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Pueraria mirifica

Oestrogenic Effects of Pueraria mirifica on the Menstrual Cycle and Hormone-Related Ovarian Functions in Cyclic Female Cynomolgus Monkeys

Hataitip Trisomboon, Suchinda Malaivijitnond, Gen Watanabe and Kazuyoshi Taya Journal of Pharmacological Sciences, Vol. 94 (2004), No. 1 pp.51-59

This study investigated the estrogenic effect of Pueraria mirifica (P. mirifica) on menstrual cycle length and hormone-related ovarian function. Nine normal cyclic monkeys (Macaca fascicularis) were separated into 3 groups; each group was force fed with a single dose of 10, 100, and 1,000 mg of P. mirifica. The experimental schedule was separated into the pre-treatment and post-treatment periods. Blood samples were collected on days 3, 9 - 14, 19, 24, 29, and every 10 days until the next menstruation for one and two menstrual cycles during two consecutive periods and assayed for serum levels of gonadotropins and ovarian hormones. The result showed a significant increase in lengths of the follicular phase and total menstrual cycle in monkeys treated with 1,000 mg of P. mirifica, but no change in menstrual cycle length in monkeys treated with 10 and 100 mg of P. mirifica. Serum levels of follicle stimulating hormone, luteinizing hormone, oestradiol, progesterone, or immunoreactive inhibin did not change during the first and second menstrual cycles of the post-treatment period for all monkey groups. Our findings demonstrate that although changes in hormonal levels could not be observed in this study, a single dose of 1,000 mg of P. mirifica can disturb ovarian function and menstrual cycle in monkeys.

Different Effects of Pueraria mirifica, a Herb Containing Phytoestrogens, on LH and FSH Secretion in Gonadectomised Female and Male Rats

Suchinda Malaivijitnond, Patthama Kiatthaipipat, Wichai Cherdshewasart, Gen Watanabe and Kazuyoshi Taya Journal of Pharmacological Sciences, Vol. 96 (2004), No. 4 pp.428-435

To investigate the effect of Pueraria mirifica (P. mirifica) containing phytoestrogens on reproductive systems, both sexes of rats were gonadectomised and treated orally with 0, 10, 100, and 1,000 mg/kg BW per day of P. mirifica suspended in water (abbreviated as P-0, P-10, P-100, and P-1000), respectively. The treatment schedule was separated into 3 periods: pre-treatment, treatment, and post-treatment. The duration for each period was 14 days. Blood samples were taken once a week. Serum LH and FSH levels were significantly increased within 1 week after gonadectomy; and there were no changes after administration of P-0, P-10, and P-100. However, the increase of LH levels in both sexes and FSH levels in females were attenuated within 1 week after P-1,000 treatment. The attenuation of LH levels in males was smaller than that of females. The decrease of gonadotropin levels was recovered within 1 week in males and 2 weeks in females, respectively, during the post-treatment period. The increase of uterine weight and vaginal cornification were observed in female rats treated with P-100 and P-1,000, whereas only the increase of epididymis weight was found in male rats treated with P-1,000. From this study, it can be concluded that P. mirifica can influence the reproductive functions in both sexes of rats, but the response in females is greater than in males.

Major isoflavonoid contents of the phytoestrogen rich-herb Pueraria mirifica in comparison with Pueraria lobata

Cherdshewasarta W, Subtang S & Dahlan W. Journal of Pharmaceutical and Biomedical Analysis, Volume 43, Issue 2, 17 January 2007, Pages 428-434

Pueraria mirifica tubers collected from 28 out of 76 provinces of Thailand and Pueraria lobata tubers collected from Guangzhou province, China were submitted to HPLC analysis with the established gradient system comprising 1.5% acetic acid and acetonitrile. Five major isoflavonoids, including puerarin, daidzin, genistin, daidzein and genistein, were adopted as authentic standards. P. mirifica tubers showed intra- as well as inter-provincial differences in isoflavonoid and total isoflavonoid contents. The difference in both cases should be mostly influenced by genetic and environmental factors. In comparison with P. lobata, P. mirifica population exhibited differences only with a lower amount of daidzein.

Efficacy and safety of Pueraria mirifica (Kwao Kruea Khao) for the treatment of vasomotor symptoms in perimenopausal women: Phase II Study.

Lamlertkittikul, S; and Chandeying, V J-Med-Assoc-Thai. 2004 Jan; 87(1): 33-40

Pueraria mirifica, containing phytoestrogens, relatively alleviated the climacteric symptoms in perimenopausal women. The transient negative profiles occurred in a small number of subjects that included anaemia, and liver profiles. While there was a slight decrease in lipoproteins and an increase in hormonal profiles, Pueraria mirifica demonstrates great promise in the treatment of climacteric symptoms among perimenopausal women.

Variance of estrogenic activity of the phytoestrogen-rich plant.

Cherdshewasart W, Sriwatcharakul S, Malaivijitnond S. Maturitas. 2008 Dec 20;61(4):350-7. Epub 2008 Nov 5.

OBJECTIVE: To evaluate the influences of seasonal changes and plant cultivars on estrogenic activity of the phytoestrogen-rich plant, Pueraria mirifica. METHODS: Three cultivars of P. mirifica; PM-I, PM-II and PM-V, were grown in the same field trial for 3 years and random tubers collected during the summer, rainy season and winter seasons. Female Wistar rats were ovariectomized, kept for 14 days, randomly segregated into groups and treated with one of DW, 200microg/100g BW 17beta-estradiol (E2) or tuberous powder of PM-I, PM-II and PM-V at dosages of 100, or 1000mg/kg BW for the next 14 days. For the last 7 days of post-treatment period, rats received only DW. The vaginal cornification was recorded during the treatment and post-treatment period. The uterine tissues of the treated rats at the treatment and post-treatment periods were analyzed for uterine gland number and for the surface area of the myometrium, endometrium and lumen. In addition, ethanol tuberous extracts of PM-I, PM-II and PM-V was submitted to DPPH analysis. RESULTS: Vaginal cornification exhibited a dose-dependent response with plant samples collected during the winter and summer being more active than those collected in the rainy season. All plant samples-induced uterotrophic effects in the analysis at the treatment and post-treatment periods in a dose-dependent manner. The P. mirifica treated rats exhibited increasing uterine gland numbers and thickness of the endometrium and myometrium but a decreasing size of lumen, in comparison to the negative control. The results were more prominent in PM-I than other plants and also in plant samples collected during the winter and summer seasons than in the rainy season. DPPH assay of the ethanol tuberous extracts revealed variance in antioxidant activity. CONCLUSION: The results of uterotrophic and vaginal cornification assays reveal that P. mirifica exhibits a dose-dependent estrogenic activity under the influence of both seasonal changes and plant cultivars, which is confirmed by DPPH assay.

Estrogenic activity of the dichloromethane extract from Pueraria mirifica.

Sookvanichsilp N, Soonthornchareonnon N, Boonleang C. Fitoterapia. 2008 Dec;79(7-8):509-14. Epub 2008 Jun 22.

Pueraria mirifica and its extracts are widely used as the ingredient(s) in many rejuvenating products. Up to now, the extract of P. mirifica roots that has been used in most studies, is the alcoholic extract. In the present study, we investigated the estrogenic activity using uterotropic and MCF-7 cell proliferation models of the dichloromethane extract as well as the water extract, which was obtained from partitioning the ethanolic extract. The results indicated that among the three extracts, i.e. the ethanolic extract (PM1), the water extract (PM2) and dichloromethane extract (PM3), PM3 exhibited the most potent estrogenic activity in both models, followed by PM1. The extracts produced uterotropic activity associated with the increase of water content while uterotropic activity of 17beta-estradiol was related to the increase of muscle mass. The two isoflavonoids, genistein and daidzein, were not the major active phytoestrogens involving the estrogenic activity of these extracts.

Pueraria mirifica, phytoestrogen-induced change in synaptophysin expression via oestrogen receptor in rat hippocampal neuron.

Chindewa R, Lapanantasin S, Sanvarinda Y, Chongthammakun S. J Med Assoc Thai. 2008 Feb;91(2):208-14.

OBJECTIVE: To examine Pueraria mirifica (Leguminosae) containing-phytoestrogen effect on synaptic density and involvement of oestrogen receptor. MATERIAL AND METHOD: The level of synaptophysin, a presynaptic vesicle protein, was measured using Western blot analysis and immunocytochemistry in hippocampal primary cell cultures at 6 days in vitro. RESULTS: P. mirifica and 17beta-estradiol (0.1 microM) treatment for 4 days, but not for 2 days, significantly increased synaptophysin immunoreactivity and level of synaptophysin. P. mirifica up to 60 microg/ml resulted in a dose related increase in the level of synaptophysin immunoreactivity. The classical oestrogen receptor antagonist, ICI 182 780, significantly blocked P. mirifica-induced increase in synaptophysin. CONCLUSION: P. mirifica-containing phytoestrogen affects synaptic density by inducing synaptophysin expression via oestrogen receptor.

Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women.

Manonai J, Chittacharoen A, Udomsubpayakul U, Theppisai H, Theppisai U. Menopause. 2008 May-Jun;15(3):530-5.

OBJECTIVE: To evaluate the effect of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women and to evaluate the safety of Pueraria mirifica on endometrium; breast tissue; and hematologic, hepatic, and renal systems. DESIGN: This was a randomized, double blind, placebo-controlled study in a university hospital of healthy postmenopausal women aged 45 to 60 years old. Women were enrolled voluntarily and randomly received 20, 30, or 50 mg Pueraria mirifica in capsules or identical placebo once daily for 24 weeks. Outcome measures were lipid profiles, bone-specific alkaline phosphatase level, endometrial thickness, endometrial histology, breast ultrasonography, complete blood count, liver function test, and renal function test. RESULTS: After 24 weeks of treatment, 71 women were evaluated. Of the 71 women, 51 randomly received varying doses of Pueraria mirifica and 20 received placebo. Pueraria mirifica and placebo significantly increased triglyceride levels by 15% from baseline levels (P<0.05). The Pueraria mirifica group showed a significant decrease in bone-specific alkaline phosphatase levels after 24 weeks of treatment compared with the placebo group; from 0.22+/-0.18 U/L to 0.13+/-0.01 U/L in the Pueraria mirifica group and from 0.20+/-0.10 U/L to 0.20+/-0.14 U/L in the placebo group. Endometrial thickness did not change after treatment in both groups (P>0.05). No endometrial proliferation or hyperplasia was reported after 24 weeks of treatment in both groups. There were no significant differences in adverse effects on breast tissue, complete blood count, and liver and renal function tests between the Pueraria mirifica and placebo groups in this study. CONCLUSION: Pueraria mirifica at a dose of 20, 30, and 50 mg/d for a 24-week period demonstrated an oestrogen-like effect on bone turnover rate. Pueraria mirifica did not demonstrate an oestrogen-like effect on endometrial thickness and endometrial histology. Mild adverse effects occurred after Pueraria mirifica and placebo treatment.

Lemon Balm

Lemon Balm (Melissa officinalis) is an approved therapy listed in the German Commission E monographs for treatment of sleep disturbance and anxiety. Experimental data have shown some antiviral effects of Lemon balm (Dimitrova et al., 1993), including an inhibitory effect against HIV-1 reverse transcriptase (Yamasaki et al., 1998). There are no specific contraindications to the use of this herb. 

Black Cohosh 

Black cohosh (Cimicifuga racemosa) has been used for many years in Europe for treatment of hot flashes (Der Marderosian, 1999) and has recently become available in the United States as an alternative to oestrogen REPLACE ment. The active constituents are believed to be triterpenoid glycosides and isoflavones (Bradley, 1992). One study demonstrated a decrease in luteinizing hormone (LH) levels, but not follicle-stimulating hormone (FSH), in women using the Cimicifuga extract (Yamasaki et al, 1998).  Other studies have shown that extracts contain substances that bind to oestrogen receptors (. Der Marderosian, 1999; Bradley, 1992; Duker et al, 1991). A small German study (N = 60) compared postmenopausal women taking black cohosh extract (80 mg/day), conjugated equine oestrogens  (0.625 mg/day), or placebo. Similar significant reductions in hot flash occurrence in both treatment arms were found, with no significant differences in reported side effects (Stoll, 1987).

The German Commission E monographs list black cohosh as an approved herbal therapy for menopausal symptoms (Blumenthal et al, 1998). However, the Commission states that therapy should not exceed 6 months at the recommended dose of 40 to 200 mg per day. A German study examining the effects of Remifemin (a trade name for a black cohosh preparation) did not show any stimulatory effects on oestrogen-dependent breast tumor cell lines or the endometrium, suggesting that progestin therapy is not necessary to protect against endometrial proliferation (Der Marderosian, 1999). Unfortunately, no large, well-controlled, double-blinded studies currently exist that document either efficacy or safety of this treatment.

Side effects and contraindications

Side effects of black cohosh include gastrointestinal discomfort, and overdose may lead to vomiting, dizziness, visual disturbance, and bradycardia (Der Marderosian, 1999). Large doses have also been associated with miscarriage (Reader’s Digest Editors, 1986). Because of its oestrogen receptor–binding affinity, it should be avoided in women with oestrogen-responsive tumours, and more studies are needed to determine long-term safety. Black cohosh is not recommended for use in pregnant women, and should not be used in addition to oestrogen therapy. 

Black cohosh appears to be effective in reducing symptoms of hot flashes in women who choose not to take oestrogen therapy. Large randomized trials, however, are needed prior to making standard recommendations regarding the use of black cohosh. 

Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial.

Geller SE, Shulman LP, van Breemen RB, Banuvar S, Zhou Y, Epstein G, Hedayat S, Nikolic D, Krause EC, Piersen CE, Bolton JL, Pauli GF, Farnsworth NR. Menopause. 2009 Nov-Dec;16(6):1156-66.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of menopausal vasomotor symptoms. METHODS: This study was a randomized, four-arm, double blind clinical trial of standardized black cohosh, red clover, placebo, and 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA; n = 89). Primary outcome measures were reduction in vasomotor symptoms (hot flashes and night sweats) by black cohosh and red clover compared with placebo; secondary outcomes included safety evaluation, reduction of somatic symptoms, relief of sexual dysfunction, and overall improvement in quality of life. RESULTS: Reductions in number of vasomotor symptoms after a 12-month intervention were as follows: black cohosh (34%), red clover (57%), placebo (63%), and CEE/MPA (94%), with only CEE/MPA differing significantly from placebo. Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo. Secondary measures indicated that both botanicals were safe as administered. In general, there were no improvements in other menopausal symptoms. CONCLUSIONS: Compared with placebo, black cohosh and red clover did not reduce the number of vasomotor symptoms. Safety monitoring indicated that chemically and biologically standardized extracts of black cohosh and red clover were safe during daily administration for 12 months.

Effects of black cohosh extract on body weight gain, intra-abdominal fat accumulation, plasma lipids and glucose tolerance in ovariectomized Sprague-Dawley rats. 

Rachoñ D, Vortherms T, Seidlová-Wuttke D, Wuttke W. Maturitas. 2008 Jul-Aug;60(3-4):209-15. Epub 2008 Aug 8.

Extracts of the black cohosh (Actaea/Cimicifuga racemosa (CR)) have long been used to treat oestrogen deficiency symptoms in women after menopause. Recent data from randomized controlled studies have shown that CR consumption alleviates "hot flushes" and due to the lack of uterotropic effects can be a safe alternative to oestrogen REPLACE ment therapy. OBJECTIVE: To evaluate the effects of dietary CR extract consumption on body weight (BW) gain, intra-abdominal fat (IAF) accumulation, plasma leptin, lipids and glucose tolerance in ovariectomized rats and to compare them with the effects of 17beta-estradiol. DESIGN: Twenty-seven female Sprague-Dawley rats were ovariectomized and fed soy-free chow with the addition of estradiol-3 benzoate (E2B) (10mg/kg, n = 10) or CR BNO 1055 extract (6.67 g/kg, n = 9). The control group (n = 8) received soy-free chow only. Weight and food intake were recorded once a week. After 6 weeks, intra-abdominal fat was measured using computer tomography and the intraperitoneal glucose tolerance test was performed. In the seventh week of the experiment animals were sacrificed, blood was collected for plasma and uteri were removed. RESULTS: Dietary CR BNO 1055 extract had no effects on uterine mass but significantly reduced serum luteinizing hormone (LH) levels (P< 0.05). Although, the average weekly food consumption throughout the experiment (calculated in g/kg of BW) did not differ between our studied groups, E2B or CR BNO 1055 treated animals gained less weight and had significantly less IAF accumulation compared to control animals (P< 0.05). E2B treatment also decreased plasma total (T-,) high-density lipoprotein (HDL-) and low-density lipoprotein (LDL)-cholesterol (P< 0.05). Plasma T-Ch levels in CR BNO 1055 treated animals did not differ from the controls whereas LDL-Ch levels were significantly higher and plasma triglycerides (TG) significantly lower (P<0.05). In the glucose tolerance test, the area under the curve (AUC) was significantly smaller in the E2B treated animals compared to controls (P<0.05). AUC in CR BNO 1055 treated animals did not differ significantly from the controls (P>0.05). Nevertheless, fasting plasma insulin (FPI) levels were significantly lower in E2B and CR BNO 1055 treated animals (P<0.05). CONCLUSIONS: In OVX rats, CR BNO 1055 extract consumption decreases enhanced pituitary LH secretion, attenuates body weight gain and IAF accumulation, lowers FPI and has no effects on uterine mass. The effects on plasma lipids seem to be more complex and are characterized by an increase of LDL-Ch and decrease of TG levels, which is in contrast to the effects of oestrogen.

Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy.

Borrelli F, Ernst E. Pharmacol Res. 2008 Jul;58(1):8-14. Epub 2008 Jun 8.

Since conventional hormone REPLACE ment therapy has fallen out of favour, alternatives are now being sought by many women. These therapies include herbal preparations such as black cohosh (Cimicifuga racemosa). The purpose of this update of a previous systematic review is to evaluate the clinical evidence for or against the efficacy of black cohosh in alleviating menopausal symptoms. Five computerized databases (Medline, Embase, Amed, Phytobase and Cochrane Library) were searched to identify all clinical data that provided evidence on the efficacy of C. racemosa. Bibliographies of the articles thus located were scanned for further relevant publications. Only double blind, randomized, clinical trials (RCTs) were included in the evaluation of efficacy. No language restrictions were imposed. Trials were excluded if they did not focus on menopausal problems, they included women suffering medically induced menopause, they did not use black cohosh mono-preparations, or they did not use placebo or a standard drug treatment for the control group. Six studies with a total of 1112 peri-and post-menopausal women met our inclusion criteria. The evidence from these RCTs does not consistently demonstrate an effect of black cohosh on menopausal symptoms; a beneficial effect of black cohosh on peri-menopausal women cannot be excluded. The efficacy of black cohosh as a treatment for menopausal symptoms is uncertain and further rigorous trials seem warranted.

Chasteberry

Chasteberry (Vitex agnus-castus) has been used widely in Europe for treatment of hot flashes, breast tenderness, and dysmenorrhea, and it is recommended by the German Commission E for these disorders (Blumenthal et al., 1998). However, there are no controlled studies documenting any effects in postmenopausal women, and there are no documented beneficial effects in the treatment of hot flashes. There are data supporting its use in reducing symptoms of breast tenderness in premenopausal women (Halaska et al., 1998). Chasteberry is thought to act by decreasing the release of prolactin. A study in rat pituitary cells showed binding of the D2 receptors by an extract of the herb, therefore inhibiting prolactin secretion (Jarry et al., 1994).

Contraindications

Due to the effects on dopaminergic receptors, chasteberry should not be used with other medications affecting dopamine or prolactin secretion, such as anti-psychotics, anti-parkinsonian agents, or bromocriptine. 

Vitex agnus castus as prophylaxis for osteopenia after orchiectomy in rats compared with oestradiol and testosterone supplementation.

Sehmisch S, Boeckhoff J, Wille J, Seidlova-Wuttke D, Rack T, Tezval M, Wuttke W, Stuermer KM, Stuermer EK. Phytother Res. 2009 Jun;23(6):851-8.

Osteoporosis research undertaken in males is rare and there are only a few therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis. Sixty 3-month-old male rats were orchidectomised and divided into five groups. The groups either received soy-free food (C), oestradiol (E), testosterone (T) or Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The tibia metaphysis was tested biomechanically and histomorphometrically. The AC high group reached 87% of the biomechanical values of the oestradiol group and was significantly superior to the control group. Testosterone supplementation resulted in poor biomechanical properties. The cortical bone parameters of the AC group were similar to the control group, while supplementation with oestradiol and testosterone demonstrated a reduction of cortical bone. The AC high group reached 88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number of trabecular nodes compared with oestradiol supplementation. Vitex agnus castus demonstrated osteoprotective effects in males. It preserves the cortical as well as the trabecular bone and might be a safe alternative for HRT. Testosterone supplementation has positive effects on trabecular bone, which are concurrently counteracted by the loss of cortical bone.

Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt.

Ibrahim NA, Shalaby AS, Farag RS, Elbaroty GS, Nofal SM, Hassan EM. Nat Prod Res. 2008 Apr 15;22(6):537-46.

Flavonoid glycosides, orientin and apigenin 3, 8-di-C-glycosides in addition to, iridoid compound, aucubin were isolated from the ethanolic extract of Vitex agnus-castus fruits. Their structures were identified on the basis of the spectroscopic data. The estrogenic activity of the ethanolic extract in two dose levels 0.6 and 1.2 g kg(-1) per body weight (b.w.) was studied by the vaginal smear, and uterine weight methods for normal and ovariectomized female rats. The extract induced significant increase in the uterine weight of ovariectomized rats at two dose levels comparable to that of control group. The percentages of the total average number of scores were increased significantly too. Significant increases in plasma progesterone and total oestrogens levels were shown at the two dose levels when compared to that of control group. On the other side, the extract induced significant reduction in luteinizing and plasma prolactin hormones.

The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice.

Nasri S, Oryan S, Rohani AH, Amin GR. Pak J Biol Sci. 2007 Jul 15;10(14):2300-7.

The purpose of this study was to evaluate the probable effects of Vitex agnus castus (Vac.) on the male reproductive physiology. It is a well-known fact that LH secretion from the anterior pituitary of mammals is controlled by many neurotransmitters such as dopamine. In this experiment, we have studied the effect of Vac. extract on the LH and testosterone hormones and its interaction with the dopaminergic system on male mice. In order to evaluate these effects, we used the hydro alcoholic Vac. extract (for extraction we used percolation technique) injection with the following doses: 65, 165, 265, 365 and 465 mg kg-', bromocriptine as a dopamine receptor agonist (5, 10, 20 mg kg(-1)) and haloperidol as a dopamine receptor antagonist (1, 1.5, 2, 2.5, 3 mg kg(-1)). To study the interaction between Vac. extract and dopaminergic system, we injected the optimum doses of Vac. with bromocriptine or haloperidol at the same time. Intraperitoneal injections were applied in all experiments, once a day for 30 days. The control group remained intact and the sham group received vehicle. After the last injection, we collected the animal blood serums for hormonal assays. LH and testosterone were measured by Radio Immuno Assay (RIA). LH and testosterone, showed significant decrease in bromocriptine group and haloperidol increased these hormones. Vac. extract decreased significantly the LH and testosterone levels. The co-administration of Vac. extract and bromocriptine decreased LH and testosterone. Co-administration of Vac. extract and haloperidol decreased LH and testosterone levels. These results suggest: dopamine regulates the gonadotroph-leydig cells axis. It appears that Vac. exerts effects through dopaminergic system and other pathways. The findings of this study show we can use Vac. extract for pathological cases of increasing LH and testosterone.

Dong Quai 

Dong quai (Angelica sinensis) has been used in traditional Chinese medicine for treatment of hot flashes and breast tenderness (Taylor, 1997; Gladstar, 1993) as well as dysmenorrhea and irregular menses (Chang & But, 1986). The active compounds are thought to include coumarin derivatives, including oxypeuce-danin, osthol, psoralen, and bergapten (Der Marderosian, 1999). It is commonly sold in the United States as a component of Rejuvex as well as singly by many manufacturers. It is thought that dong quai contains phytoestrogens and, in a low-oestrogen environment such as at menopause, estrogenic activity will prevent vasomotor symptoms. A recent randomized, controlled study evaluated 91 women who were assigned either dong quai or placebo. Measurement of endometrial thickness, vaginal cytology, and menopausal symptoms did not demonstrate any difference between the two groups. There were no significant differences in serum oestradiol, oestrone, or sex hormone binding globulin levels (Hirata et al., 1997). Interestingly, the traditional Chinese preparation did not use dong quai alone, but combined it with several other herbs (Radix Angelicae sincensis, Radix Paeoniae lactiflorae, Rhizoma ligustici, Rhizoma Atractylodes, Rhizoma Alismatis, Sclerotium poriae). This mixture has been re-ported to reduce the incidence of hot flashes by 70% (Chang & But, 1986). There are no studies documenting the effects of these other agents when used alone. 

Side effects and contraindications

Dong quai can cause photodermatitis and phototoxicity if applied externally, and there are concerns regarding carcinogenicity of one of the active components, furanocoumarin bergapten. There is also a theoretical, although undocumented, risk of bleeding from the coumarin constituents. Dong quai is recognized to be an abortifacient, and should not be used in pregnancy (Newall et al., 1996).

There is no clear evidence supporting a recommendation of dong quai alone for treatment of vasomotor symptoms of menopause. Its use in combination with other herbal agents also has not been evaluated sufficiently to support a recommendation for such use.

Estrogenic activity of standardized extract of Angelica sinensis.

Circosta C, Pasquale RD, Palumbo DR, Samperi S, Occhiuto F. Phytother Res. 2006 Aug;20(8):665-9.

Since ancient times, extracts of plants have been used for women's health to prevent menopausal symptoms. The symptoms of menopause have been attributed to a reduction in the amount of oestrogen produced by the ovaries. In this study the estrogenic activity of a commercial standardized extract of the roots of Angelica sinensis, used to relieve climacteric symptoms was evaluated using in vivo tests such as the degree of cornification of vaginal epithelium, uterotrophic assays and serum LH concentration in ovariectomized rats. Furthermore, the effects on the oestrous cycle in rat were investigated. The results obtained have shown that the administration of a standardized ethanol extract in ovariectomized rats exhibited a stimulation of the uterine histoarchitecture, a significant cornification in the vaginal epithelium and a reduction of serum LH concentration showing the estrogenic nature of the extract. Furthermore, the administration of the extract in intact female rats provoked a significant modification of the vaginal smear in 67% of treated rats. The oestrous cycle thus modified was characterized by a prolonged oestrus stage with a temporary reduction of the regular cyclicity.

The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report.

Kupfersztain C, Rotem C, Fagot R, Kaplan B. Clin Exp Obstet Gynecol. 2003;30(4):203-6.

OBJECTIVE: To assess the efficiency of a medicinal herb extract preparation (Climex) for the treatment of menopausal symptoms. METHOD: In this placebo-controlled experiment on 55 postmenopausal women who complained of hot flushes and refused hormonal therapy. The women were randomly divided into two groups, one to receive Climex (5 chewable tablets daily between meals) and the other group to receive a placebo; both groups would take the tablets for 12 weeks. The women were asked to complete a daily structured (Kupperman) questionnaire assessing the frequency and intensity of menopausal symptoms, starting one week prior to treatment to the completion of the study. All women underwent hormone profile measurements and transvaginal ultrasonography evaluation before and after treatment. RESULTS: There was a significant difference between the study group and the control group in the decrease in number and intensity of hot flushes from baseline to completion of treatment (90-96% vs 15-25%, p< 0.001). In the study group, a response was already noted during the first month of treatment (68% +/-2% reduction of hot flushes during the day and 74% +/-4% during the night). There was also a marked alleviation of sleep disturbances and fatigue. CONCLUSIONS: Treatment with Climex seems to be effective for menopausal symptoms without apparent major adverse effects. This hormone-free preparation may be used as an important modality for menopausal women with contraindications for hormone REPLACE ment therapy.

Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms.

Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL. J Agric Food Chem. 2001 May;49(5):2472-9.

Eight botanical preparations that are commonly used for the treatment of menopausal symptoms were tested for estrogenic activity. Methanol extracts of red clover (Trifolium pratense L.), chasteberry (Vitex agnus-castus L.), and hops (Humulus lupulus L.) showed significant competitive binding to oestrogen receptors alpha (ER alpha) and beta (ER beta). With cultured Ishikawa (endometrial) cells, red clover and hops exhibited estrogenic activity as indicated by induction of alkaline phosphatase (AP) activity and up-regulation of progesterone receptor (PR) mRNA. Chasteberry also stimulated PR expression, but no induction of AP activity was observed. In S30 breast cancer cells, pS2 (presenelin-2), another oestrogen-inducible gene, was up regulated in the presence of red clover, hops, and chasteberry. Interestingly, extracts of Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) induced pS2 mRNA expression in S30 cells, but no significant ER binding affinity, AP induction, or PR expression was noted in Ishikawa cells. Dong quai [Angelica sinensis (Oliv.) Diels] and Licorice (Glycyrrhiza glabra L.) showed only weak ER binding and PR and pS2 mRNA induction. Black cohosh [Cimicifuga racemosa (L.) Nutt.] showed no activity in any of the above in vitro assays. Bioassay-guided isolation utilizing ER competitive binding as a monitor and screening using ultrafiltration LC-MS revealed that genistein was the most active component of red clover. Consistent with this observation, genistein was found to be the most effective of four red clover isoflavones tested in the above in vitro assays. Therefore, estrogenic components of plant extracts can be identified using assays for estrogenic activity along with screening and identification of the active components using ultrafiltration LC-MS. These data suggest a potential use for some dietary supplements, ingested by human beings, in the treatment of menopausal symptoms.

Evening Primrose Oil 

Evening primrose oil (Oenothera macrocarpa) has been studied for use in a wide variety of disorders, including atopic dermatitis, rheumatoid arthritis, and chronic fatigue syndrome. It has also been used in treating symptoms of premenstrual syndrome, including mastalgia (Der Marderosian, 1999). It is thought to be a safe alternative to oestrogen therapy in women who suffer vasomotor symptoms at menopause, and it is often used in menopausal women who have had breast cancer who cannot take oestrogen. However, the data supporting its use in the above-mentioned disorders are contradictory at best. 

The active ingredient in evening primrose oil is thought to be gamolenic acid, a metabolite of linoleic acid, an essential fatty acid. It is believed that metabolites of gamolenic acid may elevate prostaglandin levels and decrease the affinity of estrogenic compounds for oestrogen receptors (Chenoy et al, 1994). A small study published in 1994 looked at the effect of gamolenic acid from evening primrose oil versus placebo on the incidence of vaso-motor symptoms in menopausal women. No beneficial effect of evening primrose oil was demonstrated (Horrobin & Manku, 1990).

Side effects and contraindications

Evening primrose oil appears to be relatively safe, with slight nausea as a side effect in a small trial (Chenoy et al, 1994) and sporadic reports of headache and softening of the stools (Kleijnen, 1994). Another study revealed a possible risk of inflammation and immuno-suppression with prolonged use for greater than 1 year (Phinney, 1994). Gamolenic acid has also been noted to lower the seizure threshold (Newall, Anderson & Phillipson, 1996). Therefore, evening primrose oil should be avoided in patients with seizure disorders or in combination with other medications (eg, bupropion, phenothiazine’s) that may have the same action on the seizure threshold.

Ginkgo biloba

Ginkgo biloba is a plant extract that is widely used both in Europe and the United States. Its active ingredients are thought to be flavonoids, terpenoids, and organic acids that act as free radical scavengers (Sastre et al., 1998). Ginkgo is commonly thought to improve vascular flow, and is used in the treatment and prevention of peripheral vascular disease and diseases of cerebral blood flow, including a variety of dementias. Most trials have been conducted in Germany using a standardized ginkgo extract (Egb761), and the Commission E monographs state that the extract is safe and effective for circulatory disturbances and may improve memory (Blumenthal et al., 1998). A randomized, controlled trial in the United States in 1997 demonstrated stabilization and occasional improvement in cognitive functioning in patients with mild-to-moderate dementia (eg, Alzheimer’s or multi-infarct type) (Le Bars et al., 1997). Another trial in healthy elderly patients demonstrated improved cognitive function with the use of ginkgo extract (Subhan & Hindmarch, 1984). There are no data that support the belief that ginkgo helps improve cognition or memory in younger people, and no studies to support its use to treat memory loss associated with menopause.

Side effects and contraindications

It is generally well tolerated. However, there are isolated reports of bleeding in patients taking Ginkgo biloba (Rosenblatt & Mindel, 1997; Rowin & Lewis, 1996). Therefore, patients who are taking aspirin or warfarin or those scheduled for surgical procedures should avoid using ginkgo

Effects of ginkgo biloba on testicle injury induced by diethylstilbestrol in mice.

Wang W, Zhong XH, Ma A, Shi W, Zhang XS, Liu Y. Am J Chin Med. 2008;36(6):1135-44.

To evaluate the effect of gingko biloba (EGb) on diethylstilbestrol (DES) induced testicle injury in mice. Fifty male mice were divided into a control group (A), DES group (B), and 3 EGb groups (C, D, E). The EGb-treated groups received peritoneal EGb at 8.75 (C), 17.5 (D), 35 mg/kg (E) BW daily for 7 days. The control group was given equivalent amount of normal saline. The mice in groups B, C, D and E were injected hypodermically with DES at 40 mg/kg BW daily 4 hours after the first herbal administration, while the control was given olive oil. Compared with DES group, the testis coefficients-relative testicular weight increased in the three EGb-treated groups. No significant difference was observed in epididymis coefficients. Lipid peroxidation status and antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly elevated in testes of EGb-treated groups. Lactate dehydrogenase (LDH) activities and malonaldehyde (MDA) contents were significantly decreased in testes of the EGb groups. The results indicate that EGb protects the testis from diethylstilbestrol-induced injury.

Ginkgo biloba extract enhances testosterone synthesis of Leydig cells in type 2 diabetic rats

Wu XY, Wang WY, Wang RR, Xie L, Fang ZX, Chen GR. Zhonghua Nan Ke Xue. 2008 Apr;14(4):371-6.

OBJECTIVE: To investigate the effects of Ginkgo biloba extract (EGB) on the testosterone synthesis in the Leydig cells of type 2 diabetic rats. METHODS: Thirty male SD rats were equally randomized into a normal control, a type 2 diabetic and an EGB group. Morphological changes of Leydig cells were observed by light microscopy (LM) and transmission electron microscopy (TEM), concentrations of serum luteinizing hormone (LH) and testosterone (T) were determined by enzyme linked immunosorbent assay (ELISA), and the mRNA levels in the steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (P450scc), cytochrome P450 17a-hydroxylase (P450c17), 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD1) from the Leydig cells were examined by RT-PCR. RESULTS: Compared with the normal control, there was a significant decrease in the number and volume of Leydig cells, the levels of serum LH and T and the expression of mRNA in StAR, P450scc, 17beta-HSD3 and 3beta-HSD1 in the type 2 diabetes group. And the expression of the P450c17 gene showed a tendency of descending, but with no significance. Compared with the type 2 diabetes group, 12 weeks of EGB treatment caused very slight pathological changes in the Leydig cells, significantly increased the concentrations of blood LH and T, markedly elevated the levels of mRNA in StAR and P450scc and induced an ascending tendency of the expressions of P450c17, 17beta-HSD3 and 3beta-HSD1. CONCLUSION: EGB enhances testosterone synthesis and secretion of Leydig cells by reducing the impairment of the testis in type 2 diabetic rats.

Effects of ginkgo biloba on in vitro osteoblast cells and ovariectomized rat osteoclast cells.

Oh SM, Kim HR, Chung KH. Arch Pharm Res. 2008 Feb;31(2):216-24.  

Ginkgo biloba extract (GBE) has a selective oestrogen receptor modulator (SERM)-like biphasic effect on oestrogen, and could be a potential alternative to hormone REPLACE ment therapy (HRT). Here, we investigated whether GBE can ameliorate oestrogen-depleted osteoporosis in in vitro osteoblast cells and in oestrogen-deprived ovariectomized (OVX) rats, a classical animal model for postmenopausal osteoporosis. GBE (50-150 microg/mL) significantly increased ALP (Alkaline phosphatase) activity of osteoblast cells, indicating that GBE promotes osteoblast mineralization. OVX rats exposed to GBE (100 and 200 mg/kg/day, oral treatment), raloxifene (3 mg/kg/day, oral treatment) or oestradiol (E2, 10 microg/kg/day, subcutaneous injection) decreased osteoclast resorptive activity compared with OVX rats. GBE and raloxifene did not increase uterine weight compared with OVX rats, while E2 and Sham control did, suggesting that GBE has no uterotrophic activity, which is a disadvantage of oestrogen therapy. In OVX rats, GBE did not restore severe bone density loss induced by OVX, indicating that GBE may be insufficient as therapeutic material for severe osteoporosis. However, despite its no effects on bone density loss in OVX rats, GBE did stimulate osteoblast differentiation and anti-osteoclastic activity in vitro. Therefore, GBE may have preventive potential on osteoporosis as do other phytoestrogens.

Ginseng

Ginseng is widely used in the United States as an energy booster, and it has been used in China for thousands of years as a tonic. Germany’s Commission E recommends it as a treatment for menopausal disorders (Blumenthal et al, 1998). It is difficult to assess the action of ginseng due to the wide variety of products that are available for use. American ginseng (Panax quinquefolius), Chinese ginseng (Panax ginseng), and Siberian ginseng (Eleutherococcus senticosus), the last of which is not a true ginseng (i.e., not a Panax species), are all sold as “ginseng.” A recent study using thin-layer chromatography found that only 25% of the commercially available products labelled as ginseng contained true ginseng (Liberti & Der Marderosian, 1978). Therefore, observational studies of ginseng are of little use in determining either its safety or efficacy. 

Clinical trials

A Swedish study evaluated the estrogenic effect of Ginsana (a preparation of Panax ginseng) and found no difference in frequency of hot flashes when compared with placebo, but noted a significant effect on improvement in well being (Lindgren et al, 1997). Another randomized, controlled trial in 625 patients noted an increase in quality-of-life scores in those who used ginseng (Caso et al, 1996).

Side effects and contraindications

Possible side effects of true ginseng include insomnia, tachycardia, palpitations, and hypertension (Newall et al., 1996; Siegel, 1979). Mastalgia and post-menopausal bleeding have been reported, and a case of diffuse mammary nodularity also occurred (Dukes, 19940. Estrogen-like effects on the uterus, vagina, and breasts have also been documented (Bahrke & Morgan, 1994). Ginseng extract is thought to compete with oestrogen binding sites and human myometrial cytosol (Punnonen & Lukola, 1980). Because of its action as a mild stimulant, ginseng should not be used in patients with cardiovascular disease (including hypertension) or those with psychiatric disorders (eg, bipolar disorder). Ginseng may interact with warfarin, and caused a prolonged international normalized ratio in one case (Janetzky & Morreale, 1997).

True ginseng appears to be generally safe and may improve the sense of well being in a woman in perimenopause. However, there are no data to support a recommendation of its use to treat the vasomotor symptoms of menopause (Weil et al., 2000).



Study on the Changes of Rat Testis Androgen Receptor mRNA Expression and Plasma Testosterone after Cold Stress

Wang Hong-jun, Feng Li, Chu Zheng, Yu Ning, Yang Qing, Zhang zhi-qiang, Wang Li-qiang, Wu Yi-min. Shi Zhen Guo Yi Guo Yao. 2008; 19(4): 929-930.

Objective: To study the effect of ginseng polysugar on the mRNA expression of testis tissue androgen receptor and plasma testosterone change after cold stress. Methods: Rats were divided into control group, cold stress experiment group and cold stress ginseng polysugar group, testis tissue androgen receptor mRNA expression was determined by rat androgen receptor cDNA probe dot blotting. Testosterone was determined by radioimmunoassay kit(RIA kit). Results: The content of testosterone(nmol/ L) was 10.93 ± 1.44 in control group, 6.06 ± 1.78 in cold stress experiment group, 8. 01 ± 1.38 in cold stress ginseng polysugar group. There was a significant synthesis difference between cold stress group and control group(P<0.05). Dot-blot: the mRNA expression of androgen receptor in cold stress group was weaker than that in control group, cold stress ginseng polysugar group was more than that in cold stress group. Conclusion: Testosterone has identical change with androgen receptor mRNA expression, ginseng polysugar has up regulation action for androgen receptor mRNA expression, and promote testosterone..

The Effect of Ginseng Polysugar on Secretion Function of Luteal and Granulose Cell of Rat in vitro

Sun Yan, Feng Li, Wang Hong-jun, Nian Chun-zhi, Chu Zheng, Wang Li-qiang, Zhang zhi-qiang, Wu Yi-min. Shi Zhen Guo Yi Guo Yao. 2007; 18(8): 1925-1926.

Objective: To study using of ginseng polysugar on secretion function of female rat ovary. The experiment had observed progesterone and cAMP by HCG inducing luteal and granulose cell as well as living cell rate of oocyte in vitro. Methods: Rat luteal and granulose cell and oocyte was cultivated, cell counting was worked by. Microscope, progesterone and cAMP content was determined by radioimmunoassay kit (RIA kit). Cell exist rate of oocyte was determined by MTF way, Results: Progesterone: the luteal cell test groups compare with control group, 6573.46 ± 185.14 and(4509.55 ±126.82) pmol, The granulose cell test groups compare with control group, 197.16±42.87 and (320.42±12, 46)pmol. cAMP: the luteal cell test groups compare with control group, 31.20±17.13and(65.26±15.93) fmol, the granulose cell test groups compare with control group, 121.15 ±19.96 and (296.42 ± 27.28)fmol, Conclusion: This treatise had demonstrated that ginseng polysugar can inhibit HCG inducing progesterone secretion and enhancing cAMP content of luteal and granulose cell of rat, ginseng polysugar has lower oocytes cell grow up inhibitory rate. It is evident that ginseng polysugar possesses characteristic of dose dependent..

Licorice Root 

Although Licorice root (Glycyrrhiza glabra) has been touted as a “natural” source of oestrogen and has been suggested as a treatment for symptoms of menopause (Ojeda, 1995), there are no data in the scientific literature to support this claim. Glycyrrhizin and glycyrrhetinic acid, both components of licorice root, bind to glucocorticoid and mineralocorticoid receptors. The reported affinity for oestrogen receptors is very weak (Newall et al., 1996). Components of licorice root have been found to bind to oestrogen receptors on breast cancer cells in vitro (Zava et al., 1998). It has also been found to be an oestrogen antagonist (Kraus & Kaminskis, 1969), and its action may depend on the hormonal milieu. The oestrogen action may be due to its isoflavone content (Zava et al., 1998) and these compounds tend to act as oestrogen agonists in a low oestrogen setting, and as oestrogen antagonists in a setting of high oestrogen levels.

Side effects and contraindications

The best documented effect of long-term or high-dose use of licorice root is the development of primary hyperaldosteronism, which can lead to hypertension, hypokalaemia, and sodium retention.39 Patients with hypertension or other cardiovascular diseases should avoid the use of licorice root. Because of the potential oestrogen interactions, it should be avoided in patients who are already on oestrogen therapy (Farese et al., 1991).

Liquorice (Glycyrrhiza glabra) and the adrenal-kidney-pituitary axis in rats.

Al-Qarawi AA, Abdel-Rahman HA, Ali BH, El Mougy SA. Food Chem Toxicol. 2002 Oct;40(10):1525-7.

The effect of oral administration of a water freeze-dried extract of Glycyrrhiza glabra (liquorice) has been studied at doses of 100, 250 and 500 mg/kg in rats on the plasma concentration of cortisol, adrenocorticotrophic hormone (ACTH), aldosterone, renin, sodium (Na) and potassium (K). The results indicated that treatment induced dose-dependent and mostly significant decreases in the concentration of cortisol, ACTH, aldosterone and K. There were concomitant dose-dependent increases in the concentrations of renin and Na. The results suggest a strong and dose-dependent suppression of the adrenal-pituitary axis, accompanied by stimulation of renin production from the kidney.

Binding of phytoestrogens to rat uterine oestrogen receptors and human sex hormone-binding globulins.

Hillerns PI, Zu Y, Fu YJ, Wink M. Z Naturforsch C. 2005 Jul-Aug;60(7-8):649-56.

The interaction of phytoestrogens with the most important binding sites of steroid hormones, i.e. sex hormone-binding globulin and oestrogen receptors, was investigated. Relative binding affinities and association constants for 21 compounds among them isoflavones, flavones, flavonols, flavanones, chalcones and lignan's were determined. The lignan nordihydroguaiaretic acid weakly displaced 17beta-[3H]-oestradiol from oestrogen receptor and Scatchard analysis suggests non-conformational changes. Compounds from Glycyrrhiza glabra, liquiritigenin and isoliquiritigenin, showed estrogenic affinities to both receptors. 18beta-Glycyrrhetinic acid displaced 17beta-[3H]-oestradiol from sex hormone-binding globulin but not from the oestrogen receptor. Phytoestrogens compete with 17beta-estradiol much stronger than with 5alpha-dihydrotestosterone for binding to sex hormone-binding globulin.

Anti-androgenic activities of Glycyrrhiza glabra in male rats.

Zamansoltani F, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA. Int J Androl. 2009 Aug;32(4):417-22.

Abnormal levels of androgens cause many diseases like benign prostatic hyperplasia and hormone dependent cancers. Although the reduction in serum testosterone (T) by Glycyrrhiza glabra has been reported, its effects on seminal vesicle (SV) and prostate tissues have never been reported. This study was carried out to investigate different aspects of anti-androgenic properties of this plant. Immature male rats were divided into five groups (n = 7): castrated rats without any treatment received only vehicle; castrated rats plus T REPLACE ment; three castrated groups with T REPLACE ment plus various doses of G. glabra extract (75, 150 and 300 mg/kg). All of the injections were carried out once daily in subcutaneous manner for 7 days. On the eighth day, blood samples were collected for total T measurement. Ventral prostate (VP), SV and levator ani muscle were dissected and weighed. Slides prepared from prostate were assessed histologically. The variation in the relative and absolute volume of the prostate tissue compartments was determined. Those receiving the doses of 150 and 300 mg/kg showed a significant reduction (p< 0.05) in prostate weight, total T and VP epithelium/stroma ratio (V/V). These results in SV and levator ani were shown in response to 300 mg/kg of extract. Increasing in T metabolism, down-regulation of androgen receptors or activation of oestrogen receptors could be involved mechanisms. This study showed that alcoholic extract of G. glabra has anti-androgenic properties.

Passion Flower 

Passion flower (Passiflora incarnata) has been recommended as a therapy for insomnia, muscle aches, and anxiety (Hoffman, 1985; Mindell, 1998) and it is recommended by the Commission E for therapy for hot flashes (Blumenthal et al., 1998). There are no scientific data to support its use for vasomotor symptoms. No significant human toxicity has been reported. 

Phytoestrogens

Phytoestrogens are chemical compounds found in plants. When ingested, these compounds have an estrogenic or antioestrogenic effect. 

Mechanism of action

They act as selective oestrogen receptor modulators, and their estrogenic activity is  tissue-specific and dependent on the endogenous hormonal milieu. In states of high oestrogen concentration, phytoestrogens act as oestrogen antagonists and may block the effects of endogenous oestrogen or oestrogen therapy. In states of low oestrogen concentration, they act as weak oestrogens, stimulating oestrogen receptors, although not to the same degree as endogenous oestrogens (Mackey & Eden, 1998).

Categories

Phytoestrogens are abundant in many foods, and are the subject of numerous scientific studies. Some commonly studied phytoestrogens are isoflavones, lignans, and coumestans, which are found in foods such as legumes, grains, fruits, and vegetables. Interest in these compounds was generated when it was observed that cardiovascular disease and hormone-dependent neoplasms were lowest in cultures who consumed diets rich in isoflavones (Adlercreutz & Mazur, 1997; Adlercreutz, 1995), Dietary phytoestrogens play an important role in reducing the risk of certain cancers, cardiovascular disease, and menopausal symptoms (Adlercreutz et al., 1992; Messina, Barnes & Setchell, 1997; Ingram et al., 1997).

Isoflavones

The isoflavones are the most highly researched type of phytoestrogen. Plants rich in isoflavones include legumes (eg, soybeans) and the leaves of red clover (Eldridge, 1983). Many products containing isoflavone extracts are promoted for the management of hot flashes. However, most clinical trials investigating the efficacy of these compounds have looked at dietary soy protein intake rather than supplements containing isolated isoflavone extracts (Mackey & Eden, 1998; Albertazzi et al., 1998; Dalais et al., 1998). It is unclear whether these supplements have the same effect as dietary intake of soy protein. 

Clinical trials

Clinical trials evaluating the role of isoflavones in the treatment of hot flashes reveal a 30% to 46% reduction in the severity of hot flashes (Mackey & Eden, 1998; Adlercreutz & Mazur, 1997; Adlercreutz et al., 1992; Albertazzi et al., 1998; Dalais et al., 19980). Efficacy lies somewhere between placebo and standard low-dose oestrogen therapy. In one study, 60 g/day of isolated soy protein powder was given to postmenopausal women. After 12 weeks, the treated women had a 45% reduction in daily hot flashes, compared with a 30% reduction in women taking placebo. There was no difference in side effects between the two groups (Albertazzi et al., 1998).

Risks and contraindications

Because isoflavones and other phytoestrogens bind oestrogen receptors, they may promote the gr