17β-estradiol modifies diabetic wound healing by decreasing matrix metalloproteinase activity 

Postmenopausal women are more susceptible to poor wound healing. This phenomenon can be reversed by estrogen replacement therapy in non-diabetic individuals. Postmenopausal women with type 2 diabetes are more susceptible to wound healing complications, potentially secondary to an estrogen deficiency. Few studies have examined the mechanism of action and effects of estrogens on diabetic wound healing in females. It appears that multiple factors influence delayed wound healing among individuals with diabetes including: an imbalance in cytokines, growth factors, extracellular matrix (ECM) turnover, and oxidant stress (OS). Estrogens have been shown to regulate the expression of genes important for extracellular matrix turnover, including collagen and matrix metalloproteinases (MMP).

For this reason, the effects of 17β-estradiol (E2) on MMP-2, MMP-13, and MMP-14 and estrogen receptor alpha and beta (ER-α and -β) expression in the wound tissue of estrogen-deficient female mice with established type 2 diabetes mellitus (C57BL/6J-m Leprdb/2+) were studied.

Topical E2 upregulates ERα in wound tissue thereby improving and accelerating diabetic wound healing in estrogen deficient mice.

The mechanism appears to decrease MMP-2, MMP-13, and MMP-14 mediated tissue matrix destruction and increasing collagen content. .