Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care—A Post Hoc Analysis of the Randomized, Controlled Trial ‘Palliative-D’

SIMPLE SUMMARY: Previous studies have shown an association between low 25-hydroxyvitamin D levels and fatigue in cancer patients. In the recently published randomized, placebo-controlled, double-blind, multicenter trial ‘Palliative-D’, the correction of vitamin D deficiency reduced opioid use and fatigue in vitamin-D-deficient cancer patients admitted to palliative care. No subgroup analyses in women and men were made in the Palliative-D study. This post hoc analysis suggests that the positive effect of vitamin D supplementation on cancer-related fatigue may be more pronounced in men than in women. The vitamin-D-induced effect on fatigue could not be explained by reduced opioid doses among the vitamin-D-treated patients. Future studies focused on analyzing sex differences in the effect of vitamin D in palliative cancer care is needed before firm conclusions can be drawn. ABSTRACT: In the randomized, placebo-controlled, double-blind trial ‘Palliative-D’, vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; −1.50 ESAS points (95%CI −2.57 to −0.43; p = 0.007) but not in women; −0.75 (95%CI −1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (−0.33 (95%CI −0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.