Post Reproductive Health

The human life span is increasing and there is a need to maintain functional wellbeing in old age. Cognitive function is a major determinant of quality of life in older age. Cognitive impairment can be influenced by a number of factors and the effect of nutrition on cognitive function has become a topic of increasing scientific and public interest. The data available are not sufficient for definitive conclusions to be drawn regarding the relationship between diet and dementia, which is the most common form of cognitive impairment in the elderly; however, there is evidence that dietary lipids, oxidative stress and related antioxidant vitamins, and homocysteine-related vitamins can affect the risk of dementia. This review provides a brief overview of this topic.

The most extensively studied class of phytoestrogens, isoflavones, occur in soybeans and other legumes. Six systematic reviews have assessed the effects of soy isoflavones on lipid levels, and suggested that a diet supplemented with soy protein isolate (ISP) containing isoflavones reduces low-density lipoprotein (LDL) cholesterol by around 0.15 mmol/L, but without clear effects on triglycerides or high-density lipoprotein (HDL) cholesterol. However, no review has suggested that purified soy isoflavones or soy protein without isoflavones (where the isoflavones have been removed by an alcohol wash) have statistically significant effects. It remains unclear which are the active components of soy. They may include soy protein which has not been denatured by alcohol wash, interaction of isoflavones within the intact soy matrix, or other compounds removed in the alcohol-extracted fraction. The reduction in total cholesterol may be greater in men than in postmenopausal women. There is little evidence that the effectiveness of soy varies with baseline serum lipid levels, or the amount of isoflavone or soy protein consumed. However, changes in triglycerides may be related to baseline levels. While there is no evidence of beneficial effects of phytoestrogens on blood pressure, arterial compliance or oxidation of LDL cholesterol, there may be beneficial effects on endothelial function in postmenopausal women, and on homocysteine concentrations. There is little suggestion of adverse effects of soy or isoflavones at physiological doses, although those taking soy isoflavone supplements do appear to have higher levels of gastro intestinal and menstrual complaints. There have been no published trials on the effects of phytoestrogens on mortality or cardiovascular events, so studies currently rely on the above bio markers of risk. Most evidence relates to soy isoflavones, but there is some evidence for lignans. Further robust studies assessing the effects of whole soy foods on cardiovascular outcomes are needed.

Ovarian cancer is the most lethal gynaecological malignancy and it most commonly occurs in postmenopausal women. Ninety per cent of ovarian cancers are derived from the ovarian surface epithelium and these neoplasms are classified into serous, mucinous, endometrioid, clear-cell and transitional-cell types. The molecular pathology of ovarian carcinomas is heterogeneous and involves various putative precursor lesions and multiple pathways of development. The most common subtype, high-grade serous carcinoma, is characterized by p53 mutations, and BRCA1 and/or BRCA2 dysfunction. It most likely arises from epithelium within inclusion cysts or from the surface of the ovary. In contrast, low-grade serous carcinomas are characterized by KRAS or BRAF mutations and appear to arise via an adenoma–borderline–carcinoma sequence. Similarly, mucinous carcinomas have KRAS mutations and probably develop via an adenoma–borderline–carcinoma sequence. Low-grade endometrioid carcinomas, however, are characterized by mutations in PTEN and CTNNB1, and microsatellite instability, and may arise from ovarian endometriosis or borderline endometrioid tumours. High-grade endometrioid carcinomas have similar changes to high-grade serous carcinomas. Clear-cell carcinomas are characterized by mutations of TGFbetaR2 and over-expression of HNF-1beta, and probably arise from ovarian endometriosis. The molecular changes in transitional-cell carcinomas of the ovary remain largely unknown. The identified molecular changes and pathways of development in epithelial ovarian cancer will facilitate the rationalized development of new diagnostic modalities and tailored therapies for this malignancy.

Age-related macular degeneration is a common cause of blindness. Its incidence is increasing, partly due to the advancing age of the population in North America and Europe, but there is no doubt that the age-adjusted rates are also increasing, which points to some environmental influence. The condition is characterized by the appearance of retinal deposits called drusen. These and other changes form a barrier between the retinal pigment epithelium and the choroidal circulation. As a result, new vessels may grow from the choroid and penetrate the retina. These new vessels are delicate and can leak or bleed. Such episodes occur in the 'wet' form of age-related macular degeneration and cause the well known disciform degeneration, which in turn leads to distortion of the image and rapid loss of vision. Even when this does not happen, areas of retina may atrophy, probably due to anoxia: this is the 'dry' form of the disease, also called geographic atrophy. In trials, scattered laser burns have been applied to the retina but the long-term benefits of this are as yet uncertain. New micro-pulse lasers are coming into use which may be more effective. Surgical treatments include translocation of the retina and photodynamic therapy. Medical therapies attracting attention are intraocular injections of anti-angiogenic drugs, such as ranibizumab. These need further evaluation, as does the role of diet. Within a few years blindness due to age-related macular degeneration may be reduced by combining dietary control, screening for visual loss, and medical and surgical methods of treatment.

Objectives. The objectives of the study were to identify the average age at menopause in Karachi and to assess knowledge of and attitudes to the menopause among Pakistani women in different social strata.

Study design. A population-based cross-sectional study of 960 women aged over 35 years was conducted.

Results. As insufficient data were available for 35 women, 925 interviews were analysed. There were 287 menopausal women, whose mean (SD) age at menopause was 47.1 (4.7) years (95% CI 46.8 to 47.6). Of these 287 women, 135 (47%) wanted their menses to continue and 235 (82%) had consulted a physician after the menopause. Of all 925 women, 58% knew the correct definition of the menopause, all had consulted a physician for various symptoms related to the menopause and 53% said that women should consult a physician premenopausally. Symptoms experienced by premenopausal women included lack of sleep (25%), fear of infertility (13%) and urinary incontinence (18%). The majority of the overall sample (52%) were sexually active. Of the sexually active women, 16% had marital problems, compared with 44% of sexually inactive women, and this difference was statistically significant (P < 0.0001). Source of knowledge about the menopause included relatives (35%), television (18%), neighbours (17%), friends (17%) and health-care providers (14%).

Conclusions. Evidence-based information about the menopause should be provided for Pakistani women.

The risks and benefits of hormone replacement therapy (HRT) need to be put in perspective. In the analysis of clinical trials, emphasis is often placed on relative risks, statistical significance and 95% confidence intervals, whereas, from a clinical perspective, more may be gained from a consideration of the absolute and attributable risks of therapy. The Council for International Organizations of Medical Sciences recommended that the frequency of adverse events be categorized as 'rare' if less than 1/1000 but more than 1/10,000, and as 'very rare' if less than 1/10,000. In the analyses of the Women's Health Initiative (WHI), the attributable risks were 'appreciable' (i.e. more than 1/1000) only in women aged over 70 years, with the exception of the risks of venous thromboembolism and stroke. The women in the WHI trial do not represent the relatively younger, healthy, postmenopausal women most commonly prescribed HRT, who are probably at much lower risk. Moreover, the WHI trial did not take into account the benefit of relief of menopausal symptoms, which is, for many women, paramount and outweighs the 'rare' long-term risks. Age may be a useful guide to risks and some simple guidelines for management, based on age, are suggested. Many women have been denied or have discontinued HRT because of the fear of risks, which may not have been put in perspective or fully understood. The care of postmenopausal women is not static, and sufficient has now been learned to enable each menopausal woman, with the help of her medical adviser, to come to a balanced and reasonable decision.