Sex Hormones and Wound Healing

Desiree May Oh, MD, and Tania J. Phillips, MD

In recent years, the increasing size of the geriatric population and the consequently bigger burden of nonhealing or difficult-to-heal wounds associated with this age group has heightened interest in finding novel treatment modalities for wound healing. Sex hormones play a key role in numerous physiologic processes and functions and could potentially impact wound healing in the elderly.1


Estrogens are steroidal hormones predominantly responsible for secondary sexual characteristics in women. They are mainly produced by the ovaries and exist in several forms within the body: estradiol, estrone, and estriol. Estradiol is the most potent and predominant of these hormones.2
The production of estrogen is controlled by the hypothalamic-pituitary axis and is related to female reproductive age. During puberty, estrogen levels rise steadily until maturity is achieved. During the reproductive years, estrogen levels follow a pattern determined by the menstrual cycle. With menopause, there is a decline in estrogen production and an increase in estrone levels, a less potent estrogen.
In the skin, estrogen exerts its actions via receptors ER-α and ER-β.3 Cutaneous symptoms associated with aging and menopause include dryness, atrophy, wrinkling, laxity, and poor wound healing. Lack of estrogen may play a role in some of these changes. In clinical studies, exogenous estrogen supplementation with hormone replacement therapy has resulted in increased skin hydration,4 thickening of the epidermis, altered lipid composition of the stratum corneum, and improved barrier function.5 In the dermis, estrogen functions in both prevention and treatment of collagen loss depending on the stage of menopause and the baseline skin collagen content at initiation of treatment.6,7 Estrogen reduces collagen loss in women with higher initial collagen levels (early menopause) and stimulates collagen synthesis in women with lower initial collagen levels (late menopause). Topical application of estrogen has been reported to improve the appearance of postmenopausal facial skin.8 In some studies, systemic treatment limited the age-related increase in skin extensibility9 and enhanced elasticity by increasing the concentration and size of elastic fibers10 and improving their morphology.11
Various animal and human studies have been conducted in vitro and in vivo in an attempt to characterize the effects of estrogen on wound repair as well as to elucidate the biomolecular mechanisms behind these actions.


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