Can I Take Pregnenolone and DHEA Together?

Today, in conversations around anti-aging and hormonal health optimization, few compounds receive as much attention as DHEA (dehydroepiandrosterone) and pregnenolone.

Both of these substances are endogenous steroid precursors that play roles in the steroidogenesis pathway and are being explored for their potential to support cognitive function, healthy aging, and hormonal balance.

However, a critical question arises: Can pregnenolone and DHEA be taken together? This article will delve into the biochemical roles of these two precursors, explore their interactions, and assess the scientific literature to help you make an informed and evidence-based decision.

What is DHEA?

DHEA (Dehydroepiandrosterone) is an endogenous steroid hormone primarily produced by the adrenal glands via the cholesterol synthesis pathway. It acts as a vital precursor for the biosynthesis of several key sex hormones, including androgens (such as testosterone) and estrogens (such as estradiol).

The body begins to produce DHEA in early childhood, with levels increasing after the age of 7, peaking during late adolescence and early adulthood (approximately between the ages of 20 to 24).

After this peak, DHEA levels decline steadily with age—at an estimated rate of 20% per decade. This means that if your DHEA level is 100% at age 25, by the time you reach 65, it may drop to approximately 20%, leading to symptoms associated with aging, such as fatigue, reduced cognitive performance, and diminished libido(Baulieu et al., 2000).

In addition to age-related decline, DHEA levels are also adversely affected by external stressors such as physiological stress, trauma, or infection. This makes declining DHEA a growing concern in the context of today’s demanding lifestyle.

The Role of DHEA in Hormone and Human Health

DHEA is primarily synthesized by the adrenal cortex, with smaller amounts produced by the ovaries in women and the testes in men.

Unlike systemic (endocrine) hormones that travel through the bloodstream, DHEA functions predominantly in a local (intracrine) manner—being converted and acting within specific tissues such as the brain, skin, and adipose tissue. Therefore, serum DHEA levels often fail to capture the full spectrum of its biological activity(Labrie et al., 2005).

The diagram below illustrates DHEA’s metabolic pathway, helping to clarify its role in hormone synthesis and physiological impact:

DHEA plays a critical role in maintaining endocrine homeostasis, particularly in aging individuals whose natural hormone production begins to wane. Several studies have demonstrated that DHEA supplementation can improve both physical and psychological health markers.

These include increases in muscle strength, bone density, and reductions in age-related fat accumulation and skin atrophy. It has also been shown to stimulate the production of procollagen and sebum (Rutkowski et al., 2014).

However, due to its potent hormonal activity, improper supplementation can lead to undesirable side effects, such as oily skin, hirsutism, or mood alterations—especially in the absence of professional medical oversight.

DHEA is also associated with improved reproductive function in women. For example, one clinical study reported that DHEA supplementation enhanced pregnancy rates and reduced miscarriage incidence among women with diminished ovarian reserve.

In this study, among 109 infertile women aged 36–40 undergoing IVF, the DHEA group showed a significantly higher live birth rate compared to the control group(Massimo Tartagni, et al. 2015).

However, the study, despite its promising results, was limited by its small sample size, unrepresentative subjects, and lack of clarity about the study design. Therefore, larger, well-controlled clinical trials are needed to confirm the true effects of DHEA on fertility.

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What is Pregnenolone?

Pregnenolone—often referred to as the “mother hormone”—is the precursor to many other steroid hormones. Like DHEA, pregnenolone is synthesized from cholesterol, primarily within the mitochondria of the adrenal glands. However, it is also produced in smaller amounts in the brain, skin, liver, ovaries (in females), and testes (in males).

Pregnenolone is the origin of many important hormones such as progesterone, cortisol, estrogen, and testosterone. Similar to DHEA, pregnenolone levels decline over time.

Specifically, pregnenolone sulfate levels in women peak around the age of 32 and then steadily decrease, whereas in men, the peak occurs about five years earlier and then remains relatively stable(Helena et al., 2002) .

Furthermore, pregnenolone is associated with memory, concentration, responsiveness, and interaction with stress. For example, pregnenolone and its derivatives, such as pregnenolone sulfate, improve memory and learning ability in animal models.

These compounds influence neuroplasticity and enhance signaling through GABA and glutamate — two major neurotransmitter systems (Baulieu et al., 2000).

Moreover, pregnenolone sulfate has been shown to reduce anxiety-like behavior and increase adaptability under stressful conditions by modulating the GABAergic and glutamatergic systems (Darbra et al., 2009).

This is mainly because pregnenolone is found at higher concentrations in the central nervous system compared to peripheral tissues, highlighting its importance to brain function.

Therefore, changes in pregnenolone levels have the potential to affect these brain functions. For this reason, more specific studies are needed to accurately assess pregnenolone’s effects.

However, most existing evidence is based on animal models, and well-designed clinical trials in humans are needed to confirm the cognitive benefits and safety profile of pregnenolone.

The Role of Pregnenolone in Hormone and Human Health

To fully understand pregnenolone’s importance, one must recognize it as the first steroid hormone derived from cholesterol—a conversion that occurs mainly in the mitochondria, appearing in the adrenal glands, brain, testes, ovaries, and placenta (Miller, et al. 2013).

This biosynthetic step is catalyzed by the mitochondrial enzyme CYP11A1 (cholesterol side-chain cleavage enzyme), converting cholesterol into pregnenolone. From there, pregnenolone undergoes multiple metabolic pathways to generate:

• Glucocorticoids (e.g., cortisol)
• Mineralocorticoids (e.g., aldosterone)
• Androgens (e.g., DHEA, testosterone)
• Estrogens (e.g., estradiol, estrone)
• Progesterone, a hormone critical for menstrual function and pregnancy

Pregnenolone also interacts with neurotransmitter receptors such as GABA and NMDA, suggesting a neuromodulatory role in cognitive adaptation. Studies indicate that pregnenolone may enhance sleep quality, regulate circadian rhythms, and reduce sleep disturbances(Teran-Perez et al., 2012).

In addition, pregnenolone also has the potential to support neuroprotection; it is involved in disorders related to stress, anxiety, as well as in addiction processes that significantly impact cannabinoid-related disorders (Vallee et al., 2016).

This means that pregnenolone has a certain effect on protecting and maintaining healthy and normal neurological functions in adults.

Moreover, Animal studies have examined how pregnenolone may influence brain function, with some findings pointing to possible relevance in areas related to mental health, including schizophrenia (Marx et al., 2011); however, these remain preliminary findings that require validation through large-scale clinical trials before any firm conclusions can be drawn.

Can I Take Pregnenolone and DHEA Together?

The short answer is yes—pregnenolone and DHEA can be taken together under appropriate conditions. However, the dosage, ratio, and timing of administration are critical variables that must be managed carefully. Unlike nutritional supplements, these are potent hormonal precursors, and improper use can lead to adverse outcomes.

In studies, the dosage of DHEA and pregnenolone typically ranges around 400 mg per day. For example, a study investigating the combined effects of these two compounds on stress response and emotions used a similar dosage and observed positive differences after the study period (Rebecca K. et al., 2013).

Another study using a comparable dosage demonstrated support for improved cognitive functions, while a 200 mg dose of DHEA did not provide significant benefits (Ritsner et al., 2010).

Therefore, the dosage range of 200–400 mg for each compound should be considered. However, the exact dosage should be advised by healthcare professionals and follow the recommendations of product manufacturers combining these substances.

Overuse or mismanagement may result in hormonal dominance (e.g., estrogen or testosterone excess), leading to endocrine disorders such as hormonal imbalances, development of secondary sexual characteristics inappropriate for one’s sex, and potential drug interactions.

Additionally, through a discussion thread on Reddit titled “Pregnenolone/DHEA side effects,” users shared experiencing symptoms such as fatigue and brain fog. Meanwhile, another user reported having difficulty sleeping for several consecutive months along with brain fog.*

Therefore, consulting with healthcare professionals is necessary in such cases to be aware of and adequately prepare for potential side effects. For these reasons, medical supervision is strongly recommended.

Despite these risks, combining pregnenolone and DHEA may offer synergistic benefits, especially for purposes such as adrenal support, cognitive enhancement, and healthy aging.

Since both hormones originate from cholesterol metabolism and influence neurological and endocrine function, their combined use—when carefully balanced—can provide enhanced physiological effects.

To better understand this combination, we will now explore what the scientific literature reveals about these two powerful hormone precursors.

What Does Science Say About Pregnenolone and DHEA in Cognitive and Anti-Aging Health?

To better evaluate the potential of combining pregnenolone and DHEA, let’s examine what scientific research reveals:

In a study exploring adjunctive therapies for schizophrenia and schizoaffective disorders, an 8-week clinical trial investigated the use of pregnenolone (at 30 mg and 200 mg/day) and DHEA (400 mg/day).

Results showed that low-dose pregnenolone (30 mg/day) significantly reduced positive symptoms and improved working memory, while DHEA supplementation alleviated extrapyramidal side effects associated with antipsychotic medications (Ritsner et al., 2010) [12].

Furthermore, a cross-sectional study involving 122 healthy adults found a positive correlation between serum pregnenolone levels and both working memory and verbal fluency in men.

Additionally, DHEA and its sulfated form (DHEA-S) were associated with improved quality of life and cognitive function, particularly in males—highlighting the essential role of these neurosteroids in preserving cognitive health and psychological well-being (Chen et al., 2018) [14].

However, further clinical evidence and controlled studies are warranted to establish the optimal dosage, safety, and efficacy for the above effects.

Conclusion

In conclusion, the combination of pregnenolone and DHEA presents a promising strategy for individuals seeking to optimize cognitive performance, support anti-aging efforts, and restore hormonal balance.

However, such interventions must be highly individualized, guided by scientific evidence, and carried out under medical supervision, including appropriate lab testing and a thorough understanding of potential contraindications.

It’s critical to acknowledge that these hormones are not “magic pills.” Yet, when used responsibly and appropriately, pregnenolone and DHEA can serve as powerful tools for enhancing brain health, mental clarity, and endocrine function—regardless of gender.