Opposing Influences of Prenatal and Postnatal Weight Gain on Adrenarche in Normal Boys and Girls

Abstract

Associations between low birth weight and higher adrenal androgen secretion before puberty have yet only been reported in case-control studies in girls. We examined the influence of birth weight and early postnatal weight gain on overnight-fasting adrenal androgen and cortisol levels in 770 children from a large normal United Kingdom birth cohort at age 8 yr. In univariate analyses, adrenal androgen levels were inversely related to birth weight SD score in each sex [dehydroepiandrosterone sulfate in boys: regression coefficient (B) ‫؍‬ ؊2.5 g/dl/SD; 95% confidence interval (CI), ؊4.7 to ؊0.2; in girls: B ‫؍‬ ؊3.8 g/dl/SD; 95% CI, ؊6.2 to ؊1.4; androstenedione in boys: B ‫؍‬ ؊0.15 nmol/liter/SD, 95% CI, ؊0.25 to ؊0.6; in girls: B ‫؍‬ ؊0.13 nmol/liter/SD; 95% CI, ؊0.24 to ؊0.02). In multivariate analyses, both lower birth weight and larger current body weight predicted higher adrenal androgen levels (P < 0.005 for all comparisons). Allowing for current weight, children who showed rapid postnatal weight gain between 0 and 3 yr had higher dehydroepiandrosterone sulfate (P ‫؍‬ 0.002) and androstenedione (P ‫؍‬ 0.004) levels at 8 yr. In contrast, cortisol levels were unrelated to birth weight or current body size. In summary, the relationship between lower birth weight and higher childhood adrenal androgen levels was continuous throughout the range of normal birth weights, and was similar in boys and girls. Adrenal androgen levels were highest in small infants who gained weight rapidly during early childhood. We suggest that higher adrenal androgen secretion could contribute to links between early growth and adult disease risks, possibly by enhancing insulin resistance and central fat deposition. (J Clin Endocrinol

Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

“…An inverse relation of birth size with adrenal androgen levels in 8-year-old children has also been found for children of normal birth size (Ong et al, 2004). In a recent study of hormone levels in premenopausal women, there was a suggestive inverse association of birth weight with DHEAS (Tworoger et al, 2006), with which our adolescent DHEAS findings accord.…”

“…However, should it do so, this would be in conflict with the association between BC risk and the levels of adrenal androgens in adulthood (Kaaks et al, 2005a, b), as a smaller birth size is associated with reduced risk. As for age at menarche, opposing influences of birth size and childhood growth, weight gain and overweight have also been reported for adrenal androgen production in children (Ong et al, 2004), indicating that the combined pattern of prenatal and postnatal growth may define the subsequent risk profile.…”

“…Adult tallness is associated with higher BC risk, and the positive association between birth size and body height suggests that longitudinal growth in childhood and adolescence may be important determinants for subsequent BC (Michels and Willett, 2004). Birth size has also been inversely related to adrenal androgen production during childhood (Ong et al, 2004) and adolescence (Ibanez et al, 1999). Adult levels of both adrenal and gonadal androgens have been associated with BC risk (Kaaks et al, 2005a, b).…”

Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

“…Environmental factors have been thought to account for the reduction in menarcheal age that has been reported since 1850 till 1960 in Scandinavian countries (Tanner, 1962) and further in many European countries and USA (reviewed in Parent et al (2003)). These findings were interpreted as a result of the improvement in life standards and socio-economical conditions (Biro et al, 2006;Dunger et al, 2006;Ong et al, 2004Ong et al, , 2006Cheng et al, 2012;Himes, 2006;Roa and Tena-Sempere, 2010). A projection after 1960 of the former reduction seen in Scandinavian countries ( Fig.…”

“…Altogether, those data are consistent with a prominent role of nutrition availability. The "critical weight/fat mass" theory proposed by Frisch and Revelle (1970) and subsequent work (Biro et al, 2006;Dunger et al, 2006;Ong et al, 2004Ong et al, , 2006Cheng et al, 2012;Himes, 2006;Roa and Tena-Sempere, 2010) have put emphasis on the role of nutritional conditions based on adiposity in puberty, at the time of menarche. The discovery of leptin (Zhang et al, 1994;Campfield et al, 1995) and its prerequisite role in the neuroendocrine control of pubertal maturation and reproduction (reviewed in SanchezGarrido and Tena-Sempere (2013)) has added to the importance of energy balance in the prepubertal period to enable onset and progression of puberty.…”