An examination of the relationship between sunlight exposure and hot flush in working women

ABSTRACT

We examined whether sunlight affects hot flushes in working menopausal women and explored effect modification by shift work and season. In this prospective cohort study, daily hot flush score (outcome) was measured by the 7-day North Central Cancer Treatment Group Daily Vasomotor Symptoms Diary. Daily duration of sunlight (≥2000 lux) was recorded by the HOBO MX2202 pendant. Both variables were measured in two 7-day data collection phases. T0 data were collected during the Australian Summer (December 2017, January and February 2018); and T1 data were collected in the Australian winter (June, July and August 2018). Linear mixed effects model was used. Shift work and season were both confounders and effect modifiers. To detect a median effect size of R² = 0.2, 34 women were required to achieve an effective sample size of 41. A total of 49 menopausal women were recruited, 11 shift and 38 day workers. Some 13 women had various missing observations. For shift workers, an hour increase in sunlight exposure was associated with a 1.4-point reduction in hot flush score (p = .016). This relationship was not significant for day workers (p = .185). The finding of this study suggests increased sunlight exposure might improve hot flushes in menopausal shift workers who are moderately bothered by hot flushes, but probably not in day workers. The possible role of shift-work associated circadian disruption on estrogen level in regard to elevated intensity and frequency of hot flush in menopausal women is discussed.     

Physiological aspects of menopausal hot flush.

Eighteen hot flushes experimenced by eight menopausal women were studied and compared with the effects of warming in six premenopausal women. The hot flushes were associated with an acute rise in skin temperature, peripheral vasodilatation, a transient increase in heart rate, fluctuations in the electrocardiographic (ECG) baseline, and a pronounced decrease in skin resistence. Although premenopausal women had greater maximum increases in skin temperature and peripheral vasodilatation, they showed a much smaller decrease in skin resistance and no changes in heart rate or ECG baseline. These findings suggest that the onset of the hot flush is associated with a sudden and transient increase in sympathetic drive. Further investigations may lead to the development of a more specific alternative to oestrogen for relieving menopausal hot flushes.     

Similarities between morphine withdrawal in the rat and the menopausal hot flush

Skin temperature, cardiovascular and neuroendocrine responses to morphine withdrawal in the rat were evaluated in an effort to develop a potential animal model for the menopausal hot flush in women. Morphine dependency was produced by s.c. implantation of pellets containing morphine alkaloid. In response to precipitous, naloxone-induced withdrawal, rats showed surges in tail skin temperature (TST) which were similar in magnitude (4.8 to 7.2 degrees C) and duration (60 to 90 min.) to peripheral skin temperature increases reported during menopausal hot flushes. Additionally, a brief period of accelerated heart rate (59%) and a 9-fold hypersecretion of luteinizing hormone (LH) preceded the TST response to morphine withdrawal. These cardiovascular and neuroendocrine responses are observed to precede or coincide with the menopausal hot flush. Additionally, protracted morphine withdrawal subsequent to abstention, resulted in TST instability characterized by spontaneous, high amplitude TST fluctuations. Thus, the alteration in skin temperature, heart rate and LH secretion during precipitated morphine withdrawal in the rat are similar in magnitude, duration and in their temporal relationship to those observed during the hot flush. These data suggest a possible opioid etiology in this vasomotor disturbance. Acute withdrawal in the morphine addicted rats may serve as an animal model by which to study the neural mechanism underlying the menopausal hot flush.     

Peripheral blood flow in menopausal women who have hot flushes and in those who do not.

OBJECTIVE--To compare blood pressure, heart rate, and peripheral vascular responsiveness in menopausal women who have hot flushes and in those who do not, and to assess the effect on these variables of treating women who have hot flushes with oestriol, a natural oestrogen, given vaginally. DESIGN--An open, non-randomised cohort study of flushing and non-flushing menopausal women. A before and after investigation of the effects of vaginal oestriol treatment on the circulation. SETTING--Referral based endocrinology clinic. PATIENTS--88 Consecutive menopausal women, 63 complaining of frequent hot flushes and 25 who had not flushed for at least a year. INTERVENTION--Treatment with vaginal oestriol 0.5 mg at night for six weeks in 18 of the women who had hot flushes. MEASUREMENTS AND MAIN RESULTS--Peripheral blood flow was measured by venous occlusion plethysmography at rest and in response to stressful mental arithmetic and anoxic forearm exercises. Blood flow in the forearm and its variability were significantly higher in flushing than in non-flushing women (4.1 (SD 1.7) and 3.1 (0.9) ml/100 ml tissue/min and 17% and 13% respectively). Blood pressure, heart rate, and blood flow in the hand were, however, similar in the two groups. No difference was found in the peripheral incremental response to either stress or anoxic exercise. Vaginal oestriol significantly lowered forearm blood flow from 4.4 (1.5) to 3.3 (1.1) ml/100 ml tissue/min but dilator responsiveness was unaffected. CONCLUSIONS--The peripheral circulation is different in menopausal women who have hot flushes compared with those who do not, with selective vasodilatation in the forearm. The lowered blood flow in the forearm after vaginal oestriol in flushing women may be relevant to the alleviation of vasomotor symptoms induced by oestrogen treatment.     

Effect of oral gamolenic acid from evening primrose oil on menopausal flushing.

OBJECTIVE--To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN--Randomised, double blind, placebo controlled study. SETTING--District general hospital and teaching hospital. SUBJECTS--56 menopausal women suffering hot flushes at least three times a day. INTERVENTION--Four capsules twice a day of 500 mg evening primrose oil with 10 mg natural vitamin E or 500 mg liquid paraffin for six months. MAIN OUTCOME MEASURES--Change in the number of hot flushes or sweating episodes a month. RESULTS--56 diaries were analysed, 28 from women taking gamolenic acid and 28 from those taking placebo. Only 18 women given gamolenic acid and 17 given placebo completed the trial. The mean (SE) improvement in the number of flushes in the last available treatment cycle compared with the control cycle was 1.9 (0.4) (P < 0.001) for daytime flushes and 0.7 (0.3) (P < 0.05) for night time flushes in women taking placebo; the corresponding values for women taking gamolenic acid were 0.5 (0.4) and 0.5 (0.3). In women taking gamolenic acid the only significant improvement was a reduction in the maximum number of night time flushes (1.4 (0.6); P < 0.05). CONCLUSION--Gamolenic acid offers no benefit over placebo in treating menopausal flushing.     

Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.     

Comparison of the efficacy and tolerability of a new once-a-week matricial estradiol transdermal system (Estrapatch 40 and Estrapatch 60) with a twice week system

OBJECTIVE: To compare the efficacy and tolerability of three transdermal systems (Estrapatch 40, Estrapatch 60 and Oesclim 50). METHODS: Multicentre, randomized, open, 3 parallel group study on 421 postmenopausal women presenting with at least 35 hot flushes in the week preceding inclusion and treated for six 28-day cycles with either Estrapatch 40 (n = 141) or Estrapatch 60 (n = 140) once a week or Oesclim 50 (n = 140) twice a week, associated to oral NETA (Millligynon 2x 0.6 mg tablets daily) from day 15 to day 28. Hot flushes, mastodynia, bleeding, local skin tolerability and adhesiveness were reported on daily cards. Endometrial thickness and estrogens were measured before and after treatment. RESULTS: Efficacy was clearly established for the three devices as early as after one cycle of treatment, with success rates (% of women with a decrease > or = 50% of the number of hot flushes) over 97% from cycle 2. The three treatments were equivalent on this criteria, except at cycle 1 for Estrapatch 40 which was not equivalent to both other treatments. Incidence and severity of mastodynia, bleeding pattern, endometrial thickness and specific estrogen-related adverse events reflected a significant higher estrogenic stimulation with Oesclim 50. Adhesiveness was very satisfactory for the three systems. CONCLUSIONS: Estrapatch 40 and 60 presents a better benefit/risk ratio compared to Oesclim 50. Thus Estrapach 40 appears to be a good choice for a first-line estrogen replacement therapy with the possibility to increase the dose to Estrapatch 60.     

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

The lack of a safe and reliable alternative to hormone therapy (HT) for treating menopausal symptoms underscores the need for alternative therapies. OBJECTIVE: The purpose of this study was to assess the in vivo estrogenic effects of the botanical dietary supplements Trifolium pratense (red clover) and Humulus lupulus (hops), and two compounds obtained from H. lupulus, isoxanthohumol and 8-prenylnaringenin (8-PN) using the ovariectomized uterotrophic adult rat model. A H. lupulus extract and a 30% isoflavone extract of T. pratense were tested at three escalating doses as was one dose of isoxanthohumol for 21d. 8-Prenylnaringenin, the major estrogen in H. lupulus, was also tested at three relevant escalating doses. In order to determine the in vivo metabolism of 8-PN, the major phases I and II metabolites were also identified. The primary outcome measure, uterus weight gain, indicated that H. lupulus and T. pratense did not have an estrogenic effect on the uterus, and none of the secondary outcome measures were positive. In contrast, there was a clear dose response when 8-PN was evaluated where the middle and high doses of 8-PN were active. 8-Prenylnaringenin in rat plasma, liver, and mammary gland was measured and the major phases I and II 8-PN metabolites were detected. Our findings suggest that while both the H. lupulus and T. pratense extracts do not have an effect on the rat uterus, 8-PN at equivalent doses to those previously used in humans did have an effect, and may therefore have a deleterious effect in women.     

Soy,Red Clover,and Isoflavones and Breast Cancer: A Systematic Review

Background

Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence.

Methods

We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer.

Results

Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects.

Conclusion

Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥100mg) isoflavones can be recommended for breast cancer patients.     

The influence of progesterone-induced proteins on glucose metabolism in early equine embryos

The influence of different maternal plasma progesterone concentrations on embryonic glucose metabolism was studied. Uterine flushes were obtained after treating ovariectomized mares (n = 3) with 0 (control), 100 or 200 mg progesterone daily for 7 d. A group of progesterone-induced proteins (PIP) of Mr approximately 20,000 were identified in flushes from progesterone treatments by SDS-PAGE but were not observed in control flushes. Progesterone-induced proteins were removed from half the pooled flush in each treatment group by Sepharose blue CL-6B. In a 3 x 2 factorial (progesterone treatments, progesterone-induced proteins) experiment, 6 groups of Day 7 equine embryos (n = 6 per group) were incubated in culture media (MEM:DPBS; 1:3) containing radioactively-labeled glucose. Contributions of the Embden-Meyerhof pathway (EMP) and the pentose-phosphate pathway (PPP) to the total metabolism of glucose in early equine embryos were assessed separately. In the 200 mg progesterone treatment group, the presence of progesterone-induced proteins in the culture medium resulted in a 4-to 5-fold increase in the activities of the Embden-Meyerhof pathway and the pentose-phosphate pathway. These results lead to the following conclusions: 1)Addition of progesterone-induced uterine proteins from mares with high levels of circulating progesterone enhance the metabolic activities of the Embden-Meyerhof pathway and the pentose-phosphate pathway in Day 7.5 equine embryos in culture. 2)Uterine secretion of progesterone-induced proteins which is quantitatively and/or qualitatively adequate to modify embryonic glucose metabolism in vitro is dependent on a minimal concentration of maternal plasma progesterone.     

Modifications du rythme de fructification de Coprinus congregatus par le dépôt de carpophores mûrs exogènes à la surface des cultures

Changes in Fruiting Rhythm of Coprinus congregatus by Addition of Exogenous Mature Sporophores on the Surface of Cultures. Researches were performed over the regulating effect of mature sporophores on the fruiting rhythm of Coprinus congregatus Bull. ex Fr. Placing exogenous mature fruit-bodies on the vegetative mycelium before the accomplishment of the first flush gives an abundant and perfectly synchronized fructification for this flush. But the fruiting rhythm is then disturbed: compared to control cultures, less sporophores are produced in the following flushes, and, in most cases, the cultures are finally characterized by fewer flushes than the controls. The nature of the substance(s) hypothetically produced by mature sporophores, which may regulate the production of other fruit-bodies, and, correlatively, the fruiting rhythm, is as yet unknown.     

Association between SHBG Asp327Asn (rs6259) polymorphism and breast cancer risk: a meta-analysis of 10,454 cases and 13,111 controls

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that plays an important role in breast cancer pathophysiology and risk definition, since it regulates the bioavailable fraction of circulating estradiol. Epidemiological studies have evaluated the association between SHBG Asp327Asn polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 10 studies were identified for the meta-analysis, including 10,454 cases and 13,111 controls for SHBG Asp327Asn polymorphism. When all studies were pooled into the meta-analysis, there was no evidence for significant association between SHBG Asp327Asn polymorphism and breast cancer risk (for Asn/Asn vs. Asp/Asp: OR = 1.20, 95 % CI = 0.94-1.55; for Asp/Asn vs. Asp/Asp: OR = 0.94, 95 % CI = 0.87-1.01; for dominant model: OR = 0.95, 95 % CI = 0.90-1.02; for recessive model: OR = 1.22, 95 % CI = 0.95-1.57). In the subgroup analyses by ethnicity, menopausal status, and source of controls, no significant associations were found in all genetic models. Interestingly, further analyses stratified by menopausal status in different ethnicities revealed that this polymorphism might provide protective effects against breast cancer risk in postmenopausal Asian women (for dominant model: OR = 0.83, 95 % CI = 0.70-0.97). Sensitivity analyses were performed by sequential removal of individual studies and cumulative statistics have showed combined ORs were not materially altered by any individual study under all comparisons. In summary, this meta-analysis suggests that SHBG Asp327Asn polymorphism is not associated with breast cancer risk overall, while it might be an important genetic susceptibility factor in postmenopausal Asian women for developing breast cancer. Larger and well-designed studies are warranted to confirm our findings in the future.     

Responses of benthic invertebrates in an experimental channel to artificial flushes

A large experimental channel was used to examine the responses of benthic invertebrate communities to artificial flushes. Two artificial flushes were done at a 20-day interval with a 2-fold difference in peak discharge and duration between them. The effects of the flushes on macroinvertebrates were monitored by comparing the abundance of individual taxa, taxon richness, diversity measures, and similarity indices. Taxon richness and abundances of invertebrates were drastically reduced by every flush. However, the diversity of invertebrates was not significantly reduced by the flushes, and the composition was similar before and after each flush. The fast recruitment of some taxa, having short life cycles, reduced the diversity of invertebrates in the interval between the two flushes. The flushes caused significant reductions in the abundance of epiphytes and fauna living in the streambed. The fauna more resistant to flushes were invertebrates that fasten their cases or retreats by silk threads to substrata. Taxa living in sediment under stones and having a sucking apparatus were also resistant to flushes. Handling editor: R. Bailey     

Seasonal dynamics, dispersion, sequential sampling plans and treatment thresholds for the citrus leafminer, Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae), in a mature lemon block in coastal New South Wales, Australia

Abstract  Studies of citrus leafminer in a coastal orchard in NSW, Australia indicated that an increase in abundance to about one mine per flush was followed during the midseason flush by a rapid increase in population that was related to an increase in the percentage of leaves infested within flushes and the number of mines per leaf. The fits of frequency distributions and Iwao's patchiness regression indicated that populations were highly contagious initially, and as the exponent k of the negative binomial distribution increased with increasing population density, the distribution approached random. Concurrently, the coefficient of variation of mines per flush (which was strongly related to the proportion of un-infested flushes) decreased to about unity as the proportion of un-infested flushes reached zero and fell further as the number of mines per flush increased. Both numerative and binomial sequential sampling plans were developed using a decision threshold based on 1.2 mines per flush. The binomial sampling plan was based on a closely fitting model of the functional relationship between mean density and proportion of infested flushes. Functional relationships using the parameters determined from Iwao's patchiness regression and Taylor's power law were equally satisfactory, and one based on the negative binomial model also fitted well, but the Poisson model did not. The three best fitting models indicated that a decision threshold of 1.2 mines per flush was equivalent to 50% of flushes infested. From a practical point of view, the transition from 25% infestation of flushes through 50% is so rapid that it may be prudent to take action when the 25% level is reached; otherwise, the 50% may be passed before the crop is checked again. For valuable nursery stock should infestation be detected in spring, it may be advisable to apply prophylactic treatment as the midseason flush starts.     

Re-supplementing and re-casing mushroom (<Emphasis Type="Italic">Agaricus bisporus</Emphasis>) compost for a second crop

Experiments were performed to determine the effect of adding nutrient supplements to colonized mushroom compost (MC) for the production of a second crop of mushrooms. Mushrooms were harvested for 1, 2 or 3 flushes, the casing removed and the MC then was fragmented and re-supplemented with delayed release supplements treated or non-treated with fungicide (thiophanate-methyl; Topsin M 70WP) and re-cased. Overall double-crop yields were higher when MC was re-supplemented after 1st flush (1st flush MC) as compared to re-supplementation after the 2nd or 3rd flushes. Mean double-crop BEs were 128, 119 and 109% when 1st-, 2nd- and 3rd-flush MCs were used, respectively. Treatment of delayed release supplement with thiophanate-methyl fungicide did not affect mushroom yields. Soluble salts and potassium concentrations increased 350 and 900%, respectively, in the casing overlay through three flushes suggesting that removal of the casing would help to alleviate the build up of these potential growth-limiting materials. Re-supplementing and re-casing of MC represents a potential opportunity for growers to increase revenues and reduce costs associated with preparation and disposal of compost. The ability to double-crop mushroom compost would provide growers a chance to increase yields by 40% or more, depending on whether they re-supplement and re-case after 1st, 2nd or 3rd flush.     

Benefits of a Working Memory Training Program for Inattention in Daily Life: A Systematic Review and Meta-Analysis

Background

Many common disorders across the lifespan feature impaired working memory (WM). Reported benefits of a WM training program include improving inattention in daily life, but this has not been evaluated in a meta-analysis. This study aimed to evaluate whether one WM training method has benefits for inattention in daily life by conducting a systematic review and meta-analysis.

Methods

We searched Medline and PsycINFO, relevant journals and contacted authors for studies with an intervention and control group reporting post-training estimates of inattention in daily life. To reduce the influence of different WM training methods on the findings, the review was restricted to trials evaluating the Cogmed method. A meta-analysis calculated the pooled standardised difference in means (SMD) between intervention and control groups.

Results

A total of 622 studies were identified and 12 studies with 13 group comparisons met inclusion criteria. The meta-analysis showed a significant training effect on inattention in daily life, SMD=-0.47, 95% CI -0.65, -0.29, p<.00001. Subgroup analyses showed this significant effect was observed in groups of children and adults as well as users with and without ADHD, and in studies using control groups that were active and non-adaptive, wait-list and passive as well as studies using specific or general measures. Seven of the studies reported follow-up assessment and a meta-analysis showed persisting training benefits for inattention in daily life, SMD=-0.33, 95% CI -0.57 -0.09, p=.006. Additional meta-analyses confirmed improvements after training on visuospatial WM, SMD=0.66, 95% CI 0.43, 0.89, p<.00001, and verbal WM tasks, SMD=0.40, 95% CI 0.18, 0.62, p=.0004.

Conclusions

Benefits of a WM training program generalise to improvements in everyday functioning. Initial evidence shows that the Cogmed method has significant benefits for inattention in daily life with a clinically relevant effect size.     

Pharmacological activities of Genistein,an isoflavone from soy (Glycine max): part II--anti-cholesterol activity,effects on osteoporosis & menopausal symptoms

Phytoestrogens represent a family of plant compounds such as isoflavones, flavones and lignans. A wide range of commonly consumed foods contains appreciable amounts of different phytoestrogens such as isoflavones and lignans. Soy and its products are particularly good sources of isoflavones and lignans. The evidence reviewed here represents the beneficial effects of most potential and promising isoflavone, Genistein in various types of diseases such as osteoporosis, cardiovascular diseases, menopausal symptoms by accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials. This review suggests that phytoestrogens may potentially confer health benefits related to various diseases such as cardiovascular disorder, menopausal symptoms, and osteoporosis.     

Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone

Around the menopause, changes in ovarian secretion of steroids result in changes in brain function: hot flushes and sweating later followed by changes in mood, libido and cognition. The relationship between sex steroids and brain functions are reviewed, with focus on hormonal treatments, in particular tibolone, on the postmenopausal brain and on associations between tissue levels and brain functions. Data on steroid levels in human brain are limited. Exogenous oestrogens alone or combined with progestagens reduce hot flushes and sweating, and may favourably affect anxiety, depression and mood. Testosterone alone or combined with E₂ improves libido and mood. Tibolone reduces hot flushes and sweating, and improves mood and libido, but does not stimulate endometrium or breast, like oestrogens. Tibolone is an ideal compound for studying steroid levels and metabolism in brain in view of its structural differences from endogenous steroids and its extensive metabolism required to express its endocrine effects.

Brain levels of tibolone metabolites were measured in ovariectomized cynomolgus monkeys receiving tibolone for 36 days. Compared to serum, higher levels of the oestrogenic 3/β-hydroxytibolone and the androgenic/progestagenic Δ⁴-tibolone, and lower levels of sulphated metabolites are found in various brain regions. The high levels of oestrogenic metabolites in the hypothalamus explain hot flush reduction. Combined with the presence of Δ⁴-tibolone, the tibolone-induced increase in free testosterone through SHBG reduction explains androgenic effects of tibolone on mood and libido. The levels of tibolone metabolites in the monkey brain support tibolone's effects on brain functions.     

Comparison of hormonal activity (estrogen,androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy

Extracts from red clover (Trifolium pratense), soybean (Glycine max.) and black cohosh (Cimicifuga racemosa) are frequently used as alternative compounds for hormone replacement therapy (HRT) to treat menopausal disorders. Fifteen commercially available products made either from red clover, soybean or black cohosh were tested in in vitro assays in this study. The main polycyclic phenolic compounds of soy and red clover products were biochanin A, genistein, daidzein, formononetin, and glycitein. In red clover products glycitein was not abundant. All the compounds showed clear estrogenic activity through estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) and affinity to progesterone receptor (PR) and androgen receptor (AR), whereas the compounds from black cohosh did not. This was corroborated by synthetic isoflavones such as biochanin A, daidzein, genistein and formononetin. They exerted affinity to PR and AR in the range of 0.39-110 mM. Statistical analysis applying principal component analysis (PCA) revealed that all red clover and soy products are grouped in different clusters. Red clover products showed a higher affinity to AR and PR than soy products, which is explained by the higher amount of isoflavones present. In vitro assays and chemical analysis showed that theoretical estrogenic activity expressed as equivalent E2 concentration is in the same range as recommended for synthetic estrogens. Broader spectrum of action and hypothesized lower side effects by action through ERbeta make them suitable for alternative hormone replacement therapy.     

Soy isoflavones and their relationship with microflora: beneficial effects on human health in equol producers

The bioavailability of soy isoflavones depends on the composition of the microflora for each subject. Bacteria act on different isoflavones with increased or reduced absorption and cause biotransformation of these compounds into metabolites with higher biological activity. S-equol is the most important metabolite and only 25–65 % of the population have the microflora that produces this compound. The presence of equol-producing bacteria in soy product consumers means that the consumption of such products for prolonged periods leads to lower cardiovascular risk, reduced incidence of prostate and breast cancer, and greater relief from symptoms related to the menopause such as hot flushes and osteoporosis.