Osteoporotic fractures in patients with untreated hyperprolactinemia vs. those taking dopamine agonists: A systematic review and meta-analysis.

OBJECTIVE Hyperprolactinemia is associated with bone fragility. Traditionally attributed to prolactin-induced hypogonadism, recent studies have identified increased fracture rates independent of gonadal function. METHODS We performed a systematic review to identify studies assessing fracture risk in patients with untreated hyperprolactinemia compared to those on dopamine agonists. MEDLINE, EMBASE, Cochrane, Web of Science and BIOSIS Previews databases were searched from inception to December 2013 for studies of hyperprolactinemia with fractures as an outcome. Two authors independently performed title and abstract searches, full-text searches, data abstraction, and quality assessment. A summary odds ratio (OR) was calculated using a random effects model. RESULTS Of the 197 articles identified, 2 met inclusion criteria. Both cross-sectional studies examined cabergoline use (or non-use) in patients with prolactin-secreting adenomas, with vertebral fractures as the primary outcome. For women, vertebral fractures were identified in 46% of untreated patients, vs. 20% of patients on cabergoline (OR: 0.29, 95% CI: 0.10-0.78). For men, the results were 67% in untreated, vs. 26% in cabergoline treated patients (OR: 0.18, CI: 0.03-0.94), with no difference between gonadal and hypogonadal men (p=0.8). Combining studies gave a summary odds ratio of 0.25 (CI: 0.11-0.59), I2=0%. CONCLUSIONS In the limited studies available, fracture prevalence was increased in patients with untreated hyperprolactinemia compared to those on treatment, independent of gonadal function. Further studies are needed to clarify if post-menopausal women, or high-risk men, with no other indication for treatment, should be on dopamine agonists to decrease fracture risk.