摘要:

Hypogonadism, irrespective of its etiology, has a negative impact on various physiologic parameters. These parameters may improve with testosterone replacement therapy. Before 1990, intramuscular testosterone esters were the principal modality of testosterone replacement in men with hypogonadism. Although effective, they have a non-physiologic pharmacokinetic profile.Recently, transdermal preparations of testosterone have become widely available. These include a scrotal patch, non-scrotal patches and, the most recent development, a gel. Several studies have shown that transdermal testosterone replacement is physiologic, efficacious and has a good safety profile. Transdermal testosterone replacement improves bone mass and lean body mass, decreases fat mass, and improves mood and sexual function. There are no harmful effects on the prostate and lipids. Acne, polycythemia, and gynecomastia are less common with this form of therapy than with the intramuscular esters.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The current goals for the therapy of children and adolescents with type 1 diabetes mellitus are to achieve near-normal glycemia, minimize the risk of severe hypoglycemia, limit excessive weight gain while achieving adequate growth, improve quality of life for both the patients and their families, and delay or prevent vascular complications. Insulin pump therapy provides a treatment option that can significantly aid in achieving all of these goals across all age ranges of pediatric patients. Continuous subcutaneous insulin infusion (CSII) pump therapy can provide greater flexibility in the timing of meals and snacks, has programmable basal rates to optimize overnight glycemic control, can reduce the risk of exercise-induced hypoglycemia, and enhances the ability of the patient and the family members to achieve acceptable diabetes control. In pediatric patients, CSII has been shown to reduce both glycosylated hemoglobin levels and the frequency of severe hypoglycemia without increasing the risk of diabetic ketoacidosis. The effectiveness of CSII, improvements in pump technology, and the availability of very rapid-acting insulin analogs have fueled a dramatic increase in the use of this therapy.This review presents practical guidelines for the selection of patients, initiation of treatment and patient education, as well as guidelines for use while exercising and at school. Keys to the success of CSII are to have a multidisciplinary team of clinicians who are expert in the care of children with diabetes, and patients and families who are able to carry out the tasks of intensive treatment, including self-monitoring of blood glucose levels, carbohydrate counting, and infusion pump management. Patients and parents need to be able to recognize and treat hypoglycemia, and prevent the development of ketoacidosis. School personnel need to be involved in the treatment plan and individual algorithms developed for periods of extra exercise and activity. The recent introduction of methods for continuous glucose monitoring provides a new means to optimize the basal and bolus capabilities of CSII and offers hope for the development of a feedback-controlled artificial pancreas.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Hyperprolactinemia is commonly found in both female and male patients with abnormal sexual and/or reproductive function or with galactorrhea. If serum prolactin levels are above 200 μg/L, a prolactin-secreting pituitary adenoma (prolactinoma) is the underlying cause, but if levels are lower, differential diagnoses include the intake of various drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia. When a pituitary tumor is present, patients often have pressure symptoms in addition to endocrine dysfunction, such as headaches, visual field defects, or cranial nerve deficits.The large majority of patients with prolactinomas, both micro- and macroprolactinomas, can be successfully treated with dopaminergic drugs as first-line treatment, with normalization of prolactin secretion and gonadal function, and with significant tumor shrinkage in a high percentage of cases. Surgical resection of the prolactinoma is the option for patients who may refuse or do not respond to long-term pharmacological therapy. Radiotherapy and/or estrogens are also reasonable choices if surgery fails. In patients with asymptomatic microprolactinoma no treatment needs to be given and a regular follow-up with serial prolactin measurements and pituitary imaging should be organized.Currently, the most commonly used dopamine agonists are bromocriptine, pergolide, quinagolide and cabergoline. When comparing the plasma half-life, efficacy and tolerability of these drugs, cabergoline seems to have the most favorable profile, followed by quinagolide. If prolactin levels are well controlled with dopamine agonist therapy, gradual tapering of the dose to the lowest effective amount is recommended, and in a number of cases medication can be stopped after several years.Evidence to date suggests that cabergoline and quinagolide appear to have a good safety profile for women who wish to conceive, but hard evidence proving that dopamine agonists do not provoke congenital malformations when taken during early pregnancy is currently only available for bromocriptine. Once pregnant, dopamine agonist therapy should be immediately stopped, unless growth of a macroprolactinoma is likely or pressure symptoms occur.At our institution patients with symptomatic prolactinomas, both micro- and macroadenomas, are treated with cabergoline as the first-line aproach. In the small group of patients who do not respond to this treatment, or who refuse long-term therapy, surgery is offered. Radiotherapy is given if both pharmacologic therapy and surgery fail.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Two landmark intervention studies, the Diabetes Control and Complications Trial (DCCT) in patients with type 1 diabetes mellitus and the United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes mellitus, have unequivocally demonstrated that intensive diabetes therapy reduces the risk of long-term diabetic complications. As a result, the commonly accepted treatment goal for most patients with diabetes is the achievement and maintenance of glycemic control that is as close to the normal range as safely possible. Important adverse effects of intensive diabetes therapy, particularly when the treatment includes insulin or several of the oral antihyperglycemic agents, are an increased risk of hypoglycemia and undesired weight gain.Improvement of glycemic control with insulin, insulin secretagogues (sulfonylureas, meglitinides), and insulin sensitizers (thiazolidinediones) is often accompanied by weight gain. The etiology of this weight gain is likely multifaceted, including a reduction of glucosuria, increased caloric intake to prevent hypoglycemia, and anabolic effects on adipose tissue.Biguanides and α-glucosidase inhibitors have a neutral or even positive effect (decrease) on weight, which may partly be attributable to their non-insulinotropic mechanism of action, a modest effect on satiety, and to their gastrointestinal adverse effect profile.Several antihyperglycemic agents that are currently in clinical development may improve glycemic control in conjunction with weight reduction. These include an analog of the pancreatic β-cell hormone amylin (pramlintide), as well as glucagon-like peptide-1 (GLP-1) and exendin, and their analogs.Pharmacological agents with antihyperglycemic and positive weight effects have the potential to become important additions to our therapeutic armamentarium, in that they may help to achieve glycemic targets while addressing the long-standing clinical problem of weight gain as an adverse effect of intensive diabetes therapy.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Ethinylestradiol 30μg/drospirenone 3mg (Yasmin®, petibelle®1) [EE/DRSP] is a combined contraceptive pill (CC) for the prevention of pregnancy in women of reproductive age. Drospirenone is a novel progestogen with antimineralocorticoid, progestogenic and antiandrogenic activity.The theoretical (0 to 0.07) and corrected (0.41 to 0.71) Pearl indices and pregnancy ratios (0.3 to 0.84) in young, healthy women aged 18 to 35 years (or 18 to 30 years if smokers) given 13 to 26 cycles of EE/DRSP in large multicenter trials indicate that this CC is highly effective in preventing pregnancy. EE/DRSP is equally as effective as ethinylestradiol 30μg/desogestrel 150μg (EE/DSG; corrected Pearl index 0.28 to 0.41) in preventing pregnancy.EE/DRSP is generally well tolerated. The frequency and type of adverse event reported in clinical trials are typical of those observed with other CCs, and comparable to those in women receiving EE/DSG.The incidence of intermenstrual bleeding (spotting, breakthrough bleeding or both) during treatment with EE/DRSP in young, healthy women decreased rapidly after the first cycle to 9 to 18% in the second cycle and 6% after 26 cycles, indicating good cycle control. The incidence of intermenstrual bleeding was similar in recipients of EE/DSG (9 and 14% in cycle 2 and 10% in cycle 26).Bodyweight was maintained ±2kg in most young women who received EE/DRSP for up to 26 cycles. Neither EE/DRSP nor EE/DSG showed clinically significant effects on blood pressure.EE/DRSP improved premenstrual and menstrual symptoms (negative affect, water retention, increased appetite) compared with baseline in a noncomparative trial. A similar improvement in skin condition (acne, seborrhea) was observed in women receiving EE/DRSP or ethinylestradiol 35μg/cyproterone acetate 2mg in a randomized, double-blind trial.Conclusions: Data from several 1- to 2-year studies show that EE/DRSP is an effective oral contraceptive, with Pearl index values similar to those of established low-dose CCs. This combination is well tolerated, demonstrating good cycle control and a beneficial effect on skin condition and well-being (including some premenstrual and menstrual symptoms). EE/DRSP has demonstrated similar efficacy and tolerability to EE/DSG, but long-term clinical experience is required to establish the position of EE/DRSP among other available CCs and to clarify any potential tolerability advantages. Nevertheless, because the management of tolerability is complicated by the idiosyncratic nature of the response of women to CCs containing different progestogens, EE/DRSP appears to be a useful treatment option for women desiring oral contraception.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Insulin aspart (NovoLog®, NovoRapid®2), a rapid-acting human insulin analog, provides more rapid absorption than regular human insulin after subcutaneous administration.In most randomized, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated hemoglobin (HbA1c) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomized, nonblind trial.Preliminary data from randomized, nonblind trials suggest insulin aspart had a trend towards lower HbA1c levels compared with regular human insulin in patients with type 2 diabetes mellitus.Biphasic insulin aspart (30% soluble [rapid-acting] and 70% protamine-bound insulin aspart [BIAsp30]) [NovoLog®Mix 70/30, NovoMix®302] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomized, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomized, nonblind trial in patients with type 2 diabetes mellitus.Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30.The overall incidence of hypoglycemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycemia and severe hypoglycemic events than regular human insulin.Conclusion: The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycemic control and led to a similar or lower number of hypoglycemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycemic control which offers clinical and practical advantages over regular human insulin.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS