The role of sex hormones in neurological and functional recovery following spinal cord injury in females: a systematic review of the literature

Abstract

Systematic review. To synthesize human and animal evidence on the potential neuroprotective effects of sex hormones in women with spinal cord injury (SCI) and in female animal models, with the aim of comparing findings across experimental and clinical studies and identifying gaps in clinical research. EMBASE, Medline, Cochrane CENTRAL, and Web of Science were searched from inception to August 22, 2025, without language restrictions. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. Of 2832 screened records, 26 studies were included (23 preclinical and 3 clinical). Human evidence was scarce and primarily addressed functional recovery after acute SCI, as well as cardiovascular risk factors and bone outcomes in small cohorts of pre- and postmenopausal women with chronic SCI. Preclinical studies consistently demonstrated broad neuroprotective effects of estradiol across multiple outcomes. Inhibition of estrogen synthesis with letrozole was associated with impaired motor recovery, while the presence of intact ovaries was linked to improved sensory outcomes, supporting a protective role of endogenous estrogens. Evidence for progesterone and dehydroepiandrosterone (DHEA) was mixed, although DHEA showed promising effects in two of three studies, including improved motor and sensory recovery and tissue preservation. This review highlights the therapeutic potential of sex hormones in SCI recovery while also revealing substantial gaps in human research. Future studies should investigate endogenous hormone profiles and hormone-based interventions during the acute and subacute phases of SCI to guide therapeutic development and bridge the gap between animal models and clinical practice.