The Estrogen and Fat Storage Trifecta
The Estrogen and Fat Storage Trifecta
The vicious cycle of hormonal weight gain
Let’s break down exactly what is going on when I say that excessive estrogen is capable of causing excess fat storage.
What is Too Much Estrogen?
Estrogen is an incredibly important hormone for both men and women. While estrogen is classically associated with female reproductive health, it plays many other roles in the body. Some of these roles include bone density maintenance, cognitive health, weight regulation, and cardiovascular well-being.
However, estrogen levels can climb to excessive levels in certain individuals. This is when estrogen levels are too high, or other balancing hormones (mainly progesterone) are too low. This causes either an overt or relative estrogen dominance in the body. Because estrogen promotes growth, elevated levels can lead to abnormal tissue growth. The symptoms of this can range from weight gain to fibroids to even breast cancer in the most serious cases. For the sake of today’s Substack, I will be talking about how this influences weight gain.
COX-2 Activation
When estrogen levels soar high enough, our body will begin to make high quantities of an enzyme called cyclooxygenase-2 (COX-2). This enzyme converts the omega-3 and omega-6 fatty acids from our diet into eicosanoids. These are small molecules that can be either pro- or anti-inflammatory.
For the most part, when omega-3 is converted to eicosanoids by COX-2 the result is anti-inflammatory particles. When omega-6 is converted into eicosanoids by COX-2, the molecules are pro-inflammatory. Since the average American consumes 20x more omega-6 than omega-3, the effect of COX-2 creating eicosanoids is going to be largely pro-inflammatory.
Of note, omega-6 fatty acids are converted into eicosanoids such as prostaglandin-E2 (PGE2). PGE2 is highly inflammatory and causes all kinds of issues in the body. Though PGE2 is not inherently a negative molecule in the body (it is needed to maintain health), it contributes towards low grade inflammation when chronically elevated.
Fun fact: NSAIDs (e.g., aspirin, ibuprofen) inhibit the COX-2 enzyme, reducing inflammation by preventing the production of PGE2.
Androgen Production
With PGE2 levels sufficiently elevated, the next step in this cascade is androgen synthesis. Androgens are male sex hormones (think testosterone) and synthesis means that the cells in our body are making it from scratch. In this way, PGE2 is able to force the ovaries to produce more androgens. The specific androgen in this case is called androstenedione, which is very similar to testosterone.
Insulin Resistance
At the same time, high PGE2 levels wreak havoc on the body’s insulin system. Insulin is the hormone we use to keep blood sugar levels within range. PGE2 causes issues in the insulin receptor which makes it less sensitive to insulin. This phenomenon is known as insulin resistance, which is very common and detrimental to health.
Insulin functions like a key, unlocking the insulin receptor, which acts like a lock on the surface of our cells. When the two come together, the cell opens its doors to sugar which allows the sugar to leave the blood and enter the cell. The net result is a decrease in blood sugar levels.
When PGE2 causes problems with the insulin receptor, it makes the key (insulin) not fit very well into the lock. As a result, the cell doors don’t open and blood sugar levels cannot lower. The body enters a state of panic and produces much more insulin to force the cell doors open. The net result of insulin resistance is therefore high blood sugar, high insulin levels, and insulin receptors that don’t work very well.
Aromatization of Androgens
Another thing that happens when insulin levels are high is the aromatization of androgens. I know…. it’s a mouthful. Let me break it down.
When insulin levels are elevated, our bodies become prone to storing fat and become bad at breaking down fat. As a result, our fat cells become full and swollen (hypertrophy) and eventually we create new fat cells when we need new areas to store excess fat (hyperplasia). This is, of course, still in the context of a caloric surplus.
The complicating factor is that insulin up-regulates (increases) production of an enzyme called aromatase. This is an enzyme that largely occurs in fat cells. Aromatase converts androgens into estrogens. This means that all the androgens formed from PGE2 are now converted into more estrogen. That is, the molecule that caused PGE2 levels to rise in the first place. Uh oh…
Putting it Together
Let’s review. Excessive estrogen levels cause the creation of an inflammatory molecule called PGE2. PGE2 drives increases in both insulin and androgen production (male sex hormones). The insulin increases fat storage and an enzyme called aromatase. The aromatase converts the androgens into estrogen. This creates a self-perpetuating cycle of estrogen dominance, insulin resistance, and fat storage.
This is why I call it the estrogen and fat storage trifecta: PGE2, insulin, and aromatase. Below is the completed diagram.
Weight Gain
Elevated insulin resistance and estrogen dominance both contribute to increased fat storage, especially in the hips and thighs. Insulin resistance causes the body to produce more insulin, promoting fat storage and reducing fat breakdown. At the same time, high estrogen levels encourage fat deposition in the lower body, a natural but exaggerated process in estrogen dominance. Together, these hormonal imbalances create a cycle of fat accumulation, particularly in the hips and thighs, making weight loss more challenging.
Solving the Puzzle
Stopping this vicious cycle is difficult and almost always requires a skilled functional practitioner to find the root cause. This is my shameless plug. If this sounds like you, please don’t try to fix this on your own. Book a free discovery call using the button below.
The best way to unravel this puzzle is to block this cascade at each step. Let’s revisit this one step at a time.
Estrogen
Remember, this starts with the idea of estrogen dominance. We need to figure out why estrogen is high in relation to other hormones. I will have to write a completely separate post on this since it is such a complex topic.
COX-2
The COX-2 enzyme converts omega-6 into PGE2. There are certain nutraceuticals that can slow down this enzyme to buy some time. Below is my favorite.
Omega-6
Omega-6 is converted to PGE2 by the COX-2 enzyme. Omega-6 comes from our diet and is something we have control over. Most of us are consuming way too much omega-6. By decreasing intake of seed oils like soy, corn, and mayonnaise, we can work to lower the total omega-6 index in our cells.
Additionally, increasing omega-3 intake can help balance omega-6 levels. This means consuming foods like fatty fish (salmon, anchovies, mackerel, herring, sardines), flax, chia, and walnuts can help to balance omega-6 levels.
Insulin
Insulin resistance causes high insulin levels and high blood sugar levels. Insulin resistance can be managed by lowering intake of simple carbohydrates (bread, pasta, white rice, crackers, etc.). Blood sugar can be stabilized by increasing intake of fiber, protein, and healthy fats.
Insulin resistance can also be balanced through nutraceutical and pharmaceutical intervention. Below is one of my favorites.
Aromatase
Lastly, we can work to decrease the efficiency of aromatase and prevent the conversion of androgens into estrogen. Below is one of my favorite nutraceuticals for this.
Conclusion
Understanding the relationship between estrogen dominance, fat storage, and insulin resistance is key to addressing weight gain. By recognizing the cascade of events starting with elevated estrogen, it becomes possible to target each step—from controlling inflammation with dietary changes to managing insulin resistance and regulating aromatase activity. Working with a functional medicine practitioner can help you uncover the root causes of your symptoms and break the cycle.