Pregnenolone

Pregnenolone for Men: What You Need to Know - Discounted Labs

Pregnenolone, a natural steroid hormone and steroid in the human body, has become the center of attention in recent medical research, especially when it comes to men’s health. This article will go over the studies on pregnenolone, including the administration of pregnenolone and brain function, hormone balance, and how it can be used to treat schizophrenia. We will look into the findings of several research papers to give you an overall understanding of how pregnenolone affects men’s health.

What is the Neurosteroid Pregnenolone?

You could say pregnenolone is the "granddaddy" 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 turn 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).

But that first step (turning cholesterol into pregnenolone) is the most critical step. Pregnenolone is the precursor to all these other hormones as you’ll see in the chart below:

In a young adult male, pregnenolone levels are at their highest. But as we age, the levels of this precursor hormone drop, and by age 75 our bodies only produce 40% of the pregnenolone we need. That’s a big drop in the precursor hormone which means a big drop in all the hormones made from pregnenolone.

Before we get into the studies, let’s first understand what pregnenolone is and what it does. Pregnenolone is often referred to as a neurosteroid, it’s a precursor to other steroids including testosterone. It’s made in the adrenal glands, brain and gonads. This neurosteroid is involved in synaptic plasticity, cognitive function and mood regulation.

Pregnenolone for Men- Supplementation Routes and Doses

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

There is very little 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 found that 3 hours after a single 400mg dose of pregnenolone, pregnenolone levels were 60% higher. 2 hours after that allopregnanolone levels were 3 times higher. Another study found that a single 175mg oral dose of pregnenolone increased pregnenolone levels by 100% over 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 approach where patients took 500mg per day for the last 4 weeks. Pregnenolone and certain downstream metabolites were measured in the serum. Pregnenolone sulfate was 3 times higher, allopregnanolone was 5 times higher and serum pregnenolone was 4 times higher when taken orally. Oral pregnenolone also increased progesterone in the blood by 4 times 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 body and the precursor to allopregnanolone. This is important because allopregnanolone is involved in mood and emotional states through the central nervous system and the body’s stress response. Increased allopregnanolone levels have been shown to reduce anxiety symptoms. This anxiolytic effect is the hormone’s effect on mental wellbeing. Allopregnanolone blockade or inhibition 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 wellbeing.

Have you ever wondered how your brain handles emotions especially during stress or anxiety? Scientists have been wondering this for a long time. A recent study looked at the role of a neurosteroid called allopregnanolone in emotional regulation. This substance is known to be calming and has been shown to reduce anxiety. But how it affects our brain’s emotional control circuits has been a mystery until now.

To understand allopregnanolone better researchers did an innovative experiment. They gave 16 participants 400mg of pregnenolone (the precursor to allopregnanolone) and 15 participants a placebo. Then they had the participants do a brain scan (3T fMRI) while doing a task called the Shifted-Attention Emotion Appraisal Task (SEAT). This task is designed to assess 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 are the areas of the brain that generate negative emotions like fear and anxiety.

Allopregnanolone made the dorsal medial 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 at pregnenolone for schizophrenia treatment, a mental disorder with cognitive and mood disturbances. For example Marx et al (2014) did a randomised controlled trial to test pregnenolone in schizophrenia. They found some improvement in cognitive function and symptoms.

Marx et al (2009) also looked at pregnenolone on cognitive and negative symptoms in schizophrenia. This proof of concept study showed the benefits of pregnenolone for cognitive function in schizophrenia patients.

Ritsner (2010) gives a broader view of pregnenolone and dehydroepiandrosterone (DHEA) in schizophrenia. This study tells us a lot about the hormonal changes in men with schizophrenia so the possible therapeutic effect of pregnenolone is even clearer.

Cognitive and Mood Enhancements

Beyond schizophrenia, pregnenolone’s role in general cognitive health and mood improvements has been looked at especially in relation to deep sleep. Osuji et al (2010) looked at the effects of pregnenolone on cognition and mood in dual-diagnosis patients. They found some cognitive and mood improvement but the scope was limited to a specific patient group.

Hormonal Effects in Men

The hormonal effects of pregnenolone especially on testosterone and total testosterone have been studied. In 2023 Bracci et al looked at pregnenolone and testosterone levels in male shift workers. This study showed how work schedules can affect hormonal balance. They found out that pregnenolone plays a big role in maintaining hormonal balance for sexual health.

Pregnenolone in Age-Related Hormonal Changes

Morley (2013) has looked at the role of pregnenolone in age-related hormonal changes especially on rejuvenation and vitality. His review 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 used 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.

Imagine how these roads can change. 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 basically the brain’s ability to rewire itself based on experiences, learning and memory. That’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) looked into the role of pregnenolone in synaptic plasticity. Their study showed the role of neurosteroid 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 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 out 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 something called G-protein-coupled receptors. Also, pregnenolone can increase the levels of calcium inside brain cells which is very 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 understand pregnenolone fully, 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 reacted to anabolic steroids and testosterone administration. This study gave us a basic understanding of how pregnenolone works with other hormones.

High doses of testosterone and anabolics were used in power athletes for 26 weeks 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 during the steroid use but 5-androstene-3 beta, 17 beta-diol and testosterone sulfate remained the same during the follow-up period.

During drug use, SHBG decreased by 80-90% and remained low for 16 weeks after steroid withdrawal. Steroids had no effect on CBG. In summary, taking testosterone and anabolics by itself messed up the testicular endocrine system. Low levels of testosterone precursors, high ratio of testosterone to its precursor steroids and low SHBG were the indicators of this. Low SHBG and testicular steroids were still present 16 weeks after drug withdrawal. If dehydroepiandrosterone and its sulfate are low in the blood, it means anabolics also shut down 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 taking it with DHEA or other steroid hormones. This may be because pregnenolone increases the production of ALL sex hormones including estradiol (the precursor to estrogen). Increase in estrogen can cause water retention and bloating.

• High Estrogen Levels -- As mentioned above, pregnenolone is converted into many sex hormones including various forms of estradiol. This increase in estradiol can cause your estrogen levels to go up.

• Weird Dreams -- Many people taking pregnenolone have reported vivid, 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 swings, acne, anger, anxiety, irritability and insomnia. For those with hormone sensitive conditions (breast, ovarian or uterine cancer, endometriosis) the hormone can exacerbate health problems since pregnenolone increases estrogen production.

• But the truth is these side effects are minimal. Pregnenolone is generally a safe supplement with limited side effects. But you need to know what you're getting into when taking 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 Quest Diagnostics Manual, normal circulating levels of pregnenolone are:

• 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)

Typical dose of pregnenolone is 50 to 200 mg per day, taken in the morning. Pills are to be taken on an empty stomach or you can use a cream (transdermal application).

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

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Pregnenolone for Men

Does pregnenolone increase testosterone?

Pregnenolone is a hormone that is a precursor to other hormones including testosterone. Pregnenolone itself doesn't directly increase testosterone but can play a role in the body's production of testosterone and other hormones. The effect of pregnenolone on testosterone levels varies 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 help with ED?

Pregnenolone is a hormone that is sometimes used as a supplement to help with various conditions but its effectiveness in treating ED has not been scientifically proven. If you have ED, you should 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 used by men for hormonal balance?

Pregnenolone is a hormone that is 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 like DHEA and testosterone boosters directly target specific hormones, pregnenolone is a building block for various 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 pregnenolone from a reputable source to ensure quality and effectiveness. Before starting any new supplement regimen consult with a healthcare provider to determine the right dosage and to make sure it's safe for your health.

Research on pregnenolone is showing its many roles in men's health especially on 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.

References

1. Marx, Christine E. et al. “Proof-of-Concept Randomized Controlled Trial of Pregnenolone in Schizophrenia.” Psychopharmacology 231.17 (2014): 3647–3662.

2. Bracci, Massimo et al. “Pregnenolone and Testosterone Levels in Male Shift Workers.” International journal of environmental research and public health 20.4 (2023): 3195-.

3. MARX, Christine E et al. “Proof-of-Concept Trial with the Neurosteroid Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia.” Neuropsychopharmacology 34.8 (2009): 1885–1903.

4. Osuji, I. Julian et al. “Pregnenolone for Cognition and Mood in Dual Diagnosis Patients.” Psychiatry research 178.2 (2010): 309–312.

5. Ritsner, Michael S. “Pregnenolone, DHEA and Schizophrenia: Changes and Clinical Trials.” CNS neuroscience & therapeutics 16.1 (2010): 32–44.

6. Morley, John E. “Overview of Hormone Therapy for Rejuvenation.” Fertility and sterility 99.7 (2013): 1807–1813.

7. Smith CC, Gibbs TT, Farb DH. Pregnenolone sulfate. Psychopharmacology 231.17 (2014): 3537–3556.

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