LifeCare Chiropractic

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estrogens

2-Methoxyestradiol, a Promising Anticancer Agent – (03-31-03)

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2-Methoxyestradiol, a Promising Anticancer Agent.

It is very interesting that researchers are viewing this compound as a potential anti cancer compound. Past issues of the Updates have reviewed the concept that estrogens are broken down by several pathways in the body, primary of which are the 16-, 4- and 2-hydroxyestradiol. The 16 pathway is well demonstrated to be genotoxic while the 2 pathway is protective. The 2/16 ratio (which is easily checked in urine or serum) has been linked with several types of cancer, including prostate, breast, endometrial and throat. The wonderful thing about this ratio is that it is modifyable by indole-3-carbinol in cruciferous veggies (unless of course you are on acid-suppressive therapy because stomach acid is needed to activate the compound from foods).

Pharmacotherapy 23(2):165-172, 2003

Estrogens occurring naturally in the body are metabolized to catecholestrogens (2- and 4-hydroxyestradiol) by the cytochrome P450 enzymes. 2-Hydroxy catecholestrogens are further metabolized by catechol-O-methyltransferase to 2-methoxyestradiol, which is known to be protective against tumor formation. 2-Methoxyestradiol exhibits potent apoptotic activity against rapidly growing tumor cells. It also possesses antiangiogenic activity through a direct apoptotic effect on endothelial cells. Other molecular mechanisms, including microtubule stabilization by inhibition of the colchicine-binding site, have been reported. The exact mechanism of action of 2-methoxyestradiol is still unclear, but it has been shown to be effective in preventing tumor growth in a variety of cell lines. 2-Methoxyestradiol also possesses cardioprotective activity by inhibiting vascular smooth muscle cell growth in arteries. It has a lower binding affinity for estrogen receptor alpha compared with that of estradiol, and its affinity for estrogen receptor-beta is even lower than that of estrogen receptor alpha, thus it has minimal estrogenic activity. 2-Methoxyestradiol is distinct because of its inability to engage estrogen receptors as an agonist, and its unique antiproliferative and apoptotic activities are mediated independently of estrogen receptors alpha and beta. A phase I clinical trial of 2-methoxyestradiol 200, 400, 600, 800, and 1000 mg/day in 15 patients with breast cancer showed significant reduction in bone pain and analgesic intake in some patients, with no significant adverse effects. Another phase I study of 2-methoxyestradiol 200-1000 mg/day in combination with docetaxel 35 mg/m2/week for 4-6 weeks performed in 15 patients with advanced refractory metastatic breast cancer showed no serious drug-related adverse effects. A phase II randomized, double-blind trial of 2-methoxyestradiol 400 and 1200 mg/day in 33 patients with hormone-refractory prostate cancer showed that it was well tolerated and showed prostate specific antigen stabilizations and declines. We have started a phase I clinical trial to explore dosages greater than 1000 mg/day.

Gestagens May Reduce Estrogen’s Effects on Bone Resorption – (05-21-01)

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Gestagens May Reduce Estrogen’s Effects on Bone Resorption

So, we add synthetic progesterone to synthetic estrogen to protect against endometrial and breast cancer, right? But, by adding them in, this study suggests that the synthetic progesterone reduces the synthetic estrogens’ ability to protect bone. Does anyone see a problem here?

JCEM — Abstracts: Tobias et al. 86 (3): 1194

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Ultra-Low-Dose Oral Contraceptive Effectively Treats Acne – (09-10-01)

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Ultra-Low-Dose Oral Contraceptive Effectively Treats Acne

Many times, acne can be caused by excess testosterone. In today’s lifestyle patterns, high insulin levels can effect the conversion of estrogen into testosterone effectively increasing testosterone levels. One of the best ways to approach acne actually comes from within…balancing insulin levels, restoring health of the GI tract (probiotics, glutamine…), Vit A, essential fatty acids… Giving estrogens in this study may work by blunting the difference between estrogen and testosterone levels in the body, but does not actually work by lowering the excess testosterone.

Fertil Steril. 2001;76(3):461-468 An ultra-low-dose oral contraceptive has been shown to be just as effective in treating acne as pills with higher doses of estrogen, according to a study published in the September issue of Fertility and Sterility. “Our study confirms that an oral contraceptive containing only 20 micrograms of estrogen — the lowest dose on the market today — is effective in suppressing androgen production and reducing acne lesions,” said Diane Thiboutot, MD, lead study investigator and associate professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania. “This clinical trial is good news for women because it shows that we now have more birth control choices that are not only 99% effective in preventing pregnancy, and offer numerous other health benefits, but can also treat acne lesions without causing a change in weight — a common estrogen-related side effect,” said Dr. Thiboutot.”In addition, the choice of a low-dose contraceptive resulted in a low occurrence of estrogen-related side effects like nausea, headaches, and breast tenderness, in addition to weight gain,” she added. “If women experience fewer side effects and can treat their acne, they may be less likely to discontinue pill use, to switch to a less effective method of birth control, or to use no birth control at all.”

Chemoprevention strategies with antioxidants – (05-20-03)

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Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants

Had to leave the long title for effect… I know this goes into some heavy biochemistry, but the take home message is this… A woman (and a man to a lessor degree) are at risk from the breakdown of her of estrogens. These are not benign compounds that do only good things. Their breakdown, if unfavorable, can strongly increase risk of DNA damage and several types of cancer. This article shows that this risk can be lowered with antioxidants and diets high in fruits and veggies. Cruciferous veggies, additionally, will favorably effect the breakdown of estrogens so that protecting against DNA damage is not even an issue.

PNAS — Abstracts: Samuni et al. 100 (9): 5390

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Regulation of cell cycle 16a-hydroxyestrone in breast cancer cells – (12-31-01)

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Regulation of cell cycle 16a-hydroxyestrone in breast cancer cells

The breakdown of estradiol (one of the three circulating estrogens in humans) can yield several pathways. The 2- pathway is generally considered beneficial and anti-carcinogenic, while the 16 pathway is considered damaging and carcinogenic. Promotion of the 2 pathway over the 16 is aided by the intake of substances found in cruciferous vegetables. There are now functional medicine labs checking 2/16 hydroxylation ratio to assess a woman’s risk of breast cancer.

J S LEWIS et al.: 16a-Hydroxyestrone and cell cycle regulation (Journal of Molecular Endocrinology)

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Steroid and Cytokine Regulation of MMP Expression in Endometriosis – (10-10-02)

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Steroid and Cytokine Regulation of MMP Expression in Endometriosis

Cutting through the technical jargon, this article brings to light a potentially important factor for treatment of endometriosis. Progesterone is key here. Progesterone inhibits the ability of an enzyme, MMP, to establish endometriosis. This ability of progesterone can itself be inhibited by certain mechanisms. This study finds that the use of retinoic acid (vitamin A related compounds) and transforming growth factor beta (a cytokine controlling cell maturation) can restore progesterone’s protective ability. As added info, many women today, as a result of exposure to way too many exogenous estrogens, go through anovulatory cycles. Without the release of an ovum during a normal menstrual cycle, the body lacks that normal exposure to progesterone that is so needed for normal female reproductive function.

JCEM — Abstracts: Bruner-Tran et al. 87 (10): 4782

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Prunes on the ratio of 2- to 16alpha-hydroxyestrone – (12-05-02)

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Prunes on the ratio of 2- to 16alpha-hydroxyestrone

Remember that estrogens can be broken down by several pathways in the body, with the 2-hydroxyestrone pathway being considered protective and the 16- pathway being genotoxic. Thus, the 2/16 ratio has been shown to be a risk factor for several types of cancer, including breast and endometrial. Brassica family of veggies (broccoli, cauliflower, brussel sprouts) are well known to favorably effect this ratio. Seems we can add prune juice to the list.

AJCN — Abstracts: Kasim-Karakas et al. 76 (6): 1422

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Reproductive hormonal dynamics in the perimenopause – (01-10-02)

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Reproductive hormonal dynamics in the perimenopause

This is an older article but one I had to throw in just to blow apart standard thinking. So many people (and physicians included0 believe that perimenopausal symptoms are a result of lack of estrogens. The treatment? More estrogen, of course (in the form of equine estrogens foreign to the human body). Unfortunately, the reality is that perimenopause is associated with elevated estrogens. The symptoms of perimenopause are from rapid changes in estrogen levels, not elevated estrogen. Blunt the peaks with progesterone cream (downregulates estrogen receptors and makes cells less sensitive to estrogen) and fill in the troughs with phytoestrogens and most of the symptoms and signs of perimenopause disappear…

JCEM — Abstracts: Santoro et al. 81 (4): 1495

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