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Pregnenolone

Author: Dr. George Shanlikian, M.D.  |   Last Updated: March 26th, 2024

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Pregnenolone is a steroid hormone produced primarily in the adrenal glands. Smaller amounts of pregnenolone are also produced in other organs such as the brain, skin, gonads, liver, and eyes. In the body, all hormones work in harmony to create a healthy balance. If you picture steroid hormones as a cascade, where one hormone has an impact on one another, pregnenolone would be at the top of the cascade.

Pregnenolone is manufactured directly from cholesterol – which is one reason why experts believe that below the normal levels of cholesterol can cause hormonal imbalance. In turn, several other hormones including testosterone, DHEA, estrogen, and cortisol are synthesized from pregnenolone that’s why it is called as the “mother of all steroid hormones”. Just as it’s used to synthesize other steroid hormones, adequate amounts of pregnenolone are used to create neurohormones in the brain, which act to maintain healthy nerve cell function and regulate mood.

Potential Health Benefits of Pregnenolone

  • Boosts cognitive function [1-4]
  • Boost the immune system [15-19]
  • Improves learning and memory [20-27]
  • Stimulates deep sleep [28-35]
  • Improves mood and wards off depression [36-47]
  • Kills cancer cells [48-50]
  • Lowers cholesterol level [51-56]

Functions of Pregnenolone

Pregnenolone has several important functions in the body aside from acting as the main precursor for most steroid hormones. It seems to have a balancing effect to many other hormones by increasing or decreasing their levels when necessary. In addition, pregnenolone also regulates the transmission of messages between each nerve cell (neuron) to strongly influence many other processes in the brain and other body systems.

Symptoms of Low Pregnenolone

As we age, the levels of pregnenolone fall dramatically to as much as 60 percent. Researchers have linked this hormonal imbalance to a wide array of debilitating medical conditions that can affect overall quality of life. Unpleasant symptoms related to low pregnenolone include:

  • Decreased sex drive in men and women
  • Eye dryness
  • Fatigue and reduced mobility
  • Hot flashes
  • Impaired memory and mental awareness
  • Low energy levels
  • Low mood
  • Sleeping difficulties
  • Thinning of pubic hair
  • Trouble thinking

Proven Health Benefits of Pregnenolone

Several Bioidentical hormone replacement programs tend to use pregnenolone because it is touted as the “mother of all steroid hormones”, thus, it can boost overall health by bringing the levels of other vital hormones up as needed. In fact, pregnenolone is effectively used in conjunction with testosterone and estrogen to help relieve various symptoms of menopause and andropause (male menopause). With pregnenolone supplementation, the goal is to support overall healthy levels of this hormone in order to stimulate the body to produce internal pregnenolone in areas that need a boost of another steroid hormone. This powerful hormone is available in the form of injections, tablets, and topical creams. Strong scientific evidence suggests that different modes of prenenolone administration are highly safe and effective in treating various medical conditions and improving overall health:

Boosts Cognitive Function

Pregnenolone is a nootropic agent or “cognitive enhancer”. This means that it has the ability to improve various aspects of cognitive function including memory, learning, and thinking skills. Studies show that pregnenolone boosts cognitive function through several important mechanisms:

  1. In the brain, pregnenolone acts as a signaling molecule where it stimulates the activity of neurons (nerve cells). [57-58]
  2. Pregnenolone increases the growth of neurons. [59]
  3. Pregnenolone enhances myelination (formation of protective covering of neurons) and the transmission of electrical signals. [60]
  4. Pregnenolone enhances the survival of newborn neurons. [61]
  5. Pregnenolone improves recovery of neurons. [62]
  6. Pregnenolone protects neurons against cell toxicity and toxin-induced cell death. [63-64]
  7. In the elderly, low blood levels of pregnenolone are associated with increased risk of dementia. [65]
  8. Pregnenolone helps regulate neuronal function by activating and deactivating various signaling pathways. [66]
  9. Pregnenolone helps stabilize neurons and stimulate its development. [67-68]
  10. In mice and rats, pregnenolone administration enhances learning and memory. [69-70]
  11. In mice and rats, pregnenolone supplementation improves performance in various mazes. [71]
  12. In rats, pregnenolone blocks chemical-induced amnesia. [72-74]

Stimulates Deep Sleep

In both men and women, pregnenolone deficiency can dramatically affect sleeping pattern and quality. As a pro-hormone responsible for the production of several vital sex hormones, pregnenolone in its healthy levels can stimulate deep sleep. Research into sleep is showing a strong connection between pregnenolone and its ability to promote normal sleep pattern:

  1. In men and women with sleeping difficulties, pregnenolone supplementation increases the amount of time spent in deep sleep. [75]
  2. In patients with sleeping problems, pregnenolone supplementation improves sleep by impairing the quality of wakefulness. [76]
  3. Pregnenolone plays a role in sleep-wake cycle regulation. [77]
  4. In men, pregnenolone administration induces sleep-EEG changes. [78]

Relieves Schizophrenia Symptoms

Schizophrenia is a long-term mental health condition that causes a wide array of psychological symptoms such as hallucinations, delusions, muddled thoughts, and changes in behavior. Currently, treatment for schizophrenia includes antipsychotic medicines and cognitive behavioral therapy (talking therapy). There is increasing evidence that pregnenolone administration can be considered as a therapeutic option for this debilitating mental condition:

  1. In patients with schizophrenia and schizoaffective disorder, pregnenolone treatment reduces severity of negative symptoms. [79]
  2. In patients with schizophrenia, pregnenolone improves attention, as well as verbal and working memory performance. [80]
  3. Administration of low-dose pregnenolone together with antipsychotics reduces drug-induced side effects in schizophrenic patients. [81]
  4. In mice, pregnenolone reduces schizophrenia-like symptoms and prevents cognitive deficits. [82]

Improves Mood and Wards off Depression

Decreased levels of pregnenolone are strongly linked with depressed mood. [83-84] Because depression can be very challenging to treat, with current medications requiring months before its therapeutic effects are achieved, research into pregnenolone on mood can be a game-changer. Interestingly, clinical studies assessing the beneficial effects of pregnenolone on mood, depression, anxiety, and other mental disorders show positive results:

  1. In women with bipolar disorders, elevated levels of pregnenolone are associated with stable mood state. [85]
  2. Pregnenolone boosts mood through activation of neurocircuits that control emotion. [86]
  3. Blocking pregnenolone production impairs social and emotional functioning. [87]
  4. In patients with bipolar disorder, recurrent major depressive disorder, and history of substance abuse/dependence, pregnenolone administration reduces symptoms of depression. [88-90]
  5. Depressive disorders are caused by neuronal abnormalities in brain microtubule function. [91] By boosting the production and stability of tubules, pregnenolone promotes growth of neurons, thus fighting depression. [92]
  6. Individuals with generalized anxiety disorder appear to have lower levels of pregnenolone than those without anxiety. [93]
  7. Preclinical findings suggest that pregnenolone plays a major role in anxiety and depression-regulatory mechanisms. [94-95]
  8. Patients experiencing a depressive episode, either unipolar or bipolar type, had lower levels of pregnenolone than healthy controls. [96]
  9. Pregnenolone administration reduces self-reported anxiety. [97]
  10. In adults with autism spectrum disorder, pregnenolone reduces irritability. [98]
  11. Pregnenolone enhances mood by activating the brain chemical GABA. [99]

Strengthens the Immune System

With advancing age, the immune system weakens making us susceptible to various infections. Interestingly, pregnenolone does have immune-modulating properties that can help boost the immune response, thereby warding off a wide array of diseases. Strong scientific evidence supports the beneficial effects of pregnenolone on the immune system:

  1. Synthetic pregnenolone derivatives possess potent antiviral properties against the herpes simplex virus. [100]
  2. Pregnenolone restores immune balance by suppressing excess immune action. [101]
  3. Pregnenolone is involved in the physiological regulation of the body’s immune response. [102-103]
  4. Pregnenolone strengthens the immune system by augmenting the inflammatory responses. [104]

Reduces Alcohol Preference and Intake

Chronic alcohol intake significantly increases the risk of liver disease and other fatal medical conditions. Studies show that pregnenolone administration may offer long-term solution to chronic alcoholism:

  1. In rats, acute pregnenolone administration significantly reduces alcohol preference and intake. [105]
  2. Pregnenolone treatment also reduces alcohol self-administration in rats. [106]

Kills Cancer Cells

In addition to its already potent neuroprotective properties, pregnenolone might also be able to combat certain types of cancer. There is strong scientific evidence that supports the cancer-fighting properties of pregnenolone:

  1. Pregnenolone kills tumors in the central nervous system by activating programmed cell death (apoptosis). [107]
  2. Oximes, hydazones, and pyrazoles derivatives of pregnenolone appear to have potent anti-cancer properties. [108]
  3. The addition of pregnenolone enhances the anticancer properties of titanocene dichloride, a chemotherapeutic drug. [109]

Protects against Cannabis Intoxication

Marijuana, also known as cannabis, is the most commonly used illegal drug in the world. While some states or countries permit its use, chronic marijuana administration can lead to serious side effects such as panic attack, intense anxious or fearful feelings and thoughts, and acute psychosis. With its neuroprotective properties, studies show that pregnenolone may help protect against the negative effects cannabis intoxication:

  1. In rats, pregnenolone administration reduces several effects of cannabis in the brain. [110-111]
  2. Pregnenolone does not only protect against cannabis intoxication but also treats cannabis addiction. [112]

Lowers Cholesterol Levels

The logic behind the cholesterol-lowering effect of pregnenolone is simple – it is manufactured directly from cholesterol. To put it simply, when pregnenolone levels increase, cholesterol levels decrease. Studies on pregnenolone support its cholesterol-lowering effects:

  1. In rats, administration of cholesterol substrates increases pregnenolone synthesis, suggesting that cholesterol is vital for pregnenolone production. [113-114]
  2. Other studies show that cholesterol is converted into pregnenolone via several mechanisms, thus reducing its levels in the body. [115-116]
  3. A study conducted in guinea pigs shows that higher pregnenolone levels were associated with lower levels of low density lipoprotein (bad cholesterol). [117]

Increases Libido

Sexual desire and function declines with advancing age. This is because the levels of many other hormones that regulate sex drive (testosterone and estrogen) also decline gradually. As the “mother of all hormones”, studies show that pregnenolone can help restore youthful levels of other hormones, thereby ramping up sexual power:

  1. Pregnenolone is a precursor for the synthesis of testosterone, [118] the primary male sex hormone known to regulate sex drive and erection.
  2. Pregnenolone also boosts the production of estrogen and progesterone in women, [199-120] both of which increases sex drive and improves sexual function.
  3. In mice, pregnenolone co-treatment restores the production of sex hormones necessary for maintenance of libido. [121]
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Reference

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  81. Wong P, Sze Y, Chang CCR, Lee J, Zhang X. Pregnenolone sulfate normalizes schizophrenia-like behaviors in dopamine transporter knockout mice through the AKT/GSK3β pathway. Translational Psychiatry. 2015;5(3):e528-. doi:10.1038/tp.2015.21.

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  86. Sripada RK, Marx CE, King AP, Rampton JC, Ho S, Liberzon I. Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits. Biological psychiatry. 2013;73(11):1045-1053. doi:10.1016/j.biopsych.2012.12.008.

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  97. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2014;44(11):2971-2977. doi:10.1007/s10803-014-2144-4.

  98. Turkmen S, Backstrom T, Wahlstrom G, Andreen L, Johansson I-M. Tolerance to allopregnanolone with focus on the GABA-A receptor. British Journal of Pharmacology. 2011;162(2):311-327. doi:10.1111/j.1476-5381.2010.01059.x.

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  104. Rezvani AH, Levin ED. Assessment of pregnenolone effects on alcohol intake and preference in male alcohol preferring (P) rats. European journal of pharmacology. 2014; 740:53-7.

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Pregnenolone

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Pregnenolone for Women

Pregnenolone is a steroid hormone manufactured primarily in the adrenal glands, similar to testosterone, DHEA, and other sex hormones. Smaller amounts of pregnenolone are also produced in other organs such as the brain, skin, gonads, liver, and eyes. Among women, adequate pregnenolone is essential in treating overall hormone imbalance, symptoms related to menopause, and maintaining a positive mood.
In the body, all hormones work in harmony to create a healthy balance. If you picture steroid hormones as a cascade, where one hormone has an impact on one another, pregnenolone would be at the top of the cascade. Because of this, some researchers have nicknamed pregnenolone the “master hormone” or “mother hormone.”

Pregnenolone for Women

What Does Pregnenolone Do for Women?

Pregnenolone is manufactured directly from cholesterol. Some experts believe that low cholesterol can lead to hormone imbalance because your body doesn’t have sufficient raw material to produce enough pregnenolone. This in turn would affect levels of estrogen, DHEA, testosterone, and other hormones synthesized from pregnenolone.

Pregnenolone is also used to create neurohormones in the brain. These neurohormones are used to regulate mood, meaning it’s essential to maintain adequate pregnenolone to avoid mood-related disorders.

Unfortunately, there is still much we don’t know about pregnenolone, mostly because the research community has focused on steroid hormones like estrogen and progesterone. In the 1940s, when the focus of research is on how adrenal hormones worked, pregnenolone was extensively studied together with cortisol as an anti-inflammatory. In the 1950s, researchers discovered how to make synthetic cortisol, so the study of pregnenolone declined. Because pregnenolone, unlike cortisone, couldn’t be patented, there was no financial incentive to pursue the research.

Today, pregnenolone is used to improve energy, vision, memory, cognition, well-being, and sexual enjoyment or libido. It is considered a brain enhancer, and studies have shown that it is one of the most effective and powerful memory boosters. Women use pregnenolone for treatment of lumpy breasts (fibrocystic breast disease), endometriosis (disorder in the lining of the uterus), hot flashes, and other premenstrual symptoms.

What Does Pregnenolone Do for Women?

Low Pregnenolone Symptoms Female

As women age, levels of pregnenolone can fall as much as 60 percent. Researchers have linked this decline to depression, anxiety, cognitive impairment, and other mental illness. In women, low levels of pregnenolone are associated with low energy and mood and increased symptoms of menstruation. Other symptoms related to low pregnenolone include:

  • Decreased female sex drive
  • Eye dryness
  • Fatigue
  • Hot flashes
  • Impaired memory
  • Reduced mood
  • Thinning pubic hair
  • Trouble thinking

Pregnenolone Benefits for Women

Women are at higher risk for hormone imbalance, thanks to their more complicated hormonal picture. Because of its role as the mother hormone, pregnenolone is frequently included in bioidentical hormone programs so there is plenty of material to make other sex hormones. Pregnenolone is also used to help relieve various symptoms of menopause. Other benefits of pregnenolone include:

  • Boost the immune system
  • Improves brain function
  • Improves levels of neurohormones
  • Improves memory
  • Improves mood and relief from depression
  • Improves mobility
  • Reduces stress and prolongs the life
  • Reduces anxiety
  • Relief from fatigue
  • Relief of symptoms related to low testosterone

With pregnenolone supplementation, the goal is to support overall healthy levels of pregnenolone in order to stimulate the body to produce internal pregnenolone in areas that need a boost of another steroid hormone. Pregnenolone is available in the form of injections, tablets, and topical creams.

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Pregnenolone

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What is Pregnenolone?

Pregnenolone is a steroid hormone similar to testosterone, DHEA and other sex hormones. It is manufactured primarily in the adrenal glands, but smaller amounts are also produced in other organs including the skin, brain, gonads, liver and even the eyes.

In the body, all hormones work together to create a healthy balance. If you picture steroid hormones as a cascade, where one hormone affects another, and hormones can be synthesized from each other, pregnenolone would be at the top of the cascade. It’s manufactured directly from cholesterol (which is one reason that some experts believe excessively low cholesterol can actually contribute to a hormone imbalance). In turn, other hormones such as testosterone, DHEA, estrogen, and cortisol are synthesized from pregnenolone. Low pregnenolone levels are directly related to an overall deficiency in other, more biologically active hormones.

Pregnenolone is also highly concentrated in the brain, where it helps maintain cognitive health and healthy brain function. Just as it’s used to synthesize other steroid hormones, pregnenolone is used to create neurohormones in the brain, which act to support healthy nerve cell function and regulate mood. Because pregnenolone levels fall dramatically with age, as much as 60 percent, some researchers have linked pregnenolone deficiency in older adults to depression, anxiety, cognitive deficits and mental illness.

What is Pregnenolone?

What Does Pregnenolone Do for Men?

Besides acting as the main precursor for most steroid hormones, pregnenolone has a number of important functions in the body. Low levels of pregnenolone have been linked to memory problems and cognitive deficits, fatigue and low energy, low mood, and even increased symptoms of menstruation.

Unfortunately, researchers haven’t focused on the specific effects of pregnenolone in the body. This has more to do with how drugs are researched than it has to do with pregnenolone. In the 1940s, when researchers were just beginning to unravel how adrenal hormones worked, pregnenolone was extensively studied alongside cortisol for the relief of inflammatory conditions such as arthritis. In the 1950s, however, researchers figured out how to make synthetic cortisol, so the research focused on the more profitable hormone and the study of pregnenolone by itself declined.

What Does Pregnenolone Do for Men?

Low Pregnenolone Symptoms in Male

Because of its role as the body’s main steroid hormone precursor, pregnenolone is typically included in a comprehensive hormone panel. Low levels are often indicative of an overall hormone imbalance and deficiency. However, it’s hard to isolate specific symptoms caused by low pregnenolone because these symptoms likely overlap with more powerful downstream hormones such as testosterone.

Symptoms of low pregnenolone in men include:

  • Hot flashes
  • Poor memory
  • Poor mood
  • Irritability
  • Anxiety
  • Low levels of neurohormones
  • Reduced libido
  • Low energy
  • Fatigue
  • Limited mobility
  • Poor brain function

Pregnenolone Benefits for Men

Pregnenolone Benefits for Men

Bioidentical hormone replacement programs tend to use pregnenolone as a general balancing hormone. There is some evidence that healthy pregnenolone levels support overall healthy hormone levels, as well as boost the immune system, reduce stress and prolong life. Pregnenolone is effectively used alongside testosterone and estrogen to help relieve symptoms of estrogen imbalance, andropause and testosterone deficiency in men.

  • Improved memory
  • Improved mood and relief from depression
  • Reduced anxiety
  • Improved levels of neurohormones
  • Relief of symptoms related to low testosterone (e.g., reduced libido, low energy)
  • Relief from fatigue
  • Improved mobility
  • Improved brain function

In the body, which hormone created from pregnenolone depends on where the pregnenolone is synthesized. For example, pregnenolone which is synthesized in the adrenal glands (the majority of it) is likely to be used to create cortisone or the body’s main stress hormone. Pregnenolone synthesized in the ovaries, by contrast, is likely to be used to synthesize estrogen. With pregnenolone supplementation, the goal is to support overall healthy levels of pregnenolone, which encourages the body to make internal pregnenolone in areas that need a boost of another steroid hormone. Pregnenolone can also be applied topically, and there is some evidence it can reduce wrinkles and improve skin elasticity.

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What to expect during your consultation:

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