Seminars in reproductive medicine
-
Semin. Reprod. Med. · May 2003
ReviewGenomics' role in understanding the pathogenesis of endometriosis.
Endometriosis is a benign, estrogen-dependent disorder that has multifactorial components presumed in its pathogenesis. The molecular mechanisms underlying endometrial tissue attachment to the peritoneal surface or metaplasia of the mesothelium, and subsequent invasion and establishment of a blood supply and survival of the endometriotic implants, are not well understood. Recent advances in molecular biology and genomics suggest an intrinsic abnormality in the eutopic endometrium of women with endometriosis that predisposes to these processes. These are discussed herein.
-
Semin. Reprod. Med. · Feb 2003
ReviewRandomized clinical trials: the meeting place of medical practice and clinical research.
Randomized clinical trials (RCTs) have been used to assess interventions affecting health since biblical times. They provide the most valid means of measuring the true effects of intervention compared with no treatment or placebo. Although they can also be used to assess the value of diagnostic tests, this article focuses on randomized trials in the context of treatment. ⋯ It is also essential to establish that the question posed is ethical, the methods of study are valid, and that follow-up is complete, with an "intent to treat" analysis. Results are best presented using both proportions and absolute numbers. By providing clinical decision-makers with numbers needed to treat or harm, decisions may be better informed and easier to understand, than if proportions alone are used.
-
Systematic review and meta-analysis procedures make use of explicit methods to methodically search and critically appraise and synthesize the medical care research literature. The methods involve refining a clinical question, designing a search procedure to find eligible studies, and determining the validity of the eligible studies. Independent data extraction by two or more reviewers is preferred. ⋯ To evaluate a systematic review, first determine whether it addresses a question that is relevant to the patients, treatments, and outcomes that are usual in your clinical practice. Then assess the validity of the systematic review, which is reflected by quality of the individual studies, the rigor with which the systematic methods were applied, and the extent of heterogeneity. If the results of the systematic review are valid, then is the effect important enough to make a difference in your clinical practice? Applying the results to an individual patient involves the absolute treatment effect or the number needed to treat, and an awareness of the patient's specific level of risk and personal preferences.
-
Semin. Reprod. Med. · Aug 2002
ReviewCongenital adrenal hyperplasia: 11beta-hydroxylase deficiency.
The most potent corticosteroids are 11beta-hydroxylated compounds. In humans, two cytochrome P450 isoenzymes with 11beta-hydroxylase activity, catalyzing the biosynthesis of cortisol and aldosterone, are present in the adrenal cortex. CYP11B1, the gene encoding 11beta-hydroxylase (P450c11), is expressed in high levels in the zona fasciculata and is regulated by adrenocorticotropic hormone (ACTH). ⋯ Molecular genetic studies of the CYP11B1 gene in 11beta-hydroxylase deficiency have led to the identification of several mutations. Transfection experiments showed loss of enzyme activity in vitro. Molecular genetic studies have practical importance for the prenatal diagnosis of virilizing CAH forms.
-
Semin. Reprod. Med. · May 2002
ReviewLeptin and the onset of puberty: insights from rodent and human genetics.
Deficiency of the adipocyte-derived hormone leptin in ob/ob mice results in severe, early-onset obesity and infertility. Administration of leptin results in complete reversal of the phenotype, suggesting that leptin is needed for the development of puberty in rodents. ⋯ This work suggests that leptin is a metabolic gate for the onset of puberty in humans. Leptin's actions may be mediated by central pathways and by direct action on peripheral organs.