Pregnenolone by Metabolic Response Modifiers

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral pregnenolone for aging, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Alcohol use disorder. It is unclear if oral pregnenolone is beneficial in patients with alcohol use disorder. Details: Preliminary clinical research in adults with alcohol use disorder undergoing guided imagery shows that taking pregnenolone 150-250 mg orally twice daily for 8 weeks improves alcohol craving severity scores and anxiety scores when compared with placebo. Taking pregnenolone also improved physiological markers of stress such as heart rate and blood pressure (112726).
• Alzheimer disease. Although there has been interest in using oral pregnenolone for Alzheimer disease, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Autism spectrum disorder. It is unclear if oral pregnenolone is beneficial in patients with autism spectrum disorder. Details: Two small clinical studies show pregnenolone as add-on therapy may improve symptoms in patients with autism spectrum disorder. One small clinical study shows that taking pregnenolone 100 mg orally twice daily as an add-on to risperidone for 10 weeks further improves ratings of irritability, stereotypy, and hyperactivity in drug-naïve adolescents aged 11-17 years with autism when compared with risperidone and placebo (104275). A very small open-label study in adults with autism shows that taking pregnenolone 50-250 mg orally twice daily as an add-on to therapy with psychotropic medications for 12 weeks may improve sensory abnormalities and symptoms of irritability and lethargy (94026). However, the lack of a control group limits the validity of these findings.
• Back pain. It is unclear if oral pregnenolone is beneficial in patients with back pain. Details: One small clinical study in otherwise healthy veterans with chronic low back pain shows that taking pregnenolone orally, titrated up to 500 mg daily, for 4 weeks reduces pain intensity by 0.56 when compared with placebo, as measured on a visual analog scale ranking pain intensity from 0 to 10. This small reduction is not likely to be considered clinically significant. Taking pregnenolone also seemed to modestly reduce the extent that pain interfered with activity or work when compared with placebo; however, there were no significant changes in the other 5 measures of pain interference (104274).
• Bipolar disorder. It is unclear if oral pregnenolone is beneficial in patients with bipolar disorder. Details: Preliminary clinical research in adults with bipolar disorder and depressive episodes shows that taking pregnenolone orally, titrated up to 500 mg daily, as add-on therapy for 12 weeks improves depression symptom scores when compared with placebo (94027).
• Cocaine dependence. It is unclear if oral pregnenolone is beneficial in patients with cocaine dependence. Details: Preliminary clinical research in adults with cocaine dependence undergoing guided imagery shows that taking pregnenolone 150-250 mg orally twice daily for 8 weeks improves cocaine craving severity scores when compared with placebo. Taking pregnenolone also improved physiological markers of stress such as heart rate and blood pressure (112728).
• Coronavirus disease 2019 (COVID-19). Oral pregnenolone has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows in adults with persistent symptoms at least 3 months after a COVID-19 infection shows that taking a combination product containing pregnenolone 40 mg, beta-caryophyllene 40 mg, and other ingredients orally twice daily for 4 weeks improves respiratory and other symptoms when compared with baseline (112727). The validity of this study is limited by the lack of a comparator group. It is unclear if this effect is due to pregnenolone, other ingredients, or the combination.
• Critical illness (trauma). Although there has been interest in using oral pregnenolone for trauma, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Depression. Although there has been interest in using oral pregnenolone for depression, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Endometriosis. Although there has been interest in using oral pregnenolone for endometriosis, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Fatigue. Although there has been interest in using oral pregnenolone for fatigue, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Fibrocystic breast disease. Although there has been interest in using oral pregnenolone for fibrocystic breast disease, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Memory. Although there has been interest in using oral pregnenolone for memory, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Menopausal symptoms. Although there has been interest in using oral pregnenolone for menopausal symptoms, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Multiple sclerosis (MS). Although there has been interest in using oral pregnenolone for MS, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Premenstrual syndrome (PMS). Although there has been interest in using oral pregnenolone for PMS, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Psoriasis. Although there has been interest in using oral pregnenolone for psoriasis, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Schizophrenia. It is unclear if oral pregnenolone is beneficial in patients with schizophrenia. Details: The effects of pregnenolone adjunctive therapy on negative symptoms of schizophrenia are conflicting. Several clinical studies in patients with schizophrenia and schizoaffective disorder and suboptimal response to previous antipsychotic treatments show that taking pregnenolone 50 mg orally daily alone or as add-on therapy with L-theanine 400 mg daily, for 8 weeks, reduces negative symptoms based on the negative symptom scale of the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) when compared with placebo (94029,97923). However, conflicting results exist. One study shows that taking pregnenolone 30 mg or 200 mg daily for 8 weeks does not improve negative symptoms based on the negative symptom scale of the PANSS in patients with schizophrenia and schizoaffective disorder (94028). Furthermore, another clinical study conducted in women hospitalized with an acute episode of schizophrenia shows that taking pregnenolone 50 mg orally daily for 8 weeks in combination with risperidone 2-6 mg daily does not reduce negative symptoms when compared with risperidone plus placebo (97924). Reasons for the conflicting results may relate to concomitant use of psychotropic medications such as mood stabilizers and antidepressants, prenenolone dosage, and schizophrenia subtypes of the included patients. Despite some conflicting results (94028), most research shows that taking pregnenolone orally as adjunctive therapy does not significantly improve positive symptoms based on the positive symptom subscale of the PANSS compared to placebo in patients with schizophrenia and schizoaffective disorder (94029,94032,97923,97924). One clinical study shows that taking pregnenolone 50 mg orally daily for 8 weeks in combination with antipsychotics might improve visual attention but does not appear to improve other neurocognitive symptoms of schizophrenia such as deficits in sustained attention or executive function compared with placebo (97925).
• Scleroderma. Although there has been interest in using oral pregnenolone for scleroderma, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Seizures. Although there has been interest in using oral pregnenolone for seizures, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Systemic lupus erythematosus (SLE). Although there has been interest in using oral pregnenolone for SLE, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Stress. Although there has been interest in using oral pregnenolone for stress, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose. More evidence is needed to rate pregnenolone for these uses.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Pregnenolone has been used safely for up to 12 weeks, with doses titrated up to 500 mg daily (94026,94027,97923,104274). There is insufficient reliable information available about the safety of pregnenolone when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Pregnenolone has been used safely for up to 10 weeks at doses of 200 mg daily in adolescents aged 11-17 years (104275). There is insufficient reliable information available about the safety of pregnenolone in younger children or when used orally for longer durations.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant use of pregnenolone may reduce the effects of benzodiazepines.  Details Very preliminary clinical research shows that chronic use of pregnenolone reduces sedative effects of diazepam when compared with chronic use of placebo. This effect may be related to the activity of pregnenolone at GABAA receptors (94031).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of estrogens.  Details Pregnenolone is a precursor for several steroid hormones, including estrogens (3008).

PROGESTERONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of progesterone.  Details In humans, some research shows that oral administration of pregnenolone can increase levels of progesterone (94032). However, other research shows no effect on progesterone levels (94028). It is possible the impact of pregnenolone on progesterone levels may be dose dependent.

PROGESTIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of progestin.  Details Pregnenolone is a precursor for several steroid hormones, including progestin (3008).

TESTOSTERONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of testosterone.  Details Pregnenolone is a precursor for several steroid hormones, including testosterone (3008). However, preliminary clinical research shows that taking pregnenolone 30-500 mg orally daily for up to 8 weeks does not affect testosterone levels (94028,94032).

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General ...Orally, pregnenolone is generally well tolerated.
Most Common Adverse Effects:
Orally: Acne, agitation, diarrhea, drowsiness, excitement, hair loss, skin abscess, sweating, tremor.

Cardiovascular ...A case of palpitations has been reported after oral use of pregnenolone (94031).

Dermatologic ...Orally, pregnenolone has been reported to cause skin abscesses, acne, and hair loss (94027,94031). A case of skin rash accompanied by a burning sensation on the back and sides of the hands has also been reported with oral pregnenolone use, possibly related to a photosensitivity reaction. The rash cleared on its own (94031).

Gastrointestinal ...Orally, pregnenolone may cause diarrhea. Constipation has also been reported after oral use; however, it is not certain if this effect was due to pregnenolone (94026).

Musculoskeletal ...A case of muscle pain/stiffness has been reported after oral use of pregnenolone (94032).

Neurologic/CNS ...Orally, pregnenolone has been reported to cause restlessness, tiredness, sweating, and a case of cold extremities (94026,94032). Sleep problems, drowsiness, and tremor have also been reported; however, it not certain if these effects were due to pregnenolone (94026,94031).

Psychiatric ...Orally, pregnenolone has been reported to cause depressive affect and increased appetite (94026,94031). Increased excitement, agitation, increased motor activity, and anorexia have also been reported; however, it is not certain if these effects were due to pregnenolone (94026).

Pulmonary/Respiratory ...A case of sinusitis has been reported after oral use of pregnenolone (94027).

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