17‐beta estradiol and prednisolone as potential stimulators of hair re‐growth in chemotherapy‐induced human hair follicle damage via ‘dystrophic catagen’ promotion?

Abstract

Chemotherapy‐induced hair follicle (HF) damage and alopecia are common side‐effects of cancer therapy and constitute a major burden of disease in clinical oncology. Although several potential treatment strategies have shown promising effects in animal models, e.g. on cyclophosphamide‐induced alopecia (CIA) in C57BL/6 mice, these strategies remain to be transferred to human therapy. 17‐beta estradiol (E2) and glucocorticoids are potent modulators of murine CIA in vivo: topical treatment accelerates the regrowth of normally pigmented hair shafts by shifting HFs into the ‘dystrophic catagen’ pathway, which is associated with greater initial alopecia, but much faster HF recovery. In the current study, we asked whether E2 and/or prednisolon display similar activities in the human system, using our recently established human HF dystrophy in vitro‐model (Bodó et al., Am J Pathol 2007: 171(14):1153–67). E2 and/or prednisolon were pre‐ and co‐administered with a key cyclophosphamide metabolite (4‐HC). Indeed, E2 shifted 4‐HC‐treated human HFs into the dystrophic catagen pathway in vitro, and potentiated the 4‐HC‐induced pigmentary disturbances. 4‐HC‐induced hair growth inhibition was further enhanced by E2, associated with an additional reduction of proliferation and increased apoptosis of matrix keratinocytes. These effects tended to be further enhanced by co‐administration of prednisolon to the HF organ culture medium. These observations suggest that, just as in murine CIA in vivo, E2 and glucocorticoids can force chemotherapy‐damaged human HFs into the dystrophic catagen pathway. The preclinical data provide first indications that a combination of E2 with prednisolone may indeed serve as an effective clinical tool for accelerating hair re‐growth in human CIA.