Pregnenolone
Synopsis of pregnenolone
Pregnenolone is a naturally occurring steroid hormone synthesized primarily from cholesterol in the mitochondria of adrenal glands, liver, brain, and gonads. It serves as a precursor, or "mother hormone," in the steroidogenesis pathway, giving rise to a variety of essential hormones including progesterone, cortisol, aldosterone, estrogen, testosterone, and DHEA (dehydroepiandrosterone).
As a supplement, pregnenolone is used in integrative and anti-aging medicine for its role in cognitive enhancement, hormonal balance, adrenal support, and mood regulation. It has been studied for its effects on memory, mental clarity, and stress resilience, particularly in cases of age-related cognitive decline or chronic fatigue. In the brain, pregnenolone functions as a neurosteroid, modulating GABA and NMDA receptors, thereby influencing mood, anxiety, and neuroplasticity.
Pregnenolone levels decline with age and can also be suppressed by chronic stress, illness, or corticosteroid use. Supplementation is sometimes used to support hormonal health, mental performance, and recovery from adrenal exhaustion, though it should be approached with caution due to its wide-ranging hormonal impact. It is typically administered in low doses (5–50 mg), often under the supervision of a healthcare provider familiar with hormone therapy.
Historical Use in Medicine:
Pregnenolone was first isolated in the 1930s, shortly after the discovery of cholesterol’s role in steroid hormone synthesis. It quickly became a subject of interest in early endocrinology for its potential to enhance energy, reduce stress, and improve mental performance. In the 1940s and 1950s, pregnenolone was tested in clinical settings for arthritis, adrenal insufficiency, and depression, with some positive outcomes—particularly in reducing fatigue and enhancing mood.
However, it fell out of mainstream medical use with the rise of corticosteroids, which were more potent and easier to control. Interest in pregnenolone resurfaced in the 1990s and early 2000s, especially within the anti-aging and functional medicine communities, as researchers explored its neurosteroid functions and its role in maintaining brain and endocrine health during aging.
Unlike many over-the-counter hormones, pregnenolone affects multiple downstream hormone pathways. Historically, it has been used as a gentle hormonal modulator, often considered when DHEA or cortisol imbalances are present. Today, it remains part of personalized hormone replacement therapy (HRT) regimens and is researched for potential roles in neurodegenerative diseases, stress-related disorders, and cognitive decline, offering a bridge between endocrinology and neurobiology.
Pregnenolone is used for these health conditions
Alzheimer's Disease (Scientific)
Anxiety (Scientific)
Anxiety Disorders (Scientific)
Arthritis (Traditional)
Bipolar Mood Disorder (Scientific)
Depression (Scientific)
Memory and Brain Function (Scientific)
Mood Swings (Scientific)
Post Traumatic Stress Disorder (Scientific)
Stress (Scientific)
pregnenolone is used to support these body systems
Brain (Scientific)
Glandular System (Traditional)
