Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response

The effects of intrinsic aging on the cutaneous wound healing process are p rofound, and the resulting acute and chronic wound morbidity imposes a subs tantial burden on health services. We have investigated the effects of topi cal estrogen on cutaneous wound healing in healthy elderly men and women, a nd related these effects to the inflammatory response and local elastase le vels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to eit her active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. Th e wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both m ales and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In a ddition, estrogen enhanced the strength of day 80 wounds. Estrogen treatmen t was associated with a decrease in wound elastase levels secondary to redu ced neutrophil numbers, and decreased fibronectin degradation. In vitro stu dies using isolated human neutrophils indicate that one mechanism underlyin g the altered inflammatory response involves both a direct inhibition of ne utrophil chemotaxis by estrogen and an altered expression of neutrophil adh esion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male a nd female subjects,