Treatment of hyperprolactinemia: a systematic review and meta-analysis.

BACKGROUND: Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia. METHODS: We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels). RESULTS: After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to -11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists. CONCLUSION: Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.

Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis.

CONTEXT: The natural history of pituitary incidentalomas (PIs) and nonfunctioning pituitary adenomas (NFPAs) remains poorly understood. OBJECTIVE: The objective of the study was to synthesize the literature on the prognostic factors involved in the progression of PIs and NFPAs in patients followed up conservatively. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL. We sought to identify further studies by reviewing the reference lists from selected studies and reviews and by querying experts. STUDY SELECTION: Eligible studies were longitudinal observational cohort studies that enrolled patients with PIs/NFPAs and followed them up without any treatment from the time of detection and reported on mortality, lesion progression, and development of pituitary hormonal deficiency, apoplexy, or visual field defects. DATA EXTRACTION: Reviewers working independently and in duplicate determined studies' eligibility and collected descriptive, methodological quality, and outcome data. Event rates per 100 person-years (PYs) and associated 95% confidence intervals (CIs) were estimated from each study and pooled using the random-effects model. DATA SYNTHESIS: The 11 included studies had noncomparative single-cohort design. Follow-up duration ranged from 3 to 15 yr. There was a greater tendency for tumor growth in macroadenomas (12.5 per 100 PYs; 95% CI 7.9, 17.2) and in solid lesions (5.7 per 100 PYs; 95% CI 2.3, 9.2) in comparison with microadenomas (3.3 per 100 PYs; 95% CI 2.1, 4.5) and cystic lesions (0.05 per 100 PYs; 95% CI 0.0, 0.2). The development of pituitary apoplexy and worsening of visual field defects were rare. The overall incidence of new endocrine dysfunction was 2.4 per 100 PYs; 95% CI 0.0, 6.4. The majority of these analyses were associated with significant heterogeneity. There was a trend that did not reach statistical significance for greater incidence of pituitary apoplexy and new endocrine dysfunction worsening in macroadenomas compared with microadenomas. The quality of the evidence (risk of bias) was very low due to heterogeneity, methodological limitations, and imprecision caused by the small number of events. CONCLUSIONS: Despite the relatively high prevalence of PIs/NFPAs, the evidence on the natural history of these entities is scarce and of low quality. PIs/NFPAs seem to have fairly rare complications that may be more common when lesions are large (>10 mm) and solid.

Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.

CONTEXT: The risks of testosterone therapy in men remain poorly understood. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. STUDY SELECTION: Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. DATA SYNTHESIS: The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. CONCLUSIONS: The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.

Aspirin for the primary prevention of cardiovascular events: a systematic review and meta-analysis comparing patients with and without diabetes.

OBJECTIVE: The negative results of two randomized controlled trials (RCTs) have challenged current guideline recommendations for using aspirin for primary prevention of cardiovascular events among patients with diabetes. We therefore sought to determine if the effect of aspirin for primary prevention of cardiovascular events and mortality differs between patients with and without diabetes. RESEARCH DESIGN AND METHODS: We conducted a systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus since their inceptions until November 2008 for RCTs of aspirin for primary prevention of cardiovascular events. Blinded pairs of reviewers evaluated studies and extracted data. Random-effects meta-analysis and Bayesian logistic regression were used to estimate the ratios of relative risks (RRs) of outcomes of interest among patients with and without diabetes. A 95% CI that crosses 1.00 indicates that the effect of aspirin does not differ between patients with and without diabetes. RESULTS: Nine RCTs with moderate to high methodological quality contributed data to the analyses. The ratios of RRs comparing the benefit of aspirin among patients with diabetes compared with patients without diabetes for mortality, myocardial infarction, and ischemic stroke were 1.12 (95% CI 0.92-1.35), 1.19 (0.82-1.17), and 0.70 (0.25-1.97), respectively. CONCLUSIONS: Whereas estimates of benefit among patients with diabetes remain imprecise, our analysis suggests that the relative benefit of aspirin is similar in patients with and without diabetes.