Estrogen: A Promising New Role in Treating Chronic Diabetic Foot

Highlights:

Complications of diabetes include chronic non-healing wounds and ulcers commonly referred to as a diabetic foot
Apart from conventional treatment options that include blood glucose control using insulin and oral hypoglycemic medications, estrogen therapy offers a promising new role in the treatment of diabetic foot
Estrogen therapy helps in faster wound healing recovery and serves a promising role

India is the new diabetes capital of the world, with a prevalence of diabetes and prediabetes of 101 million and 136 million, respectively, as per the Indian Council of Medical Research – India Diabetes study published in the Lancet Journal. It highlights the enormous burden faced by India which is much higher than earlier reported figures ().

Of the various chronic complications, long standing uncontrolled diabetes can result in diabetic foot ulcer (DFU). With an annual incidence of 2.4–2.6%, prevalence of 4–10% and a significant rate of recurrence of more than 50% after three years, DFU and its complications constitute an alarming public health problem. Diabetic foot is also leading cause of hospitalization, amputation (removal of the leg from the body) and death in diabetic patients ().

Causes and Pre-Existing Treatments of Diabetic Foot

Diabetes and persistent high body glucose affects the immunity along with damage to the nerves and blood vessels of the body. This translates as neuropathies (damage to nerves) and peripheral arterial disease (damage to blood vessels) which along with co-existing infection lead to Diabetic foot. Current therapies and management strategies aim at prevention and treatment of these processes.

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‘Chronic non-healing diabetic wounds are a major health and economic burden worldwide. Recently, female sex hormones like estrogen have been found to be beneficial in promoting wound healing in people with diabetes. #Diabetes’

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Management of DFU includes a focus on Diabetes control as well as on wound care. Apart from oral hypoglycemic drugs (medicines to reduce blood glucose), medical treatment includes anticoagulant therapy (blood thinners), neuro-protective drugs and antibiotic therapy. Other surgical techniques include wound debridement, Re-vascularization surgeries and use of skin substitutes for dressings.

Estrogen and its Role in Diabetic Wound Healing

Estrogen is a steroid hormone associated with the female reproductive organs and is responsible for the development of the female sexual characteristics. Evidenced clinical and preclinical data suggests that estrogen seems to play an important potential protective role in improving and modulating glucose balance in the body ().

Research suggests that elderly males have a higher incidence of chronic non-healing wounds, correlating with reduced levels of estrogen in the body. Additionally, topical estrogen has been shown to be beneficial in accelerating cutaneous wound healing in both genders alike ().

Various studies on animal models have proved that topical estrogen application to the chronic diabetic wound reduced the wound area, promoted new skin growth (re-epithelialization)and also lead to development of new blood supply to the affected skin (angiogenesis) thus helping in healing. This takes place due to various hormonal signaling at the cellular level which helps in new tissue growth. The exact mechanism however still remains unclear and warrants further research and evidence in humans as well ().

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Just like any other medication, estrogen replacement also has its set of risks and benefits. When given long term for chronic disease prevention, it can lead to deleterious effects on the breast and uterus. Estrogen therapy also predisposes to an increased risk of heart attack, stroke and deep vein thrombosis. These are critical future directions that will lay the foundation for improved therapies for estrogen use and diabetes ().

In conclusion, estrogen therapy seems promising for wound care management among patients with diabetes. However, these specific actions as well as the underlying mechanisms need more studies to be approved as primary treatment options for diabetic foot.

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References:

Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17) - (https://www.thelancet.com/journals/landia/article/PIIS2213-8587(23)00119-5/fulltext)
Current Therapeutic Strategies in Diabetic Foot Ulcers - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915664/)
The Role of Estrogen in Insulin Resistance - (https://ajp.amjpathol.org/article/S0002-9440(21)00245-5/fulltext)
The effect of estrogen on diabetic wound healing is mediated through increasing the function of various bone marrow-derived progenitor cells - (https://pubmed.ncbi.nlm.nih.gov/30064832/)
Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes - (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264572)
Estrogen - (https://www.ncbi.nlm.nih.gov/books/NBK538260/)

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