Key Takeaways

• Estrogen enhances insulin sensitivity and modulates glucose metabolism through complex receptor pathways
• Estrogen deficiency, as seen in menopause, increases the risk of insulin resistance, type 2 diabetes, and visceral fat accumulation.
• Hormone replacement therapy and lifestyle interventions (diet, exercise, sleep) can support hormonal and metabolic health.

 {{mid-cta}}

When you eat carbohydrates, your pancreas produces the hormone insulin. Insulin is a key that unlocks your body’s cells to let in glucose (carbs), which can be broken down to produce energy. When your body has optimal insulin sensitivity, it doesn’t take much insulin to unlock your cells. But when you are insulin resistant, not all of the keys work.

Without enough keys to unlock the cells, glucose builds up in the bloodstream, causing blood sugar to rise. Meanwhile, your body tries to compensate by producing more insulin, hoping some of the keys will work better. If not treated, this increased insulin secretion strains your pancreas and will eventually wear it out. This results in the development of type 2 diabetes and puts you at risk for metabolic syndrome and other chronic diseases.

Many factors influence insulin action, including the hormone estrogen. Because both men's and women’s bodies produce estrogen, it is important to understand its role in managing blood sugar and the risk of developing diabetes. This is especially true for women undergoing hormonal changes, such as those in perimenopause. Read on to learn about women’s health, estrogen, and its effects on insulin and glucose metabolism.

Understanding Estrogen and Its Functions

Estrogen is a sex hormone produced primarily by the ovaries but also by adipose tissue (fat tissue), adrenal glands, and the placenta during pregnancy. Hormones are messengers that regulate different processes in the body. For example, during puberty, estrogen levels in females rise, stimulating the growth of breasts and other mature sexual organs. During a woman’s reproductive years, estrogen (along with several different hormones, including progesterone, luteinizing hormone, and follicle-stimulating hormone) regulates the menstrual cycle, supporting ovulation and thickening the uterus to prepare it for pregnancy. And during menopause, estrogen levels decrease, halting ovulation. In men, estrogen impacts sex drive and the ability to get an erection.

There are three naturally occurring forms of estrogen:

1. Estrone (E1): This is the primary form of estrogen produced by the female body after menopause.
2. Estradiol (E2): This is the primary form of estrogen produced during reproductive years.
3. Estriol (E3): This is the primary form of estrogen produced during pregnancy.

Regardless of the form, the role of estrogen in the body goes beyond reproductive health. Here are several ways that estrogen impacts overall health:

• Skeletal health: Estrogen increases osteoblast (bone-building) activity, strengthening bones. The drop in estrogen in menopause in part explains why older women are at increased risk of osteoporosis and bone fractures.¹
• Cardiovascular health: Estrogen promotes the relaxation and dilation of blood vessels.² This can improve blood flow and reduce the risk of plaque buildup in the arteries and the development of cardiovascular disease. Estrogen also acts on the liver, improving lipid metabolism by reducing LDL (bad) cholesterol and increasing HDL (good) cholesterol production.³
• Metabolic health: Estrogen improves insulin sensitivity, lowering blood glucose and insulin levels and the risk of type 2 diabetes.⁴

Mechanisms Linking Estrogen to Insulin Sensitivity

How does estrogen affect insulin sensitivity? The link is complex but involves a pathway of events. ERα and ERβ are estrogen receptors found primarily in sex organs. Estrogen binds to and activates these receptors. The primary role of ERα is to mature the uterus and other sex organs, but it is also involved in producing insulin. ERβ has more complex roles related to suppressing tumors and promoting cardiovascular health. Similar to ERα, it also plays a role in insulin production. Research indicates that lower expression of these estrogen receptors is linked with insulin resistance and obesity.⁵

This link may be explained by considering the transcription factor FoxO1. Transcription factors act as on/off switches for genes. Turning a gene off impairs that gene from making its product, usually a protein. In the case of FoxO1, turning off specific genes can impact glucose metabolism and insulin sensitivity.⁶ FoxO1 can bind to GLUT4, a transporter that moves glucose into skeletal muscle and adipose tissue cells, lowering blood glucose levels.

When estrogen binds to and activates ERα, a series of downstream pathways are activated, which turn off FoxO1. Without FoxO1, glucose production in the liver is suppressed, resulting in improved blood glucose levels.⁷ When estrogen levels are low, such as in menopausal women, this pathway does not occur, resulting in metabolic dysfunction.

Impact of Estrogen Fluctuations on Metabolic Health

Changes in estrogen levels during life stages, such as menopause, can affect insulin sensitivity. During menopause, estrogen levels plummet, impairing insulin signaling and making it harder for cells to respond to insulin and absorb glucose efficiently (recall the key analogy). With less activation of the estrogen receptors ERα and ERβ, glucose production in the liver is increased, and insulin resistance is decreased.

While menopause itself may not cause diabetes, there is a growing body of research linking estrogen deficiency to a higher risk of insulin resistance and type 2 diabetes. Estrogen deficiency in mice has been linked to worsened insulin resistance.⁸ Furthermore, women who have had surgery to remove their ovaries have an increased risk of diabetes mellitus related to decreased estrogen production.⁹ Estrogen also affects fat distribution, with lower levels associated with more visceral fat.¹⁰ Visceral adiposity can increase the risk of heart disease, diabetes, metabolic syndrome, and certain cancers.

Note that more estrogen isn’t always better; high estrogen levels can cause many undesirable side effects, such as insomnia, weight gain, migraines, or high blood sugar. While estrogen decline increases metabolic risk, not every woman is affected equally. Genetics, body composition, lifestyle, and other risk factors play a role.

Therapeutic Implications and Hormone Replacement Therapy

Hormone replacement therapy (HRT) involves taking hormones to replace those that the body no longer produces. There are two primary forms of HRT: estrogen replacement therapy and combination HRT, which includes both estrogen and progesterone. HRT is most commonly used during menopause when the female body produces less estrogen and progesterone. HRT is often used to treat symptoms of menopause, such as hot flashes, night sweats, and mood swings.

Beyond symptom management, another benefit of HRT may be improved metabolic health. A meta-analysis pooling the results of 107 clinical trials found that HRT reduces abdominal obesity and insulin resistance in women with and without diabetes.¹¹ Similar results were found in a randomized, double-blind, placebo-controlled trial of nearly 3000 postmenopausal women with coronary heart disease. Women in the study who took combination HRT were 35% less likely to develop diabetes throughout the 4-year trial compared with the women who did not take HRT.¹²

But HRT does not come without its risks. HRT in menopause has been associated with poor vascular health outcomes, including deep vein thrombosis, pulmonary embolism, and stroke.¹³ Breast cancer risk is also increased by HRT use, especially with long-term use (5 years or longer) of combination HRT.¹⁴

In a 2017 position paper on hormone therapy, the North American Menopause Society stated that the benefits of HRT outweigh the risks for women younger than 60 or within 10 years of menopause with no contraindications or risk factors (including a history of breast cancer).¹⁵ They recommend that women who need to take HRT for an extended period to manage symptoms should use estrogen only rather than combination HRT.

If you are unsure if HRT is right for you, it is best to talk with a healthcare provider to weigh the risks and benefits and discuss other options.

Lifestyle Interventions to Support Hormonal and Metabolic Health

HRT is not the only way to support hormonal and metabolic health. A holistic approach to metabolic health incorporates diet, exercise, and other lifestyle factors to maintain estrogen levels and improve insulin sensitivity.

Choose a diet that is rich in fiber, vitamins, minerals, and lean protein, like the Mediterranean Diet or a plant-based diet. These diets are associated with lower blood sugar levels, improved insulin sensitivity, and lower blood pressure¹⁶, among other health benefits.

Diets high in cruciferous vegetables, like broccoli or cabbage, soy products, and nuts, may help manage menopause symptoms. These foods are high in phytoestrogens, plant compounds that mimic the effects of estrogen. In addition to reducing hot flashes, phytoestrogens can improve cardiovascular and metabolic health markers.^17,18

Other strategies to improve insulin sensitivity include managing energy balance and stress, regular physical activity (aim for 150 minutes of moderate-to-vigorous activity per week), and quality sleep (at least 7-9 hours per night). These strategies can reduce your risk of other chronic conditions and may even help you lose weight.

The Bottom Line

Estrogen is crucial in maintaining insulin sensitivity and overall metabolic health, particularly during life stages like menopause when hormone levels shift. While hormone replacement therapy may offer benefits for some, lifestyle interventions like balanced nutrition, regular exercise, and stress management are essential tools for supporting hormone balance and preventing chronic disease. If you are experiencing changes in blood sugar or hormone-related symptoms, talk to your healthcare provider to explore a holistic approach that’s right for you.

Learn More With Signos’ Expert Advice

Blood sugar health seriously affects how you feel and how well your body functions. That’s why it’s so important to understand how different things affect your blood sugar levels. 

Signos CGM empowers you to improve your health by tracking your diet, exercise, sleep habits, and blood sugar. Knowledge is power, and a CGM can give you specific information about how your habits affect your health. 

Signos has a team of health experts who compile evidence-based nutrition information to help you improve your health and wellness. Check out the resources here.

Take a quick quiz to determine if Signos is a good fit for you.