Pregnenolone

• Cognitive support
• Hormone balance
• Stress adaptation
• Neuroprotection

• Mood enhancement
• Memory support
• Energy production
• Anti-inflammatory
• Joint health
• Sleep quality

Pregnenolone exerts its biological effects through multiple mechanisms, with its roles as both a hormone precursor and a neurosteroid being the most significant. As the first steroid synthesized from cholesterol in the steroidogenic pathway, pregnenolone serves as the primary precursor for virtually all steroid hormones in the human body. This conversion begins with the transport of cholesterol into the mitochondria by the steroidogenic acute regulatory protein (StAR), followed by the cleavage of the cholesterol side chain by the enzyme P450scc (side-chain cleavage enzyme), resulting in pregnenolone formation. From this foundational molecule, two major pathways emerge: the delta-5 pathway, which leads to the formation of DHEA and subsequently androgens and estrogens; and the delta-4 pathway, which leads to progesterone and ultimately glucocorticoids and mineralocorticoids.

Through these conversion pathways, pregnenolone supplementation can potentially influence the entire spectrum of steroid hormones, though the extent and pattern of these effects vary significantly between individuals based on age, sex, enzyme activity, and existing hormone levels. Beyond its role as a hormone precursor, pregnenolone functions as a neurosteroid with direct effects on the central nervous system. Neurosteroids are steroid hormones that can be synthesized de novo in the brain and rapidly modulate neuronal excitability through non-genomic mechanisms. Pregnenolone and its sulfated form (pregnenolone sulfate) interact with several neurotransmitter receptors, most notably GABA-A and NMDA receptors.

Pregnenolone sulfate acts as a negative allosteric modulator of GABA-A receptors, reducing the inhibitory effects of GABA, the primary inhibitory neurotransmitter in the brain. This action can increase neuronal excitability and may contribute to pregnenolone’s reported effects on cognitive function, particularly learning and memory. Conversely, pregnenolone sulfate acts as a positive allosteric modulator of NMDA (N-methyl-D-aspartate) receptors, enhancing glutamatergic neurotransmission. NMDA receptors play crucial roles in synaptic plasticity, learning, and memory formation.

By potentiating NMDA receptor activity, pregnenolone may enhance long-term potentiation (LTP), a cellular mechanism underlying learning and memory. Pregnenolone also modulates other neurotransmitter systems, including sigma-1 receptors, which are involved in neuroprotection, neuroplasticity, and cognitive function. As a sigma-1 receptor agonist, pregnenolone may enhance neuronal survival and function, particularly under conditions of stress or neurodegeneration. The anti-inflammatory effects of pregnenolone involve multiple mechanisms.

It can modulate immune cell function and reduce the production of pro-inflammatory cytokines. Additionally, as a precursor to cortisol (via the progesterone pathway), pregnenolone may indirectly contribute to anti-inflammatory effects through increased cortisol production, though this pathway is subject to regulatory control by the hypothalamic-pituitary-adrenal (HPA) axis. Pregnenolone’s effects on mood and stress adaptation may be mediated through its influence on the endocannabinoid system. Research has shown that pregnenolone can act as a signaling-specific inhibitor of the cannabinoid receptor type-1 (CB1), potentially protecting the brain from the memory-impairing effects of cannabis and modulating stress responses.

In the context of neuroprotection, pregnenolone may enhance myelination and promote neuronal repair through effects on oligodendrocytes and neural progenitor cells. These actions could contribute to its potential benefits in conditions involving neurodegeneration or neuronal injury. Pregnenolone may also influence mitochondrial function, enhancing energy production and reducing oxidative stress. As mitochondrial dysfunction is implicated in aging and various neurological conditions, this mechanism may contribute to pregnenolone’s anti-aging and neuroprotective effects.

The microtubule-stabilizing properties of pregnenolone may further contribute to its neuroprotective effects. By promoting microtubule assembly and stability, pregnenolone could enhance axonal transport and neuronal structural integrity, processes that are often compromised in neurodegenerative conditions. It’s important to note that pregnenolone’s mechanisms of action are complex and interconnected, with effects that can vary based on its conversion to other hormones, local tissue concentrations, and individual physiological factors. This complexity contributes to both the wide range of potential benefits and the variability in individual responses to pregnenolone supplementation.

The optimal dosage of pregnenolone varies significantly based on age, sex, health status, and specific therapeutic goals. Clinical studies have used a wide range of dosages, typically between 5-200 mg daily. For general cognitive support and health maintenance purposes, lower doses (5-30 mg daily) are often recommended, particularly for individuals over 40 when natural pregnenolone levels begin to decline. Higher doses (50-200 mg daily) may be used for specific therapeutic purposes under healthcare supervision.

Women may require different dosing than men due to differences in hormone metabolism and sensitivity. Dosing should be guided by baseline and follow-up hormone testing whenever possible, with the goal of restoring pregnenolone levels to the optimal range for a healthy young adult, rather than exceeding physiological norms.

Pregnenolone demonstrates variable oral bioavailability, with estimates ranging from 10-30% depending on formulation and individual factors. After oral administration, pregnenolone undergoes significant first-pass metabolism in the liver, where a substantial portion is converted to other steroid hormones or conjugated for excretion before reaching systemic circulation. This extensive first-pass effect contributes to its relatively low oral bioavailability compared to other administration routes. Sublingual administration bypasses first-pass metabolism to some extent, potentially increasing bioavailability to 30-60%, though precise comparative studies are limited.

Transdermal formulations (creams, gels) may provide bioavailability of 30-70%, with the advantage of more stable blood levels and reduced hepatic processing. The absorption kinetics of oral pregnenolone show peak plasma concentrations typically occurring 1-3 hours after ingestion, with conversion to downstream hormones continuing over several hours. Pregnenolone is highly lipophilic, which affects its absorption characteristics. Taking with a small amount of dietary fat may enhance absorption of oral formulations by stimulating bile release and improving solubilization.

Micronized pregnenolone formulations, with particle sizes reduced to 5-10 micrometers, demonstrate improved dissolution rates and absorption compared to non-micronized forms, potentially increasing bioavailability by 20-50%.

Micronization significantly improves dissolution rate and absorption by increasing surface area, Liposomal formulations can enhance bioavailability by protecting pregnenolone from degradation and improving cellular uptake, Sublingual administration bypasses first-pass metabolism, potentially increasing bioavailability, Taking with a small amount of healthy fat may improve absorption of oral formulations, Transdermal delivery systems (creams, gels) bypass first-pass metabolism, Cyclodextrin complexation can improve solubility and stability, Lipid-based delivery systems enhance absorption of this lipophilic compound, Taking on an empty stomach may reduce competition with dietary components for some individuals, Avoiding simultaneous intake of substances that induce liver enzymes, Proper timing relative to circadian rhythms (morning administration mimics natural peak)

For most individuals, morning administration of pregnenolone is recommended to align with the body’s natural circadian rhythm of steroid hormone production, which typically peaks in the early morning hours and declines throughout the day. This timing may help maintain more physiological hormone patterns and minimize potential sleep disruption. For those using pregnenolone primarily for cognitive enhancement and mental energy, morning dosing is particularly appropriate, as it may enhance alertness and cognitive function during daytime hours when these benefits are most needed. If using higher doses (above 50 mg), dividing into two daily doses (morning and early afternoon) may provide more stable blood levels and reduce potential side effects compared to a single large dose.

However, avoid late afternoon or evening dosing as it may interfere with sleep patterns in some individuals due to its potentially stimulating effects. For those using pregnenolone primarily for mood support, consistent timing is more important than specific time of day, as these benefits accumulate through regular use rather than acute effects. Morning dosing is still generally preferred for mood benefits to align with natural cortisol rhythms. For individuals specifically using low-dose pregnenolone (5-10 mg) to support sleep quality, evening dosing approximately 1-2 hours before bedtime may be beneficial, contrary to the general recommendation for morning dosing.

This approach should be tested cautiously as individual responses vary significantly. If using multiple supplements or medications, separating pregnenolone from liver-metabolized medications by at least 2 hours may reduce potential interactions, particularly for medications with narrow therapeutic windows. For those using transdermal pregnenolone preparations, application in the morning is still preferred, though the time-release nature of these formulations makes timing somewhat less critical than with oral forms. For sublingual formulations, taking on an empty stomach may improve absorption, as food or beverages can wash away the hormone before complete absorption occurs.

For those new to pregnenolone supplementation, starting with lower doses in the morning and gradually increasing while monitoring for effects and side effects is recommended. This approach allows for assessment of individual response and tolerance.

• Overstimulation, anxiety, or irritability, particularly at higher doses
• Insomnia or sleep disturbances, especially with evening dosing
• Headaches
• Heart palpitations or irregular heartbeat in sensitive individuals
• Mood changes or emotional lability
• Acne or oily skin due to potential conversion to androgens
• Hair thinning or loss in some individuals (rare)
• Menstrual irregularities in women
• Breast tenderness in women
• Fatigue or lethargy (paradoxical reaction in some individuals)
• Gastrointestinal discomfort
• Dizziness or lightheadedness
• Changes in libido (either increased or decreased)
• Potential aggravation of hormone-sensitive conditions

• Hormone-sensitive cancers (breast, prostate, ovarian, uterine)
• History of seizures or epilepsy
• Bipolar disorder or history of mania/hypomania
• Severe liver disease
• Severe kidney disease
• Pregnancy and breastfeeding
• Children and adolescents
• Active hormone-dependent malignancies
• Endometriosis
• Uterine fibroids
• Severe cardiovascular disease
• Uncontrolled hypertension
• History of steroid-induced psychosis
• Known hypersensitivity to pregnenolone

• Hormone replacement therapy (estrogen, progesterone, testosterone) – potential additive or unpredictable effects
• Anticonvulsant medications – potential reduction in seizure threshold
• Psychotropic medications (antipsychotics, mood stabilizers) – potential interference with therapeutic effects
• Benzodiazepines and other GABA-ergic drugs – pregnenolone may counteract effects through GABA receptor modulation
• Stimulant medications – potential additive stimulant effects
• Corticosteroids – complex interactions with adrenal function and steroid pathways
• Anticoagulants – theoretical risk of interaction, though evidence is limited
• Tamoxifen and other selective estrogen receptor modulators – potential interference
• Aromatase inhibitors – potential interference through steroid pathway effects
• Medications metabolized by cytochrome P450 enzymes – potential competition for metabolism
• Thyroid medications – potential interactions through effects on metabolism
• Diabetes medications – potential effects on glucose metabolism

No definitive toxic upper limit has been established for pregnenolone, but clinical experience and research suggest that doses above 200 mg daily significantly increase the risk of adverse effects without proportional benefits for most individuals. Most clinical studies have used doses between 5-200 mg daily, with side effects becoming more common and pronounced at higher doses, particularly above 100 mg daily. The appropriate dose varies significantly based on age, sex, health status, and individual metabolism. Hormone testing before and during supplementation is strongly recommended to guide dosing decisions and minimize risks.

The risk of side effects appears to increase not only with dose but also with duration of use at higher doses. Short-term use of higher doses may be better tolerated than long-term use. The risk profile is also influenced by individual factors such as existing hormone levels, enzyme activity, and sensitivity to neurosteroid effects. Individuals with a history of mood disorders, particularly bipolar disorder or conditions with manic features, should exercise extreme caution with pregnenolone, as its neurosteroid effects may potentially trigger or exacerbate manic episodes.

The risk of hormonal side effects may be greater in women due to the potential for pregnenolone to be converted to androgens, which can cause symptoms such as acne, hair loss, or menstrual irregularities at higher doses. For individuals with hormone-sensitive conditions, even low doses of pregnenolone may pose significant risks and should be avoided unless specifically prescribed and monitored by a healthcare provider with expertise in hormone management. Regular monitoring is essential for anyone using pregnenolone long-term, including periodic assessment of hormone levels, liver function, and condition-specific markers. Starting with lower doses (5-10 mg daily) and gradually increasing while monitoring for benefits and side effects represents the safest approach to pregnenolone supplementation.

In the United States, pregnenolone is regulated as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. This classification allows it to be sold without prescription as long as manufacturers do not make specific disease treatment claims. The FDA does not review or approve dietary supplements before they are marketed, placing the responsibility on manufacturers to ensure safety and accurate labeling. Manufacturers are permitted to make structure/function claims (e.g., ‘supports cognitive function’ or ‘promotes hormone balance’) with appropriate disclaimers, but cannot claim to treat, cure, or prevent specific diseases.

The FDA has not established a recommended daily allowance (RDA) or adequate intake (AI) level for pregnenolone, as it is not considered an essential nutrient. Pregnenolone is not approved by the FDA as a drug for any specific medical condition, though it has been investigated for various applications including cognitive enhancement and mood disorders. As a supplement, there are no official standardized dosing guidelines established by regulatory authorities.

Canada: In Canada, pregnenolone is not approved as a natural health product (NHP) by Health Canada and is not legally available as an over-the-counter supplement. It may be available through compounding pharmacies with a prescription or through personal importation policies for limited quantities.

Eu: In most European Union countries, pregnenolone is not approved as a food supplement or medication. It falls under stricter regulatory control than in the United States and is generally not widely available without prescription. Specific regulations vary by member state, with some countries allowing limited access through compounding pharmacies or with a prescription.

Uk: In the United Kingdom, pregnenolone is not licensed as a medicine by the Medicines and Healthcare products Regulatory Agency (MHRA) and is not commonly available as an over-the-counter supplement. It may be available through compounding pharmacies with a prescription or through personal importation for individual use.

Australia: In Australia, pregnenolone is not included in the Australian Register of Therapeutic Goods (ARTG) and is not approved by the Therapeutic Goods Administration (TGA) as an over-the-counter supplement. It may be available through compounding pharmacies with a prescription from a healthcare provider.

Japan: In Japan, pregnenolone is not approved as a food supplement or medication by the Ministry of Health, Labour and Welfare. It is not commonly available for consumer purchase and would generally require special importation or prescription access.

China: In China, pregnenolone is not approved as a dietary supplement or medication by the National Medical Products Administration (NMPA). It is not commonly available for consumer purchase and would generally require special importation or prescription access.

Brazil: In Brazil, pregnenolone is regulated by the Brazilian Health Regulatory Agency (ANVISA) and is not approved as an over-the-counter supplement. It may be available through compounding pharmacies with a prescription.

Russia: In Russia, pregnenolone is not commonly available as an over-the-counter supplement. It may be available through prescription or special importation, but is not widely used in conventional medical practice.

India: In India, pregnenolone is not widely regulated or marketed. When available, it would generally be considered a pharmaceutical ingredient rather than a dietary supplement and would fall under the regulatory authority of the Central Drugs Standard Control Organization (CDSCO).

South Africa: In South Africa, pregnenolone is not registered with the South African Health Products Regulatory Authority (SAHPRA) as an approved supplement or medication. It may be available through compounding pharmacies with a prescription.

Low to medium compared to most hormone-related supplements

Typical retail pricing for pregnenolone capsules ranges from $10-30 for a 30-day supply at common dosages (10-50 mg daily), translating to approximately $0.33-1.00 per day. Higher potency products (100 mg or more per capsule) may cost $15-35 for a 30-day supply. Micronized pregnenolone formulations typically command a 20-40% premium over standard formulations, with prices ranging from $15-40 for a 30-day supply. Sublingual and liposomal formulations generally cost $20-45 for a 30-day supply, reflecting their enhanced delivery systems.

Topical pregnenolone creams typically cost $20-50 per container, with cost per application varying based on concentration and container size. Pregnenolone sulfate, the sulfated form with potentially stronger neurosteroid effects, is less commonly available and typically costs 30-50% more than regular pregnenolone when found.

Pregnenolone represents good value for specific applications, particularly considering its status as a neurosteroid and hormone precursor with multiple potential benefits. The relatively low cost compared to many cognitive enhancement supplements or hormone therapies makes it an economical option for those seeking support in these areas. The value proposition is strongest for individuals who: 1) Are over 40 and experiencing age-related cognitive changes; 2) Have documented low pregnenolone levels confirmed by testing; 3) Experience measurable benefits in memory, mood, or other parameters; 4) Are using it for specific evidence-supported applications. For cognitive enhancement purposes, pregnenolone is generally more affordable than many specialized nootropic stacks or prescription cognitive enhancers, though the evidence base is less established for some applications.

A month’s supply of pregnenolone at effective doses typically costs less than many proprietary cognitive formulations. The significant price variation between products reflects differences in quality, formulation, and marketing positioning rather than necessarily proportional differences in efficacy. Basic pregnenolone supplements from reputable manufacturers often provide similar quality at the lower end of the price spectrum. For maximum cost efficiency, consumers should compare products based on price per milligram of active ingredient rather than total price.

Micronized forms, while more expensive, may offer better value through enhanced absorption, potentially allowing for lower effective doses. Testing costs should be factored into the overall value equation when using pregnenolone. Baseline and follow-up hormone testing (typically $50-200 per panel) is recommended for optimal use, adding to the total cost of therapy. For those requiring higher doses, purchasing higher-potency capsules (50-100 mg) and splitting them can significantly reduce costs compared to taking multiple lower-dose capsules.

However, this approach requires careful measurement and may not be suitable for everyone. Sublingual formulations, while more expensive per milligram, may offer better value through enhanced bioavailability, potentially allowing for 30-50% lower doses compared to oral forms. For individuals with specific cognitive concerns using pregnenolone as part of a comprehensive approach, the cost is generally justified by potential benefits and is typically lower than many conventional treatments. For most users, the sweet spot for value appears to be basic pregnenolone capsules from reputable manufacturers, used at the lowest effective dose determined through careful self-monitoring and periodic testing.

Properly stored pregnenolone in capsule or tablet form typically has a shelf life of 2-3 years from date of manufacture. Pure pregnenolone powder may have a slightly shorter optimal shelf life of 1-2 years due to increased surface area exposure to environmental factors. Liquid formulations generally have shorter shelf lives of 1-2 years, with stability declining more rapidly after opening due to increased exposure to air and potential contamination. Transdermal preparations (creams, gels) typically have shelf lives of 1-2 years when properly stored, though efficacy may begin to decline earlier due to potential separation or degradation of the base formulation.

Sublingual tablets generally have shelf lives similar to regular tablets (2-3 years) but may be more susceptible to moisture degradation if not properly stored. Pregnenolone sulfate (the sulfated form) may have slightly different stability characteristics, with some research suggesting it may be more susceptible to degradation under certain conditions.

Store pregnenolone supplements in a cool, dry place away from direct sunlight, preferably below 75°F (24°C). Refrigeration is not necessary for most formulations and may actually increase the risk of condensation when containers are opened and closed. However, some liquid formulations may benefit from refrigeration after opening – follow manufacturer’s specific recommendations. Airtight containers are essential to prevent moisture absorption, which can accelerate degradation.

Once opened, ensure the container is tightly sealed after each use. For powders, use a dry spoon to remove product to avoid introducing moisture. Some manufacturers include desiccant packets in their products to absorb moisture; these should be kept in the container but not consumed. If purchasing in bulk quantities, consider transferring a portion to a smaller container for regular use while keeping the remainder sealed until needed.

Avoid storing near strong-smelling substances as cross-contamination of odors may occur. For capsule and tablet forms, store in their original containers with the lid tightly closed, away from heat and moisture. For transdermal preparations, ensure the container is tightly sealed after use and follow any specific storage instructions provided by the manufacturer. Some products may require refrigeration.

Sublingual tablets are particularly sensitive to moisture; ensure they remain in their original container with any desiccant packets included, and avoid handling them with wet hands. Some premium pregnenolone products are packaged in dark glass or opaque containers to protect from light, though light exposure is generally less critical for pregnenolone stability than moisture and heat exposure.

Moisture: The primary degradation factor for pregnenolone; absorption of moisture can lead to hydrolysis and degradation of the steroid structure, Heat: Elevated temperatures accelerate chemical degradation; prolonged exposure to temperatures above 85°F (30°C) can significantly reduce potency, Oxygen: Exposure to air causes oxidation, particularly of the double bond in the steroid structure, forming various oxidation products, Light: Direct sunlight and UV exposure can cause photodegradation, though this is less significant than moisture and heat factors, Microbial contamination: Can lead to both safety issues and degradation of the active compound, pH extremes: Pregnenolone is most stable at slightly acidic to neutral pH; strong acids or bases can accelerate degradation, Enzymatic degradation: Primarily a concern for liquid formulations without appropriate preservatives, Chemical interactions with excipients: Some fillers, binders, or other ingredients may potentially accelerate degradation if not properly formulated, Freeze-thaw cycles: Repeated freezing and thawing can affect physical stability, particularly of liquid and transdermal formulations, Physical stress: Excessive crushing or grinding of tablets can expose more surface area to degradation factors

Synthesis Methods

Natural Sources

Quality Considerations

Pregnenolone has a relatively short historical usage compared to many traditional botanical supplements, as it was first identified and isolated in the 20th century. The compound was initially discovered in 1934 by Adolf Butenandt and colleagues, who isolated it from pregnant mare urine and later from pig ovaries. This groundbreaking work was part of the early exploration of steroid hormones that would eventually earn Butenandt the Nobel Prize in Chemistry in 1939. In 1943, biochemist Russell Marker developed a method to synthesize pregnenolone from diosgenin, a compound found in wild yams (Dioscorea species).

This process, known as the Marker degradation, revolutionized steroid hormone production and made pregnenolone and its derivatives more accessible for research and medical applications. The 1940s saw the first investigations into pregnenolone’s potential therapeutic applications. During World War II, the U.S. Air Force conducted studies on pregnenolone as a potential agent to improve performance and reduce fatigue in pilots during extended missions.

These early studies showed promising results for cognitive function and stress resilience, though the findings were not widely published at the time. In the late 1940s and early 1950s, pregnenolone was briefly used clinically for rheumatoid arthritis and other inflammatory conditions. Initial results were promising, with some patients experiencing significant relief from joint pain and inflammation. However, the emergence of synthetic corticosteroids like cortisone, which showed more potent anti-inflammatory effects, quickly overshadowed pregnenolone’s medical use.

By the mid-1950s, pregnenolone had largely been abandoned as a therapeutic agent in conventional medicine, though research into its biochemical role continued in academic settings. The 1960s and 1970s brought significant advances in understanding the steroid hormone pathway, with pregnenolone firmly established as the ‘mother hormone’ or precursor to all steroid hormones. During this period, research focused primarily on pregnenolone’s biochemical role rather than its therapeutic potential. A major turning point came in the 1980s and early 1990s with the discovery that pregnenolone and its sulfated form (pregnenolone sulfate) function as neurosteroids, capable of being synthesized in the brain and modulating neuronal activity.

Pioneering work by researchers like Étienne-Émile Baulieu demonstrated that these neurosteroids could affect neurotransmitter receptors, particularly GABA and NMDA receptors, suggesting potential applications for cognitive and neurological conditions. The 1994 Dietary Supplement Health and Education Act (DSHEA) in the United States created a regulatory framework that allowed pregnenolone to be marketed as a dietary supplement rather than a drug. This legislative change dramatically increased its availability to the general public and sparked renewed interest in its potential benefits. The late 1990s and early 2000s saw an expansion of research into pregnenolone’s effects on cognitive function, mood, and neurological conditions.

Studies in both animals and humans began to explore its potential for conditions ranging from cognitive decline to depression, schizophrenia, and anxiety disorders. During this period, pregnenolone also gained popularity in the anti-aging and complementary medicine communities, often promoted for its potential benefits for memory, mood, and overall brain health. The 2000s and 2010s brought more sophisticated understanding of pregnenolone’s mechanisms of action, particularly its effects on neurotransmitter systems and its role in neuroplasticity and neuroprotection. Research during this period has become more focused on specific clinical applications, with controlled trials examining its potential for conditions like schizophrenia, bipolar disorder, and cognitive impairment.

Recent years have seen increasing interest in pregnenolone’s potential role in stress resilience and trauma-related conditions. Research has begun to explore its effects on the endocannabinoid system and its potential for conditions like PTSD and chronic stress. Throughout its history, pregnenolone has occupied a unique position between conventional medicine and complementary health approaches. While some potential medical applications are being investigated in clinical trials, many of its uses remain in the realm of complementary and alternative medicine, with ongoing debates about appropriate applications, dosing, and monitoring.

Today, pregnenolone continues to be widely available as a dietary supplement in the United States and some other countries, while remaining more restricted in many parts of the world. This regulatory divergence reflects the ongoing scientific uncertainty about its risk-benefit profile and optimal clinical applications.

No comprehensive meta-analyses specifically focused on pregnenolone supplementation have been published to date.

Pregnenolone for Cognitive Enhancement in Mild Cognitive Impairment (PREG-COG-2023), Neurosteroid Supplementation for Treatment-Resistant Depression (NEURO-DEPR-2022), Pregnenolone for Stress Reduction in High-Stress Occupations (PREG-STRESS-2023), Comparative Analysis of Different Neurosteroids on Cognitive Function (NEURO-COG-2022)