Editor's Corner
Prof. Margaret Rees
Editor-in-Chief
The Editor's corner is a new feature of Maturitas. It summarises for the public the most important research published in the journal on midlife and ageing and the papers are openly available.
Anti-Müllerian hormone (AMH) levels , a product of the granulosa cells of small growing ovarian follicles, reflect ovarian reserve. AMH declines with age in adult women, and emerging data suggest a relationship with remaining reproductive lifespan and age at the menopause. The most established role for AMH measurement is in women about to start IVF treatment, where it is predictive of the ovarian response and is of clear value in identifying women at risk of ovarian hyperstimulation syndrome or whose response will be poor and thus their expectations can be tailored. AMH is detectable in childhood, and although relationships to puberty are not yet available, it appears that AMH rises to a peak in the early 20s. Developing indications include in assessment and individualisation of the risk to fertility from chemotherapy, in the diagnosis of PCOS and as a tumour marker in granulosa cell tumours.
It is now well known that oral and transdermal estrogens are differentially associated with venous thromembolic (VTE) risk but progestogens may be another important determinant of the thrombotic risk among hormone therapy (HT) users. Both randomized controlled trials and meta-analysis of observational studies suggest that the VTE risk is higher among users of estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, there is evidence for a deleterious effect of medroxyprogesterone acetate on VTE risk. In addition, observational studies showed that norpregnane derivatives are significantly associated with an increased VTE risk whereas micronized progesterone could be safe with respect to thrombotic risk. Thus individual progestogens may have differential effects on VTE risk.
Aging is an inescapable reality of human existence. Skin begins to age from birth which inevitably leads to loss of elasticity, soft tissue and volume loss, as well as a reduction in bony and cartilaginous support of the face. In contrast, extrinsic or photoaging, results from cumulative exposure to ultraviolet radiation and causes wrinkling, keratoses, loss of elasticity and translucency, telangiectasias, and cutaneous pre-cancers and malignancies. Therapies for the treatment of photodamage can be subdivided into primary, secondary and tertiary prevention. Primary prevention, in the form of photoprotection, will reduce development of extrinsic aging. Secondary prevention, in the form of topical retinoid therapy, aids in attenuating the effects of photoaging. Lastly, tertiary prevention ameliorates the effects of photoaging as well as intrinsic aging via the use of botulinum toxin, soft tissue fillers, and superficial chemical and laser skin resurfacing. Paramount to all treatment paradigms is photoprotection to prevent further damage.
Within the past two years, three agents received approval by the US FDA for the specific treatment of metastatic castration resistant prostate cancer (mCRPC) — (1) abiraterone, (2) cabazitaxel and (3) sipuleucel-T. In separate phase III studies, each agent led to an improvement in overall survival of 2–4 months over a suitable comparator. As these therapies are costly the authors provide an algorithm for sequencing US FDA approved agents for mCRPC. They also note that novel antitumor agents are typically used concomitantly with bone-directed therapies (i.e., zoledronic acid or denosumab) and lutenizing-hormone releasing hormone (LHRH) agonists.
The elderly are vulnerable to the effects of extreme heat. With heat-related mortality and morbidity expected to rise as a result of increased frequency of summer heat waves caused by climate change, the researchers looked at the heat adaptation measures used by the elderly in Detroit.
Residents aged over 65 kept an hourly log of eight heat-adaptive behaviours for 3 summer months: opening windows/doors, turning fans or the air conditioner on, changing clothes, taking a shower, going to the basement, the porch/yard, or leaving the house.
The use of all adaptive behaviours, except going to the porch or yard, was significantly associated with indoor temperature. Non-mechanical adaptations such as changing clothes, taking showers, and going outside or to the basement were rarely used. Residents living in high-rises and highly impervious areas reported a higher use of adaptive behaviours. The odds of leaving the house significantly increased as outdoor temperature increased.
These findings suggest that the full range of heat adaptation measures may be underused by the elderly. As serious health consequences may result, care-givers and providers of services to the elderly should help encourage adaptation practices at a personal and community level.
Calcium supplementation has been widely accepted as a key strategy in the prevention and treatment of osteoporosis. However there is accumulating evidence that calcium supplement use is associated with an increased risk of myocardial infarction and, possibly, stroke. The latest data, based on meta-analysis of trials involving 29,000 participants, indicate that this risk is not mitigated by co-administration of vitamin D, and that the number of cardiovascular events caused is likely to be greater than the number of fractures prevented. These findings indicate that calcium supplementation probably does not have a role as a routine preventative agent and that dietary advice is the appropriate way to attain an adequate calcium intake in most situations. Patients at high risk of fracture need to take interventions of proven anti-fracture efficacy. Available evidence suggests that this efficacy is not dependent on the co-administration of calcium supplements. The authors conclude that there is an urgent need for more research to gain insight into the mechanisms of the adverse vascular effect of calcium and to change current routine use of calcium supplements in clinical practice.
The epidemic of overweight and obesity has become a serious public health concern across the world. According to the World Health Organization (WHO), in 2008 approximately 1.5 billion adults (age=20) were overweight, and more than 500 million of those were obese. According to WHO's estimates, by 2045 the number of overweight adults will increase to 2.3billion and more than 700 million adults will be obese.
Treatments for overweight and obesity include dietary therapy, exercise/behavioral interventions, weight loss medications, and bariatric surgery. Yet studies have shown that all of these options except surgery have been ineffective in long-term weight control. However bariatric procedures expensive and like all other surgical procedures associated with morbidity and mortality.
This paper is the first to conduct cost-effectiveness analyses of bariatric surgery comparing obese patients with obesity-related diseases to obese people without comorbidities across different BMI categories, using the meta-analysis results of surgery outcomes for our effectiveness inputs. The authors find that surgery treatment is in general cost-effective for people whose BMI is greater than 35 kg/m2 with or without obesity-related comorbidities, and it is even cost-saving for super obese (BMI = 50 kg/m2) with obesity-related comorbidities. Furthermore surgery can be cost-effective for the mildly obese (BMI = 30 kg/m2). The bottom line recommendation is that bariatric surgery should be universally available to all classes of obese people and should be headed by health service managers making decisions about what should be available and to whom.
Climate change is predicted to yield a growing number of temperature extremes with heat waves and cold spells increasing in both intensity and frequency. The authors of this review looked at the effects of heat waves in the elderly. As this population is expanding due to increased longevity, the effect of heat waves is becoming a public health issue. Studies consistently reported increases in cardiovascular and respiratory mortality, as appeared also respiratory admissions to do during hot days and heat waves. The death rates in the previous winter modified the effect of heat waves during the following summer (i.e. if the winter was particularly cold, mortality in vulnerable elderly was high, conversely if the winter was mild, more vulnerable elderly survived). There is some evidence that the first heat wave of the season is the deadliest, particularly following a mild winter, due to a larger fragile population. The authors recommend that future research should focus on identifying predictive factors of heat related illnesses and the effects of adapting buildings and cities to reduce heat stress.
This cross sectional study of women aged 20-50 who had undergone premenopausal hysterectomy and bilateral salpingo-oophorectomy (BSO) examined hormone therapy (HT) use and their experience of hot flashes and other menopausal symptoms. Mean age at surgery was 44.3 (±5.2) years and mean time since surgery was 10.2 (±3.8) months at the time of interview. Twenty-eight women (40%) were started on HT after surgical menopause; 23 (33%) were still taking HT at the time of the interview. Estrogen therapy (ET) was the only HT prescribed in all instances. Women not taking HT were more likely to experience daily hot flashes (74% vs 30%, p=0.006) and to classify them as moderate or severe intensity (57% vs 47%, p=0.033). It is of concern that over 2/3rd of women were not taking HT after a surgical menopause despite the majority having no contraindications. This has implications not only with the management of menopausal symptoms but also the long term health consequences of untreated early menopause namely osteoporosis, cardiovascular disease, dementia, cognitive decline and parkinsonism.
Various foods have been promoted for the prevention of cardiovascular disease. Lycopene, a carotenoid found in tomatoes, is an antioxidant with a protective effect on lipid peroxidation and anti-atherosclerotic capacity. This review summarises current evidence on the effect of lycopene on serum lipid concentrations and blood pressure. Twelve studies (13 trial arms) meeting the inclusion criteria investigated the effect of lycopene on serum lipids, and four studies examined its effect on blood pressure. Meta-analysis on serum lipids revealed a significant cholesterol-lowering effect of lycopene for total serum cholesterol (mean change±SE: −7.55±6.15mg/dl; p=0.02) and low-density-lipoprotein (LDL) cholesterol (mean change±SE: −10.35±5.64mg/dl, p=0.0003) in the subgroup of trials using lycopene dosages of =25mg daily, whereas subgroup meta-analysis of trials using lower lycopene dosages was not significant. Meta-analysis of the effect of lycopene on systolic blood pressure of all trials suggested a significant blood pressure reducing effect (mean systolic blood pressure change±SE: −5.60±5.26mm Hg, p=0.04). This is the first study to summarise the effect of lycopene on blood lipids and blood pressure. The results suggest lycopene to be effective in reducing LDL cholesterol and total serum cholesterol if taken in doses higher than 25mg daily, and in reducing systolic blood pressure in hypertensives. The LDL cholesterol-reducing effect of lycopene of about 10% is comparable to the effect of low dose statins. While statins are highly effective cholesterol-lowering medications, side effects including muscle pain, muscle weakness, and neuropathy are experienced by some patients. Lycopene may be considered as alternative to low dose statins without these side effects in patients with slightly elevated cholesterol levels. More research is needed to explore whether doses higher than 25–44mg/day of lycopene, provide additional beneficial effects on blood lipids compared with control, and confirm whether lycopene is effective in reducing blood pressure in hypertensives.
People are bombarded about the benefits of some diets over others. The increasing number of centenarians is allowing examination of whether some dietary patterns are associated with longevity. The authors reviewed studies of dietary intake and patterns of long-lived people as well as current knowledge of nutritional status of centenarians. The studies indicate that body mass index and nutritional status as indicated by circulating levels of antioxidant vitamins, vitamin B12, folate, homocysteine and 25(OH)vitamin D of centenarians is quite heterogeneous and influenced by region of residency and many of the demographic, dietary and lifestyle factors that influence nutritional status in other older adults. Thus, it seems unlikely that there is one particular dietary pattern that promotes exceptional longevity.
Endocrine disrupters are a hot topic. They are chemicals that alter steroid metabolism or function and so might have effects on the human population that could be long-term. While many are of industrial origin ( some pesticides and fungicides), others such as phytoestrogens are naturally found in plants. This review discusses the mechanisms of action of endocrine disrupters and the implications for women's health of both medical and environmental exposure to these chemicals. The authors conclude that there are some indications that we should consider ‘cocktail effects’, where the environment contains complex mixtures of natural and synthetic endocrine disrupters which may interact additively, subtractively or synergistically. Homeostatic mechanisms in the body may well be protective against the potential effects of endocrine disrupters for most women most of the time. However, the possibility cannot be ruled out that some women are more susceptible than others and that all women may be susceptible at critical stages such as before birth, at puberty and in pregnancy. Research in the next decades may clarify the situation but until then, the answer to the question “Are endocrine disrupters a threat to women's health?” must remain a definite “Maybe.”
In the past two decades, there has been an exponential increase in the use of complementary and alternative medicine, including herbal products in the United States, as well as in other industrialized nations around the world. In various countries, these products are classified and promoted as foods, not pharmaceuticals, which facilitate their availability on the international market without requiring a medical prescription.
With increasing longevity, older adults are an important and growing sector of the population in many countries. It is important to know the prevalence of their herbal product use, since many older adults take herbs along with diverse quantities of prescriptions for chronic diseases and over the counter medications. Furthermore the majority does not discuss this with their health care provider. The potential for herb drug interactions exists, which can be potentially fatal such as interactions with warfarin. Thus there needs to be increasing awareness among the public and health professionals of the risks associated with herb drug interactions.
Tamoxifen which is a common adjuvant therapy for breat cancer induces menopausal symptoms such as hot flashes. Certain medications and natural supplements taken or prescribed to alleviate symptoms interact with tamoxifen. This paper reviews potentially problematic interactions which could adversely affect survival and provides a scientific basis as to what can be safely offered.This review will be extremely useful for the busy clinician. Venlafaxine is effictive for the treatment of hot flashes and depression and safe to use in combination with tamoxifen. Gabapentin is also effictive in treating tamoxifen-induced hot flashes and, since it does not interact with cytochrome P450 system, is likely safe to use in patients using tamoxifen. Desvenlafaxine and pregabalin may be alternatives to venlafaxine and gabapentin, respectively, although desvenlafaxine has not yet been studied in this population. Paroxetine, fluoxetine and bupropion are strong CYP2D6 inhibitors which should be avoided in tamoxifen users. Fluvoxamine and nefazodone both inhibit CYP3A, which could potentially affect the metabolism of tamoxifen. Clonidine can be an alternative agent but may carry significant side effects. Evidence of supplements or diets rich in isoflavones for the treatment of tamoxifen-induced hot flashes is equivocal at best.
Patellofemoral knee osteoarthritis (OA) is a common disease, and a significant cause of knee pain. Female gender and increased body mass index, both risk factors for patellofemoral OA, have been associated with increased patella cartilage loss over 2 years but there are few long term data. The authors performed a study to examine factors affecting change in patella cartilage volume over 4.5 years in people with symptomatic knee OA.
They found that cartilage was lost at a higher rate in women compared to men.
Thus the increased rate of cartilage loss in women may contribute to their increased prevalence of the disease.
The health benefits of foods and various diet are now the subject of research. Garlic is part of the Mediterranean diet which is associated with good health. This study assessed the effect, tolerability and acceptability of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with treated, but uncontrolled, hypertension.
The authors undertook a double-blind parallel randomised placebo-controlled trial involving 50 patients with treated but uncontrolled hypertension. The active treatment group received four capsules of aged garlic extract daily for 12 weeks, and the control group received matching placebos.
In patients with uncontrolled hypertension (SBP*140mmHg at baseline), systolic blood pressure was on average 10.2 plus or minue 4.3mmHg (p=0.03) lower in the garlic group compared with controls over the 12-week treatment period.Changes in blood pressure between the groups were not significant in patients with SBP less than 140mmHg at baseline. Aged garlic extract was generally well tolerated and acceptability of trial treatment was high (92%).
Schizophrenia and bipolar disorder are severe mental illnesses (SMI) that Affect around 1% of the population. They are amongst the leading causes of disability and impact social, work, occupational, interpersonal and self-care functioning. Following the introduction of antipsychotic medication in the 1950s, the lives of many people with SMI have been transformed. As treatments have improved, there has been an increasing awareness of their side effects. There are concerns that treatment with certain antipsychotics may lead to the development of osteoporosis. The most likely mechanism linking antipsychotics with decreased bone density is through hyperprolactinaemia and secondary suppression of sex steroids. The prevalence of hyperprolactinaemia is higher in people receiving antipsychotics than virtually any other patient or population group. Cross-sectional studies have indicated that the prevalence of hyperprolactinaemia ranges from 42% to 93% in women and 18 to72% in men. Hyperprolactinaemia varies markedly between antipsychotics. The author concludes that health professionals caring for people with SMI to consider osteoporosis and take steps to prevent and treat this to reduce the risk of fracture.
Following the media scares after publication of the results of the US
Women's Health Initiative (WHI) study and the UK Million Women Study
(MWS) in2002 and 2003, the search for alternative treatments that
were perceived to offer beneficial effects with less risk
intensified. Herbal products were considered to be more natural and hence
safer. A recent report suggested that about 49% of older adults in the US
use dietary supplements concurrently with prescription medications.
The authors of this review examine the safety of herbal products.
They conclude that there are concerns about herb-drug interactions
and long-term safety assessments because women may use these products
for prolonged periods of time. Products produced to high quality
standards are essential for ensuring consumer safety. Regulatory
frameworks must be in place to ensure that herbal ingredients’ identities
have been verified, that they have been properly quantified per unit
dose, that the product is within tolerance limits for contaminants, that
the product's safety and effectiveness under the recommended conditions
of use have been assessed before sale to the public, and that a system
is in place to detect and deal with adverse reactions when they
arise.
International collaboration in the development of harmonized
quality specifications and causality algorithms specifically tailored to
herbal products is highly advisable, as is stronger collaboration
between regulatory agencies around the globe for the early detection of
any significant safety issues associated with a particular product.
From 2002 to 2003, the breast cancer incidence in the United States, as reported by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER 9) database, appeared to decrease by 6.7%. This was attributed to a reduction in the use of menopausal hormone therapies (HT) after the initial publication of the Women's Health Initiative (WHI) study results in July of 2002. However, while prescriptions of estrogen-plus-progestin HT, which are associated with increased rates of breast cancer, fell by 53% from 2002 to 2003, those of estrogen-only therapies fell by only 27%. The authors analyzed the effects of the higher rate of discontinuation of estrogen-plus-progestin HT relative to estrogen-only treatments in 2002–2003. They found that the relative persistence with estrogen-only therapies — as compared to estrogen-plus-progestin therapies — can explain the reduction in breast cancer incidence from 2002 to 2003. They conclude — as previously demonstrated in the estrogen-only arm of the WHI trials — that menopausal estrogen-only use is not responsible for increasing the risk of breast cancer in menopausal women and may, in fact, be protective. Thus it is essential to make a distinction between the effects of different types of HTs on the risk of breast cancer.
This systematic review is included in thefirst part of a special issue on complementary and alternative therapies. Womenhave increasing been exploring these because of concerns about the safety ofestrogen-based hormone therapy. The advantage of mind body therapies is thatthey avoid interactions with standard therapies such as can occur with herbalremedies.The authors have systematically reviewed the peer-reviewed literatureregarding the effects of self-administered mind-body therapies on menopausalsymptoms.
Interventions included yoga and/or meditation-basedprograms, tai chi, and other relaxation practices, including muscle relaxationand breath-based techniques, relaxation response training, and low-frequencysound-wave therapy. Collectively, findings of these studies suggest thatyoga-based and certain other mind-body therapies may be beneficial foralleviating specific menopausal symptoms. However, the limitationscharacterizing most studies hinder interpretation of findings and preclude firmconclusions regarding efficacy. The authors conclude that additional large,methodologically sound trials are needed to determine the effects of specificmind-body therapies on menopausal symptoms, examine long-term outcomes, andinvestigate underlying mechanisms.
As more women are surviving breast cancer, lifestyle interventions to prevent recurrence, new breast cancer events, and mortality is of considerable public health importance. The authors of this review have focussed on physical activity, diet, and adiposity. The most consistent finding from observational studies was that adiposity was associated with a 30% increased risk of mortality. Physical activity appeared to be associated with a 30% decreased risk of mortality. Given that a high proportion of breast cancer patients appear to be both sedentary and obese/overweight, clinical trials are needed to investigate whether the combination of increased physical activity and reduced adiposity can improve breast cancer prognosis.
Male breast cancer is an unrecognised uncommon condition. In recent years, the incidence of breast cancer in women appears to be falling. In contrast, the incidence of male breast cancer appears to be rising. In this review the authors examine the new treatments available for the disease.
Coronary heart disease mortality in women increases after the sixth decade. The authors looked at risk factors for the disease in 1730 women included in the French MONICA cross-sectional survey. They found that cholesterol levels were higher in postmenopausal women compared to their premenopausal counterparts.
The authors examine the consequences of obesity on health at midlife and beyond. The article is in a special issue devoted to predictors of midlife heath. A burgeoning pandemic of obesity is well characterized. The wide spectrum of morbidities related to excess body mass includes risks for diabetes, hypertension, coronary artery disease, dyslipidemia, malignancy, venous thrombosis, degenerative joint disease, pulmonary compromise, sleep apnea, cholelithiasis, depression and overall reduced quality of life. Bariatric surgery literature suggests that, in the morbidly obese, increase in the lifespan is achievable with reversal of obesity, reinforcing the realization that sequelae therein are by no means inevitable. This article concludes that the consequences of obesity are major and aggressive efforts must be targeted towards population-based strategies to prevent and reduce excessive body mass.
Interstitial cystitis or painful bladder syndrome, is a debilitating condition, which affects women more than men, where there is sensory hypersensitivity of the bladder. Consequently a small volume of urine will generate an exaggerated sensation of pain or pressure resulting in urinary urgency and frequency day and night. The precise cause is unknown. Therefore managing patients with interstitial cystitis or painful bladder disease still remains a challenge in the twenty-first century. Over 150 types of treatment have been recorded. There is clear need for further research into causes and effective treatments.
With the advent of highly active antiretroviral agents, women with HIV infection can expect to live longer than ever before. This increased survival has led to concerns about the long-term implications of HIV disease and its treatment. Women with HIV appear to become menopausal early and can have worse symptoms such as hot flushes. They have an increased risk of osteoporosis, diabetes and heart disease. The risk of some cancers such as lung and cervical cancer is also increased. It is too early to declare victory on the war against HIV and AIDS. As better treatments have been developed both women with HIV infections and their doctors now need to focus on the long term health implications.
Since publication of the US Women's Health Initiative and the UK Million Women Study, women have had concerns about using standard hormone therapy to treat menopausal symptoms. They have turned to "bioidentical hormones." These are defined as compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body and which are made chemically from plants such as yams.
Bioidentical hormones are available in some countries from compounding pharmacies and these formulations have not been approved by regulatory bodies such as the FDA in the US. There are therefore concerns that we have no evidence from clinical studies that they are as good as or safer than standard hormone therapy which has been approved by regulatory bodies.
So what can women do? "Bioidentical hormones" are available as approved drugs. For example oestradiol is available as tablets, patches or gels. Progesterone is available as a tablet.
Population health outcomes are determined by complex interactions between individuals and the environments in which they live, work and play. Environments encompass streets and buildings (physical environment), attitudes, supports and relationships with others (social environment), as well as social and political systems and policies. The impact of environments on the physical, mental health and functioning of individuals is a growing area of health research as current long term care policies are shifting the care of older adults away from nursing homes and into the home and community setting. The authors reviewed the current state of the health literature on physical environments for healthy ageing. They found a growing body of work identifying environmental effects on a wide range of physical and mental heath outcomes in older adults. These findings stress the role of supportive, barrier-free environments particularly for older adults who are at greater risk for disability and poor health. They conclude that interdisciplinary training that brings together health professionals with urban planners has the potential to generate initiatives that could minimize the negative consequences of underlying disease and impairments for the independence of older adults, so that they can continue to maximize their health, well-being, and participation within their communities as they age.
Obesity is currently a major public health concern and is reaching epidemic proportions. In the U.S. 41% of adults are projected to be obese by 2015. This review article examines the impact of obesity in an elderly population looking at studies undertaken in people aged 50 or over. The authors found that among elderly persons, obesity increases the risks for a variety of conditions including cancers, diabetes, high blood pressure, stroke, heart disease, obstructive sleep apnea syndrome, osteoarthritis, depression, disability, and lower quality of life. In some reports, obesity has been linked to Alzheimer's disease. Obesity significantly increases healthcare costs and nursing homes are currently ill equipped to address the needs of the rising number of obese residents. It is therefore imperative that research efforts and funding are devoted to studying the effects and the reduction of obesity in the elderly population.
Ageing is often associated with the aged and the diseased, nevertheless ageing is a process that starts before birth. This paper describes the results of a meeting of international experts whose purpose was to identify potential mechanisms and interventions to improve healthy life expectancy of the population; and to highlight areas within ageing research that should be prioritised in the future. General agreement was reached in recognising ageing research as a field with little communication between basic science. A more holistic, multi-disciplinary approach is urgently required. Future research should concentrate on understanding the mechanisms that allow individuals to maintain optimal health. Finally it is fundamental that scientific research findings are constantly translated into clear messages delivered to governmental institutions, the industry and society in general.
Diabetes affects almost 6% of the world's population. The number of diabetic patients will reach 300 million in 2025. More than 97% of these patients will have type 2 diabetes, which increases the risk of heart disease. Type 2 diabetes is one of the fastest growing public health problems worldwide. This is mainly as a result of the obesity epidemic. Functional foods are defined as foods having health-promoting benefits over and above their usual nutritional values. The may have the potential to improve control of blood glucose, but little evidence is known about the efficacy of these foods. This literature review examined the effects of functional foods - such as nuts, omega-3 fatty acids (found in oily fish) and cinnamon — on blood sugar control in type 2 diabetes. It found that while nuts and omega-3 fatty acids appear to have an overall beneficial effect on heart disease; however, their effect on glucose control is uncertain. In addition, cinnamon appears to inconsistently improve blood sugar control. The most effective intervention is weight loss. A large amount of research has to be undertaken on functional foods before they can be recommended to help control blood glucose.
