Pregnenolone for Men: What We Need to Know

Author: Nelson Vergel

Pregnenolone for Men: An Overview of this Neurosteroid and Men’s Health

Pregnenolone is a steroid hormone and natural steroid in the human body and has recently been in the spotlight in medical research, especially when it comes to men’s health. Low pregnenolone levels can cause muscle loss in aging men. This article will look into different studies that are looking into the role of pregnenolone, including the administration of pregnenolone for brain function, hormone balance, and how it can be used to treat schizophrenia. By looking into research papers, we will give you an overview of how pregnenolone affects men’s health.

What is the neurosteroid pregnenolone?

You could say pregnenolone is the “father” of all hormones!

Your body makes hormones from cholesterol, the sterol lipid molecule made in our liver. But your body has to go through a process to make hormones like testosterone, estrogen, DHT, and so on. First it has to convert the cholesterol into pregnenolone, the mother of all hormones. From there it can make progesterone (where cortisol comes from) and DHEA (which is needed to make testosterone). This process is important because pregnenolone is a precursor to testicular steroid hormones, including testosterone, which are important for reproductive health and male sexual function.

The synthesis of testicular steroid hormones happens in the mitochondria, where pregnenolone is produced and then converted into testosterone and other hormones. This process is important for overall hormonal balance and has big implications for reproductive health.

But that first step (converting cholesterol into pregnenolone) is the most important step. Pregnenolone is the precursor to all these other hormones, as you can see in the chart below:

In a young adult male, pregnenolone levels are at their peak. But as you age, the levels of this precursor hormone drop and the body’s response to it. At 75 years old, our body produces only 40% of the pregnenolone it needs. That’s a big drop in the precursor hormone, which means a big drop in all the hormones derived from pregnenolone.

Before we get into the studies, let’s first understand what pregnenolone is and its basics. Pregnenolone is often referred to as a neurosteroid; it’s a precursor to many other steroids, including testosterone. It’s produced in the adrenal glands, brain, and gonads. This neurosteroid plays a big role in synaptic plasticity, cognitive function, and mood regulation.

Definition and Biochemical Profile of Pregnenolone

Pregnenolone is a naturally occurring steroid hormone in the human body produced primarily in the adrenal glands, brain, and gonads. It’s produced from cholesterol through the action of the enzyme cholesterol desmolase. This process converts cholesterol into pregnenolone, which then becomes a precursor to many other steroid hormones. Pregnenolone is lipophilic, meaning it can easily cross cell membranes, including the blood-brain barrier, so it can exert its effects all over the body. Its biochemical profile is characterized by its ability to be converted into other steroid hormones such as testosterone, progesterone, and cortisol through a series of enzyme-catalyzed reactions. This versatility is the reason why it’s important for many physiological functions.

Role of Pregnenolone in the Body

Pregnenolone plays a big role in many physiological processes, including stress response, mood regulation, and immune system modulation. As a precursor to other steroid hormones like testosterone, progesterone, and cortisol, pregnenolone is important for overall hormonal balance. As a neurosteroid, it’s especially important for cognitive health. Research has shown that pregnenolone can improve memory, protect against neural degeneration, and potentially improve focus and mental clarity. Pregnenolone also supports overall hormonal balance, which is important for overall health and well-being. By being a precursor to other steroid hormones, pregnenolone regulates many bodily functions, from stress response to reproductive health.

Pregnenolone for Men: Supplementation Routes and Doses

Pregnenolone can be administered orally, subcutaneously, intravenously, intranasally, topically, or transdermally. Oral pregnenolone has high metabolism and low bioavailability. It’s lipophilic and can cross the blood-brain barrier.

There is very limited data on the pharmacokinetics of exogenous pregnenolone. When taken orally, allopregnanolone breaks down pregnenolone faster than other hormones made from pregnenolone substrates like cortisol or DHEA. One study showed that 3 hours after oral intake of 400 mg of pregnenolone, pregnenolone serum levels increased by 60%. 2 hours after that, allopregnanolone serum levels tripled. Another study showed that a single oral dose of 175 mg of pregnenolone doubled pregnenolone serum levels for 4-8 hours.

One study by Marx et al. (2009) looked at the effects of exogenous pregnenolone in patients with schizophrenia or schizoaffective disorder. Participants were given 8 weeks of oral pregnenolone with an escalating fixed dose, 500 mg for the last 4 weeks. Pregnenolone and downstream metabolites were measured in the serum. Pregnenolone sulfate was 3x higher, allopregnanolone was 5x higher and serum pregnenolone was 4x higher when taken orally. Oral pregnenolone also increased progesterone in the blood by 4x and DHEAS by 16%. Exogenous pregnenolone did not increase serum testosterone, free testosterone, cortisol, DHEA, estradiol, or androstenedione.

Pregnenolone and Allopregnanolone in Anxiety:

Pregnenolone is a hormone in the human body and is the precursor to allopregnanolone. This is important because allopregnanolone regulates mood and emotional states through the central nervous system and the body’s stress response. Higher levels of allopregnanolone have been linked to reduced anxiety symptoms. This anxiolytic effect shows the hormone’s impact on mental health. Blocking or inhibiting allopregnanolone can have negative effects on social and affective functioning. So if allopregnanolone production or activity is slowed down, it can make it harder to interact with others and control your emotions. This is how important the hormone is for mental health and social well-being.

Have you ever wondered how your brain handles emotions, especially during stress or anxiety? This has been a question for scientists for a long time. A recent study looked into the role of a neurosteroid called allopregnanolone in emotional regulation. This is a calming substance and has been linked to anxiety reduction. But how it affects our brain’s emotional control circuits has been a mystery until now.

To better understand allopregnanolone’s role, researchers did an innovative experiment. They gave 400 mg of pregnenolone (a precursor to allopregnanolone) to 16 participants and a placebo to 15 others. The participants then did a brain scan (3T fMRI) while doing the Shifted-Attention Emotion Appraisal Task (SEAT). This task is designed to measure emotional processing and regulation.

The results were interesting. Compared to the placebo group, the allopregnanolone group had reduced activity in two brain regions: the amygdala and the insula. These areas are responsible for generating negative emotions like fear and anxiety.

Allopregnanolone made the dorsomedial prefrontal cortex work harder during the emotion judgment part of the task. This is the part of the brain that controls emotions. It also increased the connection between the amygdala and this region. This was correlated with lower self-reported anxiety in the participants.

Pregnenolone in Schizophrenia Treatment

Several studies have looked into the use of pregnenolone in schizophrenia, a mental disorder characterized by cognitive and mood disturbances. For example, Marx et al. (2014) did a randomized controlled trial to test the efficacy of pregnenolone in schizophrenia. They found some improvement in cognitive functions and symptom reduction.

Marx et al. (2009) also looked into the effects of pregnenolone on cognitive and negative symptoms in schizophrenia. This proof-of-concept study confirmed the potential of pregnenolone in improving cognitive functions in schizophrenia patients.

Ritsner (2010) gives a broader view of pregnenolone, dehydroepiandrosterone (DHEA), and their changes in schizophrenia. This study tells us a lot about the hormone changes in men with schizophrenia so the potential therapeutic role of pregnenolone is even clearer.

Cognitive Function and Mood Enhancements

Beyond schizophrenia, pregnenolone’s role in general cognitive health and mood improvement has been looked into, especially in relation to promoting deep sleep. Osuji et al. (2010) studied the effects of pregnenolone on cognition and mood in dual-diagnosis patients. Their study suggested the potential of pregnenolone to improve cognitive function and mood but only in a specific patient group.

Hormonal Effects in Men

The hormonal effects of pregnenolone, especially on testosterone and total testosterone, have been studied. Pregnenolone is converted into testosterone in the testes and changes in pregnenolone levels can affect overall reproductive health and male sexual function. In 2023, Bracci et al. looked into the changes in pregnenolone and testosterone in male shift workers. This study showed how work schedules can affect hormonal balance. Their results showed the importance of pregnenolone in maintaining hormonal balance for sexual health.

Pregnenolone in Age-Related Hormonal Changes

Morley (2013) reviewed the role of pregnenolone in age-related hormonal changes, specifically on rejuvenation and vitality. His overview of hormone treatments for rejuvenation mentions the importance of pregnenolone in maintaining hormonal balance as men age.

Pregnenolone’s role in synaptic plasticity

Synaptic plasticity is a term in neuroscience, the study of the brain and nervous system. To understand it, think of your brain as a network of roads, where each road is a connection between brain cells (neurons). These roads are called synapses.

Think of these roads as changeable. Some can become wider or more used, making the travel (or communication) between brain cells faster and stronger. Others can become less used or even disappear. This changing nature of the roads (synapses) is what we call synaptic plasticity.

This is like learning and memory in the brain. When you learn something new or remember something, the roads in your brain adjust. Some connections become stronger because you use them more (like practicing a skill), and others weaken because you use them less.

So, synaptic plasticity is the brain’s ability to rewire itself based on experiences, learning, and memory. It’s why we can learn new things and remember them. This flexibility is important for our brain’s growth and adaptation throughout our lives.

Smith et al. (2014) reviewed the role of pregnenolone in synaptic plasticity. Their study showed the role of neurosteroids in modulating synaptic plasticity, which has implications for cognitive functions and mental health.

One of the important findings of Dr. Smith’s team was that pregnenolone helps brain cells communicate, especially in ways that are important for learning and remembering things. This communication happens through something called the N-methyl-D-aspartate receptor (NMDAR), which is like a tiny receiver on brain cells that helps them talk to each other. These scientists found that pregnenolone can move these NMDARs to where they’re needed on the brain cell surface. It does this with the help of calcium ions (tiny particles) and G-protein-coupled receptors. Also, pregnenolone can increase the levels of calcium inside brain cells, which is really important for strengthening brain cell connections. This strengthening is what helps us learn and remember things.

Testosterone Replacement Therapy and Anabolics Decrease Upstream Hormones like Pregnenolone

To fully understand pregnenolone’s effects, we also need to understand its relationship with testosterone and other steroid precursors. In 1985, Ruokonen et al. studied how serum testosterone and its precursor steroids responded to anabolic steroids and testosterone administration. This study gave us a basic idea of how pregnenolone works with other hormones.

High doses of testosterone and anabolic steroids were used for 26 weeks by power athletes and then stopped for 16 weeks. During the 26 weeks of steroid use, SHBG and CBG in their blood changed. After 16 weeks of follow-up, serum testosterone and androstenedione increased (P < 0.05), but pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol, progesterone, and 17-hydroxyprogesterone decreased (P < 0.001). Pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone sulfate in the blood and free steroids changed, but 5-androstene-3 beta, 17 beta-diol, and testosterone sulfate remained the same during follow-up.

During drug use, SHBG decreased by 80-90% and remained low for 16 weeks after steroid withdrawal. Steroids had no effect on serum CBG. In summary, taking testosterone and anabolic steroids by themselves messed up the testicular endocrine system. Low levels of testosterone precursors, a high ratio of testosterone to its precursor steroids and low SHBG were the indicators of this. Low levels of SHBG and testicular steroids were still present during the 16 weeks after drug withdrawal. If dehydroepiandrosterone and its sulfate are low in the blood, it means anabolic androgenic steroids also stop the adrenal glands from producing androgens.

Pregnenolone Side Effects

Now, as with any hormone, there are downsides to pregnenolone supplementation. Not everyone will experience side effects but most users report one or more of the following:

Bloating—Many pregnenolone users have reported feeling bloated and puffy with regular use even when taken with DHEA or other steroid hormones. This may be because pregnenolone increases the production of ALL sex hormones, including estradiol (the precursor to estrogen). An increase in estrogen can cause water retention and bloating.
High Estrogen Levels—As mentioned above, pregnenolone is converted into all sorts of sex hormones, including various forms of estradiol. This increase in estradiol can raise your estrogen levels.
Weird Dreams—Many people taking pregnenolone have reported weird dreams after taking the supplement. While pregnenolone can reduce anxiety and stress (as above), it can make your brain overactive when you sleep and may cause weird dreams.
Other Side Effects -- According to WebMD, "There isn't enough information to know if pregnenolone is safe when taken by mouth." However, it can cause effects similar to other steroid hormones: arrhythmia, hair loss, facial hair growth, headaches, mood changes, acne, anger, anxiety, irritability, and insomnia. For those with hormone-sensitive conditions (breast, ovarian, or uterine cancer, endometriosis), the hormone may exacerbate health problems since pregnenolone increases estrogen production.
But the truth is, these side effects are really minimal. Pregnenolone is generally a safe supplement with limited side effects. Just be aware of what you're getting into when taking pregnenolone.

Pregnenolone Safety and Side Effects

Pregnenolone is generally safe but be aware of the side effects, especially with high doses or long-term use. Common side effects may include headaches, dizziness, and nausea. Consult with a healthcare provider before taking pregnenolone, especially if you're taking other medications or have underlying health conditions. Pregnenolone can interact with certain medications like hormone replacement therapy, blood thinners, or immune system modulators, which may alter their effectiveness or increase the risk of side effects. Getting proper medical guidance can minimize these risks and ensure safe and effective use of pregnenolone.

How Much Pregnenolone Do You Need?

If you're taking it to increase natural hormone production, you need to know HOW MUCH to take. You don't want to overdo it and end up with side effects!

According to the Quest Diagnostics Manual:

Men: 10 to 200 ng/dL
Women: 10 to 230 ng/dL
Children: 10 to 48 ng/dL
Adolescent boys: 10 to 50 ng/dL
Adolescent girls: 15 to 84 ng/dL

Mean levels of pregnenolone don't differ significantly in postmenopausal women and elderly men (40 and 39 ng/dL, respectively).

The typical dose of pregnenolone is 50 to 200 mg per day taken first thing in the morning. The pills are to be taken on an empty stomach or you can use a cream (transdermal application).

But you may want to consult with your endocrinologist for professional medical advice before taking any pregnenolone. They may recommend a higher or lower dose depending on your pregnenolone levels or may advise against it, especially if you have underlying health conditions like cardiovascular diseases. Get a recommendation from a medical professional before taking any supplement, especially hormones like pregnenolone.

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Questions About Pregnenolone for Men

Does pregnenolone increase testosterone?

Pregnenolone is a hormone that's a precursor to other hormones, including testosterone. While pregnenolone itself doesn't increase testosterone levels, it can play a role in the body's production of testosterone and other hormones. The effect of pregnenolone on testosterone levels may vary from person to person and depends on individual hormonal balance, overall health, and dosage. Consult with a healthcare provider or endocrinologist for personalized advice on hormone levels and supplementation.

Does pregnenolone work for erectile dysfunction?

Pregnenolone is a hormone that's being used as a supplement for various health conditions but has not been scientifically proven to treat erectile dysfunction. If you have erectile dysfunction, consult with a healthcare provider or a doctor who can give you options based on your individual health and situation.

How does pregnenolone compare to other supplements men use for hormonal balance?

Pregnenolone is a hormone that's a precursor to other hormones like testosterone, estrogen, and cortisol. When it comes to hormonal balance in men, pregnenolone has a unique role compared to other supplements used for this purpose. While supplements such as DHEA and testosterone boosters target specific hormones, pregnenolone serves as a building block for various other hormones in the body. This means pregnenolone can support overall hormonal balance by providing the raw material for hormone production. Consult with a healthcare provider before adding any new supplement to your regimen, especially when it comes to hormonal health.

Where to buy Pregnenolone for Men?

Pregnenolone for men can be found at health food stores, pharmacies, online supplement retailers, and some medical or wellness clinics. Make sure to buy from a reputable source to ensure quality and efficacy. Before starting any new supplement regimen, consult with a healthcare provider to determine the right dosage and if it's safe for your health needs.

Buying Guide: What to Look For

When choosing a pregnenolone supplement, consider the following factors to get a high-quality product. Look for supplements from reputable companies that have third-party testing for purity and potency. Check the dosage to match your individual needs and health goals. Also check the manufacturing standards of the product and opt for GMP. Consult with a healthcare provider before starting any supplement regimen, especially if you have underlying health conditions or are taking other medications. This will help you choose the right supplement and dosage for your needs.

Research on pregnenolone shows its many roles in men's health, especially in cognitive function, mood regulation, and hormonal balance. While it shows promise in treating schizophrenia and improving cognitive and mood functions, more research is needed to fully understand its therapeutic potential and long-term effects.

Buy your own pregnenolone test here.

References

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