Ovarian Cancer is the deadliest of all gynecological malignancies in women worldwide, largely due to the difficulty in identifying the cancer at an early stage. Epidemiological data shows that onset and progression of ovarian cancer is related to lifetime estrogen exposure, and that ovarian cancer cells share similar estrogen regulated pathways with other hormone-dependent cancers, such as breast and endometrial cancer.
There are three naturally occurring estrogens, the distribution of each changing over time. Estradiol, or E2, is the most biologically active form of estrogen, produced primarily in the ovaries in premenopausal women. Estrone, or E1, while also produced in smaller amounts in the ovaries in premenopausal women, is the most prevalent estrogen in post-menopausal women, converted from DHEA and testosterone in adipose tissue through the process of aromatization. Elevated estradiol and estrone are associated with an increased risk for female cancers (breast, ovarian, endometrial). Estriol, or E3, is the weakest of the three estrogens but has the most protective benefits; it serves as a competitive inhibitor at receptor sites for estradiol and estrone. It tends to be low in women with breast cancer.
The estrogen quotient is a tool that enables providers to better understand the distribution and metabolism of the three estrogens. In the 1970’s, Henry Lemon, MD noted that women who developed breast cancer had a significantly reduced level of E3 relative to E1 and E2, and that women with a lower estrogen quotient had a higher risk of breast cancer. The EQ can serve as a screening tool for women who are at higher risk for breast cancer or who are already using estrogen. Because estrone and estradiol are interconvertible, and are both capable of converting into the more protective estriol, one can employ certain biological agents to tip this equation into the protective range by influencing estrogen metabolism.
How do you positively influence the estrogen quotient? Diet and nutrition have been shown to have positive effects on estrogen metabolism:
Lignans – polyphenols found in plants such as flaxseeds, sesame seeds, kale and broccoli (among others), lignans stimulate the production of sex hormone binding globulin (SHBG) in the liver, therefore reducing the levels of free estrogen. They also inhibit aromatase activity, thereby decreasing the conversion of testosterone and androstenedione into estrogens in fat and breast cells.
Indole-3-Carbinole (I3C) and DIM – these nutrients found in cruciferous vegetables, such as broccoli, brussels sprouts and cabbage, have been shown to promote the breakdown of estrogen into the beneficial metabolite, 2-OH. DIM can block estrogen receptors and inhibit the growth of estrogen responsive breast cancer and has been shown to inhibit the growth of both estrogen dependent and estrogen independent cancer cells by approximately 60 percent.
Resveratrol – a polyphenol found in the skin of red grapes, peanuts and berries that acts as a potent antioxidant, resveratrol has been shown to inhibit breast cancer growth in vitro.
Calcium-D-glucarate – the calcium salt of D-glucaric acid is found in many fruits and vegetables, with the highest concentration in oranges, apples, grapefruits and cruciferous vegetables. It inhibits beta-glucuronidase, an enzyme produced by colonic microflora which is associated with an increased risk for hormone dependent cancers such as breast, prostate and colon. It has been shown to regulate estrogen metabolism by inhibiting carcinogenesis, promoting cellular differentiation and enhancing the excretion of carcinogens.
Chrysin – a bioflavanoid that inhibits aromatase activity, chrysin slows the conversion of androgens into estrogen.
Melatonin - Epidemiologists and experimentalists have speculated that lack of melatonin, due in part to our sleep-deprived modern society, put women at higher risk for breast cancer as there is an inverse relationship between melatonin levels and breast cancer. Recent research has showed melatonin’s ability to inhibited the growth of cancer stem cells even in the presence of estrogen and BPA, by decreasing estrogen from binding to breast cancer stem cells. It’s also postulated that one of the reasons for the inverse relationship between melatonin and breast cancer is due to melatonin’s ability to inhibit estrogen production in breast tissue, by inhibiting aromatase.
The Estrogen Quotient is an effective tool for identifying the distribution of the three naturally occurring estrogens: estrone, estradiol and estriol. Because identifying ovarian cancer at an early stage is so difficult, and estrogen exposure has been identified as a risk factor, the estrogen quotient may be able to serve as a component of early risk assessment, as well as a tool for monitoring the progress of therapies undertaken to influence positive estrogen metabolism.
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