Topical Estrogen Accelerates Cutaneous Wound Healing in Aged Humans Associated with an Altered Inflammatory Response

Abstract

The effects of intrinsic aging on the cutaneous wound healing process are profound , and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women , and related these effects to the inflammatory response and local elastase levels , 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 either 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. The 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 males 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 addition , estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers , and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects. (Am J Pathol 1999, 155:1137-1146) Acute and chronic wound healing morbidity in the elderly imposes a substantial burden on health services.1 Healing of an acute wound involves a reduction in wound size secondary to contraction and re-epithelialization and is accompanied by an increase in collagen deposition.

Encouraging results in the treatment of haemorrhagic cystitis with estrogen – report of 10 cases and review of the literature

“…27 Some authors reported that estradiol enhances the healing of tissue damaged by trauma. 28,29 It is known that estradiol promotes endothelial cell activities. 30,31 In our group, the duration of estrogen administration varied from 5 days to 16 weeks with a median duration of 5.5 weeks.…”

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

“…46 In addition, oestrogenic effects on thermal injury have been well studied, for example, in the brain, where reduced inflammation and apoptosis are linked to lower levels of DAMPs. 68,69 Although oestrogen has been shown to promote acute wound healing in humans, 45 no data exist for its effect on infected cutaneous wounds. Here we show that oestrogen exerts beneficial effects on both epidermal and dermal aspects of cutaneous healing in a local LPS bacterial infection model.…”

“…Previous studies have shown a physiologically relevant role for oestrogen deficiency in delayed wound healing 44 and demonstrated beneficial effects of oestrogen supplementation in both mice and humans. [45][46][47] To our knowledge, the effects of oestrogen on bacterial infection of cutaneous wounds has yet to be studied. We thus assessed the effect of oestrogen treatment in our simple bacterial TLR4-stimulated wound model, showing for the first time that LPS-induced delayed healing can be reversed by the anti-inflammatory, pro-healing effects of oestrogen.…”

Sex differences and estrogen modulation of the cellular immune response after injury

“…Ashcroft et al [72] reported on dermal wound healing in aged males and females. Subjects had two upper inner arm punch biopsies and received either estrogen treatment or placebo for 24 hours.…”