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Epidemiology Studies - Hypotheses
  Hypotheses
    Prepubertal obesity, driven by environmental, psychosocial, and genetic factors, leads to a pathway of pubertal development in which estrogen and insulin-like growth factors stimulate breast development as the first sign of puberty. Girls with a family history of breast cancer are more likely to develop through this pathway.

Our underlying hypothesis is that prepubertal obesity, driven by environmental exposures, as well as psychosocial and genetic factors, leads to a pathway of pubertal development in which estrogen and related growth factors stimulate breast development as the initial manifestation of puberty, and that girls with a family history of breast cancer are more likely to develop through this pathway. This pathway leads to earlier menarche, as well as other physiological states such as central adiposity, that increases the susceptibility of the breast to subsequent factors that occur during life to increase risk of developing breast cancer.

A recent longitudinal study followed girls annually from ages 9 and 10 through 19 and 20. 443 of 949 girls demonstrated had either areolar or pubic hair development without maturation of the other (asynchronous maturation). Of those 443 with asynchronous maturation, 291 (65.7%) had areolar and breast development without pubic hair at the onset of puberty (thelarche pathway) and 152 (34.3%) had pubic hair without areolar or breast development (adrenarche pathway). Girls who had breast development (thelarche) prior to pubic hair development (adrenarche) had similar ages at onset of puberty, but an earlier age of menarche (12.6 years v 13.1 years, p < 0.001). At the time of menarche, these girls in the thelarche pathway had a greater percent body fat (23.9% v 21.4%, p < 0.01), body mass index (21.2 v 19.3, p < 0.001), and waist to hip ratio (0.779 v 0.759, p < 0.001). Additionally, despite indistinguishable differences in age of pubertal onset, these girls had greater body fat and body mass index one year prior to onset of puberty (Biro FM, Lucky AW, Simbartl LA, Barton BA, Daniels SR, Striegel-Moore R, Kronsberg SS, Morrison JA. Pubertal maturation in girls and relationship to anthropometric changes: Pathways through puberty. J Pediatr 2003;142:643-6).

These girls who are noted to have areolar development prior to pubic hair have a maturation and anthropometric profile similar to epidemiologic studies in women with breast cancer.


Pathways thru Puberty Model