Every hormone in our body comes from cholesterol. There are a lot of processes that the cholesterol would have to go through before they become hormones. Pregnenolone is the precursor or prohormone to a variety of hormones such as testosterone, progesteron, cortisol, and estrogen. This means that when our body would process cholesterol to make testosterone, progesterone, etc., it will have to make pregnenolone first and then process it further to create the aforementioned hormones.
We could say that the pregnenolone hormone has some influence over the processes that the testosterone, progesterone, cortisol, and estrogen hormones are involved in. Although it is not fully understood how pregnenolone influences these processes, pregnenolone supplements are currently being utilized for various purposes. Some health professionals might prescribe pregnenolone in cases of fatigue. Since some studies have shown pregnenolone’s potential to improve cognitive functioning, they have been prescribed for Alzheimer's disease, memory enhancement, neurological trauma and injuries, stress management, and immune regulation, this includes management of psoriasis and scleroderma. On top of this, since pregnenolone is a precursor hormone to a number of reproductive hormones, intake is also advised in cases of premenstrual syndrome, menopause, abnormal lining of the uterus or endometriosis, and lumpy breasts or fibrocystic breast disease. Although uncommon, it is also used for seizures, prostate problems, multiple sclerosis, lupus, allergic reactions, arthritis, depression, slowing aging, improving cardiovascular health, and for detoxification.
Studies on Possible Health Benefits
The effects of neurosteroid pregnenolone sulfate on cognition have been investigated on mice. In 1996, a research was conducted to determine whether pregnenolone can suppress the negative effects of scopolamine in mice’s ability to perform the appetitive learning task or not. This research was published in the Psychopharmacology journal and the researchers indicated several interesting findings. First, scopolamine does in fact negatively affect mice’s cognitive abilities. The researchers noted that the mice that were given scopolamine only performed poorly in the appetitive learning task. Second, the mice that were given scopolamine and pregnenolone performed better than those who were given scopolamine only. This indicates that pregnenolone may suppress the negative effects of scopolamine. Third, the mice that were given pregnenolone only may have better memory as they performed better in the appetitive learning task. However, pregnenolone does not suppress scopolamine’s negative effect on motor functions.
In a systematic review published last 2001 in the Brain Research Reviews regarding pregnenolone and other steroid hormone’s effect on age-related mental decline, researchers indicated that pregnenolone may prevent memory loss due to aging. However, they indicated that the human-based studies had mixed results, that some studies indicated that pregnenolone and other steroid hormones can prevent age-related mental decline while other studies do not. Animal studies on the other hand yielded consistent results, they indicated that steroid hormones can improve memory.
In a study published last 2014 in the Neuropsychopharmacology journal, researchers indicated that pregnenolone may be used to improve symptoms of depression in people afflicted with Bipolar Disorder with depressed mood states. In this study, 80 adults with Bipolar Disorder with depressed mood states were assigned to an experimental group, those who would take in 500 mg/day pregnenolone, and a placebo group, those who would take a fake pregnenolone pill, randomly. After 12 weeks, researchers noted that the patients who took pregnenolone exhibited less depression-related symptoms compared to the placebo group throughout the duration of the study.
A different animal-based study published in The National Academy of Sciences of the United States of America conducted tests on rats. The researchers discovered that pregnenolone may alleviate symptoms of depression. They went on to explain that pregnenolone can treat abnormalities in the brain cells of depressed rats which leads to relief from depression.
Literature has reported that pregnenolone may play a role in regulating neuronal excitability, response to stress, and synaptic plasticity. In other words, pregnenolone has been associated with cognitive performance and mood regulation. With this in mind, last 2010, researchers investigated pregnenolone’s effect on psychotic symptoms by adding it to the pre-existing antipsychotic treatments of those patients afflicted with chronic schizophrenia or schizoaffective disorder. After which, the researchers published their findings in the Journal of Clinical Psychiatry. In this study 58 chronic schizophrenic or schizoaffective disorder patients were assigned to an experimental group and a placebo group at random. 200 mg of Pregnenolone and 400 mg of Dehydroepiandrosterone or DHEA, on top of the usual antipsychotic drugs, were given to the patients in the experimental group each day. The placebo group was given the usual antipsychotic drugs everyday. This experiment was conducted for 16 months. Researchers observed that the schizophrenia and schizoaffective disorder patients who were given pregnenolone responded well to the antipsychotic treatment, and exhibited improvements in their attention span and working memory.
A systematic review on several studies regarding the use of pregnenolone as treatment for schizophrenia, published in Neuroscience last 2011, also indicated that pregnenolone could be a viable option for treating schizophrenia. Through their analysis, the researchers reported that pregnenolone can improve the schizophrenic patient’s brain by positively affecting the steroid compounds present in it. Furthermore, they theorized that it may be the pregnenolone’s ability to increase the gamma-aminobutyric acid concentration in the schizophrenic patient’s brain that is responsible for alleviating the condition.
Cannabinoid induced psychosis
Legalization for the recreational and even medical use of cannabinoid is still up for debate. Although several studies have shown the great potential of cannabis as treatment for numerous diseases and conditions, the greatest drawback is still its psychoactive side-effect which can lead to cannabis-induced psychosis. This is a huge problem for the proponents of medical marijuana. Fortunately, pregnenolone has shown promising results in studies investigating its ability to inhibit cannabis-induced psychosis.
One animal-based study investigated the effect of pregnenolone on mice with cannabis-induced psychosis. The psychoactive compound in cannabis is the delta-9-tetrahydrocannabinol or THC. Researchers found that pregnenolone can block a variety of THC-induced endotypes which are often linked to psychotic-like states, impaired cognitive function, somatosensory gating, and social interaction. In other words, this chimes in with the notion that pregnenolone is a potential pharmaceutical treatment for cannabis-induced psychosis.
12 autistic adults were selected for a pilot, open-label, 12-week trial aimed at assessing their tolerability towards pregnenolone and the efficacy of the hormone in reducing autism-related irritability. During the duration of the study, the autistic adults did not experience any notable vital sign changes. Researchers reported that pregnenolone is moderately effective and well-tolerated by the autistic adults. However, mild side effects such as tiredness, diarrhea, and depressive states were indicated.
Female Reproductive Disorders
Female reproductive disorders are often tied to hormonal imbalances. Thus in 2018, researchers investigated the effects of pregnenolone, a known reproductive hormone precursor, on female reproductive disorders to try and find out whether it is a viable drug for hormonal therapy or not. This was an animal-based study using immature female rats given pregnenolone. The researchers observed that pregnenolone decreased ovarian cell proliferation which makes it a good anti-ovarian-cancer hormonal treatment candidate. Aside from this, pregnenolone promoted favorable changes in the female rats’ reproductive organs such as the upregulation of Estrogen Receptor Alpha and downregulation of Estrogen Receptor Beta in their uteri, and downregulation of estrogen receptor 1, receptor 2, and P4 receptor in their ovaries.
Doctor Reddy and Kulkarni, from Panjab University’s Institute of Pharmaceutical Sciences, Department of Pharmacology, reported that pregnenolone sulfate can make mice eat less. In their research paper regarding the effects of neurosteroids on mice’s food intake and how Gamma Aminobutyric Acid A or GABA-A and mitochondrial diazepam-binding inhibitor receptors are involved in the process; they starved several mice and observed their feeding behavior upon administration of neurosteroids like pregnenolone sulfate. They observed that administration of 1 to 10 milligrams per kilogram of the mice's weight of pregnenolone sulfate made the mice eat less compared to the other food-deprived mice. What’s more is that the effect of allopregnanolone, a different neurosteroid that increases the mice’s food intake, can be suppressed with the administration of pregnenolone sulfate. Doctor Reddy and Kulkarni concluded that their data shows the importance of GABA-A and mitochondrial diazepam-binding inhibitors, and neurosteroids like pregnenolone in regulating the appetite of mice.
Research studies have indicated that Pregnane X Receptors or PXR are receptors that are involved in maintaining physiological homeostasis. What’s more is that there is evidence that its activation can prevent unhealthy eating habits, obesity, and insulin resistance. Thus, in the study entitled “Activation of Pregnane X Receptor by Pregnenolone 16 α-carbonitrile Prevents High-Fat Diet-Induced Obesity...”, researchers investigated pregnenolone’s ability to activate Pregnane X Receptors in mice and whether or not this leads to prevention of unhealthy eating habits, obesity, and insulin resistance as well. Results show that Pregnenolone does in fact activate PXR and positively influence the mice’s eating habits. What’s more is that pregnenolone treatments reduced lipogenesis and gluconeogenesis in the liver. Furthermore, accumulation of fats in the liver and adipose tissues was reduced. Results also revealed the importance of PXR in lipid and energy metabolism and that treatments for obesity and insulin resistance can be based on PXR activity regulation.
In 1996, a study regarding human cytochrome P450-1A1 activity and how it hydroxylates pregnenolone at the 7-Beta position has shown insights as to how important cytochrome and pregnenolone is to the immune system. In this study, researchers noted that both pregnenolone and DHEA require cytochrome P450-containing compounds for its hydroxylation. Through tedious usage of laboratory tests such as gas chromatography-mass spectrometry analysis, the researchers discovered that yeast-expressed human cytochrome P450-1A1 was able to hydroxylate pregnenolone at the 7-beta position. This finding solidifies cytochrome P450-1A1’s involvement in the hydroxylation of pregnenolone. Furthermore, this also shows that cytochrome P450-1A1 is indirectly responsible for the production of immune-activating 7-hydroxylated steroids and that this compound along with the hormone pregnenolone are important in regulating the immune system.
Breast-Cancer-Specific Anti-Cancer Drugs
Alkylating agent Chlorambucil, an anti-cancer drug, was processed to generate four prodrug-esters and one nitro-derivative, 3-nitro-chlorambucil. These prodrug-esters and nitro-derivatives were conjugated to pasterone and pregnenolone. Researchers then tested these drug-hormone conjugates against eight human cancer cell lines. They compared the efficacy of this drug-hormone conjugates to the traditional anti-cancer drugs, 3-nitro chlorambucil and chlorambucil. The researchers noted that the four drugs esters that were conjugated to pasterone or pregnenolone exhibited specificity towards the breast adenocarcinoma cell lines. These findings indicate that drug conjugation to hormones like pasterone and pregnenolone may increase specificity of anti-cancer drugs limiting their damage towards healthy cells while increasing efficacy of treatment.
Special Precautions & Warnings
Pregnenolone is a hormone that has a huge impact on reproductive hormone. Since not a lot is known about its effects, to be on the safe side, pregnant and lactating women are prohibited from taking this hormone.
Individuals with conditions like breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids must take extra care when taking in pregnenolone for these conditions are sensitive to hormonal changes. Since pregnenolone is a precursor to many reproductive hormones, taking this hormone might have a negative effect on those who have the aforementioned conditions. Aside from this, people with conditions or diseases that are sensitive to estrogen exposure must avoid pregnenolone as well for the same reason.
Possible Side effects
Although research has yet to verify, people have reported side effects to pregnenolone intake such as insomnia, irregular heart rhythm, headache, anxiety, and mood changes; this is probably due to the changes in hormone levels. There are some reports that men and women experienced hair loss and or facial hair growth. Research on the safety of long-term or regular use of pregnenolone supplements are yet to be conducted, so caution is advised.
Pregnenolone is a precursor to estrogen. Thus, one must avoid taking drugs that increase estrogen levels in your body when you are taking pregnenolone supplements, for this might lead to abnormally high estrogen levels. The same is true for testosterone. Taking in testosterone pills along with pregnenolone can lead to abnormally high levels of testosterone. There are several other hormones that progesterone is a precursor to. So to be on the safe side, avoid taking hormone supplements along with pregnenolone supplements for this could cause imbalances within the body.