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Updated: Jul 10, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Selective estrogen receptor modulators accelerate cutaneous wound healing in ovariectomized female mice
Matthew J Hardman1, Elaine Emmerson, Laura Campbell
1Faculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester, UK.
Abstract:
A lack of systemic hormones in elderly postmenopausal women leads to delayed cutaneous wound healing. This effect can be reversed by systemic or topical estrogen replacement in both humans and rodent models. Over recent years selective estrogen receptor modulators have been developed in an attempt to achieve the beneficial effects of estrogen clinically, while minimizing the detrimental side effects. The effects of selective estrogen receptor modulators on the skin are poorly understood, and the effects on wound healing have not been assessed. In this study we treated 10-wk-old ovariectomized mice with estradiol, tamoxifen (TAM), raloxifene (RAL), or vehicle and examined the effect on healing of full-thickness incisional wounds. Both TAM and RAL substantially accelerate healing, associated with a dampened inflammatory response and altered inflammatory cytokine profile. In vitro TAM and RAL demonstrate antiinflammatory activity comparable to estrogen. These results have significant implications for the clinical modulation of wound healing.
Insights
Selective estrogen receptor modulators like tamoxifen (TAM) and raloxifene (RAL) significantly accelerate skin wound healing in mice. These compounds reduce inflammation, offering potential therapeutic benefits for delayed healing in postmenopausal women.
Area of Science:
- Dermatology
- Endocrinology
- Pharmacology
Background:
- Postmenopausal hormonal changes, specifically estrogen deficiency, are linked to delayed cutaneous wound healing.
- Estrogen replacement therapy can improve wound healing, but carries potential side effects.
- Selective estrogen receptor modulators (SERMs) offer a targeted approach to estrogenic effects, but their impact on skin healing is largely unknown.
Purpose of the Study:
- To investigate the effects of SERMs, tamoxifen (TAM) and raloxifene (RAL), on cutaneous wound healing in a mouse model.
- To assess the anti-inflammatory properties of TAM and RAL in vitro and their impact on inflammatory cytokines during wound healing.
Main Methods:
- Ovariectomized mice were treated with estradiol, TAM, RAL, or vehicle.
- Full-thickness incisional wounds were created and their healing was examined.
- In vitro assays were used to evaluate the anti-inflammatory activity of TAM and RAL.
Main Results:
- Both TAM and RAL significantly accelerated the healing of incisional wounds compared to the vehicle control.
- TAM and RAL treatment led to a dampened inflammatory response and altered inflammatory cytokine profiles during healing.
- In vitro studies confirmed that TAM and RAL possess anti-inflammatory activity comparable to estrogen.
Conclusions:
- Selective estrogen receptor modulators (TAM and RAL) effectively promote skin wound healing in a preclinical model.
- The pro-healing effects of these SERMs are associated with reduced inflammation.
- These findings suggest a potential clinical application for SERMs in managing delayed wound healing, particularly in estrogen-deficient states.
