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糖尿病研究与治疗的最新进展(7)

时间:2005-08-27 19:51来源:本站原创 作者:ouyetao1972 阅读:

In particular, metformin is the only drug currently in widespread clinical use for treatment of PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.

24. [Insulin resistance and polycystic ovary syndrome] [Article in French]

Gynecol Obstet Fertil. 2003 Feb;31(2):109-16. Bernard L, Christin-Maitre S, Basille C, Chabbert-Buffet N. Service d'endocrinologie, hopital Saint-Antoine, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France. [email protected]

Polycystic ovary syndrome (PCOS) is a frequent disease, characterized by disturbed ovarian function with hyperandrogenism. Anovulation is secondary to an absence of follicular dominance. Apart from a primary ovarian defect, insulin resistance is observed in PCOS women, even in the absence of overweight. This insulin resistance could be secondary to a defect in the insulin transduction pathway, mainly by a defect in receptor phosphorylation.

It enhances hyperandrogenism as it increases ovarian androgen production. Therefore treating insulin resistance by weight loss or drugs reducing insulin resistance might improve fertility of PCOS women. Metformin has been shown to reduce ovarian production, enhance ovulatory cycles and in some cases increase fertility. However, there are few randomized studies on large numbers of patients to prove an effect on pregnancies as well as on the occurrence of early pregnancy loss.

There are currently no recommendation on dose and duration of metformin treatment. It is noteworthy that metformin has no authorization in France to be prescribed apart from diabetic patients' care. Considering the medical care of PCOS women, the cardiovascular risk needs to be taken into account.

Therefore hypertension, dyslipidemia and diabetes must be treated in those women who need to be followed carefully all over their life.

25. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.

Cochrane Database Syst Rev. 2003;(3):CD003053.

Comment in: ACP J Club. 2004 May-Jun;140(3):75.

Lord JM, Flight IH, Norman RJ. Department of Endocrinology and Metabolism, Peninsula Medical School, South West Centre for Reproductive Medicine, Derriford Hospital, Plymouth, Devon, UK, PL6 8DH.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogenaemia and insulin resistance. Hyperinsulinaemia is known to be associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.

OBJECTIVES: To assess the effectiveness of insulin sensitising drugs in improving clinical and biochemical features of PCOS.

SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (December 2002), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2002),

MEDLINE (January 1966 to December 2002), and EMBASE (January 1985 to December 2002).

SELECTION CRITERIA: Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent.

DATA COLLECTION AND ANALYSIS: Performed by two reviewers, one blinded to information that could have identified the authors, publisher or results of each study. Fifteen trials were included for analysis, 13 of them using metformin and involving 543 participants.

MAIN RESULTS: Meta-analysis showed that metformin is effective in achieving ovulation in women with PCOS with odds ratios of 3.88 (CI 2.25 to 6.69) for metformin versus placebo and 4.41 (CI 2.37 to 8.22) for metformin and clomifene versus clomifene alone. An analysis of pregnancy rates suggests a significant treatment effect for metformin and clomifene (OR 4.40, CI 1.96 to 9.85). Metformin has a significant effect in reducing fasting insulin levels (WMD -5.37, CI -8.11 to -2.63), blood pressure and low-density lipoprotein cholesterol (LDL). There was no evidence of effect on body mass index or waist:hip ratio. Metformin was associated with a significantly higher incidence of nausea, vomiting and other gastrointestinal disturbance, but no serious adverse effects were reported.

REVIEWER'S CONCLUSIONS: Metformin is an effective treatment for anovulation in women with PCOS. Its choice as a first line agent seems justified, and there is some evidence of benefit on parameters of the metabolic syndrome. Ovulation rates are higher when combined with clomifene (76% versus 46% when used alone), but there is no evidence to indicate whether there is an increased multiple pregnancy rate with this combination. There is no data regarding its safety in long-term use in young women. It should be used as an adjuvant to general lifestyle improvements, and not as a replacement for increased exercise and improved diet.

26. Metformin therapy and diabetes in pregnancy.

Med J Aust. 2004 May 3;180(9):462-4.

Simmons D, Walters BN, Rowan JA, McIntyre HD. Waikato Clinical School, Waikato Hospital, Hamilton, New Zealand. [email protected]

No adverse pregnancy outcomes with metformin use have been reported, except in one unmatched study. Otherwise, the studies are small and non-randomised, with the exception of one prospective, randomised controlled trial, currently under way, comparing metformin with insulin in women with gestational diabetes mellitus (the MiG trial).

No long-term follow-up data for offspring of mothers receiving metformin have been published. Any woman with diabetes should be as close to euglycaemia as possible before pregnancy. In some circumstances (eg, severe insulin resistance), metformin therapy during pregnancy may be warranted. When metformin treatment is being considered, the individual risks and benefits need to be discussed with the patient so that an appropriate decision can be reached.

27. Metformin in obstetric and gynecologic practice: a review.

Obstet Gynecol Surv. 2004 Feb;59(2):118-27.

McCarthy EA, Walker SP, McLachlan K, Boyle J, Permezel M. University of Melbourne, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, East Melbourne, Australia. [email protected]

Metformin is a common treatment for women who have insulin resistance manifesting as type 2 diabetes or polycystic ovarian syndrome (PCOS). With an increasing number of these patients conceiving, it is expected that the use of metformin in and around the time of pregnancy will increase.

This article reassesses the mechanisms, safety, and clinical experience of metformin use in obstetrics and gynecology.

Metformin is an attractive therapeutic option because administration is simple, hypoglycemia rare, and weight loss promoted. There is a large volume of research supporting the use of metformin treatment in diabetes mellitus, androgenization, anovulation, infertility, and recurrent miscarriage. Although metformin is known to cross the placenta, there is, as yet, no evidence of teratogenicity.

Metformin has an array of complex actions, accounting for the varied clinical roles, many of which are still to be fully evaluated. Much research is still needed.

28. Metformin: new understandings, new uses.

Drugs. 2003;63(18):1879-94.

Hundal RS, Inzucchi SE. Diabetes & Metabolic Disease Center, Christiana Care, Wilmington, Delaware, USA.

Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years. Over this period of time, it has become the most widely prescribed antihyperglycaemic agent.

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