Sex Hormones and Cellular Energy

How Estrogen, Progesterone, and Testosterone Influence Mitochondrial Function

Tracy Tranchitella, ND – Sunrise Functional Medicine

Most of us think of hormones as the messengers that control things like mood, metabolism, or reproduction—but their influence goes much deeper. Our sex hormones—estrogen, progesterone, and testosterone—don’t just regulate the body’s systems; they actually affect how every cell creates and manages energy.

That energy comes from mitochondria, the “powerhouses” inside each cell. They produce adenosine triphosphate (ATP), the molecule that fuels nearly everything your body does. But mitochondria don’t work in isolation. Their performance depends in large part on your hormonal balance—and, in turn, mitochondria provide the energy hormones need to do their jobs. It’s a fascinating partnership between hormones and energy at the most fundamental level of life.

Mitochondria: Your Body’s Energy Engines

Mitochondria make ATP through a process called cellular respiration—a series of steps that convert glucose into usable energy. It starts with glycolysis (the breakdown of sugar), continues through the Krebs cycle, and ends with oxidative phosphorylation, a process that yields about 30 ATP molecules for every molecule of glucose. This energy production drives everything from muscle contraction to memory formation. When mitochondria are running efficiently, you feel it—in your stamina, focus, and overall vitality.

The Hormonal Connection

Here’s where it gets interesting: the very first step in making steroid hormones happens inside the mitochondria. Cholesterol is converted into pregnenolone—the “parent” hormone that leads to estrogen, progesterone, and testosterone—right within the inner mitochondrial membrane. That means mitochondria aren’t just influenced by hormones; they’re essential for hormone production itself. In a sense, hormones and mitochondria support one another in a continuous feedback loop—each enhancing the other’s function.

Keeping Oxidative Stress in Check

When mitochondria generate energy, they also create reactive oxygen species (ROS)—tiny molecules that can cause oxidative damage if they build up. Normally, antioxidants help keep these in check, but hormones also play a protective role.

Research shows that both estrogen and progesterone help mitochondria work more efficiently, reducing oxidative stress and limiting cellular damage. In studies with animals, these hormones enhanced mitochondrial function and decreased lipid peroxidation (a marker of cell membrane damage). This may be one reason women often experience shifts in energy and brain clarity when hormone levels fluctuate—those hormones are part of the cell’s built-in antioxidant system.

Hormones and Energy Efficiency

Estrogen, progesterone, and testosterone each have distinct but complementary effects on mitochondrial performance.

• Estrogen improves mitochondrial efficiency by increasing the number of mitochondria in cells (a process called biogenesis) and enhancing energy output. Mitochondria actually contain estrogen receptors that regulate the expression of energy-related genes, helping to boost ATP production while reducing oxidative stress.
• Progesterone supports energy metabolism by strengthening the mitochondrial membrane and increasing ATP generation. It also helps protect cells from apoptosis (programmed cell death), playing a dual role in both energy production and cellular longevity.
• Testosterone enhances mitochondrial activity in tissues like muscle, liver, and brain. Through its interaction with androgen receptors, it stimulates genes involved in fat and glucose metabolism. Low testosterone levels, in both men and women, are linked with lower energy production and weaker mitochondrial structure.

Together, these hormones help your body produce, use, and protect its energy at the cellular level.

Building and Renewing Mitochondria

Your mitochondria aren’t static—they grow, divide, and renew themselves over time, a process known as mitochondrial biogenesis. Exercise, healthy eating, and calorie balance all support this renewal, but sex hormones play a crucial part too. Testosterone helps maintain the structure of mitochondria and the folds within them (called cristae) where energy is produced. When testosterone levels are low, these folds can deteriorate, leading to lower energy output. Estrogen, on the other hand, stimulates genes that promote mitochondrial replication, helping your cells stay youthful and resilient.

Clearing Out the Old: The Role of Mitophagy

Just as important as building new mitochondria is removing old or damaged ones. That cleanup process—known as mitophagy—keeps your cells healthy and efficient. Both estrogen and testosterone influence mitophagy in complex ways. Depending on the tissue, testosterone can either promote the creation of new mitochondria or help the body recycle older ones. Estrogen supports this process too; in studies of cartilage cells, it enhanced mitophagy and helped protect tissues from degeneration.

When mitophagy is disrupted, the result can be chronic conditions such as diabetes, fatty liver disease, and even neurodegenerative disorders.

Hormones, Mitochondria, and the Aging Brain

The brain is one of the most energy-hungry organs in the body—and also one of the most sensitive to mitochondrial decline. As we age, mitochondrial function naturally decreases, and that process accelerates with the loss of sex hormones.

This decline has been linked to neurodegenerative conditions like Alzheimer’s and Parkinson’s disease. Estrogen and progesterone, in particular, offer strong neuroprotective effects by improving mitochondrial respiration and reducing oxidative damage. When those hormones drop, the brain becomes more vulnerable to energy loss and inflammation.

In women, the abrupt decline in estrogen at menopause may help explain why Alzheimer’s affects women about twice as often as men. Men retain some neuroprotection because testosterone can convert to estrogen in the brain, continuing to support mitochondrial health. Interestingly, even when estrogen levels fall, the number of estrogen receptors inside mitochondria often remains steady. That’s one reason hormone therapy may help restore mitochondrial efficiency and protect brain function later in life.

Bringing It All Together

Healthy mitochondria are essential for vitality, resilience, and longevity—and hormones are key to keeping them that way. Estrogen, progesterone, and testosterone each play distinct roles in regulating how efficiently your cells produce and manage energy. When hormone levels decline with age, so does mitochondrial performance, affecting metabolism, brain health, and overall energy. Supporting balanced hormones—through lifestyle habits, nutrition, and, when appropriate, testing and targeted therapy—can help preserve mitochondrial strength and slow age-related decline.

Your hormones and your mitochondria depend on each other. By caring for both, you’re not just maintaining energy—you’re investing in long-term cellular health.

Testing hormone levels through saliva or blood spot analysis can offer valuable insights into how well your body’s energy systems are functioning. Working with a practitioner trained in functional medicine can help you find the right balance to support optimal mitochondrial function and vibrant health at every age.  Learn more and request a consultation >>