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The 2nd part of a review on medical therapy of endometriosis discusses pseudopregnancy brought on by oral contraceptives, and pseudomenopause induced by Danazol and GnRh agonist therapy. Oral contraceptives are not FDA approved for endometriosis, but many physicians prescribe 1 tablet daily for 2 weeks, then 2 tablets daily for 6-12 months, or higher doses in case of breakthrough bleeding. Pills cause endometrial decidual changes initially then atrophy. Danazol selectively inhibits release of FSH and LH by the pituitary, resulting in anovulation and atrophy of the endometrium. It is currently the preferred and most effective medical therapy for endometriosis, and is approved for this indication. It is used in doses of 200-800 mg in 2 divided doses, or 400-800 mg/day preoperatively. Side effects are androgenic, some of which are not reversible, antiestrogenic, metabolic and nonspecific, i.e., muscle spasms. Drug interactions such as increased insulin requirements have been reported. The GnRH antagonists, nafarelin, buserelin, histrelin and leuprolide must be given subcutaneously or nasally. The anti-ovarian side effects, hot flashes, calcium loss, vaginal dryness and insomnia are more prevalent than the androgenic side effects, weight gain, edema, myalgia, and decreased libido reported with Danazol. Clinical and laparoscopic evidence of improvement is temporary with drug treatment, in contrast to surgery. Infertility is common even with mild endometriosis, and the condition may recur, even after pregnancy.
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PMID:Clinical therapeutics of endometriosis, Part 2. 268 3

Cancer has the potential to provoke worries which should be assessed in order to adequately respond to patients' problems. We highlight in this paper the problems that concerned 30 women with cervical cancer (mean age 51.2) and 76 with breast cancer (mean age 44.9), how these concerns affected their emotional lives, and the factors associated with these worries. They were interviewed with the 33-item modified version of a German questionnaire rating psychosocial concerns (FBS) by Sullwold, and Goldberg's General Health Questionnaire (GHQ-12) for psychopathological symptoms. Cervical cancer patients had significantly higher FBS and GHQ-12 scores than breast cancer. Breast cancer cases had FBS scores similar to those of women with sickle cell disease and insulin-dependent diabetes mellitus. The commonest recurrent worries in both groups were depression about their condition (45%), thoughts of death (37%), insomnia (33.3%), bodily odour (30%), impairment of work efficiency (30%) terrifying dreams (27%) and fear of illness being life-long (25%). Over 90% denied experience of worries indicating social stigma. FBS scores were significantly correlated with GHQ scores and both were negatively associated with adequacy of social contacts. These data suggest the need for psychosocial intervention in such cases in Nigeria.
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PMID:Psychosocial concerns of Nigerian women with breast and cervical cancer. 988 90

In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time.
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PMID:Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. 1139 22

Sibutramine is a combined serotonin(5-HT) and noradrenaline (NA)re-uptake inhibitor. Sibutramine works predominantly through its two pharmacologically active metabolites (i.e. primary and secondary amines) which induce marked weight loss by affecting both food intake and energy expenditure. It is able to enhance the physiological process of satiety, and to stimulate thermogenesis, increasing the efferent sympathetic activity to thermogenically active brown fat. There is a dose-related reduction in body weight in clinical trials with sibutramine, with weight loss up to 11% below baseline, which can last up to 18 months with continued treatment. When weight loss is induced with a very low calorie diet (VLCDL), patients randomized to the sibutramine treatment continued to lose weight over a 1 year period, reaching 15% below baseline, whereas the placebo-treated patients regained some weight. Sibutramine improves metabolic fitness, by decreasing the biochemical risk factors associated with obesity, such as plasma triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol, glucose and insulin, and increasing HDL-cholesterol. In controlled studies, 84% of sibutramine-treated patients reported side effects, most commonly including dry mouth, constipation and insomnia, compared with 71% of patients receiving placebo. A small increase in heart rate and blood pressure also occurs and persists for as long as treatment is continued, which, therefore, requires monitoring. Nevertheless, successful treatment of moderately hypertensive obese patients with sibutramine has been demonstrated without undue blood pressure problems and even a mean lowering of blood pressure associated with weight loss. Finally, sibutramine does not have the potential for abuse that is characteristic of amphetamine and it is indistinguishable from placebo in abuse potential studies.
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PMID:An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action. 1211 86

Exercise improves insulin resistance and has beneficial effects in preventing and treating type 2 diabetes. However, aerobic exercise is hindered in many type 2 diabetic patients because of advancing age, obesity, and other comorbid conditions. Weight lifting or progressive resistance training (PRT) offers a safe and effective exercise alternative for these people. PRT promotes favorable energy balance and reduced visceral fat deposition through enhanced basal metabolism and activity levels while counteracting age- and disease-related muscle wasting. PRT improves insulin sensitivity and glycemic control; increases muscle mass, strength, and endurance; and has positive effects on bone density, osteoarthritic symptoms, mobility impairment, self-efficacy, hypertension, and lipid profiles. PRT also alleviates symptoms of anxiety, depression, and insomnia in individuals with clinical depression and improves exercise tolerance in individuals with cardiac ischemic disease and congestive heart failure; all of these aspects are relevant to the care of diabetic elders. Moreover, PRT is safe and well accepted in many complex patient populations, including very frail elderly individuals and those with cardiovascular disease. The greater feasibility of using PRT over aerobic exercise in elderly obese type 2 diabetic individuals because of concomitant cardiovascular, arthritic, and other disease provides a solid rationale for investigating the global benefits of PRT in the management of diabetes.
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PMID:Battling insulin resistance in elderly obese people with type 2 diabetes: bring on the heavy weights. 1271 22

From the age of 30 yrs on, the (free) testosterone [(F)T] levels decrease continuously with age, mean total T level at age 70 yrs, being only 2/3rds of the mean level at age 25 yrs, whereas mean FT level is only 40% of the mean level in young adults. However, inter-individual variations are wide and whereas at least 30% of men over age 70 yrs have clearly subnormal (F)T levels, 20% have still levels in the upper range of values in young men. Aging in males is accompanied by a series of signs and symptoms, reminiscent of androgen deficiency in young adults, such as decrease in muscle mass and strength, increase in abdominal, mainly visceral, fat with insulin resistance and atherogenic lipid profile, decrease in libido and sexual hair, osteopenia, decrease in cognitive performances, insomnia, excessive sweating and decrease in general well-being, and it is tempting to relate these symptoms to the age associated decrease in androgen levels, the more that often a significant, albeit generally weak, correlation of these symptoms with the (F)T levels is observed. Moreover, the preliminary data suggest favourable effects of androgen supplementation in the elderly. The decrease in (F)T levels is, however, only one of the factors responsible for the signs and symptoms of the aging male which have a multifactorial origin. Hence, the diagnosis of androgen deficiency in elderly men should be based on both the clinical symptomatology and the biochemistry, i.e. decreased (F)T levels, the latter being defined, more or less arbitrary, as levels below the lowest 1% of levels in young healthy males.
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PMID:Diagnosis of partial androgen deficiency in the aging male. 1277 44

The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.
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PMID:[Pharmacological treatment of obesity]. 1538 15

The hypothalamic-pituitary-adrenal (HPA) axis plays important roles in maintaining alertness and modulating sleep. Dysfunction of this axis at any level (CRH receptor, glucocorticoid receptor, or mineralocorticoid receptor) can disrupt sleep. Herein, we review normal sleep, normal HPA axis physiology and circadian rhythm, the effects of the HPA axis on sleep, as well as the effects of sleep on the HPA axis. We also discuss the potential role of CRH in circadian-dependent alerting, aside from its role in the stress response. Two clinically relevant sleep disorders with likely HPA axis dysfunction, insomnia and obstructive sleep apnea, are discussed. In insomnia, we discuss how HPA axis hyperactivity may be partially causal to the clinical syndrome. In obstructive sleep apnea, we discuss how HPA axis hyperactivity may be a consequence of the disorder and contribute to secondary pathology such as insulin resistance, hypertension, depression, and insomnia. Mechanisms by which cortisol can affect slow wave sleep are discussed, as is the role the HPA axis plays in secondary effects of primary sleep disorders.
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PMID:On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. 1572 14

We evaluated the prevalence and risk factors for erectile dysfunction (ED) and interest in ED treatment among Japanese men being treated for type 2 diabetes mellitus. Patients (40-79 years; n=1118) completed the 5-item version of the International Index of Erectile Function (IIEF-5), and questions related to interest in ED pharmacotherapy, subjective symptoms of diabetes, and general quality of life. A separate survey completed by physicians examined the relationships between age, diabetic treatments (insulin or oral), symptoms of diabetes (poor glycemic control, microangiopathy), complications of diabetes (hypertension, ischemic heart disease, cerebrovascular disease), and ED. The prevalence of ED in patients with diabetes was 90%, a rate double that of non-diabetic individuals. Multivariate analyses revealed that age, insulin therapy, microangiopathy, hypertension, history of cerebrovascular or cardiovascular disease, leg dysesthesia, dysuria, insomnia, and anorexia all represented significant risk factors for ED. Half of all respondents were interested (29%) or would consider pharmacotherapy for ED (21%). These findings suggest that ED is a significant problem in Japanese men with diabetes, and that specific risk factors increase the prevalence of ED. Furthermore, the survey results expose national attitudes toward treatment of ED.
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PMID:Prevalence and risk factors for erectile dysfunction in Japanese diabetics. 1612 26

Stages of different depth characterize the temporal organization of sleep. Each stage exerts an effect on blood pressure (BP) regulation and contributes to its 24-h variation. The main determinant of the circadian influences of sleep and wakefulness on BP is the daytime sympathetic and nighttime parasympathetic prevalence, but many other physiologic mechanisms known either to induce sleep or determine arousal may play an important role in the mediation of sleep influences on BP. Alteration of one or more of such mechanisms may be reflected in altered circadian BP rhythms. Sleep- and arousal-related mechanisms and phenomena that affect circadian BP rhythms include neurohumoral sleep factors (arginine vasopressin, vasoactive intestinal peptide, somatotropin, insulin, steroid hormones and metabolites, and serotonin among others) and waking factors (corticotropin-releasing factor, adrenocorticotropin, thyrotropin-releasing hormone, endogenous opioids, and prostaglandin (E(2))). Pathologic respiratory variations (sleep-disordered breathing) and insomnia are major causes of the sleep-related alteration of the circadian BP profile, including loss of the expected normal decline in BP by 10-20% from the daytime level. A great number of medical disorders can cause insomnia, but objective sleep studies have been performed only in a minority of them. Overall, the sleep-related pathophysiological mechanisms actually involved in causing altered circadian BP rhythms in different normotensive and hypertensive conditions are not completely understood. In any case, changes in the circadian BP rhythm are known to be strongly related to one's risk of cardiovascular morbidity and mortality, thus representing strong prognostic indicators worthy of further investigation.
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PMID:Role of sleep-wake cycle on blood pressure circadian rhythms and hypertension. 1738 36


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