Bailliere's clinical endocrinology and metabolism最新文献

Mammalian lignans are produced from plant precursors such as secoisolariciresinol diglycoside (SDG) and matairesinol via the action of bacteria in the human or animal colon. While precursors are found in many plant foods, flaxseed is the richest source of SDG and was therefore used as a model to determine the anti-cancer effects of lignans. This paper reviews the experimental studies in animals and humans demonstrating the anti-cancer effects of flaxseed and its SDG as well as other studies relevant to the clinical use of lignans, such as those on their food sources, bio-availability and safety.

Chronic renal failure, dialysis and transplantation have major effects on male reproductive health because of the impairment of spermatogenesis, steroidogenesis and sexual function. Hypothalamo-pituitary testicular dysfunction in uraemia is manifest clinically as delayed growth and puberty, sexual dysfunction, androgen deficiency, impaired spermatogenesis and infertility. Apart from renal anaemia, there are at present no proven indications for androgen therapy in chronic renal failure. This chapter reviews the basis and scope for various clinical applications of gonadotropin and androgen therapy as an adjunct to the standard medical care of chronic renal failure. The therapeutic possibilities implied by experimental and clinical findings suggesting that uraemic hypogonadism may be a functional state of gonadotropin deficiency are emphasized.

Natural testosterone and its esters, even when applied in supraphysiological doses, rarely produce side-effects. Via a negative feedback mechanism, exogenous testosterone suppresses the production of lutenizing hormone and follicle stimulating hormone, and leads to reduced testicular sperm production and, consequently, reduced testicular volume. The main concerns for the potential adverse effects of testosterone treatment are the prostate and the cardiovascular system. Androgens play a permissive role in the development of prostate cancer and benign prostate hyperplasia; however, there are no data to indicate that testosterone administration can lead to the progression of pre-clinical or clinical prostate cancer. Whether the effects of testosterone treatment on lipid metabolism are clinically relevant is as yet undetermined. The effects of testosterone on behaviour, especially on aggression, have not been firmly established. Some androgen effects, such as virilization and coarsening of the voice, considered normal in adult men are inappropriate in women and children.

Chronic obstructive pulmonary disease (COPD) afflicts millions of people and is severely disabling. Exercise intolerance is usually the chief complaint. There are few effective therapies. Pulmonary rehabilitation seeks to return the patient to the highest possible level of function but cannot reverse the underlying pulmonary abnormalities. Several lines of evidence have recently pointed to abnormalities of the muscles of ambulation as a remediable source of exercise intolerance in COPD. Possible mechanisms of the muscle abnormalities include deconditioning, malnutrition, low levels of anabolic hormones and, perhaps, a specific myopathy. To date, most reports of attempts to reverse muscle dysfunction in COPD have focused on exercise training. However, abnormalities in the level of circulating anabolic hormones have recently been described, suggesting that anabolic hormone supplementation may be rational therapy for these patients. Accumulating evidence that anabolic steroids increase muscle mass and improve strength in older men is encouraging trials of anabolic steroids in men with COPD.

Central or visceral obesity is recognized as a main risk factor for cardiovascular disease and type 2 diabetes mellitus. The co-existence of visceral obesity, increased blood lipid levels, hypertension and impaired glucose tolerance defines the metabolic syndrome that today is widely recognized as one of the prime factors behind cardiovascular morbidity and mortality.

Endocrine disorders such as insulinoma, hypothyroidism and hypercortisolism are known to cause obesity. However, it is only hypercortisolism that is associated with increased abdominal fat accumulation.

Recently, new findings have shed light on subtle endocrinopathies that are prevalent in individuals presenting with the metabolic syndrome. Such derangements are of borderline character and often fall within the normal reference range. Intervention studies demonstrate that correction of relative hypogonadism in men with visceral obesity and other manifestations of the metabolic syndrome seem to decrease the abdominal fat mass and reverse the glucose intolerance, as well as lipoprotein abnormalities in the serum. Further analysis of the underlying mechanism has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Longitudinal epidemiological data demonstrates that relatively low testosterone levels are a risk factor for development of visceral obesity.

The primary event that triggers the initial development of visceral obesity is not known, but it seems plausible that increased activity in the hypothalamus-pituitary-adrenal axis can be of major importance.

Testosterone therapy is commonly used to treat male hypogonadism, androgen deficiency of severe illness, androgen deficiency of ageing and microphallus in infancy. The effects of testosterone are mediated directly as testosterone or after conversion to either dihydrotestosterone (DHT) or oestradiol. DHT is a potent androgen and cannot be aromatized to oestrogens, therefore acting as a pure androgen. DHT has been proposed as an androgen replacement therapy, with possible advantages over testosterone in certain circumstances in the ageing population as well as in patients with gynaecomastia and microphallus. A potential advantage of DHT over testosterone as an androgen replacement therapy is the reported and seemingly paradoxically muted effects of DHT on prostate growth. The decreased effect of DHT compared with testosterone on the prostate gland of humans may be due to the decrease in intraprostatic oestradiol levels. The potential beneficial effect of less prostate growth after DHT requires substantiation and, if true, must be balanced against any negative effects that might occur on bone, lipids and sexuality when a pure androgen replaces treatment with an aromatizable androgen.

Testosterone functions as a contraceptive by suppressing secretion of the pituitary gonadotropins luteinizing hormone and follicle stimulating hormone. Low levels of these hormones decrease endogenous testosterone secretion from the testis and deprive developing sperm of the signals required for normal maturation. Interference with sperm maturation causes a decline in sperm production and can lead to reversible infertility in men, raising the possibility that testosterone could be utilized in a commercially available contraceptive. To this end, testosterone has been studied alone and in combination with either gonadotropin releasing hormone analogues or progestins in efforts to improve its contraceptive efficacy. In this chapter, we will review efforts to use testosterone to create a safe, convenient, efficacious contraceptive method for men.