Pregnenolone
Pregnenolone is called the mother of all steroid hormones for a good reason. It is a steroid hormone at the top of the hormonal production cascade. It is also the precursor in the synthesis of female hormones such as estrogen and progesterone, mineralocorticoids such as aldosterone that is responsible for sodium regulation, glucocorticoids such as cortisol that suppresses inflammation and helps to reduce stress, and androgens such as testosterone. Pregnenolone is therefore aptly called a pro-hormone.
Back in the 1940's, when researchers started experimenting with the use of pregnenolone, they realized that it could be helpful for people who were under stress and that it could also increase energy in those who were fatigued. However, at about the same time, cortisol, another closely related hormone, was discovered and it stole the limelight, as it was far more potent. When cortisol was given to individuals with rheumatoid arthritis or other inflammatory conditions, there were outstanding short-term improvements.
During periods of stress, the output of adrenal steroids such as cortisol will increase, which will put a great demand on pregnenolone production. This may lead to pregnenolone deficiency, which in turn may lead to reduction of both glucocorticosteroids and mineralocorticoids such as cortisol and aldosterone respectively.
Numerous studies have shown the effects of pregnenolone on the body and brain. In normal people, pregnenolone will boost energy, elevate mood and improve memory and mental performance. Pregnenolone will also create a sense of well being while improving the ability to tolerate stress. Furthermore, pregnenolone has a host of other benefits, which include the ability to influence cerebral function, the female reproductive cycle, immune defenses, inflammation, mood, skin health, sleep patterns, stress tolerance, and wound healing. As an anti-aging tool, taking pregnenolone will therefore rejuvenate the entire adrenal cascade. However, in the case of Adrenal Fatigue, replacement tends to be more complex.
Some with Adrenal Fatigue find pregnenolone replacement improves their energy, vision, memory, clarity of thinking, well being, and often sexual enjoyment or libido. Some women report lessening of hot flashes or premenstrual symptoms and this is likely due to the rise of progesterone (the biological daughter of pregnenolone) reduction in estrogen dominance. Others, however, may find pregnenolone worsen existing fatigue and may even trigger adrenal crashes. Such paradoxical reactions are common. The more advanced the adrenal weakness, the more likely such experiences are common.
Part of the reason can be explained by pregnenolone's unusual response curve. Many studies have found a U-shaped distribution in the therapeutic response to pregnenolone therapy. The U-shaped distribution describes a benefit associated with low dose pregnenolone, a loss of effect with increasing dose of pregnenolone, and a second peak of benefit with higher doses of the steroid. It is unknown what dosage range is represented in either part of the U-shaped curve for humans and whether or not this curve is altered by disease.
The cells of the adrenal glands, as well as the central nervous system, synthesize pregnenolone. In Adrenal Fatigue, pregnenolone level usually stays high in early stages, but tends to be low as adrenal weakness progresses due to a phenomena known as “pregnenolone steal” as the pregnenolone level drops because the body bypasses pregnenolone production in favor of producing more down-stream hormones such as DHEA and cortisol.
Taking pregnenolone for adrenal fatigue can therefore be challenging for multiple reasons as paradoxical reaction is a major concern. In addition, one can take what appears to be an adequate dosage but will not benefit from this if the body is shunting it towards cortisol production. On the other hand, overdose is possible if too much is taken over time.
The normal starting dose is 15 mg, increasing up to 100 mg for men or women. Pregnenolone should be derived from a pharmacologically pure product and not a yam-derived "precursor.” Oral pregnenolone pills work well. Sublingual administration is an excellent option by bypassing the initial liver metabolism that occurs after swallowing an oral pill but it tends to be "spiky" and not well tolerated by those who are sensitive or in advanced s adrenal fatigue state.
Pregnenolone is converted in the body to progesterone and these two hormones have some overlapping similarities. Pregnenolone is also converted into DHEA, which, in turn may convert into androstenedione, testosterone, and estrogens. Pregnenolone supplementation may increase progesterone levels and consequently other hormones in the body (testosterone and estradiol).
Side effects include
- Over stimulation and insomnia - low doses can be helpful for sleep when taken in the morning. This is especially prominent in those with advanced adrenal fatigue.
- Irritability, anger or anxiety - low doses can actually ease a person into a relaxed feeling, while higher amounts may lead to irritability. The exact reason for this is not known.
- Acne can occur due to the probable conversion of this hormone into androgens.
- Headaches are possible with high dosages - possible scalp hair loss if used daily for prolonged periods. Pregnenolone converts into DHEA, which in turn converts into testosterone and possibly onto DHT. Pregnenolone can also be converted into progesterone.
- Irregular heart rhythm, heart palpitations, even when the dose is as low as 10 mg. This side effect can be serious in the elderly or in those with heart rhythm disturbances.
- Pregnenolone may cause disturbances in the endocrine system, including changes in the menstrual cycle and problems associated with hormone sensitive diseases, or it may interact with hormone therapy such as oral contraceptives.
Due to the possible side effects, pregnenolone should be taken under the supervision of a health care professional. Do not rely on blood or saliva tests alone to determine how much pregnenolone should be taken as the clinical correlation is unreliable in Adrenal Fatigue.
Due to its antagonistic effects on the GABA receptor in the central nervous system, pregnenolone therapy may be contraindicated in some people with a history of seizures. Pregnenolone may inhibit drugs used to increase GABA activity (i.e. Neurontin); these drugs are frequently used in the treatment of epilepsy and depression.
Both pregnenolone and DHEA can be taken together for adrenal fatigue. Since some pregnenolone is converted into DHEA, the intake amount of DHEA can be lowered if both are taken together.
