Estrogen and cancers of the colorectum, breast, and lung in postmenopausal women

Abstract

As estrogens play an important role in maintaining physiological function in various organs, the estrogen decrease after menopause is thought to cause various diseases frequently observed in postmenopausal or elderly women. With the aging of society and a decrease in infectious or vascular diseases, neoplasms have now become the most frequent cause of death in Japan. Cancers of the colorectum, breast, and lung have been rapidly increasing both in incidence and death, especially among postmenopausal women. Interestingly, all three of these cancers are associated with estrogens. In premenopausal women, ovarian estrogens plays major roles in the female reproductive organs through the classic estrogen receptor, ER-α. In postmenopausal women, however, estrogens produced/ activated by peripherally localized estrogen-metabolizing enzymes such as aromatase, which converts androgen into estrogens, are thought to play physiologically and pathobiologically important roles in various organs through second ER, namely ER-β, distributing systemically. In this article, the association of estrogens with these cancers in postmenopausal or elderly women are reviewed, especially focusing on the role of ER-β and peripheral estrogen metabolism. The possibility of prevention or treatment of these diseases through estrogenic control is also discussed.

Apoptotic Bax Gene Expression in Glioblastoma Cells Exposed to Estradiol valerate

“…It has also been reported that estrogen may have protecting effects against various cancers [9]- [10]. The research revealed that estrogen has improving effects on glioblastoma treatment [11].…”

Estrogen-Related Factors in the Frontal Lobe of Alzheimer’s Disease Patients and Importance of Body Mass Index

“…The relative dominance of HSD-1 over HSD-2 would accelerate the conversion of E1 into E2, leading to marked condensation of E2 in the frontal tissue (Fig. 1) 12 . Such a high level of estrogens concentrations in the frontal lobe, together with distinct nuclear ER-β1 expression in glias among controls, may add further evidence for the physiologically important role of the estrogen signaling system in the brain.…”

“…These observations suggest a protective effect of estrogens against AD; however, in Women’s Health Initiative (WHI) hormone therapy trials, where the effect of external female hormone use was tested against a placebo, the risk of AD was reported to increase in women treated with hormone (estrogen-progesterone combined) replacement therapy, raising controversies in this study area 11 . Generally, in postmenopausal women, where estrogens from the ovary markedly decrease, peripheral estrogen synthesis via estrogen-metabolizing enzymes (EMEs) is important as the source of estrogens 12 . EMEs include aromatase, steroid sulfatase (STS), estrogen sulfotransferase (EST), and some types of 17β-hydroxysteroid dehydrogenase (HSD).…”

“…EST and HSD type 2 (HSD-2) play opposite roles to STS and HSD-1, respectively (Fig. 1) 12 . Examining EMEs as well as estrogen levels in the tissue of interest is important for studying the relationship between estrogens and diseases in postmenopausal women 12 .…”

“…Examining EMEs as well as estrogen levels in the tissue of interest is important for studying the relationship between estrogens and diseases in postmenopausal women 12 . Further, examination of the expression of estrogen receptors (ERs) in the target tissues is necessary in this study area, because estrogens cannot exert their function in the absence of ERs even if estrogen concentrations are high enough 8, 12 . Although many studies have examined the association between estrogens and AD, few studies have systematically examined estrogen-related factors (e.g.…”