Female Hormone Restoration
Phytoestrogens and Nutritional Support
Phytoestrogens are dietary bioactives and natural compounds found in some plants that are similar in structure to estrogens. Although several types of plant compounds are classified as phytoestrogens (Landete 2016), the most studied of these are isoflavones and lignans (Chen 2015). Phytoestrogens in plants are largely inactive but are metabolized into active compounds by intestinal bacteria (Vitale 2013; Gencel 2012). Once absorbed, activated phytoestrogens exert estrogen-like effects in the body and may be an alternative to bioidentical HRT for some women (Sirotkin 2014; Landete 2016).
Some of the best evidence to support the use of phytoestrogens comes from Asia, where menopausal symptoms are milder and less common, and breast cancer incidence is lower than in Europe and North America. One explanation may be the phytoestrogens found in soy and other plant products commonly consumed in Asian diets (Aso 2010; Cho 2010; Sarkar 2003).
Phytoestrogens bind to estrogen receptors and help modulate estrogen activity (Zittermann 2003; Hajirahimkhan, Dietz 2013; Vitale 2013). The estrogenic effects of phytoestrogens vary but are generally weak relative to estradiol; in the presence of estradiol, they appear to have anti-estrogenic effects as they compete with estradiol for estrogen receptor binding sites (Hajirahimkhan, Dietz 2013; Ko 2014). Phytoestrogens have been shown to reduce menopausal symptoms and may decrease the risk of some chronic diseases including cardiovascular disease, osteoporosis, and breast cancer (Bawa 2010; Cho 2010; Miyake 2009; Vitale 2013; Messina 2014; Mainini 2013).
Intriguingly, phytoestrogens seem to preferentially bind estrogen receptor (ER)-beta, as opposed to ER-alpha, which is more strongly activated by estradiol and some other mammalian estrogens (Sirotkin 2014; Messina 2014). ER-beta activation has been proposed as a mechanism for preventing emotional and neurological aspects of aging and menopause (Vargas 2016), and appears to protect against cancerous changes in breast, ovarian, and possibly other tissues (Gallo 2012; Bardin 2004; Bossard 2012; Omoto 2015).
Dietary and supplemental phytoestrogens present a way for women to obtain limited hormonal support without the use of hormone therapy.
Cardiovascular benefits. Unlike conventional HRT, which has been shown to raise the risk of heart attack among postmenopausal women, phytoestrogens appear to have a positive effect on the heart (Gencel 2012; Sirotkin 2014). In 1999, the FDA authorized the use of health claims on food labels that link increased soy consumption with a reduced risk of coronary artery disease (Vincent 2000).
There are many studies examining the cardiovascular effects of phytoestrogens. Overall, research suggests isoflavones may lower high blood pressure (Sureda 2017; Messina 2014), improve lipid disturbances, lower homocysteine levels (Li 2016), improve vascular health, and prevent atherosclerosis (Gencel 2012; Messina 2014). Lignans similarly have been associated with lower blood pressure (Khalesi 2015), improved lipid metabolism (Gencel 2012), and reduced cardiac risk (Chun 2014; Landete 2016).
In addition to their ability to weakly activate estrogen receptors, phytoestrogens have strong anti-inflammatory and oxidative stress-reducing effects, which may contribute to their cardiovascular benefits (Gencel 2012; Landete 2016).
Brain protection. Estrogen and estrogen-like compounds protect brain cells from degenerative changes due to aging, oxidative stress, and stroke-induced damage (Nabavi 2015; Evsen 2013; Bhavnani 2003; Linford 2002). Several studies have shown that the phytoestrogen genistein protects experimental animals from the effects of brain ischemia, the kind of injury seen in stroke (Schreihofer 2009; Donzelli 2010; Ma 2010). In addition, genistein has demonstrated anti-apoptotic activity, protecting cultured brain cells from self-destructing over time (Yu 2009).
Osteoporosis and bone health. A number of studies have been conducted on phytoestrogens and bone health. Clinical trials have found that phytoestrogens can increase bone mineralization, reduce bone resorption, enhance bone formation, and improve markers of bone metabolism. Taken together, their findings suggest phytoestrogens (mainly soy foods and isoflavones) may help mitigate bone loss after menopause (Messina 2014; Abdi 2016; Chiang 2013).
Cancer protection. A number of studies have noted an association between isoflavone consumption and decreased breast cancer risk (Wada 2013; Dong 2011; Fritz 2013). Soy isoflavones are safe in women with a high risk of breast cancer, including breast cancer survivors (Fritz 2013; Messina 2016), and do not increase the risk of uterine cancer (Parazzini 2015). In addition, flaxseeds, which are high in phytoestrogenic lignans, have been shown to reduce breast cancer risk and reduce breast cancer tumor growth (Mason 2014; Flower 2014).
Phytoestrogens may protect against breast cancer in part by improving estrogen metabolism. A diet containing 113–202 mg daily (depending on body size) of genistein and daidzein was found in one trial to increase the ratio of protective 2-hydroxylated estrogens to harmful 16-hydroxylated estrogens in the urine of premenopausal women, an effect that may contribute to a lower long-term risk of breast cancer (Lu 2000). Furthermore, emerging evidence suggests phytoestrogens inhibit aromatase, the enzyme that catalyzes the conversion of testosterone to estrogen, and this effect may contribute to their association with lower breast cancer risk (Lephart 2015).
Lignans are phytoestrogens found mainly in flaxseeds, with smaller amounts occurring in sesame seeds, some sprouts, and many other plant foods. A comprehensive review of 21 studies found that postmenopausal women with higher lignan intake were significantly less likely to get breast cancer (Buck 2010).
In one clinical trial, 32 women awaiting surgery for breast cancer were randomized to receive a muffin either with or without (control group) 25 grams of flaxseed. Analysis of the cancerous tissue after surgery revealed that markers of tumor growth were reduced by 30‒71% in the flaxseed group, but not in the control group (Thompson 2005). A study published in 2010 found that a combination of lignans, indole-3-carbinol (I3C), and calcium-d-glucarate along with other herbs favorably altered the ratio of estrogen metabolites in 47 pre- and 49 postmenopausal women (Laidlaw 2010).
Menopause symptoms. Several studies have demonstrated that natural phytoestrogens can improve menopausal symptoms (Sirotkin 2014), particularly hot flashes (Chen 2015). A comprehensive meta-analysis that included results from 17 clinical trials found that treatment with an average of 54 mg of genistein per day for between six weeks and 12 months safely decreased hot flash frequency by 20.6% and hot flash severity by 26.2% (Taku 2012).
Additional Natural Ingredients to Target the Symptoms of Menopause
Siberian rhubarb. A special extract from Siberian rhubarb (also known as rhapontic rhubarb, Rheum rhaponticum) has been used in Germany for decades to treat problems related to female hormone imbalance, including infrequent or absent menstrual periods, and peri- and postmenopausal symptoms (Heger et al., 2006).
In the first randomized controlled clinical trial using this supplement, 109 symptomatic peri-menopausal women were given either an enteric coated tablet providing 4 mg per day of the standardized Siberian rhubarb extract or placebo for 12 weeks. After four weeks, menopause-related symptoms diminished significantly more in the Siberian rhubarb group compared with placebo, and by week 12, the difference was even more pronounced, and was measurable for each of the 11 symptoms considered in the trial. A clinically meaningful decrease in symptoms was reported by 45 of 54 women receiving the extract (83%) and one of 55 women receiving placebo (less than 2%). Furthermore, extensive investigation into possible adverse effects attributable to the Siberian rhubarb extract found none (Heger et al., 2006). A subgroup of participants then went on to use the same extract in an open-label trial for 48 to 96 weeks. In general, the women experienced continued improvement in their menopausal symptoms with no adverse side effects (Hasper et al., 2009).
Another study using the data from the initial trial found the standardized Siberian rhubarb extract to be more effective than placebo specifically for relieving menopause-related anxiety and improving general well-being. In 33 of 39 rhubarb-treated women whose anxiety was "severe" or "moderate" at the beginning of the trial (85%), anxiety was reduced to "slight" after 12 weeks. The study also noted a correlation between decreased anxiety and reduced hot flushes (Kaszkin-Bettag et al., 2007).
Other studies have confirmed the benefits of the Siberian rhubarb extract: treatment with the extract led to decreases in overall menopausal symptom scores, as well as reductions in all individual symptoms tracked, in a six-month open-label study with 363 participants (Kaszkin-Bettag et al., 2008) and a 12-week randomized controlled trial with 112 participants (Kaszkin-Bettag et al., 2009).
Laboratory research has revealed that Siberian rhubarb extract and its active components selectively activate ER-β, having no effect on ER-α (Wober et al., 2007, Konda et al., 2014). ER-β activation has been proposed as a mechanism for preventing emotional and neurological aspects of aging and menopause (Vargas et al., 2016), and appears to protect against cancerous changes in breast, ovarian, and possibly other tissues (Gallo et al., 2012, Bardin et al., 2004, Bossard et al., 2012, Omoto and Iwase, 2015).
Black cohosh. Black cohosh (Actaea racemosa or Cimicifuga racemosa) root has a long history of traditional use in treating gynecologic disorders and has become a popular herbal medicine for relieving menopausal symptoms (NIH 2017). Randomized controlled trials have demonstrated its efficacy in treating menopausal symptoms such as hot flashes, low libido, sleep disturbance, and other physical and emotional symptoms (Jiang 2015; Shahnazi 2013; Mohammad-Alizadeh-Charandabi 2013; Ross 2012). Black cohosh has a track record of safety and the preponderance of evidence supports its use in treating menopausal symptoms (Shams 2010; Beer 2013; Czuczwar 2017; Sarri 2017). Black cohosh and closely related species have conveyed anti-proliferative effects on breast cancer cells in the laboratory (Fang 2010; Al-Akoum 2007; Hostanska 2004), and the use of black cohosh is not associated with increased breast cancer risk or recurrence rates (Fritz 2014). Data from one clinical trial and several animal studies suggest it is comparable to estradiol and another anti-osteoporosis medication for preventing bone loss (Nisslein 2003; Seidlova-Wuttke 2005; Wuttke 2003; Seidlova-Wuttke 2003).
Dong quai. Dong quai (Angelica sinensis) is used in traditional Chinese medicine for gynecological symptoms such as painful menstruation or pelvic pain, recovery from childbirth or illness, and fatigue/low vitality, and is therefore referred to as “female ginseng” (Al-Bareeq 2010; Goh 2001; Hardy 2000). Randomized controlled trials have shown that dong quai, in combination with other plant extracts, can relieve symptoms of menopause (Trimarco 2016; Kupfersztain 2003), and in one animal study dong quai was as effective as estradiol at preventing bone loss (Lim 2014).
Licorice root. Licorice (Glycyrrhiza glabra) root exerts estrogen-like effects with selective activation of ER-beta (Hajirahimkhan, Simmler 2013). Laboratory research suggests licorice constituents inhibit serotonin reuptake, an effect that may contribute to its positive impact on menopausal symptoms (Ofir 2003; Hajirahimkhan, Dietz 2013). In a randomized controlled trial, treatment with 330 mg of licorice root three times daily reduced both frequency and severity of menopausal hot flashes more than placebo during eight weeks of treatment and for two weeks following the end of treatment (Nahidi 2012). Licorice root constituents have also been shown in the laboratory to support arterial and bone health, thus reducing the risk of cardiovascular disease and osteoporosis (Somjen, Knoll 2004; Somjen, Katzburg 2004).
Vitex agnus-castus. Herbal formulas containing extracts from Vitex agnus-castus (Vitex), also known as chasteberry, have been shown to improve menopausal symptoms such as sleep disturbance, hot flashes, and psychosocial wellness (De Franciscis 2017; van Die 2009; Rotem 2007). Vitex, obtained from the dried fruit of the chaste tree, has been used in the context of women’s health for centuries. It has been shown to modulate hormonal and neurotransmitter signaling and to relieve premenstrual symptoms in several small studies. Laboratory studies have shown that compounds in vitex can bind estrogen receptors and modulate hormone-responsive genes (Dietz 2016).
Nutrients to Support Healthy Estrogen Metabolism
Vitamin D. Vitamin D appears to confer significant protective effects against breast cancer. Women with higher vitamin D levels had a nearly 70% reduction in their risk of breast cancer compared to women with the lowest levels in one study (Abbas 2008), while another study linked low vitamin D levels with reduced survival in breast cancer patients (Vrieling 2011). Laboratory studies have shown that vitamin D suppresses growth and development of breast cancer by:
- blocking signals that stimulate cancer cell growth
- enhancing signals that inhibit cancer cell growth
- modulating mammary gland sensitivity to carcinogenesis (Welsh 2017)
- inducing cancer cell death (apoptosis) (Thyer 2013; Fleet 2012)
Cruciferous vegetables. Cruciferous vegetables such as, cauliflower, cabbage, kale, and Brussels sprouts contain compounds that may help detoxify estrogen breakdown products that promote cancer growth (Marconett 2012; Lampe 2009; Ambrosone 2004). One such compound is I3C, which prevents the conversion of estrogen to the breast cancer-promoting metabolite 16-alpha-hydroxyestrone, while increasing conversion to the cancer-fighting metabolite 2-hydroxyestrone form (Acharya 2010; Weng 2008; Muti 2000).
Fish oil. Fish oil, with its high omega-3 fatty acid content, reduces cancer risk by a number of mechanisms. Fish oil reduces oxidative stress and suppresses production of many inflammatory mediators that contribute to cancer development (Saoudi 2017; Kansal 2011). It can sensitize tumor cells to chemotherapy effects even when metastases are present, potentially reducing the doses of chemotherapy required for treatment (Bougnoux 2009). In an animal model of breast cancer, fish oil supplementation was shown to reduce bone metastasis (Mandal 2010).
Green tea. Green tea polyphenols, particularly one called epigallocatechin gallate (EGCG), suppressed the growth and reproduction of human breast cancer cells in the laboratory and reduced the number of breast cancer tumors in animal models of the disease (Thangapazham, Passi 2007; Thangapazham, Singh 2007; Leong 2008). Green tea has also inhibited the production of tumor blood vessels while down-regulating cancer-promoting estrogen receptors and increasing apoptosis (Leong 2008; Masuda 2002; Farabegoli 2007; Hsuuw 2007).
Pomegranate. Pomegranate has been extensively studied for its antioxidant properties and cancer-fighting potential (Taheri Rouhi 2017; Li 2017; Panth 2017). With respect to breast cancer, pomegranate is an especially promising agent due to its ability to inhibit the cancer-promoting enzyme aromatase and suppress the generation of blood vessels by tumors (Toi 2003; Sturgeon 2010).
Disclaimer and Safety Information
This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
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