Epidemiologic evidence relating use of postmenopausal hormones to risk of breast cancer by nature relies on trends in prescribing practices. Data on the adverse effect of combination estrogen plus progestin used for long durations has only become available over the past decade. Evidence is reviewed relating estrogen alone and estrogen plus progestin to increased risk of breast cancer. Whereas current evidence indicates that longer duration of use increases risk of invasive breast cancer regardless of formulation, the rate of increase in risk is greater for combination estrogen plus progestin therapy. Although data are limited, continuous combined therapy and sequential therapy seem to have comparable impact on breast cancer risk. Combination therapy is more strongly related to lobular breast cancer than is estrogen alone. Unresolved issues remain about dose of estrogen and progestin in relation to risk, and about identification of women for whom short-term use to relieve menopausal symptoms may be safe and effective.
"The model could also be improved by including combined HRT and the additional effect of progestin on breast cancer risk. Although combined HRT has a greater effect on breast cancer risk than estrogen-only HRT, the same patterns of interaction with BMI have been observed for both types of HRT . Finally, the model could be refined to reflect the greater effect of estradiol on estrogen-receptor positive than estrogen-receptor negative breast cancer . "
[Show abstract][Hide abstract] ABSTRACT: We present a mathematical model that lends support to the hypothesis that estrogen levels mediate the complex relationship between body mass index (BMI), menopausal status, estrogen-only hormone replacement therapy (HRT), and breast cancer risk. The
model predicts a decrease in the relative risk of breast cancer of 3% per unit increase in BMI
(kg/m2) for premenopausal women and an increase in the relative risk of 4% per unit increase in BMI for postmenopausal women who are not HRT users. When comparing postmenopausal women who use estrogen-only HRT to postmenopausal women who do not use HRT, the model predicts an increased risk of breast cancer associated with use of estrogen that diminishes with increasing BMI, with a relative risk of 1.6 for women with BMI of 18, 1.2 for women with BMI of 25, and 1.0 for women with BMI ≥ 30. Model predictions agree with data from five major epidemiological studies.
Computational and Mathematical Methods in Medicine 01/2012; 2012(8):792375. DOI:10.1155/2012/792375 · 0.77 Impact Factor
"Studies of blood estrogen levels among postmenopausal women have shown that higher levels are associated with increased risk of subsequent breast cancer (Colditz 1998; Friel, Hinchcliffe, and Wright 2005; Key et al. 2002). The Million Women Study (MWS) showed a significant increase in the RR of breast cancer in women taking estrogens (conjugated equine estrogens or estradiol orally) (Relative Risk ¼ 1.30), although the increase was greater for women taking estrogens combined with synthetic progestins (RR ¼ 2.00) (Beral 2003). "
[Show abstract][Hide abstract] ABSTRACT: There is growing concern that estrogenic environmental compounds that act as endocrine-disrupting chemicals might potentially have adverse effects on hormone-sensitive organs such as the breast. This concern is further fueled by evidence indicating that natural estrogens, specifically 17beta-estradiol, are important factors in the initiation and progression of breast cancer. We have developed an in vitro-in vivo model in which we have demonstrated the carcinogenicity of E2 in human breast epithelial cells MCF-10F. Hypermethylation of NRG1, STXBP6, BMP6, CSS3, SPRY1, and SNIP were found at different progression stages in this model. The use of this powerful and unique model has provided a tool for exploring whether bisphenol A and butyl benzyl phthalate have relevance in the initiation of breast cancer. These studies provide firsthand evidence that the natural estrogen 17beta-estradiol and xenoestrogenic substances like bisphenol A are able to induce neoplastic transformation in human breast epithelial cells.
"Published case reports exist regarding breast cancer among MtF patients using feminizing hormone therapy (Ganly & Taylor, 1995; Pritchard, Pankowsky, Crowe, & Abdul-Karim, 1988; Symmers, 1968). Multiple prospective studies have demonstrated an increased risk of breast cancer among menopausal women using hormone replacement therapy (Colditz, 2005; Nelson, Humphrey, Nygren, Teutsch, & Allan, 2002; Rossouw et al., 2002; Schairer et al., 2000). In these studies, risk appears to increase with combined estrogen and progestin use, and with length of therapy greater than five years. "
[Show abstract][Hide abstract] ABSTRACT: Often viewed as the definitive professional document on transgender care, the current Standards of Care for Gender Identity Disorders—Sixth Version provides a general overview of the risks and effects of adult hormone therapy, but at present offers limited guidance for the medical provider as to how best to execute this critical intervention. Newer versions need to present a comprehensive approach to transgender hormone therapy, including preventive health care, by incorporating the following key elements: the prescribing physician's responsibilities, clinical situations for hormone therapy, effects and risks of hormone therapy, assessment for initiating hormone therapy, monitoring hormone therapy, and suggested hormone regimens.
International Journal of Transgenderism 08/2009; 11(3):146-182. DOI:10.1080/15532730903383757
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