Gotowa bibliografia na temat „Oestrogen deficiency”

Surgery and radiotherapy for cancers can disrupt mental health through direct biological mechanisms in addition to the well-described psychological distress associated with the physical consequences of treatment. Upper bowel surgery and bilateral oophorectomy both frequently provoke psychopathology. Total gastrectomy, or ileal resection, causes an inevitable vitamin B12 deficiency. The molecular mechanisms by which these surgical treatments provoke depressive symptoms, or even a dementia, are considered. Raised homocysteine levels and reduced SAM availability are involved. Chronic gonadal oestrogen deprivation increases the risk of anxiety, depression, and dementia in later life. The likely molecular basis for this is discussed. Hypothyroidism, with its associated psychopathology, complicates radiotherapy for head & neck cancers in 40 per cent of patients. The chapter closes with a review of the effects of whole-brain radiotherapy on cognitive function, and the psychopathology arising from radiation-induced hypopituitarism.

Histologic bone abnormalities begin very early in the course of chronic kidney disease. The KDIGO guidelines recommend that bone disease in patients with chronic kidney disease should be diagnosed on the basis of bone biopsy examination, with bone histomorphometry. They have also proposed a new classification system (TMV), using three key features of bone histology—turnover, mineralization, and volume—to describe bone disease in these patients. However, bone biopsy is still rarely performed today, as it involves an invasive procedure and highly specialized laboratory techniques. High-turnover bone disease (osteitis fibrosa cystica) is mainly related to secondary hyperparathyroidism and is characterized by increased rates of both bone formation and resorption, with extensive osteoclast and osteoblast activity, and a progressive increase in peritrabecular marrow space fibrosis. On the other hand, low-turnover (adynamic) bone disease involves a decline in osteoblast and osteoclast activities, reduced new bone formation and mineralization, and endosteal fibrosis. The pathophysiological mechanisms of adynamic bone include vitamin D deficiency, hyperphosphataemia, metabolic acidosis, inflammation, low oestrogen and testosterone levels, bone resistance to parathyroid hormone, and high serum fibroblast growth factor 23. Mixed uraemic osteodystrophy describes a combination of osteitis fibrosa and mineralization defect. In the past few decades, an increase in the prevalence of mixed uraemic osteodystrophy and adynamic bone disease has been observed.

A major endocrine function of the human ovary is the production of oestradiol, a hormone essential for the development of the secondary sex characteristics, for normal reproduction, and for the integrity of the cardiovascular, skeletal, and central nervous systems in particular. Oestradiol is a product of the granulosa cells, and hence its secretion is dependent largely on the presence of ovarian follicles. The number of those follicles falls steeply in the last 10 years or so of reproductive life (1), to approach zero at around the time of final menses (Fig. 10.1.2.1). This results in a profound decline in oestradiol production, to levels less than 10% of those observed during reproductive life. The question of whether the consequences of this decline are to be regarded as ‘natural,’ or as giving rise to a pathological state of oestrogen deficiency, is a controversial one. This chapter describes the endocrine changes which take place from the mid-reproductive years through to the postmenopausal years, and addresses the consequences of these changes and their possible prevention.

Parenchymal and stromal cells with the potential for normal breast development are equally present in prepubertal boys and girls. Men and women do not differ in sensitivity to the hormonal action of sex steroids, and therefore men have the same potential to develop breasts as women. Whether this actually occurs obviously depends on a person’s hormonal milieu. In order to understand the pathophysiology of gynaecomastia it is essential to know that breast tissue is, for its development, under control of both stimulatory hormonal action (oestrogens and progestogens) and inhibitory hormonal action of androgens. Gynaecomastia typically occurs when there is a relative dominance of oestrogenic over androgenic action; many cases of gynaecomastia are not the result of an overproduction of oestrogens per se, but rather due to the failing inhibitory action of androgens (1). In the assessment of gynaecomastia, as much attention must be paid to a potential source of feminizing hormones as to decreased androgen production or interference with the biological action of androgens. Oestrogens stimulate the proliferation and differentiation of parenchymal ductal elements while progesterone supports alveolar development. The biological actions of oestrogens and progesterone do not appear in cases of growth hormone deficiency. Prolactin stimulates the differentiated ducts to produce milk. Testosterone inhibits the growth and differentiation of breast development, probably through an antioestrogenic action (1). Whatever the cause, gynaecomastia shows the same histological developmental pattern. At first, there is florid ductal proliferation, with epithelial hyperplasia and increase in stromal and periductal connective tissue, with increased vascularity and periductal oedema. After approximately one year, there is increased stromal hyalinization, dilation of the ducts, and a marked reduction in epithelial proliferation, a ‘burnt-out’ phase of the condition. The result is inactive fibrotic tissue which no longer responds to endocrine therapy. Gynaecomastia is not an uncommon finding and most cases will not represent a serious medical condition. However, gynaecomastia may signify the presence of a malignancy producing oestrogens, aromatase (the enzyme that converts androgens to oestrogens), or human chorionic gonadotrophin (hCG). Common locations of such tumours are the testis, lungs, liver or the gastrointestinal tract. Consequently, cases of gynaecomastia must be taken seriously and the diagnostic approach must reasonably rule out a malignancy in order to avoid any undue delay in its diagnosis.

Haemophilia is a familial X-linked disorder due to deficiency of either factor VIII (haemophilia A) or factor IX (haemophilia B), components of the intrinsic enzymatic complex that activates factor X. Clinical features and diagnosis—the main manifestations are bleeding into joints and soft tissues, with haemophilic arthropathy and joint deformity being inevitable complications in untreated patients. Other features include pseudotumours, bleeding into the urinary system, and bleeding following clinical procedures. Laboratory diagnosis is based on a modification of the classic activated partial thromboplastin time (APTT) assay, with inhibitor screening used to exclude other causes of prolonged APTT. Treatment—involves the administration of the deficient factor VIII or factor IX, most commonly ‘on demand’ in response to bleeding, with prophylactic treatment given before surgery. Von Willebrand’s disease is a common autosomal dominant disorder of platelet function caused by a functional deficiency of von Willebrand factor (VWF). VWF, normally synthesized by megakaryocytes, prevents degradation of factor VIII; VWF, also made by endothelial cells, enhances platelet activation and recruitment at sites of tissue damage. Treatment—mild von Willebrand’s disease is treated with desmopressin 1-deamino-8-d-arginine vasopressin (DDAVP), which releases factor VIII and VWF from endothelial cells. Other treatments include ε‎-aminocaproic acid, oestrogens, and factor VIII concentrates. Other hereditary disorders of coagulation, including (1) hereditary deficiency of the plasma metalloproteinase ADAMTS13; (2) combined deficiency of coagulation factors V and VIII; (3) factor XI deficiency; (4) inherited deficiencies of factors II, V, VII, and X; and (5) deficiency of the contact activating factors, factor XIII, and fibrinogen, and hypercoagulable diseases due to deficiencies of anticoagulants or propensity to thrombosis are discussed in this chapter.