Treatments in Endocrinology最新文献

There has been speculation for decades regarding the role of flushing women's fallopian tubes in improving the chance of pregnancy. More recent evidence has highlighted a possible specific role for lipiodol (ethiodized oil), an oil-soluble contrast medium, in the enhancement of fertility by these means. This systematic review was designed to assess the effectiveness of tubal flushing with various contrast media in improving the chance of pregnancy. The review was performed using Cochrane guidelines, including only data from randomized controlled trials. Results confirm the effectiveness of flushing with lipiodol in improving the chance of pregnancy and live birth. Although there was limited evidence to suggest a possible benefit of oil- over water-soluble contrast media, the answer to this question remains unclear. The specific groups who appear to benefit most from lipiodol flushing are couples with unexplained infertility, but particularly couples where the woman has endometriosis in the context of normal patent fallopian tubes. As a simple, low-cost, minimally invasive intervention that carries a low risk of complications and no increased risk of multiple pregnancy, lipiodol flushing may prove an appealing alternative to established fertility treatments for many couples.

Bisphosphonates have been approved in the US as oral medication for the treatment of osteoporosis for about 10 years. Efficacy data exists for fracture reduction for the commonly used oral bisphosphonates but not for intravenous formulations. Based on the mechanism of action that appears to allow for longer intervals between doses, it has been possible to extend the treatment choices from the original more demanding daily oral dose to an array of options including oral weekly and more recently monthly treatment (so-called cyclical therapy) and intravenous treatment with various administration regimens. The possibility of treatment with an annual (or less frequent) intravenous administration with zoledronic acid exists. Compliance, adverse effects, and efficacy vary with each administration regimen.

The range of therapeutic modalities to treat type 2 diabetes mellitus has broadened in recent years. Biguanides and thiazolidinediones are the two currently available classes of anti-hyperglycemic agents with insulin-sensitizing properties. Thiazolidinediones, in particular, have received much attention, not only for the well documented hepatotoxicity of troglitazone that led to its removal from the market in 2000, but also for the emerging data that support the beneficial effects of the thiazolidinedione class of drugs on beta-cell rejuvenation and cardiovascular risk reduction. In the US, thiazolidinediones are indicated either as monotherapy or in combination with a sulfonylurea, metformin, or insulin in cases where diet, exercise, and a single drug fail. In contrast, the UK National Institute for Clinical Excellence included in its re-appraisal of 'glitazones' in August 2003 the continued exclusion from licensed use in the UK of combination therapy with thiazolidinediones and insulin. When added to insulin therapy, thiazolidinediones appear to effectively lower glucose levels and reduce insulin dosage in clinical trials involving individuals with poorly controlled type 2 diabetes. However, weight gain, hypoglycemia, and fluid retention pose problems in certain patients. The fluid retention may exacerbate or even precipitate congestive heart failure, which usually necessitates discontinuation of the drug. Risk stratification and careful management of patients at risk for heart failure, including those taking insulin concomitantly, allow healthcare providers to safely administer combination therapy with thiazolidinediones in patients with type 2 diabetes. Hepatic toxicity with currently available thiazolidinediones has been found to be minimal overall.

The management of infertility in women with polycystic ovary syndrome (PCOS) centers around options for inducing ovulation. This is an evidence-based review of the management of PCOS, which includes a MEDLINE search of publications between 1986 and May 2005 and a search of the Cochrane Database. Weight loss, exercise, and metformin will induce ovulation in many insulin-resistant women and obese women with PCOS, and should always be the first-line treatment. Ovulation induction has been performed with clomiphene citrate (clomifene) as the first-line treatment, but the use of aromatase inhibitors has been shown to be as successful. The strategies for reducing the risks of gonadotropin therapy such as low-dose follicle-stimulating hormone (FSH) stimulation and the addition of metformin are discussed. Both gonadotropin releasing-hormone agonists and antagonists are equally effective in in vitro fertilization stimulation in conjunction with FSH therapy. Metformin may have a benefit in pregnancy in reducing the risks of miscarriage and diabetes mellitus; however, prospective trials are still lacking.

Hormonal therapy forms part of the treatment of every intersex condition. For some conditions, such as salt-wasting congenital adrenal hyperplasia, hormonal replacement therapy is life saving because hormones necessary for survival (cortisol and aldosterone) are replaced. In contrast, other hormones such as androgens or mineralocorticoids are secreted in excessive amounts in congenital adrenal hyperplasia due to an enzyme imbalance, and the role of hormonal therapy is to suppress the unwanted hormone excess by exerting negative feedback. For patients with one of the many causes of hypogonadism, sex hormone replacement therapy may be prescribed to stimulate sexual development: growth of a hypoplastic penis in a young boy, pubertal changes (male or female), psychosexual development, and adult sexual behavior. It has equally important and highly beneficial effects on bone mineral density. Hormonal therapy is also used to treat the unborn child. For the last 20 years, prenatal dexamethasone treatment administered to the pregnant woman has been used to prevent the development of ambiguous genitalia in females with 21-hydroxylase deficiency. Outcome studies show this treatment to be well tolerated and, in general, efficacious. Intersex conditions are, however, difficult to treat because they may intrinsically perturb complex aspects of the person's gender identity, gender-role behavior, sexual orientation, sexual functioning, and psychologic adjustment. Furthermore, decisions made about the sex of an infant by doctors and parents do not always turn out to be correct; the person may grow up feeling uncertain about his or her gender identity, or worse still, harbor a sense of outrage about their life and treatment experiences. Such a person will have definite views about hormonal therapy when the time comes and skillful counseling will be needed. A vigorous debate about ethical aspects of current medical practices relating to intersex conditions has been waged for the last 7 years between certain patient advocacy organizations and the medical profession, and is expected to continue for some time. The quality of the debate will be improved by evidence. The results of a number of long-term follow-up studies have been published, and more are expected. The published studies show mixed, but mainly encouraging, results.

The successful treatment of Cushing syndrome depends on specific therapy directed against the etiology of hypercortisolism. In addition to surgical procedures, various drugs have been employed in the management of this difficult disease. Compounds with neuromodulatory properties have been effective in only a limited number of cases of hypothalamic-pituitary-dependent Cushing disease, the most common form of Cushing syndrome. These agents include serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), GABA agonists (valproic acid [sodium valproate]), and somatostatin analogs (octreotide). Interesting new avenues at the pituitary level involve the potential use of thiazolidinedione compounds, such as rosiglitazone, and of retinoic acid, which are ligands of different nuclear hormone receptors involved in hypothalamic-pituitary regulation. The most exciting news, however, in the pharmacologic approach to Cushing syndrome refers to the adrenal corticotropin (adrenocorticotropic hormone; ACTH)-independent forms, in which aberrant adrenal receptors, through the binding of their respective ligands, could lead to chronic cortisol overproduction. They include receptors for gastric inhibitory peptide (GIP), beta-adrenergic agonists, luteinizing hormone (LH)/human chorionic gonadotropin, serotonin (5-HT(4) receptor), vasopressin (V(1) receptor), and angiotensin II (AT(1) receptor). In GIP-dependent Cushing syndrome, the most frequent subtype of ACTH-independent macronodular adrenal hyperplasia associated with the presence of aberrant adrenocortical hormone receptors described so far, octreotide administration before each meal showed clinical efficacy only in the first few months, probably because of somatostatin receptor downregulation in GIP-secreting cells. Long-term medical treatments with propranolol and the gonadotropin-releasing hormone analog leuprorelin (leuprolide acetate) were effective in patients with catecholamine-dependent and LH-dependent Cushing syndrome, respectively. The oral vasopressin V(1) receptor antagonist OPC-21268 and the angiotensin II (AT(1)) receptor antagonist candesartan cilexetil were also able to decrease cortisol levels during the few days of administration of the drugs in patients with specific receptor abnormalities. These adrenal forms of Cushing syndrome are rare, and clinical data are scarce. Moreover, the real clinical significance of aberrant hormone receptors is still under investigation, as is the possibility of avoiding surgery by pharmacologic manipulation. Patients in whom these intriguing syndromes are suspected require detailed investigation protocols, which should be carried out in specialized centers. While awaiting further developments, the use of traditional medical treatment at the adrenal level with adrenal steroid inhibitors is still valuable in several instances.

There is an increased risk of cardiovascular disease (CVD) mortality and morbidity in patients with type 1 diabetes mellitus compared with the general population as shown by epidemiologic studies measuring cardiovascular endpoints, as well as by autopsy, angiographic, and coronary calcification studies. Most of the excess CVD risk associated with type 1 diabetes is concentrated in the subset of approximately 35% of patients who develop diabetic nephropathy (after 20 years of diabetes duration), who also typically have dyslipidemias, elevated blood pressure, and hyperglycemia, factors contributing to CVD. For reasons that remain speculative, the relative risks from CVD are higher in women than in men with type 1 diabetes compared with the general population, which effectively eliminates the gender differences in CVD. As in the general population and in patients with type 2 diabetes, education and lifestyle changes, interventions to reduce hyperglycemia, blood pressure, micro-albuminuria, lipid control, and the use of aspirin are important management areas in order to reduce the increased risk of CVD. Whether management with aspirin and statins should be started in type 1 diabetic patients at a younger age or at a lower risk score than in the general population is still under investigation. There is a need for a better understanding of the pathophysiology of vascular complications in type 1 diabetes, more specific risk engines in type 1 diabetes, and accurate estimations of the absolute and relative risk for CVD in order to improve management of CVD in these high-risk patients.