Treatments in Endocrinology最新文献

Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving other bone qualities in addition to increasing bone mass. Teriparatide (human parathyroid hormone[1-34]) has clearly emerged as a major approach for selected patients with osteoporosis. Teriparatide increases bone mineral density and bone turnover, improves bone microarchitecture, and changes bone size. The incidence of vertebral and non-vertebral fractures is reduced. Teriparatide is approved in many countries throughout the world for the treatment of both postmenopausal women and men with osteoporosis who are at high risk for fracture. Another anabolic agent, strontium ranelate, may both promote bone formation and inhibit bone resorption. Clinical trials support the use of strontium ranelate as a treatment for postmenopausal osteoporosis and have shown that strontium ranelate reduces the frequency of vertebral and non-vertebral fractures. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, growth hormone, and insulin-like growth factor-I, have been examined, although less data are currently available on these approaches.

Polycystic ovary syndrome (PCOS) is a diagnosis made between late adolescence and the menopause in 5-10% of women. PCOS is a heterogeneous disorder of unknown etiology characterized by hyperandrogenic chronic anovulation. This syndrome consists of a diverse constellation of signs and symptoms, such as hirsutism, acne, acanthosis nigricans, obesity, menstrual irregularities, anovulation, and/or infertility. Features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia, are common in this patient population. Recent insights into the pathophysiology of PCOS have shown insulin resistance and hyperinsulinemia to play a substantial role. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Recent studies show that serum levels of inflammatory mediators, such as tumor necrosis factor-alpha and interleukin-6, are increased in the insulin-resistant conditions of obesity and PCOS. The optimal modality for long-term treatment should have positive effects on androgen synthesis, sex hormone-binding globulin production, the lipid profile, insulin sensitivity, inflammatory mediators, and clinical symptoms including acne, hirsutism, and irregular menstrual cycles. Treatment with insulin-sensitizing agents is a relatively new therapeutic strategy in women with PCOS. Current research has shown that the use of diabetes mellitus management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) can not only reverse testosterone and luteinizing hormone abnormalities and restore menstrual cycles, but can also improve glucose, insulin, proinflammatory cytokine, and lipid profiles.Clinical treatment with troglitazone, a member of the thiazolidinedione family, for the management of PCOS complications such as insulin resistance, hyperandrogenism, and anovulation was found to have beneficial effects; however, it was taken off the market over concerns of hepatotoxicity. Although troglitazone is no longer available in the US, numerous clinical trials have established the role of thiazolidinediones in the treatment of women with PCOS. Clinical data emerging regarding the utility of two of the newer, safer thiazolidinediones, pioglitazone and rosiglitazone, for this patient population, consistently demonstrate effective improvements of endocrine and ovulatory performance in women with PCOS. The benefit and importance of lifestyle modification and weight reduction, when it can be achieved, is still an important component in the long-term treatment of PCOS. Pharmacologic reduction in insulin levels using thiazolidinediones appears to offer another therapeutic modality for PCOS, which may ameliorate the progress of both hyperinsulinemia and hyperandrogenism. However, additional studies of patients so treated are necessary before these agents can be considered first-line treatment for PCOS. Convincing data from randomize

Hot flashes represent one of the most common complaints among women undergoing menopause. Despite their prevalence, the pathophysiology leading to hot flashes is only partly understood. Short-term estrogen remains the most effective treatment for hot flashes, but because of safety concerns many women are reluctant to use this treatment. Several non-hormonal pharmacologic treatments have been evaluated in randomized, prospective clinical trials. Placebo-controlled clinical trials have suggested that agents from the selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) family reduce hot flashes by 50-60%. Successful treatment of hot flashes with these compounds may also be associated with improvements in sleep, mental health, and vitality. Adverse events may cause 10-20% of individuals to withdraw from treatment. The agents should be stopped with caution to prevent a discontinuation syndrome. Given the available data, the North American Menopause Society and the American College of Obstetricians and Gynecologists have recommended that women with moderate to severe, menopause-related hot flashes, with concerns or contraindications to estrogen-containing treatments, should consider prescription progestogens, venlafaxine, paroxetine, fluoxetine, or gabapentin. Prescribing clinicians are urged to discuss the potential benefits, adverse effects, and new information that may become available for each of the treatment options. Caution should also be exercised when prescribing strong cytochrome P450 2D6 inhibitors, such as paroxetine or fluoxetine, to women who are taking tamoxifen. Further studies are required to evaluate the optimal agent and duration of SSRI/SNRI treatment in menopausal women.

Osteoporosis is a major cause of morbidity, mortality, and healthcare costs. The socioeconomic burden of osteoporosis is likely to increase dramatically if improvements in prevention are not made. Calcium supplementation effectively reduces the rate of bone loss in postmenopausal women, yet most women do not achieve an adequate calcium intake. In fact, use of calcium supplementation appears to have declined as the more effective antiresorptive therapies, such as bisphosphonates, have become available. Among patients prescribed bisphosphonates, calcium intake is often insufficient, despite the fact that adequate calcium intake may be necessary to gain the maximum benefits from antiresorptive therapy. In addition, because calcium interferes with bisphosphonate absorption, incorrect use of calcium may limit the efficacy of bisphosphonate therapy. This underscores the need for new initiatives to reduce the confusion surrounding appropriate calcium use during antiresorptive therapy. Co-packaging of bisphosphonates with calcium supplements is one strategy to help ensure that patients taking bisphosphonates not only achieve adequate calcium intake but also gain the maximum benefit from bisphosphonate therapy.

The climacteric syndrome involves a variety of symptoms such as profuse sweating, insomnia, memory loss, decreased sexual drives, joint aches, and anxiety. However, amongst these symptoms, hot flashes and sweats are generally considered the hallmark and result in the majority of the medical consultations for this condition. Hot flashes are known to respond readily to placebo, which alone decreases their frequency by 20-40%. In the ideal setting of clinical trials, with optimal patient selection and compliance, estrogen therapy reduces hot flashes by about 70-80%; this is twice as effective as placebo. However, estrogen is unable to be universally used, either because of contraindications or because of an unwillingness of women to take it. Furthermore, hot flashes may persist in spite of adequate estrogen replacement, and physicians are often faced with the dilemma of finding something to administer in place of, or in addition to, estrogen to improve symptoms. The most commonly used non-hormonal alternatives for climacteric symptoms are neurotransmitter modulators such as serotonin reuptake inhibitors and gabapentin. These are, at best, approximately half as effective as estrogen for the relief of menopausal symptoms, and are only marginally better than placebo.Complementary treatment, particularly over-the-counter phytotherapeutic extracts, are very popular and women often try a variety of such products before resorting to conventional medicine. Preparations containing isoflavones, such as soy extract and red clover or extracts from evening primrose or cimicifuga (black cohosh, Actaea racemosa, syn. Cimicifuga racemosa), in variable doses are very popular for the treatment of hot flashes. The scientific support for their efficacy certainly does not equal their popularity.Non-hormonal treatments for menopause are not as effective as estrogens in relieving hot flashes, but may have a role in therapy for women who have contraindications to gonadal steroid use.

Objectives: To assess the reasons why women chose the combined oral contraceptive (COC) containing ethinylestradiol 30mug and drospirenone 3mg, their perception of it, and their satisfaction with it when used in clinical practice.

Methods: This was an uncontrolled survey of women using the ethinylestradiol 30mug/drospirenone 3mg COC in 15 European countries from September to December 2004. The women were invited to participate in this study by their general practitioner, gynecologist, or other family planning provider. The women were asked to complete a four-part questionnaire retrospectively about why they chose the ethinylestradiol 30mug/drospirenone 3mg COC and their experiences with it.

Results: A total of 10 947 questionnaires were returned and included in the analysis. Of the respondents, 7694 (70%) had switched to the ethinylestradiol 30mug/drospirenone 3mg COC from other oral contraceptives. About two-thirds (6797 [62%]) of respondents stated that they felt better while using the ethinylestradiol 30mug/drospirenone 3mg COC compared with the time before they started using it. The severity of premenstrual symptoms including depressed mood, irritability, breast tenderness or pain, abdominal bloating or swelling, skin and hair problems, and swelling of the extremities all improved during treatment with the ethinylestradiol 30mug/drospirenone 3mg COC. Overall, 10 441 (95%) respondents were satisfied or very satisfied with the ethinylestradiol 30mug/drospirenone 3mg COC and 9016 (82%) would recommend it to a friend.

Conclusion: The additional non-contraceptive benefits of the ethinylestradiol 30mug/drospirenone 3mg COC are important factors that influence patients' perceptions of this oral contraceptive and their satisfaction with its use.

The treatment of congenital adrenal hyperplasia (CAH) before birth was instituted 20 years ago in an attempt to prevent virilization of the external genitalia in affected girls. Maternally administered dexamethasone, which readily crosses the placenta unaltered, is started very early in pregnancy to ensure adequate suppression of the fetal hypothalamo-pituitary-adrenal axis. Since the diagnosis cannot be ratified until chorionic villus sampling is performed 6 weeks later, fetuses that do not require treatment (all males and unaffected females) are also exposed to high-dose glucocorticoids for an interim period. It is not known whether this induces fetal programming of metabolic changes that may manifest as disease in adult life. The expected outcome at birth in a female fetus with CAH who has been treated with adequate amounts of dexamethasone is normal-appearing genitalia or at least a significant reduction in virilization for which genitoplasty is unlikely to be required. Short-term follow-up studies in infants and children exposed to dexamethasone indicate normal growth and development. The medical treatment of CAH before birth is a unique example of the successful prevention of a major congenital malformation. However, there is a potential concern about possible long-term consequences of exposure of the fetus to glucocorticoids during early embryogenesis and beyond. This mandates the need for prenatal treatment for CAH to be undertaken only in protocol-driven clinical trials that are obliged to follow all children exposed in utero for the long term in order to collect any evidence of adverse neurodevelopmental and metabolic consequences.

Imperfect use of contraceptive methods notably increases the likelihood of pregnancy. One means of improving user adherence with hormonal contraception is to minimize the dosing schedule. Two forms of hormonal contraceptive have currently achieved this goal: the transdermal patch and the vaginal ring. The first and only transdermal contraceptive patch to receive worldwide regulatory approval (ethinylestradiol/norelgestromin) is a convenient approach to contraception that has a similar efficacy to oral contraceptives (OCs), but with the benefit of once-weekly administration. In addition, transdermal delivery of contraceptive hormones eliminates variability in gastrointestinal absorption, avoids hepatic first-pass metabolism, and prevents the peaks and troughs in serum concentrations that are seen with OCs. Norelgestromin, the progestin contained in the patch, is the active metabolite of norgestimate and is structurally related to 19-nortestosterone. Norgestimate and norelgestromin mimic the physiologic effects of progesterone at the progesterone receptor; however, norelgestromin has negligible direct or indirect androgenic activity, suggesting that it may be suitable for women with disorders related to androgen excess (such as hirsutism, acne, and lipid disorders).Contraceptive effectiveness is usually a function of the efficacy of a contraceptive in combination with compliance with its dosing regimen. The efficacy of the contraceptive patch has been clearly demonstrated in three phase III trials, two of which were randomized comparisons with an OC. The likelihood of pregnancy was similar between these contraceptive methods; however, compliance with the patch was notably better, particularly in younger women. The safety and tolerability profile of the patch was similar to that of the OC. A cost-effectiveness analysis has suggested that the contraceptive patch is more cost effective than the OC, due to decreased costs related to unwanted pregnancy.

The glycosylated hemoglobin (HbA(1c)) goal in patients with type 2 diabetes mellitus should be to achieve as low a value as can be obtained without causing significant or frequent hypoglycemia. This is best achieved by utilizing agents that lower glucose levels without causing hypoglycemia (thiazolidinediones and metformin). To maintain these low HbA(1c) values and avoid the utilization of insulin secretagogues or insulin, which are associated with hypoglycemia and suboptimal dosing leading to higher HbA(1c) values, drugs that maintain or improve pancreatic beta-cell function (thiazolidinediones and possibly incretin-based therapies) should be utilized. Restoration of first-phase insulin release, as has been shown with thiazolidinediones, will not only improve postprandial hyperglycemia but will also improve postprandial hyperlipidemia, both of which will decrease cardiac risk. Utilizing small doses of two drugs will also result in a decreased incidence of adverse effects compared with a large dose of a single drug. The use of fixed-dose combination oral antihyperglycemics will not only improve compliance but will often decrease costs compared with individual component dual therapy.