Early and current physical activity: relationship with intima-media thickness and metabolic variables in adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Possible underestimation by sports medicine of the effects of early physical exercise practice on the prevention of diseases in adulthood

In modern society, combatting cardiovascular and metabolic diseases has been highlighted as an urgent global challenge. In recent decades, the scientific literature has identified that behavioral variables (e.g. smoking, unhealthy diet and physical inactivity) are related to the development of these outcomes and, therefore, preventive actions should focus on the promotion of physical exercise practice and a healthy diet, as well as combatting the smoking habit from an early age. The promotion of physical exercise in the general population has been suggested as a relevant goal by significant health organizations around the world. On the other hand, recent literature has indicated that physical exercise performed in early life prevents the development of diabetes mellitus, dyslipidemia and arterial hypertension during adulthood, although this protective effect seems to be independent of the physical activity performed during adulthood. Apparently, the interaction between physical exercise and human growth in early life constitutes an issue which is not completely understood by sports medicine. The aim of the present review was therefore to discuss recent evidence on the effects of physical exercise performed during childhood and adolescence on cardiovascular and metabolic outcomes in adulthood.

Is socioeconomic position early in life associated with physical activity during adulthood following the accumulation of risk model with additive effects?

L'activité physique améliore la santé, mais seulement 4.8% des Canadiens atteignent le niveau recommandé. La position socio-économique est un des déterminants de l'activité physique les plus importants. Elle est associée à l’activité physique de manière transversale à l’adolescence et à l’âge adulte. Cette thèse a tenté de déterminer s'il y a une association à long terme entre la position socio-économique au début du parcours de vie et l’activité physique à l’âge adulte. S'il y en avait une, un deuxième objectif était de déterminer quel modèle théorique en épidémiologie des parcours de vie décrivait le mieux sa forme. Cette thèse comprend trois articles: une recension systématique et deux recherches originales. Dans la recension systématique, des recherches ont été faites dans Medline et EMBASE pour trouver les études ayant mesuré la position socio-économique avant l'âge de 18 ans et l'activité physique à ≥18 ans. Dans les deux recherches originales, la modélisation par équations structurelles a été utilisée pour comparer trois modèles alternatifs en épidémiologie des parcours de vie: le modèle d’accumulation de risque avec effets additifs, le modèle d’accumulation de risque avec effet déclenché et le modèle de période critique. Ces modèles ont été comparés dans deux cohortes prospectives représentatives à l'échelle nationale: la 1970 British birth cohort (n=16,571; première recherche) et l’Enquête longitudinale nationale sur les enfants et les jeunes (n=16,903; deuxième recherche). Dans la recension systématique, 10 619 articles ont été passés en revue par deux chercheurs indépendants et 42 ont été retenus. Pour le résultat «activité physique» (tous types et mesures confondus), une association significative avec la position socio-économique durant l’enfance fut trouvée dans 26/42 études (61,9%). Quand seulement l’activité physique durant les loisirs a été considérée, une association significative fut trouvée dans 21/31 études (67,7%). Dans un sous-échantillon de 21 études ayant une méthodologie plus forte, les proportions d’études ayant trouvé une association furent plus hautes : 15/21 (71,4%) pour tous les types et toutes les mesures d’activité physique et 12/15 (80%) pour l’activité physique de loisir seulement. Dans notre première recherche originale sur les données de la British birth cohort, pour la classe sociale, nous avons trouvé que le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux chez les hommes et les femmes pour l’activité physique de loisir, au travail et durant les transports. Dans notre deuxième recherche originale sur les données canadiennes sur l'activité physique de loisir, nous avons trouvé que chez les hommes, le modèle de période critique s’est ajusté le mieux aux données pour le niveau d’éducation et le revenu, alors que chez les femmes, le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux pour le revenu, tandis que le niveau d’éducation ne s’est ajusté à aucun des modèles testés. En conclusion, notre recension systématique indique que la position socio-économique au début du parcours de vie est associée à la pratique d'activité physique à l'âge adulte. Les résultats de nos deux recherches originales suggèrent un patron d’associations le mieux représenté par le modèle d’accumulation de risque avec effets additifs.

Is socioeconomic position early in life associated with physical activity during adulthood following the accumulation of risk model with additive effects?

L'activité physique améliore la santé, mais seulement 4.8% des Canadiens atteignent le niveau recommandé. La position socio-économique est un des déterminants de l'activité physique les plus importants. Elle est associée à l’activité physique de manière transversale à l’adolescence et à l’âge adulte. Cette thèse a tenté de déterminer s'il y a une association à long terme entre la position socio-économique au début du parcours de vie et l’activité physique à l’âge adulte. S'il y en avait une, un deuxième objectif était de déterminer quel modèle théorique en épidémiologie des parcours de vie décrivait le mieux sa forme. Cette thèse comprend trois articles: une recension systématique et deux recherches originales. Dans la recension systématique, des recherches ont été faites dans Medline et EMBASE pour trouver les études ayant mesuré la position socio-économique avant l'âge de 18 ans et l'activité physique à ≥18 ans. Dans les deux recherches originales, la modélisation par équations structurelles a été utilisée pour comparer trois modèles alternatifs en épidémiologie des parcours de vie: le modèle d’accumulation de risque avec effets additifs, le modèle d’accumulation de risque avec effet déclenché et le modèle de période critique. Ces modèles ont été comparés dans deux cohortes prospectives représentatives à l'échelle nationale: la 1970 British birth cohort (n=16,571; première recherche) et l’Enquête longitudinale nationale sur les enfants et les jeunes (n=16,903; deuxième recherche). Dans la recension systématique, 10 619 articles ont été passés en revue par deux chercheurs indépendants et 42 ont été retenus. Pour le résultat «activité physique» (tous types et mesures confondus), une association significative avec la position socio-économique durant l’enfance fut trouvée dans 26/42 études (61,9%). Quand seulement l’activité physique durant les loisirs a été considérée, une association significative fut trouvée dans 21/31 études (67,7%). Dans un sous-échantillon de 21 études ayant une méthodologie plus forte, les proportions d’études ayant trouvé une association furent plus hautes : 15/21 (71,4%) pour tous les types et toutes les mesures d’activité physique et 12/15 (80%) pour l’activité physique de loisir seulement. Dans notre première recherche originale sur les données de la British birth cohort, pour la classe sociale, nous avons trouvé que le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux chez les hommes et les femmes pour l’activité physique de loisir, au travail et durant les transports. Dans notre deuxième recherche originale sur les données canadiennes sur l'activité physique de loisir, nous avons trouvé que chez les hommes, le modèle de période critique s’est ajusté le mieux aux données pour le niveau d’éducation et le revenu, alors que chez les femmes, le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux pour le revenu, tandis que le niveau d’éducation ne s’est ajusté à aucun des modèles testés. En conclusion, notre recension systématique indique que la position socio-économique au début du parcours de vie est associée à la pratique d'activité physique à l'âge adulte. Les résultats de nos deux recherches originales suggèrent un patron d’associations le mieux représenté par le modèle d’accumulation de risque avec effets additifs.

Adversity in early adolescence alters female rats' anxiety-related behaviours and serotonergic innervation profiles in adulthood

Stress during early development produces lasting effects on psychopathological outcomes. The impact of prior intermittent, physical stress (IPS) during early-adolescence (PD 22-33) on anxiety-related behaviour of female rats was analyzed in adulthood. After behavioural testing, serotonergic innervation was evaluated using immunohistochemistry for the serotonin transporter (SERT) in the medial prefrontal cortex (mPFC) and ventral hippocampus. Administration of IPS (i.e., water immersion, elevated platform, foot shock) in early adolescence increased rats’ anxiety-like behaviour in the elevated plus-maze but had no effects in the shock-probe burying test. In the social interaction test, IPS decreased social interaction, and this effect was driven by selective decreases in the duration of playfighting with no evident changes in contact or investigative behaviour. Selective stress-induced increases in SERT-immunoreactive axon density were found in the infralimbic (IL) subregion of the mPFC, but not in the cingulate or prelimbic (PL) subregions. IPS in early adolescence did not affect serotonergic innervation profiles in any sub-fields of the ventral hippocampus. The findings confirm and extend on earlier evidence that stress during early adolescence promotes the emergence of an anxious phenotype, and provide novel evidence that these effects may be mediated, at least in part, by increased serotonergic innervation of the IL mPFC.

Early life exposure to chronic intermittent hypoxia primes increased susceptibility to hypoxia-induced weakness in rat sternohyoid muscle during adulthood

Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

Screening in early childhood for risk of later mental health problems : a longitudinal study

Depression in childhood or adolescence is associated with increased rates of depression in adulthood. Does this justify efforts to detect (and treat) those with symptoms of depression in early childhood or adolescence? The aim of this study was to determine how well symptoms of anxiety/depression (A-D) in early childhood and adolescence predict adult mental health. The study sample is taken from a population-based prospective birth cohort study. Of the 8556 mothers initially approached to participate 8458 agreed, of whom 7223 mothers gave birth to a live singleton baby. Children were screened using modified Child Behaviour Checklist (CBCL) scales for internalizing and total problems (T-P) at age 5 and the CBCL and Youth Self Report (YSR) A-D subscale and T-P scale at age 14. At age 21, a sub-sample of 2563 young adults in this cohort were administered the CIDI-Auto. Results indicated that screening at age 5 would detect few later cases of significant mental ill-health. Using a cut-point of 20% for internalizing at child age 5 years the CBCL had sensitivities of only 25% and 18% for major depression and anxiety disorders at 21 years, respectively. At age 14, the YSR generally performed a little better than the CBCL as a screening instrument, but neither performed at a satisfactory level. Of the children who were categorised as having YSR A-D at 14 years 30% and 37% met DSM-IV criteria for major depression and anxiety disorders, respectively, at age 21. Our findings challenge an existing movement encouraging the detection and treatment of those with symptoms of mental illness in early childhood.

Early life predictors of preschool overweight and obesity : a case–control study in Sri Lanka

Background Childhood obesity increases the risk of obesity in adulthood and is associated with cardiovascular disease risk factors. Our aim was to assess the early life risk factors associated with overweight and obesity among preschool children. Methods In this case–control study, from the 1087 preschool children measured, age, sex and ethnicity matched 71 cases and 71 controls were recruited. Cases and controls were defined according to the WHO 2006 growth standards. The birth and growth characteristics were extracted from the child health development records. Infant feeding practices and maternal factors were obtained from the mother. Rapid weight gain was defined as an increase in weight-for-age Z score (WHO standards) above 0.67 SD from birth to 2 years. The magnitude and significant difference in mean values of the variables associated with overweight and obesity were evaluated using logistic regressions and paired t-test, respectively. Results Cases had significantly shorter duration (months) of breastfeeding (19.4, 24.6, p = 0.003), and smaller duration (months) of exclusive breastfeeding (3.7, 5.1, p = 0.001) compared to controls. Rapid weight gain (OR = 6.3, 95% CI = 2.04–19.49), first born status (OR = 3.6, 95% CI = 1.17-10.91) and pre-pregnancy obesity (OR = 4.0, 95% CI = 1.46-10.76) were positively associated with overweight and obesity. Breastfeeding more than 2 years (OR = 0.2, 95% CI = 0.06-0.57) was negatively associated with overweight and obesity. Conclusion Rapid weight gain within first two years, first–born status and pre-pregnancy obesity of the mother contributed for preschool obesity. Our results suggest that intervention may be indicated earlier in infancy and during the toddler and preschool years to tackle the increasing prevalence of obesity.

Potentiation of the early visual response to learned danger signals in adults and adolescents

The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents.

Religion, spirituality, and mental health and social behaviour in young adulthood: A longitudinal study

Background The concept spirituality appears to be gaining increasing attention for its potential relationship to mental health, despite there being an absence of consensus on what spirituality is or whether it can be distinguished from religion (or religiousness) in operational terms. Spirituality is a term that is embraced within secular and non-secular contexts alike. As a consequence, spirituality as a concept encompasses forms of religiosity that are embedded in traditional religion and those that have little or no connection to traditional religious teachings. The emergence of religious/spiritual beliefs that depart from traditional religious thought represents one key feature of widespread religious change in contemporary societies. Non-traditional religious/spiritual beliefs need to be viewed within this context and thus be differentiated from traditional religious/spiritual beliefs when investigating connections between religion, spirituality, and mental health. Aims The current study seeks to compare the mental health of those whose beliefs are rooted in religious tradition with those whose beliefs deviate from traditional religious thought. The two main objectives of this study are: (1) to determine the extent to which religious background predicts endorsement of traditional and non-traditional religious/spiritual beliefs and church attendance in young adulthood, and; (2) to determine whether differential relationships exist between current religiosity, religious background, and mental health in young adulthood, and whether any observed differences are attributable to other characteristics of respondents like sociodemographic factors and health-risk behaviours. Methods Data were derived from the Mater-University of Queensland Study of Pregnancy, a longitudinal, prospective study of maternal and child health from the prenatal period to 21 years post-delivery. Religiosity was assessed among the study children in young adulthood from three items measured at the time of the 21-year follow-up. Religious background was assessed from information provided by the study mothers in earlier phases of the study. Young adult responses to items included in the Young Adult Self Report (Achenbach, 1997) were used to assess cases of anxiety/depression and externalising behaviour, and delusional ideation was assessed from their responses to the 21-item Peters et al. Delusions Inventory (PDI) (Peters & Garety, 1996). Results Belief in a spiritual or higher power other than God was found to be positively related to anxiety/depression, disturbed ideation, suspiciousness and paranormal ideation, high total PDI scores, as well as antisocial behaviour in young adulthood, regardless of gender. These associations persisted after adjustment for potential confounders. By contrast, young adults who maintain a traditional belief in God appear to be no different to those who reject this belief in regard to anxiety/depression. Belief in God was found to have no association with antisocial behaviour for males, but was observed to have a weak negative relationship with antisocial behaviour for females. This association failed to reach statistical significance however, after adjustment for other religious/spiritual and social characteristics. No associations were found between young adult belief in God and disturbed, suspicious or paranormal ideation, although a positive relationship was identified for high total PDI scores. Weekly church attendance was observed to reduce the likelihood of antisocial behaviour in young adulthood among males, but not females. Religious ideation was found to more prevalent among young adults who attend church on either a weekly or infrequent basis. No long-term effects on anxiety/depression or antisocial behaviour were evident from maternal belief in God, church attendance or religious affiliation in the young adults’ early lives. However, maternal church attendance predicted religious ideation in young adulthood. Offspring of mothers affiliated with a Pentecostal church in the prenatal period appear to have a high rate of religious ideation and high total PDI scores. Paranormal ideation in young adulthood appears to have no association with maternal religiosity in a young adult’s early life. Conclusion The findings from this study suggest that young adults who endorse non-traditional religious/spiritual beliefs are at greater risk for poorer mental health and aberrant social behaviour than those who reject these beliefs. These results suggest that a non-traditional religious/spiritual belief system involves more than mere rejection of traditional religious doctrine. This system of belief may be a marker for those who question the legitimacy of established societal norms and values, and whose thoughts, attitudes and actions reflect this position. This possibility has implications for mental health and wellbeing at both an individual and a societal level and warrants further research attention.

Parental divorce and adjustment in adulthood: Findings from a community sample

The current study examines the link between the experience of divorce in childhood and several indices of adjustment in adulthood in a large community sample of women. Results replicated previous research on the long-term correlation between parental divorce and depression and divorce in adulthood. Results further suggested that parental divorce was associated with a wide range of early risk factors, life course patterns, and several indices of adult adjustment. Regression analyses indicated that the long-term correlation between parental divorce and depression in adulthood is explained by quality of parent-child and parental marital relations (in childhood), concurrent levels of stressful life events and social support, and cohabitation. The long-term association between parental divorce and experiencing a divorce in adulthood was partly mediated through quality of parent-child relations, teenage pregnancy, leaving home before 18 years, and educational attainment.

Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: A cohort study

Aim Scoliosis is a common co-morbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Method Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. Results After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12–0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06–0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16–1.03; p=0.06). Interpretation With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

Diet and the development of atherosclerosis: a whole-diet approach from childhood to adulthood

Cardiovascular diseases (CVDs) are the leading cause of mortality in the world. Studies of the impact of single nutrients on the risk for CVD have often provided inconclusive results, and recent research in nutritional epidemiology with a more holistic whole-diet approach has proven fruitful. Moreover, dietary habits in childhood and adolescence may play a role in later health and disease, either independently or by tracking into adulthood. The main aims of this study were to find childhood and adulthood determinants of adulthood diet, to identify dietary patterns present among the study population and to study the associations between long-term food choices and cardiovascular health in young Finnish adults. The study is a part of the multidisciplinary Cardiovascular Risk in Young Finns study, which is an ongoing, prospective cohort study with a 21-year follow-up. At baseline in 1980, the subjects were children and adolescents aged 3 to 18 years (n included in this study = 1768), and young adults aged 24 to 39 years at the latest follow-up study in 2001 (n = 1037). Food consumption and nutrient intakes were assessed with repeated 48-hour dietary recalls. Other determinations have included comprehensive risk factor assessments using blood tests, physical measurements and questionnaires. In the latest follow-up, ultrasound examinations were performed to study early atherosclerotic vascular changes. The average intakes showed substantial changes since 1980. Intakes of fat and saturated fat had decreased, whereas the consumption of fruits and vegetables had increased. Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of adult diet. Additionally, a principal component analysis was conducted to identify major dietary patterns at each study point. A similar set of two major patterns was recognised throughout the study. The traditional dietary pattern positively correlated with the consumption of traditional Finnish foods, such as rye, potatoes, milk, butter, sausages and coffee, and negatively correlated with fruit, berries and dairy products other than milk. This type of diet was independently associated with several risk factors of CVD, such as total and low-density lipoprotein cholesterol, apolipoprotein B and C-reactive protein concentrations among both genders, as well as with systolic blood pressure and insulin levels among women. The traditional pattern was also independently associated with intima media thickness (IMT), a subclinical predictor of CVD, in men but not in women. The health-conscious pattern, predominant among female subjects, non-smokers and urbanites, was characterised by more health-conscious food choices such as vegetables, legumes and nuts, tea, rye, fish, cheese and other dairy products, as well as by the consumption of alcoholic beverages. This pattern was inversely, but less strongly, associated with cardiovascular risk factors. Tracking of the dietary pattern scores was observed, particularly among subjects who were adolescents at baseline. Moreover, a long-term high intake of protein concurrent with a low intake of fat was positively associated with IMT. These findings suggest that food behaviour and food choices are to some extent established as early as in childhood or adolescence and may significantly track into adulthood. Long-term adherence to traditional food choices seems to increase the risk for developing CVD, especially among men. Those with intentional or unintentional low fat diets, but with high intake of protein may also be at increased risk for CVD. The findings offer practical, food-based information on the relationship between diet and CVD and encourage further use of the whole-diet approach in epidemiological research. The results support earlier findings that long-term food choices play a role in the development of CVD. The apparent influence of childhood habits is important to bear in mind when planning educational strategies for the primary prevention of CVD. Further studies on food choices over the entire lifespan are needed.

Rethinking Early Childhood Education and Care: Implications for Research and Evaluation

Research in disadvantaged populations demonstrates that the effect of Early Childhood Education and Care (ECEC) programs can reach into adulthood and influence a wide range of achievement and social well-being outcomes. In English-speaking developed economies, these findings have sparked new perceptions of the role ECEC programs play in both the public and private sphere. Programs that achieve improved learning and social well-being for children are seen as an investment for both individuals and society. Yet, the empirical understanding of what programs best deliver positive outcomes across the diversity of social contexts is limited. A key research task is to identify the forms of ECEC that are most effective in delivering enduring and broad positive outcomes for all children. This article explores changing policy conceptualizations of ECEC, the outcome goals of ECEC, and directions for research in identifying quality in ECEC programs.

Impact of Early Postnatal Androgen Exposure on Voice Development

Background: the impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood.Methods: the long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels.Results: of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz.Conclusions: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.