our understanding of ovarian cancer risk factors in Mexican women is limited. The aim of the present study was to prospectively evaluate associations between reproductive and lifestyle factors and incident ovarian cancer risk among Mexican women. Methods: The Mexican Teachers′ Cohort (ESMaestras) is a large, prospective, population-based cohort of women (n=115,306) living in a culturally, geographically, and economically diverse 12-state area in Mexico. Reproductive and lifestyle factors were collected on baseline questionnaires administered between 2006-2008, with additional questionnaires collected from the cohort in 2011, and 2014. During follow-up, 187 incident ovarian cancer cases were identified, including 101 via self-report on 2011 and 2014 questionnaires, as well as an additional 85 through linkage with mortality databases, and 3 via other administrative- and cancer registry-based linkages (2 of 3 were also identified via the mortality database linkage). Of the self-reported incident cases, 5 have been validated via mortality databases and 4 via linkage with an administrative database; validation of the remaining self-reported cases is ongoing. Primary analyses examined associations between established ovarian cancer risk factors and incident ovarian cancer. Age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results: Women in the Mexican Teachers′ Cohort that used hormonal contraceptives (HC), were parous, or had a tubal ligation experienced reduced ovarian cancer risks during follow-up (ever HC use vs. never HR 0.70 [95% CI 0.51-0.95], parous vs. nulliparous 0.48 [0.35-0.68], ever tubal ligation vs. never 0.87 [0.59-1.28]). Ovarian cancer risk was elevated among women with a positive family history of breast cancer (1.34 [0.76-2.36]). Women with a history of endometriosis were at increased ovarian cancer risk (3.43 [1.41-8.34]). Taller adult height (>159 cm vs <150 cm) was not associated with ovarian cancer risk among women in this cohort. Risk estimates were consistent and, in some instances, more pronounced (i.e., HC use and tubal ligation) when limited to incident ovarian cancer cases confirmed via linkage with mortality databases (n=90). Conclusions: Ovarian cancer risk factors identified in the Mexican Teachers′ Cohort were generally consistent with associations reported in predominantly non-Hispanic white populations. More research is needed to better understand ovarian cancer etiology among populations under-represented in cancer research. Citation Format: Britton Trabert, Liliana Gómez Flores Ramos, Marion Brochier, Elisa V. Bandera, Jennifer A. Doherty, Scarlett L. Gomez, Lawrence H. Kushi, Alejandro Mohar, Martín Lajous. Evaluating ovarian cancer risk factors in the Mexican Teachers′ Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2204.

Secular trends in Javanese adult height: the roles of environment and educational attainment

BackgroundSince its independence in 1945, Indonesia has undergone rapid socioeconomic development. The fastest changes occurred in Java, which is the main island where more than half of the Indonesian population lives.ObjectiveThis study aimed to analyze the secular trend in the height of adults living in Java born between 1953 and 1995 by comparing their residence (rural, small city, or large city) and considering factors that contribute to adult height.MethodsThe analysis used the following data: birth year, body height, weight, body mass index, sex, educational attainment, share of household food expenditures, and residence of 20- to 40-year-old men and women collected by the Indonesia Family Life Survey (IFLS) waves 1 to 5. Multiple linear regression was conducted to analyze several factors that influence adult height. Significance was set at p < 0.05 with a 95% confidence interval (CI).ResultsThe study included 30,656 measurements of individuals born between 1953 and 1995 (54.9% female). Positive secular trends (95% CI) were observed for men and women: 1.3 (1.1–1.4) cm and 0.9 (0.8–1.0) cm per decade, respectively. Multiple linear regression analyses showed that, in addition to the year of birth, the adult height of both males and females was independently associated with level of education and share of household food expenditure. Stratifying the data into residence in rural areas, small cities, and large cities showed that education levels influenced the adult height of men and women living in all regions, whereas the influence of birth year and share of household food expenditure differed between areas and genders.ConclusionsWe observed positive secular trends in the height of adults living in Java who were born between 1953 and 1995. The birth year, educational attainment, and share of household food expenditure significantly influenced adult height. A higher education level was consistently associated with taller adult height in both men and women living in rural areas, small cities, and large cities.

Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.

As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40–69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.

Taller adult height is associated with better performance of cognitive trajectories in Chinese over 45 years old: Evidence from the China Health and Retirement Longitudinal Study.

The association between adult height and follow-up cognition requires an update in China. We aimed to examine the association between baseline height and follow-up cognitive trajectories in Chinese subjects from the China Health and Retirement Longitudinal Study (CHARLS). A total of 6508 adults aged 45 years or older from the CHARLS were included for analysis. Latent class growth modeling was used to determine cognitive trajectories of 2011, 2013 and 2015. Multivariable linear regression and logistic regression models were used to examine the association between baseline adult height and cognitive performance and trajectories, respectively. At baseline, an increment of 1 SD (8.3 cm) of height was associated with a higher global cognitive score (β=0.492, 95% CI, 0.348-0.636), verbal episodic memory (β=0.155, 95% CI, 0.086-0.224) and mental status (β=0.337, 95% CI, 0.225-0.449). These associations were still observed even when stratified by sex. Prospectively, for females, the third quartile of height level (i.e., 155 to 158 cm) was associated with a better global cognitive function trajectory (OR=1.627, P=0.001, P for trend=0.009) and mental status trajectory (OR=1.456, P=0.012, P for trend=0.047); and the tallest height level (i.e., 159 cm or taller) was related to a better verbal episodic memory trajectory (OR=1.574, P=0.017). For males, no associations were observed. Increased stature might be associated with better cognitive trajectories for subjects in China. Geriatr Gerontol Int 2021; 21: 732-740.

Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ERα) gene in girls with precocious/early puberty.

Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty METHODS: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene. There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset <7 years, the association tended to become significant, p = 0.09. Girls with xxpp genotype were significantly taller, HSDS 1.63, p = 0.014. In controls, homozygosity for Xbal (xx) and PvuII (pp) was associated with significantly earlier menarche than in women with no polymorphism, p = 0.013 and p = 0.026, respectively, and xxpp genotype was associated with taller adult height, p = 0.017. XbaI and PvuII polymorphisms are not related to idiopathic precocious/early puberty. Early pubertal girls homozygous for both polymorphisms presented earlier onset of puberty, although statistically non-significant, and taller height than girls heterozygous or without these polymorphisms. Homozygosity for both polymorphisms is associated with earlier menarche and taller adult height.

Body Habitus Across the Lifespan and Risk of Pituitary Adenoma.

No studies have examined the association between body habitus and incidence of pituitary adenoma. To determine if body mass index (BMI), waist circumference, body somatotype, or height are associated with risk of pituitary adenoma. Pooled analysis of 3 prospective cohort studies. Population-based study. Participants of the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS), totaling 284 946 American health professionals. BMI, waist circumference, body somatotype, and height. Self-reported incident pituitary adenoma. Multivariable (MV)-adjusted hazard ratios (HRs) of pituitary adenoma were estimated using Cox proportional hazards models. During 7 350 156 person-years of follow-up, 387 incident pituitary adenomas were reported. Comparing BMI of ≥30 to <25 kg/m2, higher adult BMI was associated with higher risk of pituitary adenoma (MV HR = 1.74; 95% CI, 1.33-2.28), as was higher maximum adult BMI (MV HR = 1.76; 95% CI, 1.34-2.30), higher waist circumference (MV HR = 1.06; 95% CI, 1.04-1.09 per inch), and higher BMI during early adulthood (at age 18 to 21, MV HR = 2.65; 95% CI, 1.56-4.49). Taller adult height was associated with pituitary adenoma (MV HR = 1.05; 95% CI, 1.01-1.09 per inch). Overall findings were similar in women and men, although power was limited in men (n = 62 cases). Sensitivity analyses demonstrated that the association between adult BMI and pituitary adenoma extended to at least 14 years prior to diagnosis and that the results were not affected when analyses were restricted to participants with similar healthcare utilization. Higher BMI and waist circumference, from early adulthood to the time of diagnosis, were associated with higher risk of pituitary adenoma.

Height and risk of ischaemic stroke subtypes: a Mendelian randomisation study

Abstract Background Taller adult height is associated with lower risks of ischaemic heart disease in both conventional and Mendelian randomisation studies, providing support for a causal association, but the associations of height with ischaemic stroke and ischaemic stroke subtypes are uncertain. Purpose To examine the causal relevance of height for ischaemic stroke and ischaemic stroke subtypes. Methods Two-sample Mendelian randomisation analyses were used to examine the associations of height with: (i) ischaemic stroke and ischaemic stroke subtypes in MEGASTROKE (using summary data from 34 217 ischaemic stroke cases), and with (ii) established cardiovascular and other risk factors using individual data from 336 433 participants in UK Biobank and 57 785 in the China Kadoorie Biobank. Instruments for Mendelian randomisation were constructed from up to 3280 height-associated genetic variants, previously identified as having genome-wide significant effects on height. Results Genetically-determined taller height was inversely associated with ischaemic stroke (3% [95% CI: 1–6] lower risk per 1 standard deviation taller height) in MEGASTROKE but this masked much stronger opposing associations on risks of different ischaemic stroke subtypes: 15% (95% CI: 9–21) higher risk of cardioembolic stroke, 10% (4–15) lower risk of large-artery atherosclerotic stroke, and 15% (10–20) lower risk of small-vessel stroke (Figure). Genetically-determined taller height was strongly associated with atrial fibrillation and higher lean body mass and lung function but more weakly associated with lower levels of LDL cholesterol and blood pressure. Conclusions The findings support a causal association between taller adult height and risk of atrial fibrillation and cardioembolic stroke. The opposing associations of height with other ischaemic stroke subtypes provide further support for considering ischaemic stroke subtypes as distinct diseases in both research and clinical practice. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Medical Research Council, British Heart Foundation

Pubertal Growth, IGF-1, and Windows of Susceptibility: Puberty and Future Breast Cancer Risk

PurposeRisk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty. MethodsThis is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6–7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (E:A) ratio. ResultsPHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater E:A ratio was associated with earlier AAM. ConclusionsFactors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

As tall as my peers – similarity in body height between migrants and hosts

• This literature review evaluated the phenomenon of faster growth, earlier maturation and often taller adult height in migrant youth as compared to their non-migrant relatives.

Weight Gain and Height Growth during Infancy, Childhood, and Adolescence as Predictors of Adult Cardiovascular Risk

ObjectivesTo investigate independent relationships of childhood linear growth (height gain) and relative weight gain to adult cardiovascular disease (CVD) risk traits in Asian Indians.Study designData from 2218 adults from the Vellore Birth Cohort were examined for associations of cross-sectional height and body mass index (BMI) and longitudinal growth (independent conditional measures of height and weight gain) in infancy, childhood, adolescence, and adulthood with adult waist circumference (WC), blood pressure (BP), insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR]), and plasma glucose and lipid concentrations.ResultsHigher BMI/greater conditional relative weight gain at all ages was associated with higher adult WC, after 3 months with higher adult BP, HOMA-IR, and lipids, and after 15 years with higher glucose concentrations. Taller adult height was associated with higher WC (men β = 2.32 cm per SD, women β = 1.63, both P < .001), BP (men β = 2.10 mm Hg per SD, women β = 1.21, both P ≤ .001), and HOMA-IR (men β = 0.08 log units per SD, women β = 0.12, both P ≤ .05) but lower glucose concentrations (women β = −0.03 log mmol/L per SD P = .003). Greater height or height gain at all earlier ages were associated with higher adult CVD risk traits. These positive associations were attenuated when adjusted for adult BMI and height. Shorter length and lower BMI at birth were associated with higher glucose concentration in women.ConclusionsGreater height or weight gain relative to height during childhood or adolescence was associated with a more adverse adult CVD risk marker profile, and this was mostly attributable to larger adult size.

Season of birth is associated with birth weight, pubertal timing, adult body size and educational attainment: a UK Biobank study.

Season of birth, a marker of in utero vitamin D exposure, has been associated with a wide range of health outcomes. Using a dataset of ∼450,000 participants from the UK Biobank study, we aimed to assess the impact of this seasonality on birth weight, age at menarche, adult height and body mass index (BMI). Birth weight, age at menarche and height, but not BMI, were highly significantly associated with season of birth. Individuals born in summer (June–July–August) had higher mean birth weight (P = 8 × 10−10), later pubertal development (P = 1.1 × 10−45) and taller adult height (P = 6.5 × 10−9) compared to those born in all other seasons. Concordantly, those born in winter (December–January–February) showed directionally opposite differences in these outcomes. A secondary comparison of the extreme differences between months revealed higher odds ratios [95% confidence intervals (CI)] for low birth weight in February vs. September (1.23 [1.15–1.32], P = 4.4 × 10−10), for early puberty in September vs. July (1.22 [1.16–1.28], P = 7.3 × 10−15) and for short stature in December vs. June (1.09 [1.03–1.17], P = 0.006). The above associations were also seen with total hours of sunshine during the second trimester, but not during the first three months after birth. Additional associations were observed with educational attainment; individuals born in autumn vs. summer were more likely to continue in education post age 16 years (P = 1.1 × 10−91) or attain a degree-level qualification (P = 4 × 10−7). However, unlike other outcomes, an abrupt difference was seen between those born in August vs. September, which flank the start of the school year. Our findings provide support for the ‘fetal programming’ hypothesis, refining and extending the impact that season of birth has on childhood growth and development. Whilst other mechanisms may contribute to these associations, these findings are consistent with a possible role of in utero vitamin D exposure.

WS11.8 Early diagnosis through newborn screening (NBS) improved long-term growth and adult height at age 18 years in CF patients with pancreatic insufficiency

Objectives To determine if early growth benefit of NBS sustains to adulthood, we compared adolescent peak height velocity (PHV) between screened (diagnosed early via NBS) and control (identified by symptoms) groups in the Wisconsin RCT. Methods Data from 106 patients born in 1985–94 and followed through 2012 with the same care protocol were analyzed. Results Pancreatic sufficient patients (n = 18) achieved normal pubertal PHV and adult height at age 18 y ( th %tile). Meconium ileus patients (MI, n=25) had reduced PHV and shorter adult height at age 18 y (males: 34 th %tile; females: 17 th %tile). In non-MI patients who had pancreatic insufficiency (n = 64), boys in the screened group (n = 22) had normal and slightly higher PHV (9.5 cm/y at 13.5 y) than the control group (n = 29, 8.9 cm/y at 13.6 y), girls in the screened group (n = 13) had later and slightly lower PHV (7.3 cm/y at 12.5 y) compared to control group (n = 11, 7.9 cm/y at 11.7 y), but the lower PHV in screened girls coincided with later menarche (13.6 y vs. 12.2 y) and was compensated by longer duration of pre-pubertal growth. Thus, adult heights at age 18 y in both sexes were taller in screened compared to control (50 th vs. 29 th %tile, p=0.025), which remained significant after adjusting for parental height (32 nd vs 15 th %tile, p=0.003). Multiple regression analysis revealed that the taller adult height in the screened group was primarily due to achievement of better pre-pubertal height (e.g., 47 th vs. 27 th percentile at age 7 y) rather than greater adolescent PHV. Conclusion This longest duration cohort study shows that early diagnosis/care can promote better long term growth and is a sustained benefit of NBS.

Persistent short stature, other potential outcomes, and the effect of growth hormone treatment in children who are born small for gestational age.

Persistent short stature, other potential outcomes, and the effect of growth hormone treatment in children who are born small for gestational age.

Adolescence and breast carcinoma risk.

Breast carcinoma risk may be modified by early life factors, including physical growth and development, diet, and life-style factors of preadolescence and adolescence, as well as genetic factors. The authors tested their hypothesis that adolescent growth and development are related to breast carcinoma incidence by evaluating 65,140 women who participated in the Nurses' Health Study. During 16 years of follow-up, 806 women were diagnosed with breast carcinoma prior to menopause, and another 1485 were diagnosed after menopause. Because adolescent growth was not directly observed in this cohort, the peak height growth velocity for each participant was estimated by using a model from another longitudinal study. Finally, Cox proportional hazards regression models were used to study associations between breast carcinoma incidence and adolescent factors in the Nurses' Health Study. Later menarche (relative risk [RR] = 0.52 for > or =15 vs. < or =11 years) and more body fatness at age 10 years (RR = 0.60 for fattest vs. leanest) were associated with a decreased risk of premenopausal breast carcinoma. The risk of postmenopausal breast carcinoma was lower for girls with later menarche (RR = 0.80), more body fat at age 10 years (RR = 0.72), and shorter adult height (RR = 1.29 for > or =67 vs. < or =62 inches). Higher peak height growth velocity, derived from these 3 variables, was associated with increased risk of both premenopausal (RR = 1.31 for highest vs. lowest quintile) and postmenopausal (RR = 1.40) breast carcinoma. These analyses controlled for birth cohort, other possible risk factors from the adolescent period, and family history. These associations persisted after controlling for age at the birth of a first child, parity, adult adiposity, and age at menopause. Post-hoc analyses suggested that, although childhood body fatness was associated with lower risk, increasing body fatness between ages 10 and 20 years was not protective against either premenopausal or postmenopausal breast carcinoma. Earlier menarche, extremely lean body mass at age 10 years, and taller adult height were predictive of elevated breast carcinoma risk. The same three factors were also predictive of higher peak growth velocities during adolescence, lending credence to the hypothesis that more rapid adolescent growth may increase the risk of breast carcinoma development.

Adult height and menstrual history among patients with classical 21-hydroxylase deficiency adrenal hyperplasia: Correlation with growth and therapy during development

Study Objective: To assess the outcome variables of menstrual and reproductive history and height among adult females with 21-hydroxylase congenital adrenal hyperplasia based upon parameters of adequacy of glucocorticoid suppressive therapy, parental heights, and growth during infancy, childhood, and adolescence.Design and Participants: Forty-three women and adolescents with 21-hydroxylase deficiency were evaluated using interviews, medical record reviews, and physical examination. Patients were categorized by menstrual regularity into three groups: A—regular menses (n = 15), B—irregular menses (n = 9), and C—regular menses that subsequently became irregular (n = 10). For comparison, a group of nine currently pubertal, premenarchal girls with classical 21-hydroxylase deficiency (group D) were similarly evaluated. Age of diagnosis, growth parameters, hormonal indices, age of puberty and menarche onset, and relative glucocorticoid dosages were compared among the groups.Results: Adult height, corrected for midparental height, was taller in A compared with B and C (p < 0.03), although actual height at age 3 years and at the onset of puberty did not differ. Hormonal indices were least suppressed in B and best suppressed in D. Group C was better suppressed than B during puberty and adulthood. Age at diagnosis, concurrent mineralocorticoid therapy, glucocorticoid or equivalent dosage/M2, skeletal age Z scores, pubertal onset, and menarche age did not differ among the groups. Two women (group A) had normal pregnancies.Conclusion: Although the small numbers preclude significant differences in many of the analyses, there is a definite trend for Group A with the tallest height and regular menses to have had tighter control with lower androgen levels in infancy, childhood, puberty, and during adulthood. Results also suggest that adequate suppression during puberty will permit the onset of regular menses as the group that developed irregular menses after initial regular cycles (C) was better suppressed during puberty than the group that never menstruated regularly. Follow-up of group D, the younger, more recently treated patients, should provide better evidence as to whether tighter control will result in taller adult height and regular menses.