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Overview Of DHEA / Pregnenolone Capsules

DHEA

Dehydroepiandrosterone (DHEA) is a C19 steroid also known as 5-androsten-3 beta-ol-17-one. DHEA and DHEAS (an active, sulfated form of DHEA), are endogenous hormones secreted by the adrenal cortex in primates and a few non-primate species in response to ACTH. DHEA is a steroid precursor of both androgens and estrogens, and thus is often called ‘the mother hormone’. Endogenous DHEA is thought to be important in several endocrine processes, but current medical use of DHEA is limited to controlled clinical trials. In 1997, Pharmadigm, Inc. received an orphan drug designation to enroll patients with thermal burns who require skin-grafting into trials using injectable DHEAS, known as PB-005. Researchers continue to investigate the role of both endogenous and exogenous DHEA in CNS, psychiatric, endocrine, gynecologic and obstetric, immune, and cardiovascular functions. GeneLabs Technologies, Inc., submitted an NDA in September 2000 for its proprietary DHEA product, called prasterone (Prestara™, formerly known Aslera™ or GL-701). Prasterone appears to attentuate some symptoms of mild-to-moderate systemic lupus erythematosus (SLE) and may increase bone density based on evidence from two phase III studies in women; studies in men with SLE are ongoing. The FDA placed Prestara™ under a 6-month priority review status in October 2000; on April 19, 2001 the FDA stated that although the drug showed advantages over placebo in one study, the advantages were not statistically significant. Additional data were submitted to the FDA following a ‘not approvable’ letter on June 26, 2001. On September 2, 2002, the FDA issued an ‘approvable’ letter for the Prestara™ product, but the agency has asked for additional clinical trial data regarding the drug’s effects on bone mineral density before granting final approval for SLE. The manufacturer began a confirmatory phase III trial in early 2003; the primary endpoint will be measurement of bone mineral density of the lumbar spine; the trial is targeted for completion at the end of 2003. In October 2004, the manufacturer released information that Prestara™ therapy did not meet the primary end point in the confirmatory trial. In August 2003, Paladin Labs Inc., received orphan drug designation from the FDA for prasterone, dehydroepiandrosterone, DHEA, under the brand name Fidelin™, for adrenal insufficiency.

Exogenously administered DHEA is sold as a nutritional supplement in health and drug stores and many older individuals are using it to ‘maintain the vitality of their youth’. There is currently no objective, well-controlled, large-scale, scientific evidence to back claims that taking DHEA combats the signs or symptoms of aging, diabetes, neurologic disease, sexual dysfunction, or heart disease. Some athletes abuse DHEA believing that it can enhance the body’s synthesis of testosterone; the potential action of DHEA as an anabolic steroid has lead to the prohibition of supplementation in competitive sport, even though evidence of anabolic effects in athletes is lacking. DHEA is also abused by athletes in an attempt to normalize the testosterone:epitestosterone ratio. However, the sensitivity and specificity of currently available testing for athletic ‘doping’ can readily identify the presence of banned substances, including testosterone. Because of DHEA’s complex physiologic actions, more than 500 scientific articles investigating it have been published since 1993. Many of the short-term trials of DHEA to date have lacked the rigor and statistical applications needed to support therapeutic claims. Most claims will need to be confirmed by large-scale, properly conducted, and controlled studies. In 1984, the FDA banned the non-prescription (OTC) sale of exogenous DHEA due to concern over hepatotoxicity (hepatitis and hepatic tumors) as noted in animal studies. The FDA formally relegated DHEA to a Category II OTC ingredient at that time (i.e., not generally recognized as safe and effective). However in 1994, the passage of the US Dietary Supplement Health and Education Act (DSHEA) allowed DHEA to be marketed as a nutritional or dietary supplement.

Pregnenolone

Pregnenolone, also referred to as 5-pregnenolone or pregn-5-en-3β-ol-20-one, is a 21-carbon endogenous steroid. It is biosynthesized from cholesterol and is a precursor and a metabolic intermediate to the gonadal steroid hormones and adrenal corticosteroids, including estrogen, progesterone, testosterone, dehydroepiandrosterone (DHEA), cortisol, and cortisone. Pregnenolone is also biosynthesized from cholesterol within the central nervous system and the peripheral nervous system, which lends its classification as a neurosteroid.
Synthetic pregnenolone is sold as a supplement. It is not FDA-approved and there is little data on the safety and efficacy of long-term use of pregnenolone. Pregnenolone should be taken under the supervision of a physician.
Preliminary research shows that pregnenolone enhances learning and memory and can even reverse memory deficits in rodents. However, human studies have produced contradictory results.
Initial research shows that pregnenolone has significant anti-inflammatory properties.
Dysregulation of pregnenolone has been observed in patients with schizophrenia, bipolar disorder, depression, and Alzheimer’s disease. This data leads researchers to look at the potential of exogenous pregnenolone to treat patients with these conditions.
Early human trials show that pregnenolone significantly improves SANS scores in patients diagnosed with schizophrenia compared to placebo. Early human trials suggest that pregnenolone may improve depressive symptoms in patients diagnosed with bipolar disorder.
DHEA

Endogenous DHEA is a complex hormone, and researchers still have much to discover in regards to its physiologic effects in males and females. Less is known regarding the mechanisms of action of exogenously administered DHEA.
CNS actions: Both DHEA and DHEAS may be synthesized de-novo by the central nervous system, and concentrations of DHEA and DHEAS are higher in the brain than in other organs. The two neurohormones appear to have excitatory activity at both GABA and NMDA receptors.
Dermatologic actions after burn injury: Animal studies have suggested that DHEA and DHEAS expedite the re-epithelialization of donor skin-graft sites.
Endocrine actions: Endogenous DHEA is synthesized by the conversion of cholesterol via CYP11A1 to pregnenolone, followed by CYP17 conversion to DHEA and then to DHEAS via dehydroepiandrosterone sulfatransferase. The synthesis of DHEA occurs exclusively in the adrenal cortex in women, while in men 10—25% of DHEA is synthesized by the testes and roughly 80% of the DHEA comes from the adrenal glands. DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is of only minor importance as an androgenic substance itself. The production rate of DHEA by the body changes dramatically throughout life, typically peaking at adrenarche, the adrenal contribution to the onset of puberty. In males, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 9 years. Endogenous DHEA concentration then peaks again in males at roughly the 20th—30th years of life. In females, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 7 years. Endogenous DHEA concentration then peaks again in females at roughly the 20th and 40th year of life. DHEA levels decline steadily after the fifth decade in both males and females. DHEAS concentrations in males and females follow similar patterns. The administration of DHEA supplements results in different hormonal concentration changes in males and females; the actions are dependent on the dose, formulation and route of administration, and age of the person receiving the DHEA.
Hemostasis: Inhibition of platelet aggregation by exogenous DHEA has been demonstrated in vivo in humans; DHEA either prolonged or completely inhibited the rate of arachidonate-stimulated platelet aggregation after 14 days of administration. The degree of inhibition of platelet aggregation was noted to be time and dose dependent.
Immunologic actions: Because SLE occurs more frequently in women than men and because SLE is known to worsen during pregnancy, a hormonal etiology is suspected for this disease. DHEA up-regulates interleukin-2 (IL-2) production by T-lymphocytes in murine lupus models and reverses the clinical autoimmune disease. Lower endogenous levels of DHEA and DHEAS have been noted in both male and female patients with lupus at the time of diagnosis. Chronic corticosteroid treatment, which may cause adrenal atrophy, contributes to reduced DHEA levels in these patients. Supplementation of DHEA in SLE may augment immune system activity and potentially offset the undesired effects of chronic corticosteroid use in these patients. Exact mechanisms of DHEA on immune function are not yet clear. DHEA has been shown to increase the numbers of natural killer cells in aging women. Serum DHEA levels are observed to be reduced in patients with AIDS or age-related immunodeficiency, suggesting that DHEA may serve as a marker of the integrity of the immune system. No studies to date have shown that DHEA supplementation augments currently available therapies for AIDS.

Pregnenolone

Pregnenolone plays a crucial role in processes throughout the body, including neurogenic growth. It’s role as a substrate makes it crucial in the production of steroid hormones and adrenal corticosteroids and therefore highlights its importance in the regulation of bodily processes. It is also a precursor to other neurosteroids, including pregnenolone sulfate and allopregnanolone.
As a neurosteroid, pregnenolone modulates neurotransmission via the neuronal membrane and provokes structural changes in neurons and in astrocytes. Neurosteroids, including pregnenolone, have a modulating effect on neural excitability and synaptic plasticity. Pregnenolone is an excitatory neurosteroid and can act as an allosteric modulator of neurotransmitter receptors, such as GABAA, NMDA, and sigma receptors.
Pregnenolone is a ligand of the microtubule-associated protein 2 (MAP2) for the stimulation of the polymerization of microtubules. It is also a N-methyl-d-aspartate (NMDA) NMDA ligand. It is a negative allosteric modulator of the GABAA receptor and the CB1 receptor, and is an agonist of the σ1 receptor and the pregnane X receptor.
DHEA

As a nutritional supplement, DHEA is most commonly administered by the oral route. Many DHEA products available as nutritional supplements contain varied amounts of DHEA and do not appear to be manufactured according to good manufacturing processes (GMP). Using HPLC techniques, one study found that only 7 out of the 16 assayed products contained DHEA within a 10% variation of the labeled content.Some products contained no detectable DHEA.
The literature is lacking in pharmacokinetic studies using serial serum sampling of DHEA after supplementation. In the body, DHEA and DHEAS are widely distributed, converted to the sex hormones in peripheral tissues, and appear to cross the blood-brain barrier. The serum pharmacokinetic parameters and metabolism of DHEA and DHEAS following administration may vary among persons of different sex and age groups and the dose or route of administration. Quantification of DHEA to aide in detection of abuse by athletes may soon be accomplished. Gas chromatography-mass spectrometry (GC-MS) can evidently detect DHEA metabolites in the urine within 8 hours of a single oral dose of 50 mg. Within 24 hours, 50—75% of an oral DHEA dose is recovered as glucuronide and sulfate conjugates, androsterone, and etiocholanone in the urine.

Route-Specific Pharmacokinetics:

Oral Route: Micronization appears to enhance oral absorption and may influence the metabolic conversion of DHEA to the various sex hormones in men and women. After oral dosing, elevations in serum concentrations of DHEA and DHEAS, above endogenous levels, persist for 12 hours.

Pregnenolone

Pregnenolone can be administered orally, subcutaneously, intravenously, intranasally, and topically/transdermally. Oral pregnenolone has high metabolism and low bioavailability. It is lipophilic and readily crosses the blood brain barrier.
There is very limited data on the pharmacokinetics of exogenous pregnenolone. Oral pregnenolone is metabolized in preference to allopregnanolone, rather than other hormones biosynthesized from pregnenolone substrate, such as cortisol or DHEA. One study observed that three hours after oral consumption of a single dose of 400mg of pregnenolone, pregnenolone serum levels increased by approximately 60%. Two hours after this dose, allopregnanolone serum levels tripled. An earlier study shows that a single oral dose of 175mg of pregnenolone approximately doubled pregnenolone serum levels over the course of four to eight hours.
One study observed the effects of exogenous pregnenolone on patients diagnosed with schizophrenia or schizoaffective disorder. Participants were given eight weeks of oral pregnenolone–with an escalating fixed-dose approach, where patients took 500mg per day for the last four weeks. Serum levels of pregnenolone and certain downstream metabolites were measured. Treatment with oral pregnenolone elevated pregnenolone serum levels fourfold, pregnenolone sulfate serum levels tripled, and allopregnanolone serum levels increased fivefold. Furthermore, treatment with oral pregnenolone elevated progesterone serum levels more than fourfold and DHEAS levels by approximately 16%. In this study, exogenous pregnenolone did not increase serum levels of testosterone, free testosterone, cortisol, DHEA, estradiol, or androstenedione levels.
DHEA

Your health care provider needs to know if you have any of these conditions: breast cancer (men or women); cancer of the lining of the uterus (endometrial cancer); diabetes or high blood sugar; immune system problems; infertility; liver disease; post-menopause; prostate cancer or an enlarged prostate gland; rheumatoid arthritis; uterine cancer; vaginal bleeding or menstrual problems; vaginal cancer; an unusual or allergic reaction to progesterone, DHEA, soy, other medicines, foods, dyes, or preservatives; pregnant or trying to get pregnant; breast-feeding. Visit your doctor or health care professional for regular checks on your progress. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. DHEA use is banned in competitive sports. Both college (NCAA) and olympic (USOC) committees do not allow DHEA use among athletes.

NOTE: DHEA has not yet been evaluated by the Food and Drug Administration. Nutritional supplement products containing DHEA are not intended to diagnose, treat, cure, or prevent any disease. Consumers should also be informed that rigid quality control standards are not required for nutraceuticals and substantial variability can occur in both the potency and the purity of these products.

Dehydroepiandrosterone (free and sulfate) test systems measure dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in urine, serum, plasma, and amniotic fluid. These measurements are used in the diagnosis and treatment of DHEA-secreting adrenal cancers. It is unclear at this time if supplementation with DHEA would result in false-positives of these tests. The effect of DHEA on hormone-dependent tumors in males and females is unknown. Many hormonal agents with androgenic or estrogenic activity are contraindicated for use in persons with various hormonally-dependent neoplasms. Some data suggests an association between elevated endogenous DHEA and DHEAS serum concentrations and the development of breast cancer andovarian cancer in women. As with other hormones, DHEA supplementation in a woman with undiagnosed abnormal vaginal bleeding, endometrial cancer, endometrial hyperplasia, uterine cancer, or vaginal cancer is not recommended. DHEA may stimulate the growth of cancerous tissue and should not be used in male patients with either breast or prostate cancer. Male patients with symptoms of prostatic hypertrophy or erectile dysfunction that have not been medically evaluated should not take DHEA supplements. Because the incidence of some hormonally-dependent cancers naturally increases with age, “andropausal” men and post-menopausal women should approach DHEA supplementation with caution. It is recommended that a qualified healthcare prescriber’s recommendations be sought prior to DHEA supplementation. Benefit versus risk should be determined individually. Women taking DHEA should receive an annual clinical breast examination and pelvic examination and regular mammograms as recommended by their healthcare professional. Men taking DHEA should receive annual physical examinations, including prostate examination or PSA levels, as recommended by their healthcare provider.
Dehydroepiandrosterone, DHEA is contraindicated for use in children <= 18 years of age. Because endogenous DHEA, DHEAS, and androstenedione serum concentrations are related to the onset of puberty, there is concern that the use of DHEA supplements in children or adolescents would interfere with natural growth and sexual maturation.
Females of childbearing age with infertility due to hyperandrogenism or chronic anovulation should not take DHEA supplements. The relationship of DHEA and DHEAS to ovulation and fertility is complex and still poorly understood. However, women with hirsutism and infertility or polycystic ovary syndrome (PCOS) are commonly found to have elevated endogenous DHEA or DHEAS serum concentrations on assay. Women with higher serum levels of endogenous DHEAS and who are receiving fertility treatments have been noted to have higher rates of ovarian hyperstimulation syndrome (OHSS) associated with their treatments. DHEA may also induce changes in the normal menstrual cycle in women of childbearing age.
Dehydroepiandrosterone, DHEA should be considered a pregnancy category X drug, similar to other androgenic hormones. Studies of the role of endogenous fetal and maternal DHEA in pregnancy indicate that the ratio of DHEA or DHEAS to other hormones in the serum or placenta may influence the processes of fetal development, parturition, and labor. Endogenous DHEA and DHEAS appear to be important in the functional development of the adrenal cortex and other endocrine activities in the fetus; it is assumed that exogenous DHEA supplementation to a pregnant woman could potentially have deleterious effects on fetal development or viability. The androgenic effects of DHEA could potentially result in masculinization of a female fetus. No controlled trials of DHEA in primate or human gestation exist. Do not administer DHEA to a pregnant woman.
DHEA is a hormone and should not be supplemented in a lactating woman who is breast-feeding her infant. Most hormones are excreted in breast milk. Like other androgenic hormones, it is possible that DHEA could inhibit lactation. It is unknown what effect DHEA would have on the breast-feeding infant.
Dehydroepiandrosterone, DHEA should be considered contraindicated for use in patients with hepatic disease, hepatitis,hepatocellular cancer, or jaundice. In 1984, the FDA banned the non-prescription (OTC) sale of DHEA due to concern over its ability to cause hepatotoxicity. DHEA supplements are now able to be sold as “nutritional supplements” secondary to the US Dietary Supplement Health and Education Act (DSHEA) of 1994, and are no longer regulated as drugs outside of clinical trials. Transient drug-induced hepatitis has been reported in association with the use of DHEA nutritional supplements. Because both estrogens and androgens may exacerbate acute intermittent or variegate hepatic porphyria, DHEA, which has androgenic actions, should be used with caution in patients with these diseases.
Treatment of patients with diabetes mellitus with DHEA is currently not warranted. The role of endogenous DHEA in relationship to insulin resistance is not clear. DHEA and DHEAS may not be mediators of insulin action. Long-term trials evaluating the effectiveness and safety of exogenous DHEA supplementation in patients with diabetes are currently unavailable. Patients with diabetes mellitus who are pursuing the use of DHEA supplements should see a qualified health care professional.
DHEA treatment of patients with human immunodeficiency virus (HIV) infection should be approached with caution. DHEA may possess immunomodulating effects, perhaps by enhancing the secretion of IL-2 from activated T cells as demonstrated in murine models. While this suggests that DHEA may play a role in the function of the immune system, the role of DHEA supplementation in the treatment of human HIV infection, especially acquired immunodeficiency syndrome (AIDS), has not yet been determined. Safety and efficacy have not been established.
Most non-essential hormones are discontinued several weeks prior to major surgery where feasible. DHEA may inhibit platelet aggregation, an effect that may be important to consider during surgical procedures. The decision of when to resume DHEA after surgery would be based on the perceived additional risk from DHEA use and the need for DHEA therapy.
Soy oil is the raw product from which many DHEA supplements are manufactured. Cholesterol from soy oil is converted into DHEA. DHEA products should be used cautiously in patients with a history of allergies to soy-containing foods or who exhibit immediate-type soya lecithin hypersensitivity.
One of the functions of endogenous DHEA is to inhibit the enzyme glucose-6-phosphate dehydrogenase. Use DHEA with caution in patients with G6PD deficiency.
Prasterone (DHEA) should be used with caution in patients with bipolar disorder. One case report exists of the appearance of mania in a predisposed patient consuming large doses of a DHEA supplement on a routine basis. Until more information is known, clinicians should be aware that emotional lability or changes in mood may occur in selected patients.

Pregnenolone

There is little data on the long-term effects of oral pregnenolone. Since pregnenolone is a precursor to estrogen, its use is contraindicated in patients diagnosed with or at risk for estrogen-dependent cancers, including breast, endometrial, ovarian, and prostate. Research shows that high levels of estrogen may also contribute to a number of health concerns and conditions, including endometriosis, cardiovascular disease, lupus erythematosus, neurodegenerative diseases like Alzheimer’s, and seizure disorders.
High levels of DHEA, a pregnenolone-derived neurosteroid, might worsen psychiatric disorders and increase the risk of mania in people who have mood disorders. Pregnenolone is contraindicated in patients taking DHEA, patients with higher than normal levels of DHEA, and patients who have been diagnosed with or who are at risk for psychiatric disorders and mania.
Pregnenolone may cause rapid heart beat. Pregnenolone is contraindicated in patients diagnosed with or at risk for arrhythmia.
Pregnenolone is contraindicated in patients diagnosed with or at risk for liver or kidney disease.
Smoking increases the risk of cardiovascular disease in women taking menopausal hormone therapy. Smoking increases testosterone levels in men by as much as 15% compared to patients who do not smoke. Although more research is needed to fully understand how smoking impacts hormone levels, it is recommended that patients interested in taking pregnenolone should cease smoking before taking pregnenolone.
DHEA

DHEA should be considered a pregnancy category X drug, similar to other androgenic hormones. Studies of the role of endogenous fetal and maternal DHEA in pregnancy indicate that the ratio of DHEA or DHEAS to other hormones in the serum or placenta may influence the processes of fetal development, parturition, and labor. Endogenous DHEA and DHEAS appear to be important in the functional development of the adrenal cortex and other endocrine activities in the fetus; it is assumed that exogenous DHEA supplementation to a pregnant woman could potentially have deleterious effects on fetal development or viability. The androgenic effects of DHEA could potentially result in masculinization of a female fetus. No controlled trials of DHEA in primate or human gestation exist. Do not administer DHEA to a pregnant woman.

Pregnenolone

There is little data on the use of pregnenolone tablets in women who are pregnant or breastfeeding. As such, it is difficult to determine a drug-associated risk of adverse developmental outcomes. Women who are pregnant or breast-feeding should avoid using this product.
DHEA

DHEA is a hormone and should not be supplemented in a lactating woman who is breast-feeding her infant. Most hormones are excreted in breast milk. Like other androgenic hormones, it is possible that DHEA could inhibit lactation. It is unknown what effect DHEA would have on the breast-feeding infant.

Pregnenolone

There is little data on the use of pregnenolone tablets in women who are pregnant or breastfeeding. As such, it is difficult to determine a drug-associated risk of adverse developmental outcomes. Women who are pregnant or breast-feeding should avoid using this product.
NOTE: High concentrations of anastrozole inhibited metabolic reactions catalyzed by cytochromes P450 (CYP) 1A2, 2C8/9, and 3A4. Anastrozole did not inhibit CYP2A6 or the polymorphic CYP2D6 in human liver microsomes. Per the manufacturer, it is unlikely that anastrozole administered at the recommended dose will inhibit the metabolism of cytochrome P450-mediated drugs given concomitantly.
In a study in male volunteers (n=16), anastrozole did not alter the warfarin pharmacokinetics (Cmax or AUC), and did not alter warfarin anticoagulant activity as measured by prothrombin time, activated partial thromboplastin time, and thrombin time of both R- and S-warfarin.
Anastrozole and tamoxifen should not be administered together. Clinical and pharmacokinetic results from the ATAC study demonstrate that concurrent administration of anastrozole and tamoxifen results in a reduction of anastrozole plasma levels by 27% compared to those achieved with anastrozole alone. However, coadministration did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen.
The goal of anastrozole therapy is to decrease circulating estrogen concentrations and inhibit the growth of hormonally-responsive cancers. Anastrozole should not be given concurrently with any estrogens or estrogen-containing products, including combined oral contraceptives, as these could interfere with the pharmacologic action of anastrozole. In addition, in women receiving long-term aromatase inhibitor therapy, atrophic vaginitis due to estrogen suppression is common; atrophic vaginitis due to aromatase inhibitor therapy is sometimes treated with vaginal estrogen as the systemic exposure of estrogen from vaginal preparations is thought to be low. In a recent study of 7 women on aromatase inhibitor therapy, estrogen concentrations rose significantly after the addition of vaginally administered estrogen for atrophic vaginitis. Estrogen concentrations increased from a mean baseline level of < 5 pmol/l to 72 pmol/l at 2 weeks and to < 35 pmol/l at 4 weeks. Although the study was small, estrogen concentrations rose significantly in 6/7 patients. Clinicians should be aware that serum estrogen concentrations may increase with the use of vaginal estrogen preparations; alternative treatments for atrophic vaginitis in patients taking aromatase inhibitors should be considered.
Androstenedione is an important metabolic precursor for androgens and estrogens in both males and females. Androstenedione supplements should not be given concurrently with any aromatase inhibitors, as androstenedione could interfere with the pharmacologic action of the aromatase inhibitor. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of androstenedione in both males and females; the enzyme aromatase converts androstenedione to estrone.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole could interfere with biotransformation of DHEA.
DHEA

NOTE: Many prasterone, dehydroepiandrosterone, DHEA preparations contain a variety of other ingredients, including minerals, vitamins, hormones and/or herbs, and each individual component may need to be evaluated for the presence of drug interactions. Only drug interactions pertaining to DHEA are discussed in this monograph.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is a weak androgen that has complex hormonal effects. It is unclear what actions prasterone, dehydroepiandrosterone, DHEA would have on other exogenous hormonal regimens (e.g., androgens, estrogens, oral contraceptives, or progestins). Either additive or antagonistic effects could potentially occur. The mechanisms or results of interactions with DHEA and other hormones may be multifactorial and dependent on the sex and age of the individual being treated, the indication for hormone use, the route by which DHEA is given, and the length of concomitant use. Concurrent use of DHEA with any of these hormonal regimens is not recommended at this time.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is a weak androgen that has complex hormonal effects. It is unclear what actions prasterone, dehydroepiandrosterone, DHEA would have on other exogenous hormonal regimens. It would seem prudent to not administer DHEA with infertility or hormonal cancer treatments such as GnRH analogs (cetrorelix, ganirelix, goserelin, histrelin, leuprolide, or triptorelin) since DHEA may theoretically interfere with these therapies.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is a weak androgen that has complex hormonal effects. The action of 5-alpha reductase inhibitors (i.e., dutasteride, finasteride) could potentially be antagonized by DHEA administration. 5-alpha-reductase inhibitors have anti-androgenic effects on the prostate gland that may be antagonized by the androgenic effects of DHEA on these tissues. Avoid concurrent use.
Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto extracts appear to have antiandrogenic effects. The antiandrogenic effects of Saw palmetto, Serenoa repens would be expected to antagonize the actions of androgens; it would seem illogical for patients taking androgens to use this herbal supplement.
Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. The impact of exogenous prasterone, dehydroepiandrosterone, DHEA administration on the safety or efficacy of chronic corticosteroid treatment regimens is not yet clear. The administration of DHEA to patients on corticosteroids should only be done under the observation of a qualified health care professional.
Prasterone, dehydroepiandrosterone, DHEA appears to have anti-platelet effects, which may prolong bleeding times. Inhibition of platelet aggregation by DHEA has been demonstrated in vivo in humans; the rate of arachidonate-stimulated platelet aggregation was prolonged or completely inhibited. In addition, DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X.Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of these potential, varied effects on coagulation, patients receiving DHEA concurrently with anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Concurrent use of antidiabetic agents with prasterone, dehydroepiandrosterone, DHEA is currently not warranted. The role of endogenous DHEA in relationship to insulin action or glucose intolerance is not clear. Endogenous levels of DHEA and DHEAS may be regulated by insulin and may not mediate insulin action. It is unclear what effect DHEA supplementation would have on glycemic control. Trials evaluating the effectiveness and safety of exogenous DHEA supplementation in combination with antidiabetic agents are currently unavailable.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Prasterone, dehydroepiandrosterone, DHEA may inhibit the metabolism of triazolam, and other benzodiazepines (e.g., alprazolam, estazolam, midazolam) which undergo CYP3A4-mediated metabolism. In one study of elderly volunteers, half of the patients received DHEA 200 mg/day PO for 2 weeks, followed by a single dose of triazolam 0.25 mg. Triazolam clearance was reduced by close to 30% in the DHEA-pretreated patients vs. the control group; however, the effect of DHEA on CYP3A4 metabolism appeared to vary widely among subjects. While more study is needed, benzodiazepine-induced CNS sedation and other adverse effects might be increased in some individuals if DHEA is co-administered.
Prasterone, dehydroepiandrosterone, DHEA is a weak androgen that has complex hormonal effects. Androgens are known to stimulate erythropoiesis.58 Despite the fact that endogenous generation of erythropoietin is depressed in patients with chronic renal failure, other tissues besides the kidney can synthesize erythropoietin, albeit in small amounts. Concurrent administration of androgens can increase the patient’s response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
In vitro, both genistein and daidzein inhibit 5 alpha-reductase isoenzyme II, resulting in decreased conversion of testosterone to the potent androgen 5-alpha-dihydrotestosterone (DHT) and a subsequent reduction in testosterone-dependent tissue proliferation. The action is similar to that of finasteride, but is thought to be less potent. Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may counteract the activity of the androgens.

Pregnenolone

There is very little data on the effects of long-term use of pregnenolone. Limited studies where pregnenolone is administered for four to twelve weeks show that pregnenolone is well-tolerated. One study recorded mild side effects, including mild restlessness, mild muscle pain/stiffness, and mild cold extremities.
Pregnenolone may cause side effects similar to those known for testosterone, including acne, hair loss, aggressiveness, irritability, increased levels of estrogen, and hair growth on the face in women. In some cases, which would call for immediate termination of use, it may cause rapid heartbeat, blurred vision, and dizziness. This list may not include all possible adverse reactions or side effects.
Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.
You can order DHEA / Pregnenolone Capsules from MediLab’s compounding pharmacy in the following Florida regions:
North Florida South Florida
Jacksonville Miami West Palm Beach Weston
Pensacola Hialeah Pompano Beach Delray Beach
Tallahassee Fort Lauderdale Davie Homestead
Ocala Port St. Lucie Miami Beach Tamarac
Gainesville Pembroke Pines Plantation Sarasota
Fort Walton Beach Hollywood Sunrise Wellington
Panama City Miramar Boca Raton Jupiter
Palm Coast Coral Springs Deerfield Beach Margate
Dunnellon Miami Gardens Boynton Beach Coconut Creek
Naples Lauderhill Broward
Spring hill Orlando
 
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