How Bioidentical HRT Impacts Diabetes Risk

Diabetes mellitus is a pertinent concern as it may advance into renal failure and cardiovascular disease, the leading cause of death among women. Moreover, this issue affects millions of females all over the world, with more than 50 million women expected to be postmenopausal by 20201,2.

Evidence for the Association between Hormones and Diabetes

Support for the Use of HRT

A growing number of research points to the fact that hormone replacement therapy, or HRT, may reduce the risk of type 2 diabetes following menopause.

These findings may give insight to the astounding discovery from a large prospective cohort study that women who are current users of HRT have a 62% lower incidence of type 2 diabetes than those who do not currently use HRT7.

Cardiovascular disease and uncontrolled diabetes

The rising concern of cardiovascular disease in women and its connection to uncontrolled diabetes prompted the publication of HERS (Heart and Estrogen/progestin Replacement Study), a large, randomized, double-blind, placebo-controlled trial.

Role of Estradiol in the Regulation of Glucose Metabolism

Researchers believe that menopause increases the risk of developing type 2 diabetes largely because of the role estradiol plays in the regulation of glucose metabolism in the body.

Estradiol greatly impacts the maintenance of glucose homeostasis throughout multiple organ systems in the body. It does this by mediating effects on the body via three different receptors: G protein-coupled E2 receptor1, E2-alpha receptors and E2-beta receptors. The number of estradiol receptors across different tissues, as well as their distribution, will impact the function of the hormone. Activities of estradiol also depend on its bioavailability, which is directly related to levels of sex hormone binding globulin, or SHBG6.

Estradiol impacts the action of insulin both directly and indirectly. Direct impacts are related to estradiol’s actions on insulin-sensitive tissues, while indirect impacts are related to estradiol’s regulation of oxidative stress and other factors that contribute to insulin resistance6.>

The E2-alpha is the most important of the three estrogen receptors for insulin-glucose homeostasis. Studies show that a deficiency of E2-alpha is associated with high insulin levels, impaired glucose metabolism and increased insulin resistance12.

Estradiol also has a pronounced effect on overall metabolism and fat accumulation, both of which are associated with the development of type 2 diabetes. Effects of estradiol on metabolism are controlled by the hypothalamus, with estradiol playing a role in the regulation of appetite13. Throughout the earlier stages of life, women accumulate mostly subcutaneous fat, which is fat deposited just under the skin. However, after menopause, accumulation of visceral fat increases. Visceral fat, which is fat surrounding the internal organs, is more dangerous and increases the risk of serious complications like metabolic syndrome and cardiovascular disease. This occurs because estradiol influences the balance of lipid storage between visceral and subcutaneous regions6.

Estradiol and other menopausal symptoms

Furthermore, fluctuations in estradiol may be to blame for other symptoms women experience during menopause, including fatigue, muscle weakness, reduced stamina and propensity to gain weight. All of these symptoms may be attributed to dysfunction of mitochondria, the powerhouse for ATP or energy production. As estradiol plays an important regulatory role in mitochondrial function, it stands to reason that disturbances in estradiol levels could contribute to these issues5.

According to clinical studies published by Wang et al. and Duckles, et al., estradiol is believed to influence mitochondrial biogenesis, generation membrane potential, the production of ATP and the regulation of calcium14,15. In addition, O’Lone et al. and Chen et al. report that estradiol is defending against oxidative stress16,17.

Benefits of Bioidentical HRT

Estrogen HRT may be produced in a number of ways, such as by using non-human sources. However, bioidentical HRT may be more beneficial than other forms of HRT for patients who want to decrease their risk of type 2 diabetes. The added benefits of bioidentical estrogen HRT are related to its composition, which is identical to that of the estrogen produced in the human body.

Research has shown the effects of estrogen therapy to be dose-dependent. Thus, compounding pharmacies that produce HRT unique for each woman based on her history and comorbidities may be the best option for postmenopausal patients.