GnRH analog is ineffective in increasing adult height in girls with puberty onset after 7 years of age: a systematic review and meta-analysis.

Objective We assessed the effectiveness of puberty blockade with a gonadotropin-releasing hormone (GnRH) analog in increasing adult height (AH) in girls with puberty onset between 7 and 10 years of age. Methods We performed a systematic review and included controlled studies in which girls with early puberty (EP) were assigned to the GnRH analog or no treatment groups. The primary outcome analyzed was AH. Search strategies were applied to the MEDLINE, EMBASE, LILACS and CENTRAL databases. Results We identified 1514 references, and six studies fulfilled our eligibility criteria. Two studies were randomized and four were not randomized. At the baseline of each trial, height, chronological age, bone age, predicted AH (PAH) and target height (TH) were equal between the groups. All studies used intramuscular triptorelin every 28 days in the intervention groups. The mean duration of the therapy was 2 years. Meta-analysis of AH among the six studies (comprising 332 girls) showed no significant difference between the groups (mean difference = 0.50 cm, 95% confidence interval = -0.72 to 1.73 cm, I 2 = 0%). In a sub-group analysis based on PAH (<155 cm and 155 cm and equal to TH), there was no difference in average AH between the groups. The quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation approach was low. Conclusion We found no evidence from controlled experimental and observational studies that compared with no treatment, the use of GnRH analogs improved AH in girls with EP.

Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis.

OBJECTIVE: To compare the acromegaly mortality rates with those expected for the general population from studies published before and after 2008. METHODS: We performed a systematic review and included observational studies in which the number of deaths observed in acromegaly was compared with the expected mortality for the general population mortality observed/expected (O/E). The following electronic databases were used as our data sources: EMBASE, MEDLINE and LILACS. From the observed and expected deaths, we recalculated all standardized mortality ratios (SMR) and their respective confidence intervals (95% CI), which were plotted in a meta-analysis using the software RevMan 5.3. RESULTS: We identified 2303 references, and 26 studies fulfilled our eligibility criteria. From the 17 studies published before 2008, the mortality in acromegaly was increased, while from the nine studies published after 2008, the mortality was not different from the general population (SMR: 1.35, CI: 0.99-1.85). In six studies where somatostatin analogs (SAs) were used as adjuvant treatment, acromegaly mortality was not increased (SMR: 0.98, CI: 0.83-1.15), whereas in series including only patients treated with surgery and/or radiotherapy, mortality was significantly higher (SMR: 2.11; CI: 1.54-2.91). In studies published before and after 2008, the mortality was not increased in patients who achieved biochemical control, while it was higher in those with active disease. Cancer has become a leader cause of deaths in acromegaly patients in the last decade, period in which life expectancy improved. CONCLUSION: Mortality in acromegaly is normalized with biochemical control and decreased in the last decade with the more frequent use of SAs as adjuvant therapy. Increased life expectancy has been associated with more deaths due to cancer.