Zumoff B
Cancer Res. 1982 Aug;42(8 Suppl):3289s-3294s.
It has become conventional wisdom that estrogenic stimulation of breast tissue has something to do with the causation of breast cancer and that the reason obesity is a risk factor for breast cancer is that obese women are hyperestrogenized. However, it has been very difficult to demonstrate that excessive exogenous estrogen increases the incidence of breast cancer, that endogenous estrogen excess is present in breast cancer, or that obese women are hyperestrogenized. We have examined the last question by measuring 24-hr mean plasma estrone and estradiol levels in the midfollicular phase in 18 healthy, regularly cycling, very obese (53 to 218% above ideal weight) women and 16 regularly cycling, age matched, nonobese control women. Unlike obese men, the obese women showed no significant elevation of either estrone or estradiol. Their average estrone level was 72 compared with 64 pg/ml in controls; their average estradiol level was 65 compared with 57 pg/ml in controls. In the combined group (obese plus nonobese), there was a significant correlation of percentage of deviation from ideal weight with plasma estrone (y = 63 + 0.12x; p less than 0.05) but not with estradiol. This correlation supports the current hypothesis that there is increased androstenedione leads to estrone conversion (i.e., increased aromatase activity) in obesity. The reason plasma estrone levels are not significantly elevated in obese women is that the small amount derived from androstenedione is swamped by the much larger amount derived from ovarian secretion, which is apparently unaffected by obesity. Unless there is increased local formation of estrogens in the breast tissue of obese women, the absence of elevated plasma estrogens in them means that their breasts are not "seeing" increased estrogen levels. Thus, endogenous hyperestrogenization is unlikely to be a causative factor of breast cancer in obese women.U
雌激素对乳腺组织的刺激与乳腺癌的发生有关，肥胖是乳腺癌的一个风险因素，原因是肥胖女性处于高雌激素状态，这已成为一种传统观念。然而，要证明外源性雌激素过量会增加乳腺癌的发病率、乳腺癌中存在内源性雌激素过量，或者肥胖女性处于高雌激素状态，一直非常困难。我们通过测量18名健康、月经周期正常、极度肥胖（比理想体重高53%至218%）的女性和16名月经周期正常、年龄匹配的非肥胖对照女性在卵泡中期的24小时平均血浆雌酮和雌二醇水平，研究了最后一个问题。与肥胖男性不同，肥胖女性的雌酮或雌二醇水平均未显著升高。她们的平均雌酮水平为72，而对照组为64 pg/ml；她们的平均雌二醇水平为65，而对照组为57 pg/ml。在联合组（肥胖加非肥胖）中，与理想体重的偏差百分比与血浆雌酮存在显著相关性（y = 63 + 0.12x；p小于0.05），但与雌二醇无关。这种相关性支持了当前的假说，即肥胖中雄烯二酮增加导致雌酮转化（即芳香化酶活性增加）。肥胖女性血浆雌酮水平未显著升高的原因是，来自雄烯二酮的少量雌酮被来自卵巢分泌的大量雌酮所淹没，而卵巢分泌显然不受肥胖影响。除非肥胖女性乳腺组织中雌激素的局部生成增加，否则她们血浆雌激素未升高意味着她们的乳腺并未“接触”到升高的雌激素水平。因此，内源性高雌激素状态不太可能是肥胖女性患乳腺癌的致病因素。
