Hormonal Modulation with Withania somnifera: Systematic Review and Meta-Analysis of Randomized-controlled Trials

Hormonal imbalances, particularly involving the hypothalamic-pituitary-adrenal and gonadal axes, contribute to chronic conditions such as stress-related disorders, infertility, and metabolic dysregulation. Ashwagandha (<i>Withania somnifera L</i>.) has been proposed as a potential oral modulator of endocrine function due to its adaptogenic properties. This review aims to systematically evaluate the effects of oral ashwagandha supplementation on circulating hormone levels in adults. Our literature search included MEDLINE, Embase, and ClinicalTrials.gov. The protocol was registered in PROSPERO (CRD42024611576). We included randomized, placebo-controlled trials in adults assessing oral ashwagandha versus placebo that reported changes in hormone levels. Two reviewers independently screened studies, extracted summary data, and assessed risk of bias using the Cochrane tool. Meta-analyses were conducted using a random-effects model to calculate mean differences (MD) or standardized mean differences (SMD), with heterogeneity and publication bias assessed using I² and Egger's test, respectively. Twenty-three trials were included, encompassing 1706 patients. Ashwagandha significantly reduced cortisol (SMD =- 1.18, p < 0.04) and increased serotonin (MD = 31.75 ng/ml, p < 0.01). Subgroup analyses suggested possible dose-response effects based on withanolide content. No effect was found on TSH or T3, but T4 levels increased modestly (MD = 0.61 µg/dL, p = 0.02). Ashwagandha increased testosterone in men (MD = 57.43 ng/dl) but not in women (MD = 5.09 ng/dl), with a significant gender difference. This treatment did not influence E2 levels in either gender. Ashwagandha supplementation appears to modulate key hormonal pathways, particularly cortisol and sex hormones. However, heterogeneity and limited data on some endpoints warrant further standardized trials.