The Role of Sex Hormones in Degenerative Disc Disease

STUDY DESIGN: Narrative review. OBJECTIVES: The purpose of this review is to outline the role of sex hormones, particularly estrogen, in the pathogenesis of degenerative disc disease (DDD). METHODS: A narrative review of studies discussing sex hormones and intervertebral disc (IVD) degeneration was conducted through a search of bibliographic databases to identify various mechanisms involved in effectuating DDD. RESULTS: Estrogen-deficient states negatively impact various aspects of IVD function. These internal hormone environments reflect routine changes that commonly arise with physiologic aging and can compromise IVD structural integrity through a host of processes. Additionally, allosteric molecules such as micro-RNAs (mi-RNAs) and G protein-coupled estrogen receptors (GPER) antagonists can bind to estrogen receptors and inhibit protective downstream effects with estrogen receptor signaling. Furthermore, cursory studies have observed chondrogenic effects with testosterone supplementation, although the specific mechanism remains unclear. CONCLUSIONS: Regulation of sex hormones, namely estrogen and testosterone, significantly impacts the structural integrity and function of IVDs. Uncovering underlying interactions driving these regulatory processes can facilitate development of novel, clinical therapies to treat DDD.