Obesity has been associated with an increased incidence of a variety of neoplasms, including several arising from hormone-responsive tissues such as breast, endometrium and prostate. Nutritional and lifestyle factors may combine to generate the pandemic of obesety which seems characteristic of western societies where these obesity-linked cancers are more common. Obesity is associated with several abnormalities of androgen and estrogen production, transport and metabolism. Obese women have increased production rates of a variety of androgens, increased peripheral metabolism of androgens to estrogens and increased estrogen production rates. Further, obesity is associated with decreased levels of sex hormone binding globulin (SHBG) favoring increased circulating levels of free hormone binding globulin (SHBG) favoring increased circulating levels of free (biologically active) hormones, as well as resulting in increased hormone metabolic clearance rates. Differences in the hormones of environment and the obese women may influence tissues which normally respond to hormones and could act to augment or promote neoplastic changes which eventually result in the emergency of cancer. There now seems to be ample data to suggest that not all obesity is the same, and that perhaps different phenotypes of obesity are associated with differing hormonal environments. Upper body (android) obesity appears to be associated with carbohydrate abnormalities as well as preliminary evidence suggesting hyperandrogenism. Lower body (gynoid) obesity is more prevalent in women compared to men and exogenous estrogens seems to promote a gynoid distribution of adiposity. These adipose phenotypes need to be systematically explored, particularly regarding sex hormone production, action and metabolism. This study will explore the dynamics of sex hormone production in women with android and gynoid phenotypes of obesity. Our studies will provide the biochemical background for more classical epidemiological surveys to assess obesity phenotype vs. cancer risk. Such an attempt to """"""""fine tune"""""""" on hormonal dynamics in specific types of obesity might provide an important link between hormones and cancer risk.
| Kirschner, M A; Samojlik, E; Drejka, M et al. (1990) Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 70:473-9 |
| Ertel, N H; Akgun, S; Samojlik, E et al. (1989) Decreased 3 alpha-androstanediol glucuronide levels in plasma and random urines in male pseudohermaphroditism caused by 5 alpha-reductase deficiency. Metabolism 38:817-21 |
