Gender differences in the clinical response to balneotherapy in osteoarthritis patients: a scoping review.

Balneotherapy (BT) is widely used as a non-pharmacological intervention for osteoarthritis (OA); however, potential sex differences in treatment response remain poorly understood. This scoping review mapped randomized controlled trials (RCTs) of BT in OA to describe (i) how participants' sex was reported, (ii) whether sex-stratified or sex-by-treatment interaction analyses were performed and (iii) the sex-related findings of such analyses. Twenty-two publications, derived from 21 distinct RCTs, were included. Sex distribution was reported for 20 trials, including 2,211 participants (594 males and 1,617 females; 73.1% female). The greatest imbalance was observed in knee OA trials (497 males vs. 1,216 females). Overall, BT was associated with reduced pain, improved physical function and enhanced quality of life in predominantly female samples. However, only one trial formally tested sex as an effect modifier, reporting significant treatment × sex interactions for pain, stiffness, physical function and quality of life, and one further trial enrolled women only. No other trial, including those with a relatively balanced sex distribution, reported outcomes separately for women and men. Therefore, the available evidence is insufficient to establish whether sex modifies the clinical response to BT. Sex-related differences in thermoregulation, nociceptive processing and immune modulation provide a biologically plausible, but as yet untested, rationale for such effect modification. Future BT trials should report outcomes separately for women and men and include pre-specified, adequately powered sex-by-treatment interaction analyses.