Excess mortality in women with pituitary disease: results of a meta-analysis
Eigil Husted Nielsen, Jörgen Lindholm & Peter Laurberg
Background: Several studies of rather heterogeneous groups of patients have shown an increased mortality in patients with pituitary diseases. In patients without hypersecretion of growth hormone or ACTH the increased mortality has mostly been attributed to pituitary insufficiency. Some studies have suggested sex-specific differences in standard mortality rates (SMR) whereas others have shown increased cardiovascular and/or cerebrovascular mortality. A recent study of patients who had undergone surgery for non-functioning pituitary adenoma showed a normal SMR in men, whereas SMR was significantly increased in women. We explored this sex related difference by a meta-analysis.
Material and methods: We performed an internet-based meta-analysis using major medical science databases of MedLine, Embase and Web of Science to identify publications on mortality in patients with pituitary disease. Both Thesaurus-term and free-text searches were applied. Articles were required to provide exact information on standard mortality rates in both men and women separately, 95% confidence interval (CI) and a well-defined normal reference population. Studies including patients with Cushings disease or acromegaly were excluded as were studies with a majority of patients carrying a diagnosis of craniopharyngioma. Sex-specific overall SMR values for men and women in the meta-analysis were calculated as weighted averages of SMR from individual studies, using the inverse variance method. An additional analysis of association between first year of inclusion of new patients and SMR values in each study was also performed.
Results: Six studies fulfilled our criteria for inclusion in the meta-analysis. The weighted overall SMR for men was calculated to 2.06 (CI: 1.942.20), whereas weighted SMR for women was 2.80 (2.593.02). Mortality rates were thus significantly higher than in the reference population in both men and women, and SMR in women was significantly higher than in men. Analysis of association between first year of inclusion of new patients and SMR showed a statistically significant negative correlation in men reaching a normal value in the most recent study. In women SMR was always higher and did not normalize in recent studies.
Conclusion: Our meta-analysis showed that SMR is increased in both men and women with pituitary disease, with a significantly higher SMR in women than in men. SMR seems to be reaching normal levels in male patients treated in recent decades, whereas SMR is still clearly elevated in women. The reason for this is unknown, but most likely the high mortality in women reflects suboptimal diagnosis and/or suboptimal therapy of pituitary insufficiency.