Life Extension Magazine®

Issue: Aug 2014

Safely Manage Menopausal Symptoms

Women and their doctors have long searched for alternatives to conventional hormone drugs to treat menopausal symptoms. Studies show that natural plant-based extracts, hops and lignan extract, block menopausal discomforts such as hot flashes, irritability, and sexual problems. This combination may also provide anticancer, antimicrobial, anti-inflammatory, and immunomodulatory benefits.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, on April 2020. Written By Alicia Nadil.

Safely Manage Menopausal Symptoms  

During menopause, a woman undergoes profound and extreme biochemical changes in all aspects of her body. It can be one of the most trying periods in a woman’s life. Lasting up to 10 years, the menopausal transition includes well-known symptoms such as hot flashes, night sweats, mood swings, and sleep disturbances.1-5 Menopause also increases the risk of heart attack and stroke,6 depression, osteoporosis, arthritis, dementia, and frailty.3

While the troubling symptoms of menopause gradually fade as a woman completes the menopausal transition, the health risks remain or grow larger. By World Health Organization estimates, 1.2 billion women worldwide will be postmenopausal by the year 2030, making these health risks an impending public health disaster.3 And managing those symptoms is a clinical challenge, with few safe and effective options.2

Until the turn of the 20th century, the standard management of menopause included administration of equine estrogens derived from horse urine (Premarin®) and progestin; a synthetic female hormone that is different than natural progesterone.7

Fortunately, just when the risks of conventional hormone therapy were becoming evident8, data emerged showing that estrogen-like molecules from plant sources (phytoestrogens) could produce many of estrogen’s favorable effects minus most of the harmful ones. A 2013 study showed that these phytoestrogens were effective at decreasing hot flashes, irritability, and sexual problems.9

Use of estrogen-like molecules from plant sources is growing increasingly popular, and intense scientific research has begun to reveal the remarkable effectiveness of plant extracts in achieving relief of menopausal symptoms, while at the same time providing protection against some of the very conditions that conventional hormone therapy is notorious for causing.10-13

Two important plant extracts lead the field in bioidentical hormone therapy for relief of menopausal symptoms. Prenylflavonoid molecules in hops include the most potent phytoestrogen discovered thus far,14-17 while lignans found in the Norway spruce combine mild estrogenic actions with potential anticancer, antimicrobial, anti-inflammatory, and immunomodulatory activities that neatly fill the needs of women as they approach and transition through menopause.18

Women who are undergoing or nearing menopause, and who would like to prevent or mitigate menopausal symptoms such as hot flashes and sleep disturbances, are increasingly interested in natural phytoestrogens from hops and spruce as an alternative to mainstream hormone replacement therapy.

A Natural Solution For Menopausal Symptoms

How Alzheimer’s Disease Occurs  

Hops are the female flowers of the hop plant (Humulus lupulus). Their bitter, floral taste has been used for centuries as a flavoring and natural preservative in beer.14,19 But they also contain specialized glands that secrete powerful bioactive molecules with significant potential impact on human health.15,20

Among these compounds is a molecule called 8-prenylnaringenin (8-PN), which research suggests is the most potent known phytoestrogen (plant-derived estrogen-like molecule).14-16, 21-23 These estrogenic properties make hops and 8-PN extremely attractive for use during menopause, when estrogen levels drop and produce the disquieting symptoms of menopause.21

The estrogenic properties of hops extracts, and particularly of 8-PN, are known to alleviate menopausal symptoms and disorders, including osteoporosis, hot flashes, and low sex drive.17 8-PN is known to be rapidly and almost completely absorbed after oral dosing.24

Studies in rats whose ovaries had been removed in order to produce experimentally-induced menopause show that the animals underwent hot flashes, just like women. Administration of either estrogen or 8-PN from hops was able to reverse these symptoms (measured as increased temperature of the tail skin).25 Further studies revealed that this effect is at least partly the result of 8-PN binding to and activating estrogen receptors in tissues outside of the brain.25

In a human study, women undergoing menopause took a hops extract standardized to 100 or 250 micrograms/day of 8-PN or a placebo for 12 weeks. Even the lower dose of 100 micrograms 8-PN was significantly superior to placebo at reducing symptoms of menopause after only six weeks, especially the hot flash score on a standardized menopause scoring scale.26 A similar study, using 100 micrograms/day of 8-PN, demonstrated significant reductions after eight weeks of therapy on the same scores, as well as a patient-reported visual scale of menopausal symptoms.27

Hops Battle Breast Cancer

Hops extracts, rich in 8-PN, provide relief of troubling menopause-associated symptoms. In addition, hops extracts are now beginning to show important and promising benefits in the fight to prevent cancer, particularly cancers of the breast, which are most commonly dependent on estrogen for their growth.

The ability of hops as a plant-derived estrogen replacement therapy to prevent breast cancer is critical, especially since the mainstream’s standard animal-derived estrogen replacement therapy has produced concerns regarding the risk of promoting such cancers due to excessive estrogen.

An important step in estrogen’s initiation of cancer is its conversion into a number of active carcinogens by liver enzymes. These enzymes, normally part of the detoxification process for external toxins, act on estrogen to create new toxins that have DNA-damaging effects.11

Hops, and its natural active constituent 8-PN, inhibited these kinds of dangerous enzymatic reactions, reducing the amount of cancer-inducing DNA damage and blocking the malignant transformation of human breast cancer cells in culture.11,28 Quite recently, 8-PN has also been shown to inhibit growth of colon cancer cells in culture.29

Even more impressive anticancer effects are attributable to another hops-derived biomolecule, xanthohumol, a flavonoid that has been described as a “broad-spectrum” cancer-preventive substance because of its large numbers of potential targets and mechanisms of action.15 A closely related molecule, isoxanthohumol, also present in hops is capable of being converted to estrogen-like 8-PN by bacteria living in the intestine.14,23 Due to natural variations in the makeup of the intestinal bacteria in each woman, the amounts of protective 8-PN available from dietary sources may vary considerably, leaving 60% or more of women with sub-optimal protection.14,23

Can Drinking Beer Battle Breast Cancer?

With this discussion about hops, you might be wondering if drinking beer is a viable option for reducing the symptoms of menopause and preventing breast cancer. Unfortunately, the answer is no.

Since the concentration of beneficial hops molecules varies greatly between beer brands and styles, even regular beer consumption cannot guarantee adequate protection either against menopausal symptoms or against cancer.15 Beer also brings with it a sizable calorie load, and the alcohol content is not acceptable to many people.

Fortunately, hops extracts rich in 8-PN and xanthohumol are now available. Laboratory testing shows that these molecules accumulate in the liver and mammary glands following supplementation, where they induce important genetic control systems that protect cells.21 Following treatment with 8-PN and xanthohumol, breast cancer cells in culture showed decreased pro-oxidant production, improved mitochondrial function (a known factor in cancer prevention), and increased expression of the life-extending molecules called sirtuins.30,31

There may be additional benefits to supplementing with hops extracts, even beyond menopause and cancer prevention. 8-PN was shown in a mouse model to prevent the atrophy of skeletal muscle (sarcopenia) that is so common in older adults. Such beneficial effects on muscle might help older adults retain their strength, which in turn may help to prevent falls and other traumatic events.32

Hop extracts also show strong neuroprotective effects, promoting new brain cell growth and regeneration, and outgrowth of new neurites, the tiny spikes that brain and nerve cells use to contact and communicate with one another.16

What You Need To Know
Phytoestrogens Battle Menopausal Symptoms And Reduce Breast Cancer Risk

Phytoestrogens Battle Menopausal Symptoms And Reduce Breast Cancer Risk

  • During transition through menopause, falling estrogen levels produce a host of disquieting and disturbing symptoms that many women find nearly intolerable.
  • Menopause has also been associated with major age-related diseases such as cardiovascular disease, stroke, cancer, dementia, and osteoporosis, as the protective effects of estrogen are withdrawn.
  • Conventional treatment with estrogen derived from horse urine plus progesterone has been shown to be flawed; while effective at reducing symptoms, this treatment actually raises the risk of many chronic conditions, and is no longer routinely recommended.56,57
  • Treatment with estrogen-like compounds derived from plants (phytoestrogens) has been shown to be effective at improving many menopausal symptoms, and may provide protection against the very conditions that are aggravated by conventional treatment.
  • Hops are an abundant source of the most potent known phytoestrogen, 8-prenylnaringenin, and other important women’s health molecules.
  • Norway spruce provides abundant amounts of the lignan 7-hydroxymatairesinol, a highly cancer-protective compound that also offers symptomatic relief of hot flashes and other menopausal complaints.

Cut Hot Flashes In Half

The Norway spruce (Picea abies) produces abundant quantities of the plant lignan 7-hydroxymatairesinol, or HMR. In the digestive tract, HMR is converted to an active compound called enterolactone.18,33-35 Both HMR and enterolactone are mild phytoestrogens, and as such, offer additional support for women undergoing menopausal transition.18,35,36

In one important study, menopausal women supplemented with either 36 or 72 mg of HMR lignan per day for eight weeks.37 The supplement was readily absorbed and distributed in the women’s bodies, raising 7-HMR levels in the blood by 191% in the lower-dose group, and by 1,238% in the higher-dose group. The higher dose also produced a 50% reduction in the mean number of weekly hot flashes, from 28 to 14.3.

Safely Lower Breast Cancer Risk

In addition to drastically cutting the number of hot flashes, there is also exciting news about HMR lignan in the prevention of breast and other cancers. Several different epidemiological and laboratory studies have shown that diets rich in plant lignans are likely to reduce the risk of human breast cancer.38 This is likely due to the ability of HMR lignans to sharply reduce the concentrations of reactive oxygen species that damage DNA to trigger cancers, and also their ability to suppress inflammatory actions to slow promotion and progression of malignancies.39

Studies in rats with experimentally induced breast cancer show that HMR, at a dose equivalent to 180 mg/day in humans, decreases the number of growing tumors and increases the proportion of tumors that regress and stabilize.33 A lower dose (equivalent to 56.4 mg/day in an average human) given before experimental tumor induction was shown to reduce the size and growth of tumors, while the same dose given even after tumors were established inhibited their growth.36

Other studies show that HMR helps inhibit tumor development in liver cancer cells and helps stop the spread of tumors in rats carrying liver cancers.38 Toxicity studies have demonstrated no adverse effects at doses up to a human equivalent of 1,920 mg/day, making HMR lignan a safe supplement.40

Nutrients Proven To Ease Menopausal Symptoms
Nutrients Proven To Ease Menopausal Symptoms

In addition to the benefits provided by phytoestrogens and other protective molecules in hops polyphenols (8-PN) and spruce lignans (HMR lignan), a handful of other nutrients have shown promise in easing the menopausal transition and protecting against breast cancer. Here is a brief summary of some of the most effective nutrients:

  • Cruciferous vegetables, especially broccoli, are rich in biomolecules called isothiocyanates, which are potent inhibitors of liver enzymes that activate potential carcinogens, including estrogen. As a result, consuming cruciferous vegetables promotes breast health and can reduce the risk of breast cancer by as much as 40%.48 Eating large amounts of broccoli (more than a pound per day) shifts the important ratio of estrogen 2:16 hydroxy metabolites in favor of the protective 2-hydroxy molecule.45 In order to get the most benefit, consider taking concentrated broccoli extracts.
  • Dong quai has a long history of medicinal use in Asia for menopausal symptoms.49 Modern studies reveal that extracts of the plant have estrogenic effects in menopausal rats, suggesting a mechanism of action for its ancient properties.49 There is also some evidence that extracts may be useful in treating female arousal disorders, which are common around the time of menopause.50
  • Vitex agnus-castus (Chasteberry) contains compounds in both the berry and the leaf that have been shown to induce relief of common menopausal symptoms.51,52 Studies attribute these effects to activation of estrogen receptors, indicating that the plant has beneficial phytoestrogen properties.53

How To Measure Breast Cancer Risk

How To Measure Breast Cancer Risk  

Of special importance, a recent study demonstrated that when HMR lignan is combined with indole-3-carbinol, a beneficial compound in broccoli and other cruciferous vegetables,41 it produces a vital shift in the ways that natural estrogen is metabolized in a woman’s body.42

Although estrogen is a natural hormone produced by both women and men, it undergoes chemical changes through the actions of enzymes in the liver. One of those enzyme systems produces so-called 2-hydroxy estrogen breakdown products, while the other produces 16-hydroxy versions of the molecule.43 The 2-hydroxy version appears to offer protection against breast cancer,44 while the 16-hydroxy version remains powerful enough to raise a woman’s chances of developing breast cancer.45 The ratio of 2-hydroxy to 16-hydroxy molecules is therefore a good measure of a woman’s breast cancer risk, with the higher the ratio (meaning more beneficial 2-hydroxy and less dangerous 16-hydroxy), the lower her risk.43,46 In the recent study, a breast health nutritional formula containing HMR lignan plus indole-3-carbinol was shown to be capable of shifting estrogen metabolism toward the 2-hydroxy version and raising the 2:16-hydroxy ratio; an important step in minimizing the risk of breast (and possibly other) cancers.42 This is in line with other studies demonstrating that consumption of cruciferous vegetables nudges the 2:16-hydroxy ratio in a direction that favors protection from breast cancers.45,47

Summary

Replacing estrogen lost to menopause was once relegated to taking unnatural-to-the-body estrogen drugs and dangerous synthetic progestins (which is not the same as progesterone). These pharmaceutical approaches are declining as maturing women insist on natural hormone replacement protocols.

Treatment with plant-derived, estrogen-like molecules called phytoestrogens and natural progesterone are showing great promise in relieving symptoms of the menopausal transition and at restoring some of the protection enjoyed by premenopausal women against cancer and other chronic conditions.55

Extracts of hops and Norway spruce are rich in such phytoestrogens, as well as in other molecules that protect women against low-estrogen-induced conditions. These molecules have now been studied and appear to lead the field in the combination of symptom relief and protective effects.

Additional plant extracts, many of them in use for centuries in traditional medical systems, can add further symptomatic relief and disease-preventive effects. These natural plant derivatives are increasingly being made available in convenient combination formulations.54

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Menati L, Khaleghinezhad K, Tadayon M, Siahpoosh A. Evaluation of contextual and demographic factors on licorice effects on reducing hot flashes in postmenopause women. Health Care Women Int. 2014 Jan;35(1):87-99.
  2. Nahidi F, Zare E, Mojab F, Alavi-Majd H. Effects of licorice on relief and recurrence of menopausal hot flashes. Iran J Pharm Res. 2012 Spring;11(2):541-8.
  3. Stephenson K, Neuenschwander PF, Kurdowska AK. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. Int J Pharm Compd. 2013 Jan-Feb;17(1):74-85.
  4. Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause. 2014 Jan 27. [Epub ahead of print]
  5. Harlow SD, Paramsothy P.Menstruation and the menopausal transition. Obstet Gynecol Clin North Am. 2011 Sep;38(3):595-607.
  6. Lobo RA. Menopause and stroke and the effects of hormonal therapy. Climacteric. 2007 Oct;10 Suppl 2:27-31.
  7. Kreatsoulas C, Anand SS. Menopausal hormone therapy for the primary prevention of chronic conditions. U.S. Preventive Services Task Force recommendation statement. Pol Arch Med Wewn. 2013;123(3):112-7.
  8. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33.
  9. Tit DA, Lazar L, Bungau S, Pallag A, Bei D. The evaluation of the effectiveness of phytoestrogens in improving, reduction or suppression of the climacteric symptomatology. Studia Universitatis “Vasile Goldis” Seria Stiintele Vietil. 2013; 23(4):585-96.
  10. Overk CR, Yao P, Chadwick LR, et al. Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J Agric Food Chem. 2005 Aug 10;53(16):6246-53.
  11. Hemachandra LP, Madhubhani P, Chandrasena R, et al. Hops (Humulus lupulus) inhibits oxidative estrogen metabolism and estrogen-induced malignant transformation in human mammary epithelial cells (MCF-10A). Cancer Prev Res (Phila). 2012 Jan;5(1):73-81.
  12. Overk CR, Guo J, Chadwick LR, et al. In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin. Chem Biol Interact. 2008 Oct 22;176(1):30-9.
  13. Stansbury J, Saunders PR, Winston D. The safety of phytoestrogens in menopause, prostate and breast cancer. Journal of Restorative Medicine. 2013; 2(1), 101-8.
  14. Possemiers S, Verstraete W. Oestrogenicity of prenylflavonoids from hops: activation of pro-oestrogens by intestinal bacteria. Environ Microbiol Rep. 2009 Apr;1(2):100-9.
  15. Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry. 2004 May;65(10):1317-30.
  16. Oberbauer E, Urmann C, Steffenhagen C, et al. Chroman-like cyclic prenylflavonoids promote neuronal differentiation and neurite outgrowth and are neuroprotective. J Nutr Biochem. 2013 Nov;24(11):1953-62.
  17. Keiler AM, Zierau O, Kretzschmar G. Hop extracts and hop substances in treatment of menopausal complaints. Planta Med. 2013 May;79(7):576-9.
  18. Cosentino M, Marino F, Ferrari M, et al. Estrogenic activity of 7-hydroxymatairesinol potassium acetate (HMR/lignan) from Norway spruce (Picea abies) knots and of its active metabolite enterolactone in MCF-7 cells. Pharmacol Res. 2007 Aug;56(2):140-7.
  19. Milligan SR, Kalita JC, Heyerick A, Rong H, De Cooman L, De Keukeleire D. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol & Metabol. 1999;84:6:2249.
  20. Nagel J, Culley LK, Lu Y, Liu E, Matthews PD, Stevens JF,Page JE. EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol. The Plant Cell Online. 2008; 20(1), 186-200.
  21. Dietz BM, Hagos GK, Eskra JN, et al. Differential regulation of detoxification enzymes in hepatic and mammary tissue by hops (Humulus lupulus) in vitro and in vivo. Mol Nutr Food Res. 2013 Jun;57(6):1055-66.
  22. Rimoldi G, Christoffel J, Wuttke W. Morphologic changes induced by oral long-term treatment with 8-prenylnaringenin in the uterus, vagina, and mammary gland of castrated rats. Menopause. 2006 Jul-Aug;13(4):669-77.
  23. Bolca S, Possemiers S, Maervoet V, et al. Microbial and dietary factors associated with the 8-prenylnaringenin producer phenotype: a dietary intervention trial with fifty healthy post-menopausal Caucasian women. Br J Nutr. 2007 Nov;98(5):950-9.
  24. Rad M, Humpel M, Schaefer O, et al. Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women. Br J Clin Pharmacol. 2006 Sep;62(3):288-96.
  25. Bowe J, Li XF, Kinsey-Jones J, et al. The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. J Endocrinol. 2006 Nov;191(2):399-405.
  26. Heyerick A, Vervarcke S, Depypere H, Bracke M, De Keukeleire D. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas. 2006 May 20;54(2):164-75.
  27. Erkkola R, Vervarcke S, Vansteelandt S, Rompotti P, De Keukeleire D, Heyerick A. A randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts. Phytomedicine. 2010 May;17(6):389-96.
  28. Yuan Y, Qiu X, Nikolic D, et al. Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenylphenols. Eur J Pharm Sci. 2014 Mar 12;53:55-61.
  29. Allsopp P, Possemiers S, Campbell D, Gill C, Rowland I. A comparison of the anticancer properties of isoxanthohumol and 8-prenylnaringenin using in vitro models of colon cancer. Biofactors. 2013 Jul-Aug;39(4):441-7.
  30. Blanquer-Rossello MM, Oliver J, Valle A, Roca P. Effect of xanthohumol and 8-prenylnaringenin on MCF-7 breast cancer cells oxidative stress and mitochondrial complexes expression. J Cell Biochem. 2013 Dec;114(12):2785-94.
  31. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6.
  32. 32.Mukai R, Horikawa H, Fujikura Y, et al. Prevention of disuse muscle atrophy by dietary ingestion of 8-prenylnaringenin in denervated mice. PLoS One. 2012;7(9):e45048.
  33. Saarinen NM, Warri A, Makela SI, et al. Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies). Nutr Cancer. 2000;36(2):207-16.
  34. Heinonen S, Nurmi T, Liukkonen K, et al. In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem. 2001 Jul;49(7):3178-86.
  35. Saarinen NM, Penttinen PE, Smeds AI, Hurmerinta TT, Makela SI. Structural determinants of plant lignans for growth of mammary tumors and hormonal responses in vivo. J Steroid Biochem Mol Biol. 2005 Feb;93(2-5):209-19.
  36. Saarinen NM, Huovinen R, Warri A, et al. Uptake and metabolism of hydroxymatairesinol in relation to its anticarcinogenicity in DMBA-induced rat mammary carcinoma model. Nutr Cancer. 2001;41(1-2):82-90.
  37. Udani JK, Brown DJ, Tan MO, Hardy M. Pharmacokinetics and bioavailability of plant lignan 7-hydroxymatairesinol and effects on serum enterolactone and clinical symptoms in postmenopausal women: a single-blinded, parallel, dose-comparison study. J Am Coll Nutr. 2013 Dec;32(6):428-35.
  38. Miura D, Saarinen NM, Miura Y, Santti R, Yagasaki K. Hydroxymatairesinol and its mammalian metabolite enterolactone reduce the growth and metastasis of subcutaneous AH109A hepatomas in rats. Nutr Cancer. 2007;58(1):49-59.
  39. Cosentino M, Marino F, Maio RC, et al. Immunomodulatory activity of the lignan 7-hydroxymatairesinol potassium acetate (HMR/lignan) extracted from the heartwood of Norway spruce (Picea abies). Int Immunopharmacol. 2010 Mar;10(3):339-43.
  40. Lina B, Korte H, Nyman L, Unkila M. A thirteen week dietary toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats. Regul Toxicol Pharmacol. 2005 Feb;41(1):28-38.
  41. Chen Z, Tao ZZ, Chen SM, Chen C, Li F, Xiao BK. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro. PLoS One. 2013 Dec 16;8(12):e82288.
  42. Laidlaw M, Cockerline CA, Sepkovic DW. Effects of a breast-health herbal formula supplement on estrogen metabolism in pre- and post-menopausal women not taking hormonal contraceptives or supplements: a randomized controlled trial. Breast Cancer (Auckl). 2010;4:85-95.
  43. Bradlow HL, Telang NT, Sepkovic, DW, Osborne MP. 2-hydroxyestrone: the’good’estrogen. Journal of Endocrinology. 1996;150(3 Suppl), S259-S265.
  44. Ho GH, Luo XW, Ji CY, Foo SC, Ng EH. Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk. Ann Acad Med Singapore. 1998 Mar;27(2):294-9.
  45. Fowke JH, Longcope C, Hebert JR. Brassica vegetable consumption shifts estrogen metabolism in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):773-9.
  46. Kabat GC, O’Leary ES, Gammon MD, et al. Estrogen metabolism and breast cancer. Epidemiology. 2006 Jan;17(1):80-8.
  47. Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7.
  48. Ambrosone CB, McCann SE, Freudenheim JL, Marshall JR, Zhang Y, Shields PG. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr. 2004 May;134(5):1134-8.
  49. Circosta C, Pasquale RD, Palumbo DR, Samperi S, Occhiuto F. Estrogenic activity of standardized extract of Angelica sinensis. Phytother Res. 2006 Aug;20(8):665-9.
  50. Mazaro-Costa R, Andersen ML, Hachul H, Tufik S. Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women? J Sex Med. 2010 Nov;7(11):3695-714.
  51. Lucks BC. Vitex agnus castus essential oil and menopausal balance: a research update [Complementary Therapies in Nursing and Midwifery 8 (2003) 148-154]. Complement Ther Nurs Midwifery. 2003 Aug;9(3):157-60.
  52. Lucks BC, Sorensen J, Veal L. Vitexagnus-castus essential oil and menopausal balance: a self-care survey. Complement Ther Nurs Midwifery. 2002 Aug;8(3):148-54.
  53. Liu J, Burdette JE, Xu H, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. 2001 May;49(5):2472-9.
  54. Hess R, Thurston RC, Hays RD, Chang CCH, Dillon SN, Ness RB, et al. The impact of menopause on health-related quality of life: results from the STRIDE longitudinal study. Quality of Life Research. 2012; 21(3), 535-544.
  55. Wiseman H. The therapeutic potential of phytoestrogens. Expert Opin Investig Drugs. 2000 Aug;9(8):1829-40.
  56. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997 Oct 11;350(9084):1047-59.
  57. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013 Oct 2;310(13):1353-68.

Subscribe to Life Extension Magazine®

Subscribe Now

Advertise in Life Extension Magazine®

Learn More