Shop products for Pregnenolone 
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
Where is it found?
The cells of both the adrenal gland and the central nervous system synthesise pregnenolone. Human studies show there are much higher concentrations of pregnenolone in the nervous tissue, than in the bloodstream.14 Animal studies indicate the concentration of pregnenolone in the brain is ten-fold higher than that of other stress-related hormones (including DHEA).15 Pregnenolone is present in the blood as both free pregnenolone and a more stable form, pregnenolone-sulphate.
Who is likely to be deficient?
Since it is not an essential nutrient, pregnenolone is not associated with a deficiency state.
How much is usually taken?
Pregnenolone is generally available in amounts of 10 to 30 mg. It is not known what an appropriate intake is for humans or whether the benefits of taking this hormone outweigh the risks.
Are there any side effects or interactions?
Due to its antagonistic effects on the GABA receptor in the central nervous system, supplementation with pregnenolone could cause problems in people with a history of seizures. Pregnenolone supplementation may increase the levels of progesterone and DHEA in the body and possibly the levels of other hormones (testosterone and estradiol). In theory, pregnenolone could cause disturbances in the endocrine system, which may manifest as changes in the menstrual cycle or the development or aggravation of hormone sensitive diseases (including breast and prostate cancer). The side effects and interactions with other therapies are currently unknown.
At the time of writing, there were no well-known drug interactions with pregnenolone.
References
1. Akwa Y, Young J, Kabbadj K, et al. Neurosteroids: biosynthesis, metabolism and function of pregnenolone and dehydroepiandrosterone in the brain. J Steroid Biochem Molec Biol 1991;40(1–3):71–81.
2. Isaacson RL, Varner JA, Baars JM, de Wied D. The effects of pregnenolone sulfate and ethylestrenol on retention of a passive avoidance task. Brain Res 1995;689:79–84.
3. Flood JF, Morley JE, Roberts E. Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive. Proc Natl Acad Sci 1995;92:10806–10.
4. Flood JF, Morley JE, Roberts E. Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc Natl Acad Sci 1992;89:1567–71.
5. Steiger A, Trachsel L, Guldner J, et al. Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Res 1993;615:267–74.
6. Pincus G, Hoagland H. Effects of administered pregnenolone on fatiguing psychomotor performance. Aviation Med 1944;April:98–115.
7. Melchior CL, Ritzmann RF. Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. Pharmacol Biochem Behav 1994;48:893–7.
8. Guth L, Zhang Z, Roberts E. Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc Natl Acad Sci 1994;91:12308–12.
9. Wu FS, Gibbs TT, Farb DH. Pregnenolone sulfate: a positive allosteric modulator at the N-methyl-D-aspartate receptor. Mol Pharmacol 1991;40:333–6.
10. Maione S, Berrino L, Vitagliano S, et al. Pregnenolone sulfate increases the convulsant potency of N-methyl-D-aspartate in mice. Eur J Pharmacol 1992;219:477–9.
11. George MS, Guidotti A, Rubinow D, et al. CSF neuroactive steroids in affective disorders: pregnenolone, progesterone and DBI. Biol Psychiatry 1994;35:775–80.
12. Sternberg TH, LeVan P, Wright ET. The hydrating effects of pregnenolone acetate on the human skin. Curr Ther Res 1961;3:469–71.
13. McGavack TH, Chevalley J, Weissberg J. The use of D 5-pregnenolone in various clinical disorders. J Clin Endocrinol 1951;11:559–77.
14. Morfin R, Young J, Corpechot C, et al. Neurosteroids: pregnenolone in human sciatic nerves. Proc Natl Acad Sci 1992;89:6790–3.
15. Akwa Y, Young J, Kabbadj K, et al. Neurosteroids: biosynthesis, metabolism and function of pregnenolone and dehydroepiandrosterone in the brain. J Steroid Biochem Molec Biol 1991;40(1–3):71–81.
