What is it?

Pregnenolone serves as a precursor to other hormones, including dehydroepiandrosterone (DHEA) and progesterone.¹

The functions of pregnenolone in the body are not well known. It has been suggested the role of pregnenolone in the body is to serve as a "mother steroid" (precursor hormone). Aside from that role, it has no known functions in the body.

Many effects of pregnenolone on the nervous system have been studied. Rat studies indicate powerful memory-enhancing effects,² far beyond that of other neuroactive substances.^{3 4} In healthy men aged 20 to 30, administration of pregnenolone (1 mg daily) was found to improve sleep quality and decrease intermittent wakefulness.⁵

It has been suggested this hormone may play a role in the neuroendocrine response to stress. In a study of airplane pilots subjected to stress, administration of pregnenolone (25 mg twice daily) improved performance without causing adverse side effects.⁶ In a study of the stress response in rats, an increase in anxiety was observed following administration of pregnenolone. The researchers suggested this was a beneficial response during a stressful period and was initiated through the nervous system.⁷

In a study of rats subjected to spinal cord injury, administration of pregnenolone in combination with the anti-inflammatory medication indomethacin (Indocin®) and an immune-modulating substance (bacterial lipopolysaccharide) promoted recovery of nerve function. The effect was more pronounced with combination therapy than with any one of these substances given singly or in combinations of two. Pregnenolone has not been studied in humans with spinal cord injuries.⁸

Pregnenolone appears to exhibit an antagonistic effect on the calming receptors in the brain (gamma-amino butyric acid [GABA] receptors), resulting in an excitatory effect. It is possible this alteration in nervous system transmission could contribute to seizure activity.^{9 10}

Steroid hormones are known to affect mood and behaviour via effects on the nervous system. In people with either current depression or a history of depression, pregnenolone in the cerebrospinal fluid (the fluid that bathes the brain) was significantly lower, than levels in healthy people. In addition, it was found that patients with active depression had lower levels of pregnenolone compared with those with a prior history of depression.¹¹

In a double-blind study of elderly women with wrinkles, daily application of a 0.5% pregnenolone acetate cream improved the visible wrinkling of the skin. When the treatment was discontinued, the benefit was not maintained. Because the results were only temporary, it is suggested the beneficial effect of the cream was due to improved hydration of the skin.¹²

Researchers have reported on the use of pregnenolone in a variety of rheumatologic diseases. In a study of pregnenolone therapy (intramuscular injection, 50–600 mg daily) for rheumatoid arthritis, six of eleven people experienced moderate to marked improvement in symptoms of joint pain and joint mobility. The symptom improvement was apparent two to four days after therapy was initiated. In a study of 13 adults with osteoarthritis, pregnenolone therapy reduced the pain and improved the range of motion in seven of the study participants. Pain recurred when therapy was discontinued. In a person who suffered from gouty arthritis that was unresponsive to conventional medications, pregnenolone therapy resulted in a dramatic response within three days of initiating therapy. This patient received 300 mg daily of pregnenolone (by intramuscular injection) for four weeks, followed by 200 mg weekly of pregnenolone as a maintenance amount. This study of pregnenolone therapy in rheumatologic diseases also reports a substantial benefit in patients with systemic lupus erythematosus (SLE), psoriasis, and scleroderma. Of the 59 people reported in this paper, the only adverse effect was redness or pain at the site of injection. No systemic adverse effects were reported.¹³