The effects of phytoestrogens on postmenopausal health.

Phytoestrogens are a group of non-steroidal polyphenolic plant-based substances, commonly used for the treatment of menopause-related conditions. They have both genomic and non-genomic effects, displaying weak affinity for estrogen receptors (ER) and preferentially binding to ER-B over ER-A. However, evidence for the benefits of phytoestrogen consumption has been limited. We conducted a review of recent literature, focusing on systematic reviews and meta-analyses reporting on postreproductive health effects of phytoestrogens. While many trials concerning dietary and supplementary phytoestrogens have been conducted, evidence of clinical efficacy is heterogeneous and inconclusive. There appears to be reduction in the vasomotor symptoms of menopause with phytoestrogen intake; however, it is likely small and slow in onset. Phytoestrogens also appear to improve bone mineral density and markers of cardiovascular risk; however, there is inadequate research regarding long-term outcomes. There appear to be no harmful effects of phytoestrogens on breast, endometrial cancer or colorectal cancer and phytoestrogens intake may in fact be protective. Research regarding the effect of phytoestrogens on cognition is mixed, with most studies reporting no significant association. Overall, individual variations in the metabolism of phytoestrogens and age-related genomic effects may account for the considerable variability in the measured effects of phytoestrogens.

A brief history of the International Menopause Society.

Although some understanding of post-reproductive life dates back to Ancient Greece, the term 'menopause' was only introduced in the early 1800s by a French physician. Notwithstanding familiarity with the condition at that time, treatments were largely ineffective, often harmful and never evidence-based, and it was not until 100 years later with the identification and description of estrogen and progesterone that effective treatments became available. So efficacious were hormone therapies for menopausal symptoms that their prescription was often recommended for all postmenopausal women regardless of their needs, wishes or health status. For many there was benefit but for some there was harm. It was in this environment that a small group of clinicians determined to form an International Menopause Society (IMS) to conduct research into the appropriate use of hormone therapy in treating menopause symptoms, to hold regular congresses to educate colleagues and discuss research results and thus to improve the health and well-being of women in midlife and beyond. Formed in 1978, the IMS is now recognized as the global leader in its field, working towards these goals in collaboration with colleagues and other national and regional societies concerned with women's health. During that time, the IMS has been led by 13 Presidents and has conducted 15 World Congresses on the Menopause, all of which are reviewed in this paper.

Cardiovascular risk assessment in women - an update.

Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Although it is a disease of aging, vascular disease initiates much earlier in life. Thus, there is a need to be aware of the potential to prevent the development of the disease from an early age and continue this surveillance throughout life. The menopausal period and early menopause present an ideal opportunity to assess cardiovascular risk and plan accordingly. Generally in this period, women will be seen by primary health-care professionals and non-cardiovascular specialists. This review addresses female-specific risk factors that may contribute to the potential development of cardiovascular disease. It is important for all health-care professionals dealing with women in midlife and beyond to be cognisant of these risk factors and to initiate female-specific preventative measures or to refer to a cardiovascular specialist.

2016 IMS Recommendations on women's midlife health and menopause hormone therapy.

The International Menopause Society (IMS) has produced these new 2016 recommendations on women's midlife health and menopause hormone therapy (MHT) to help guide health-care professionals in optimizing their management of women in the menopause transition and beyond. The term MHT has been used to cover therapies including estrogens, progestogens and combined regimens. For the first time, the 2016 IMS recommendations now include grades of recommendations, levels of evidence and 'good practice points', in addition to section-specific references. Where possible, the recommendations are based on and linked to the evidence that supports them, unless good-quality evidence is absent. Particular attention has been paid to published evidence from 2013 onwards, the last time the IMS recommendations were updated. Databases have been extensively searched for relevant publications using key terms specific to each specialist area within menopause physiology and medicine. Information has also been drawn from international consensus statements published by bodies such as the IMS, the European Menopause and Andropause Society and the North American Menopause Society. The recommendations have been produced by experts derived mainly from the IMS, with the assistance of key collaborators where deemed advantageous. In preparing these international recommendations, experts have taken into account geographical variations in medical care, prevalence of diseases, and country-specific attitudes of the public, medical community and health authorities towards menopause management. The variation in availability and licensing of MHT and other products has also been considered.

Prevention of diseases after menopause.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Risks and benefits of hormone therapy: has medical dogma now been overturned?

BACKGROUND: In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. OBJECTIVES: To evaluate those claims. METHODS: Epidemiological criteria of causation were applied to the evidence. RESULTS: A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. CONCLUSIONS: Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

East is east and West is west: perspectives on the menopause in Asia and The West.

There is a school of thought that believes that menopausal symptoms are a peculiarly 'Western' phenomenon, not experienced by women from other regions and particularly not from Asia where, it has been claimed, dietary, social and cultural factors afforded protection for women living in that region. More recently, studies conducted in multi-ethnic communities living in Western countries as well as in Asian communities have found that the menopause and its consequences are similar world-wide. Ethnic differences within Asia account for small differences in endogenous hormone levels and age at menopause between Asian and Western women, and the type of menopause symptoms and their prevalence also differ between those two communities. However, like in the West and perhaps because of a Western influence, the long-term health problems of postmenopausal women including cardiovascular disease, osteoporosis and breast cancer are of major importance to Asian women and health services in the 21st century.

Oncology in midlife and beyond.

The onset of the menopause is often a time when women's concerns can act as a powerful trigger to encourage healthy modifications in lifestyle which will maintain, or improve, their general health. This document aims to help women to understand their potential risks, to encourage them to find proactive preventive strategies by modifying some of their attitudes, and to use health resources (when available) to be screened. Cancer is an important cause of death but not the primary cause of mortality. Cardio/circulatory diseases represent 35-40% of causes of death in most developed countries and 20-25% of women will die from cancers in Western Europe, Australasia, high-income North America, high-income Asia Pacific, East Asia and Southern Latin America. Breast cancer, lung cancer and colorectal cancer are prevalent in most regions of the world. Cervical cancer remains a hallmark of low access to health care. Preventive strategies (decreasing smoking and alcohol consumption, losing weight, eating a healthy diet and undertaking physical activity) and implementation of screening could help to significantly decrease the incidence of and mortality from cancer. The mortality/incidence ratio is higher in developing countries compared to high-income regions as well as in subgroups of populations in developed countries with lower socioeconomic levels. Implementation of better diagnostic methods and management of cancer according to the local resources will help to decrease the mortality rate in developing countries, and effort has to be made to decrease social inequities and improve access to health care for low-income groups. In conclusion, cancer incidence is increasing as a consequence of longer life expectancy all over the world. National health programs are mandatory to implement screening and to improve individual management. Finally, educating women so that they are aware of ways to improve their general health, to minimize their own risk factors and to identify signs of change in their own health which may be markers of impending cancer will help to reduce the burden of disease and improve the prognosis for tumors detected at an earlier stage.

Premature ovarian failure: a review.

OBJECTIVES: To present an updated review on the etiology, consequences and management of premature ovarian failure. DESIGN: A search of the English language literature using the Cochrane Library database and Medline 1966-2006, with a hand search of the references. CONCLUSION: Premature ovarian failure is defined as the occurrence of amenorrhea, hypergonadotropinemia and estrogen deficiency in women under the age of 40 years, with the prevalence being 0.9-1.2%. In the majority of cases, the etiology is unknown, but known causes include chemotherapy, radiotherapy, surgery, genetic disorders, particularly involving the X chromosome, associations with autoimmune diseases, infections, smoking and other toxins. The three critical issues of management in these women are the effect of the diagnosis on the psychological health of the patient, the consequent infertility and the long- and short-term effects of estrogen deficiency arising from ovarian decline. Promising methods of screening for premature ovarian failure are being developed.

Effects of 20-mg oestradiol implant therapy on bone mineral density, fat distribution and muscle mass in postmenopausal women.

This 64-week prospective cohort trial evaluated the effects of 20-mg oestradiol implants, replaced every 4 months, in healthy postmenopausal women aged 45-65 years. Of 20 implant and 14 control subjects who remained in the trial at 32 weeks, 13 implant and seven controls continued to 64 weeks, with no baseline differences between completing and dropout subjects. At 64 weeks, implant subjects displayed increases of 5.4-7.6% in spine and hip bone mineral density ( p<0.05 versus controls). The abdominal fat-to-lean soft tissue ratio decreased by 18% in implant subjects ( p<0.001), but did not change in controls ( p<0.05 implants versus controls). Neither group displayed significant changes in weight, %fat or appendicular skeletal muscle mass. The 32-week data were consistent with these results. Hence, oestradiol implant therapy can reduce abdominal adiposity and could lower the risk of obesity-related metabolic disorders.

The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism.

OBJECTIVE: This study was undertaken to evaluate the effects of varying doses of phytoestrogens on lipid and bone metabolism in postmenopausal women. DESIGN: A novel red clover isoflavone preparation (Rimostil) containing genistein, daidzein, formononetin, and biochanin was administered to 46 postmenopausal women in a double-blind protocol after a single-blind placebo phase and followed by a single-blind washout phase. Patients were randomized to receive either 28.5 mg, 57 mg, or 85.5 mg of phytoestrogens daily for a 6-month period. RESULTS: At 6 months, the serum high-density lipoprotein cholesterol had risen significantly by 15.7-28.6% with different doses (p = 0.007, p = 0.002, p = 0.027), although the magnitude of the response was independent of the dose used. The serum apolipoprotein B fell significantly by 11.5-17.0% with different doses (p = 0.005, p = 0.043, p = 0.007) and the magnitude of the response was independent of the dose used. The bone mineral density of the proximal radius and ulna rose significantly by 4.1% over 6 months with 57 mg/day (p = 0.002) and by 3.0% with 85.5 mg/day (p = 0.023) of isoflavones. The response with 28.5 mg/day of isoflavones was not significant. There was no significant increase in endometrial thickness with any of the doses of isoflavone used. CONCLUSION: These results show that the administration of an isoflavone combination extracted from red clover was associated with a significant increase in high-density lipoprotein cholesterol, a significant fall in apolipoprotein B, and a significant increase in the predominantly cortical bone of the proximal radius and ulna after 6 months of treatment. Interpretation of the results is undertaken cautiously because of the absence of a simultaneously studied control group.

Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women.

OBJECTIVE: To test the hypothesis that increasing the intake of isoflavones by dietary supplementation may produce a therapeutic effect in reducing the incidence and severity of hot flushes in menopausal women. METHODS: Fifty-one postmenopausal women were randomized to placebo and active (one tablet per day of a 40-mg isoflavone supplement) groups in a cross-over design trial. After a 1-week run-in period, subjects were commenced on a 12-week period of treatment (active or placebo), followed by a 1-month placebo wash-out period, then crossed over to the alternative treatment regimen for a further 14 weeks. Symptom diaries were maintained throughout the trial and at the start and end of treatment. Plasma sex hormone binding globulin (SHBG) assay, full blood count, biochemical profiles, vaginal swabs and vaginal ultrasound scans were performed and isoflavones determined in 24-h urine collections by high-pressure liquid chromatography (HPLC) analysis. RESULTS: There was no significant difference between active and placebo groups in the reduction in hot flushes between start and finish time-points. Analysis performed on interim data time-points revealed a substantially greater reduction in flushing in the active group than placebo at 4 and 8 weeks after commencement of treatment, but this was not statistically significant. There were no significant differences between groups for Greene scores or in SHBG levels, hematological or biochemical parameters and vaginal swab or ultrasound findings. The combined values for all subjects, regardless of treatment group, revealed a strong negative correlation between the level of urinary isoflavone excretion and the incidence of hot flushes. CONCLUSIONS: These data do not indicate a therapeutic benefit from dietary supplementation with isoflavones in women experiencing menopausal symptoms, but do indicate that the apparent placebo effect in many studies of menopausal symptoms may be attributable to dietary sources of isoflavones. The study also demonstrates that 3 months of isoflavone supplementation did not cause adverse events or endometrial changes.

Detection of anti-ovarian antibodies by indirect immunofluorescence in patients with premature ovarian failure.

The sera of 30 patients with premature ovarian failure (POF) and a control group of 19 menopausal women were screened for anti-ovarian and other tissue antibodies. Anti-ovarian antibodies were detected by indirect immunofluorescence using monkey ovary substrates from two different commercial sources. Serum anti-ovarian antibodies were detected in only one of the patients with POF. This test does not appear to be reliable for the detection of serum anti-ovarian antibodies, and the clinical usefulness of screening patients with POF for anti-ovarian antibodies is questionable.

The long-term effects of estradiol implant therapy for the treatment of premenstrual syndrome.

Fifty patients receiving estradiol implants for long-term treatment of premenstrual syndrome were studied over 5.6 years (range 2-8 years). There was a continued beneficial response to treatment in all symptoms, varying between 74% for bloating and 96% for depression. Menstrual cycle control improved in 31 patients and periods were less painful in 30 patients. Cyclical progestogenic symptoms occurred in 58% of patients. These were partially relieved by alterations in dose, type and duration of progestogen treatment but in 7 patients the symptoms remained severe. Eight patients had a hysterectomy during treatment; 5 for continuing progestogenic symptoms, 1 for prolapse and 2 for prolonged menstrual bleeding despite adequate progestogen therapy. Attempts to reduce the dose of progestogen led to cystic hyperplasia in 4 patients. This was treated by hysterectomy in 2 patients and corrected with two 21-day courses of progestogen in the other 2. Uterine enlargement with a mean weight of 133 g (125-145 g) associated with myometrial hypertrophy occurred in all 8 hysterectomy patients. There were no complications form venous thrombosis, pulmonary embolus, breast disease or atypical endometrial hyperplasia.

Ovum donation.

Recent advances in assisted conception and reproductive endocrinology have provided novel avenues for the treatment of couples previously thought to be irreversibly sterile.