Pregnenolone: The Overlooked Hormone That Keeps Women Sharp, Calm, and Energized

If you’ve been into the clinic recently, you’ve probably heard me mention a new hormone (new to most people, anyway!) called pregnenolone.

While I remember learning about it in endocrinology lectures back in medical school, it was mostly presented as the first step in the adrenal cascade—the molecule that eventually becomes DHEA, cortisol, adrenal estrogen, progesterone, and testosterone.

But during my recent personalized functional medicine training, I learned that pregnenolone is so much more than just a precursor. It deserves attention in its own right—and for many women, it’s a key piece of the puzzle when it comes to energy, focus, and mood.

What Is Pregnenolone?

Pregnenolone is made primarily in the adrenal glands and brain from cholesterol. It’s often called the “mother hormone” because it’s the building block for nearly every other hormone your body produces.

It’s important to note that we need cholesterol to make pregnenolone—and the rest of the adrenal hormone cascade. Cholesterol isn’t the villain it’s often made out to be; it’s actually the starting material your body relies on to make DHEA, progesterone, estrogen, testosterone, and cortisol.

If cholesterol levels are too low (below about 140 mg/dL), your body may struggle to make enough pregnenolone to keep everything else in balance.

Pregnenolone naturally declines with age, stress, and illness, which means women entering midlife—especially those under ongoing stress—are more likely to experience its effects.

The “Memory Hormone”

Dr. Pam Smith, who teaches personalized and functional medicine to physicians nationwide, refers to pregnenolone as “the memory hormone.”

Throughout her course, I found myself thinking so often of my loved ones who have struggled with cognitive decline and dementia—and wishing this information were more widely appreciated in medicine.

What’s even more striking is that when I test pregnenolone in younger, generally healthy women who come into my clinic, it’s often immeasurably low. These are women in their 30s, 40s, and 50s—juggling careers, families, and stress—who are surprised to learn that their “memory hormone” is running on empty.

It’s a powerful reminder that brain fog, forgetfulness, or mental fatigue in midlife isn’t “just getting older.” Sometimes it’s your brain asking for the support it needs.

Why It Matters for Women

Pregnenolone plays a major role in how women feel and function. It helps regulate brain chemistry, repair nerves, and calm the nervous system.

Healthy levels support:

• Sharper memory and mental clarity

• Better mood and stress tolerance

• Deeper, more restorative sleep

• Steadier energy

• Less inflammation and joint discomfort

• 
  

Pregnenolone even acts directly in the brain as a neurosteroid, helping neurons communicate and protecting against the cognitive changes that can appear during midlife and menopause.

Signs Pregnenolone Might Be Low

Low levels can develop from chronic stress, low cholesterol, or simple aging.Women often describe:

• Fatigue or “running on empty”

• Brain fog and forgetfulness

• Mood swings or irritability

• Trouble sleeping

• Joint aches or stiffness

• Feeling easily overwhelmed

  
  

Sound familiar? Many of these overlap with perimenopause or adrenal fatigue, which is why checking pregnenolone can be so helpful in understanding what’s really going on.

The Adrenal Connection

Your adrenals make pregnenolone, DHEA, and cortisol. When stress is high, your body prioritizes cortisol production, sometimes diverting pregnenolone away from sex hormone pathways—a phenomenon known as the “pregnenolone steal.”

This can lead to lower DHEA, progesterone, and estrogen levels, contributing to fatigue, poor sleep, and mood changes. Supporting adrenal health through balanced nutrition, rest, and stress management helps protect your hormone supply at its source.

Pregnenolone’s Broader Benefits

Beyond hormone balance, pregnenolone has been shown to:

• Improve memory and learning

• Promote nerve repair and brain resilience

• Reduce inflammation and autoimmune activation

• Support mood stability and calmness

• Contribute to joint and tissue repair

  
  

It has even been studied in conditions such as arthritis, multiple sclerosis, lupus, and chronic pain syndromes—showing its far-reaching influence beyond traditional hormone health.

How to Support Pregnenolone Naturally

Even without supplementation, there’s a lot you can do to encourage your body’s natural production:

• Maintain healthy cholesterol: your hormone foundation.

• Manage stress: through mindfulness, breathwork, or exercise.

• Prioritize quality sleep: the adrenals recover while you rest.

• Fuel with nutrients: especially vitamins B5, B6, C, and magnesium.

• Move regularly: gentle strength training or walking supports hormone sensitivity.

Rethinking Brain and Hormone Health

Memory and cognitive function are not just about needing more estrogen. We need to consider the entire picture—stress, sleep, lifestyle, and all the hormones that keep our brains and bodies balanced.

This was truly a practice-changing concept for me. I’m so excited to have more avenues to explore with my patients who come to me simply wanting to feel like themselves again.

Pregnenolone is one important piece of that puzzle—worth checking, and worth replacing when it’s low.

Dr. Waymire's Takeaway

At Dragonfly Menopause Care, I help women understand the “why” behind how they’re feeling. Optimizing hormones like pregnenolone is just one way to help you regain clarity, calm, and confidence—because your best years start now.