Background:The relationship between microgravity and parathyroid hormone (PTH), a keystone of bone mineral density, remains controversial. Bone loss is a prominent, ongoing issue in spaceflight, and PTH has been suggested as a treatment for microgravity-induced osteopenia, indicating the importance of this hormone. This systematic review and meta-analysis aimed to evaluate the association between exposure to microgravity and the production of PTH.Methods: PubMed, Embase, Scopus, and Google Scholar were searched for studies reporting PTH levels during and after exposure to microgravity. Non-peer-reviewed articles, studies lacking control groups, and articles published earlier than 2002 were excluded. Twelve articles from 2002 to present, with a total of 145 subjects, were identified and the standardized mean differences from baseline PTH levels were combined in a random effects model. Two-way analysis of variance (ANOVA) with Tukey honestly significant difference (HSD) testing on weighted mean differences was conducted to obtain 95% confidence intervals.Results: Compared to baseline measurements, significant changes in PTH levels are found during and after microgravity exposure. Inflight levels significantly decrease (P < 0.01), and post-flight levels show increases. Furthermore, there is evidence of an interaction between experimental condition (real or simulated microgravity) and time after removal from microgravity on PTH. Conclusions:The findings of this systematic review and meta-analysis suggest that microgravity affects parathyroid gland function during and after spaceflight, with decreases in function in-flight and an increase at 7 days post-flight. Experimental condition also appears to play a role in the recovery timeline of PTH.