Pregnenolone: Scientific View and Its Outweigh Benefit

Pregnenolone: Scientific View and Its Outweigh Benefit

Pregnenolone is often referred to as the “grandparent” of steroid hormones in mammals. Pregnenolone is made from cholesterol in the adrenal glands and to a lesser extent in the brain, liver, skin, testes and ovaries. Once synthesized, pregnenolone is converted to DHEA or to progesterone. Progesterone is used to make cortisol, aldosterone, androstenedione, estrogen, and testosterone. Pregnenolone is the first step in steroid synthesis from cholesterol to whatever steroid is to be made.


Cholesterol is the building material for the following hormones: Pregnenolone, Progesterone ,Cortisol, Aldosterone ,DHEA ,Testosterone, Estradiol. These hormones are important in many aspects of our lives, including: Mineral balance, Blood pressure regulation, Sex hormone balance, Blood sugar regulation. If the cholesterol level is too low (below 160), the building blocks may not be present in sufficient quantities. This lower level of cholesterol can restrict the body's ability to produce proper levels of hormones such as testosterone and estradiol (sex drive hormones).

Unlike DHEA which converts to estrogen (the three types) and testosterone, pregnenolone is converted directly to progesterone. Therefore, it is often an excellent choice for estrogen-sensitive women or testosterone-sensitive men (such as those with a history or risk of prostate cancer).Pregnenolone also enhances the activity of the cytochrome P450 detoxifying enzymes, which help our cells (especially the liver and brain) to detoxify poisons of all sorts, whether from the outside world, or our own metabolically produced toxins.

Result of a study suggested that in tissues where immune response takes place, the locally-produced 7-hydroxy metabolites of PREG and DHEA are involved in a process which may participate in the physiological regulation of the body's immune response. A clinical data reported that patients have found using one teaspoon a day helpful in relieving a variety of symptoms. Progesterone also prevents osteoporosis. To this end, we also recommend supplementing the diet with calcium and other nutrients essential to bone health.

Its most prominent impact appears to be related to its ability to improve brain functioning, including memory and mental focus. In a 1995 clinical study, Pregnenolone was discovered to be a potent memory enhancing sterone, possibly 100 times more effective for memory than DHEA. In animals, high Pregnenolone levels are clearly related to improved cognitive performance. Pregnenolone is being broken down differently in men and women; that is, it appears to have a testosterone-like effect in men and an estrogen-like effect in women."

Several research study shown that performance or memory tests have been shown to improve in animals when hippocampal pregnenolone levels were increased via intraperitoneal or bilateral intrahippocampal injection of pregnenolone sulfate. There is additional evidence that suggests that exogenous pregnenolone can reinforce neurotransmitter systems that normally decline with age. A "global stimulatory effect on central cholinergic neurotransmission" has been suggested by one research group. Some claims that supplemental pregnenolone is helpful in Alzheimer's disease, some forms of cancer and arthritis degenerative diseases associated with aging and in obesity are unsubstantiated.

In healthy men aged 20 to 30, administration of pregnenolone (1 mg daily) was found to improve sleep quality and decrease intermittent wakefulness. In addition, it was found that patients with active depression had lower levels of pregnenolone compared with those with a prior history of depression. Study also reports a substantial benefit in patients with systemic lupus erythematosus (SLE), psoriasis, and scleroderma.

In a study of airplane pilots subjected to stress, administration of pregnenolone (25 mg twice daily) improved performance without causing adverse side effects. Given 50-100 mg/day of pregnenolone to various types of factory workers, as well as pilots and students trained to use a flight simulator. The factory workers noted improved production rates while taking pregnenolone. They felt less fatigued, better able to cope with their jobs and experienced an enhanced sense of happiness and well-being. Interestingly, workers in stressful job environments improved more with pregnenolone than those with less demanding tasks.

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. The beneficial effects of pregnenolone on arthritis and other bone, joint, and muscle diseases are well documented. In two studies on ankylosing spondylitis-an inflamitory disease of the joints that causes back pain and stiffening-patients showed marked improvement when treated with pregnenolone. 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.

It has also been reported that pregnenolone may play an important role in the neuroendocrine response to stress. 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. Part of this long lasting effect is because it improves the body’s ability to produce its own pregnenolone.

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. 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.

Pregnenolone in “in charge of” chemical and enzymatic reactions, and may help improve cellular energy. This in turn increases the feeling of well-being and improves mood and stress levels. Studies have shown that even minute quantities increased the ability of mice to learn and navigate mazes. Because pregnenolone levels decrease as we age, supplemental amounts can make a big difference; as some company claims.

The Geriatric Research Education and Clinical Center in St. Louis, Missouri is one of the world's leading research centers on pregnenolone. A 1995 study conducted at the Center suggested that low levels of steroid hormones might be the cause of learning and memory impairment (Flood et al., 1995). They also did a study in 1992, which found a relationship between pregnenolone levels in aging and the increase of cancer, and behavioral disorders in people whom receive drugs that block the synthesis of cholesterol (the precursor of pregnenolone) (Flood et al., 1992).

Pregnenolone was tested on patients with exophthalmis (bulging eyes) from Graves’ disease. It was reported that their eyes quickly receded to a more normal position in their sockets. In recent years, growing numbers of doctors and patients have turned to bioidentical hormone replacement therapy. Bioidentical hormone replacement utilizes hormones such as estriol, estrone, estradiol, progesterone, testosterone, dehydroepiandros-terone (DHEA), and pregnenolone that are molecularly identical to those found in humans.

The National Institute of Mental Health in Bethesda, Maryland also supports that pregnenolone is important for effective memory. The NIH study found that pregnenolone positively modulates NMDA receptors in the brain, which are believed to be responsible for retention (Mathis et al., 1994). A French research study in 1995 found that when they administered a series of cognitive tests to mice, those with the highest steroid hormone levels performed significantly better (Rebel et al., 1995). In addition to memory, serum levels of pregnenolone are also a factor in depression. The NIH found that people with clinical depression have significantly lower levels of pregnenolone. Pregnenolone levels were decreased in subjects with affective illness, particularly during episodes of active depression (Mathis et al., 1994).

Side effects:

Some lab studies in cancer cells and animals have suggested that pregnenolone may stimulate the growth of hormone-responsive cancers such as prostate and breast cancer. Pregnenolone is a precursor to steroid hormones such as DHEA and testosterone. High doses may cause aggressiveness, irritability, trouble sleeping, and the growth of body or facial hair on women. It also may stop menstruation and lower the levels of HDL cholesterol ("good cholesterol"), which could raise the risk of heart disease. Other possible side effects include acne, heart rhythm problems, liver problems, scalp hair loss, and oily skin.

Pregnenolone can also raise natural levels of sex hormones, so use caution if taking other medications that affect these hormones and consequently other hormones in the body like testosterone. In the ovary, pregnenolone is a precursor to estrogens and progesterone, and, in the testis, pregnenolone is a precursor to testosterone. It can cause changes in the menstrual cycle and problems with hormone sensitive diseases. In young men, taking excess progesterone can decrease testosterone production and lead to decreased libido, so pregnenolone is preferred over progesterone for young males.

Even no studies on the long-term effects of DHEA have been conducted. DHEA can cause higher than normal levels of androgens and estrogens in the body, and theoretically may increase the risk of prostate, breast, ovarian, and other hormone-sensitive cancers. Therefore, it is not recommended for regular use without supervision by a licensed health professional. A majority of research performed has been on animals, and has not been thoroughly examined as yet for use in humans. Pregnenolone has not been reviewed by the U.S. Food and Drug Administration (FDA) to determine its effectiveness and safety.

As more and more studies documenting the dangerous side effects of prescription hormone drugs come to light, aging adults increasingly are seeking safe, effective therapies to achieve optimal hormone balance. Unlike drugs, dietary supplements are usually "self-prescribed," with little or no input from informed medical sources, like your doctor. There is a lot of wrong information out there, as well as a lack of reliable information about the safe usage and potential risks of dietary supplements.

Drug interaction:

Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum; hippocampal levels were strongly correlated with serum levels. Lanzapine also elevates pregnenolone levels, but to a lesser degree than clozapine. Pregnenolone induction may contribute to the clinical actions of clozapine and olanzapine.

Some studies suggest it may interfere with the action of certain sleeping medicines or calming medicines (benzodiazepines). Pregnenolone may affect hormone levels so those with hormonal cancers such as prostate or breast cancer may interfere.

Health care providers should continue to inquire about dietary supplement use and consider the potential for interactions, regardless of their severity. Other more serious pregnenolone side effects could include Irregularities of heart rhythm, heart palpitations, even on as low a dose as 5 to 10 mg.

Pregnenolone may cause disturbances in the endocrine system, including changes in the menstrual cycle and problems with hormone sensitive diseases, or it may interact with hormone therapy such as oral contraceptives. The side effects and interactions with other therapies are currently unknown.

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