Lignans raise testosterone, while simultaneously reducing Estrogen, Androstenedione, DHT, which could at least partly explain the significantly reduced incidence of MPB in cultures with high phytoestrogen consumption.

      Recently added to our formulas, Natural Estrogen with Pomegranate Extract and the Ultra Natural Prostate Formula are standardized lignans from flax and the Norway spruce trees. These lignans convert to enterolactones in the intestine that are then absorbed into the bloodstream where they provide significant biological effects. Enterolactones have demonstrated anti-estrogen, anti-androstenedione and anti-DHT effects that are of particular importance for prostate function, and hair loss treatment.

J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7. Epub 2005 Mar 16.

Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells.

Brooks JD, Thompson LU

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College St., Toronto, Ont., Canada M5S 3E2.

Estrogen plays a major role in breast cancer development and progression. Breast tissue and cell lines contain the necessary enzymes for estrogen synthesis, including aromatase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). These enzymes can influence tissue exposure to estrogen and therefore have become targets for breast cancer treatment and prevention. This study determined whether the isoflavone genistein (GEN) and the mammalian lignans enterolactone (EL) and enterodiol (ED) would inhibit the activity of aromatase and 17beta-HSD type 1 in MCF-7 cancer cells, thereby decreasing the amount of estradiol (E2) produced and consequently cell proliferation. Results showed that 10 microM EL, ED and GEN significantly decreased the amount of estrone (E1) produced via the aromatase pathway by 37%, 81% and 70%, respectively. Regarding 17beta-HSD type 1, 50 microM EL and GEN maximally inhibited E2 production by 84% and 59%, respectively. The reduction in E1 and E2 production by EL and the reduction in E2 production by GEN were significantly related to a reduction in MCF-7 cell proliferation. 4-Hydroxyandrostene-3,17-dione (50 microM) did not inhibit aromatase but inhibited the conversion of E1 to E2 by 78%, suggesting that it is a 17beta-HSD type 1 inhibitor. In conclusion, modulation of local E2 synthesis is one potential mechanism through which ED, EL and GEN may protect against breast cancer.

Steroids. 2000 Aug;65(8):437-41. Links

Synthesis of enterolactone and enterodiol precursors as potential inhibitors of human estrogen synthetase (aromatase).

Mäkelä TH, Wähälä KT, Hase TA

Organic Chemistry Laboratory, Department of Chemistry, P.O. Box 55 (A.I. Virtasen aukio 1), FIN-00014 University of Helsinki, Helsinki, Finland.

A series of variably substituted derivatives of lignan lactones and diols were prepared using tandem conjugate addition reaction as a key step. These theoretical precursors of the mammalian lignans enterolactone 1 and enterodiol 3 are moderate or weak inhibitors of human aromatase activity.

J Endocrinol. 1995 Nov;147(2):295-302.Links

Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids.

Evans BA, Griffiths K, Morton MS

Department of Child Health, University of Wales College of Medicine, Health Park, Cardiff, UK.

Isoflavonoids and lignans, constituents of many plant foods, have been proposed as protective agents in those populations with a low incidence of hormone-dependent cancers. They may act by their inhibition of the metabolism of growth-promoting steroid hormones. This report describes the inhibition of 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase by six isoflavonoids and two lignans in human genital skin fibroblast monolayers and homogenates, and in benign prostatic hyperplasia tissue homogenates. In genital skin fibroblasts, genistein, biochanin A and equol were the most potent inhibitors of 5 alpha-reductase activity, each resulting in greater than 80% inhibition at a concentration of 100 microM. The IC50 values for genistein and a seven-compound mixture were approximately 35 microM and 20 microM (2.9 microM of each compound) respectively. Of the lignans, enterolactone was the most potent inhibitor. Inhibition by biochanin A was shown to be reversible. When genital skin fibroblast homogenates were used, biochanin A was found to inhibit 5 alpha-reductase isozymes 1 and 2 to differing extents (30% and 75% respectively). Genistein was shown to inhibit 5 alpha-reductase 2 in a non-competitive nature (Vmax and Km values without and with inhibitor were 30 and 20 pmol/mg protein per h and 177 and 170 nM respectively). All of the compounds tested inhibited 17 beta-hydroxysteroid dehydrogenase activity in genital skin fibroblast monolayers. When prostate tissue homogenates were used, the compounds tested were better inhibitors of 5 alpha-reductase 1 than 2.