Dehydroepiandrosterone
DHEA/Drug Interactions:
AlcoholAlcohol: In humans, levels of DHEA-S are increased by moderate and heavy alcohol consumption (233; 234; 235). In other human research, acute alcohol consumption increased DHEA concentrations in blood (236). Under fasting conditions, acute alcohol ingestion resulted in reduced salivary DHEA-S levels (382), while other research noted a lack of effect (383; 384). Additionally, according to secondary sources, high doses of DHEA may cause liver damage. Theoretically, concurrent use with alcohol may increase the risk of adverse effects to the liver. AlprazolamAlprazolam: In human, animal and laboratory research, DHEA acted as a negative modulator of the GABA receptor (240; 237; 238; 239; 54). In humans, alprazolam increased DHEA concentrations, although the same effects on DHEA-S concentrations was lacking (240). In other human research, acute administration of alprazolam with DHEA before high-intensity exercise resulted in enhanced release of growth hormone induced by exercise, an effect reportedly due to reduced hypothalamic-pituitary-adrenal axis (HPA) suppression and enhanced glutamate release (385). Alzheimer's agentsAlzheimer's agents: In mice models of Alzheimer's disease, DHEA protected the growth and survival of hypoplastic neurites in newborn neurons, but did not inhibit the overproliferation of progenitor cells (386). In patients with mild-to-moderate Alzheimer's disease, DHEA-S increased VEGF, a neuroprotective growth factor typically reduced in patients with the disease (47). AndrogensAndrogens: DHEA is converted into androgens and estrogens, and in human research, DHEA supplementation has been shown to increase levels of total androgens, testosterone, dihydrotestosterone, and androstenedione, and testosterone:epitestosterone and testosterone:creatinine ratios (116; 119; 117; 118; 120; 121; 122; 99; 123; 124; 125; 126), although 50mg of DHEA daily lacked an effect on testosterone (387). In vitro, DHEA plus testosterone resulted in delayed DHEA-S production (388). Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-converting enzyme receptor blockers (ARBs)Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-converting enzyme receptor blockers (ARBs): Lower levels of serum DHEA were noted in older men using angiotensin-converting enzyme (ACE) inhibitors (201). AntiarthriticsAntiarthritics: According to laboratory research, there is a link between DHEA levels and effects (degenerative and protective) on articular cartilage (389; 390; 60; 391; 392; 393; 394). Low levels of DHEA and DHEA-S have been associated with rheumatoid arthritis and juvenile rheumatoid arthritis (389; 390; 391; 392; 393; 394). According to research in premenopausal women, basal levels of DHEA-S may serve as a marker for disease activity (395). However, available research lacks consistency (396), and only a weak relationship has been noted between DHEA and DHEA-S levels and osteoarthritis (397; 398). In addition, it is also unclear whether DHEA-S levels correlate with disease activity and severity (389; 399). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In vitro and in vivo, DHEA and DHEA-S inhibited platelet aggregation (6; 7). In humans, DHEA supplementation reduced plasminogen activator inhibitor type 1 (PAI-1) (8). AntidepressantsAntidepressants: According to a case report, the use of selective serotonin reuptake inhibitors (SSRIs) with DHEA increased the risk of psychiatric disturbances (194). In depressed patients, mirtazapine reduced DHEA-S concentrations, which also correlated with reductions in the Hamilton Depression Rating Scale (195; 196). Similar reductions of DHEA-S were also reported with venlafaxine use (196). In boys with attention-deficit hyperactivity disorder (ADHD), bupropion reduced DHEA-S levels (28). AntidiabeticsAntidiabetics: Thiazolidinediones, troglitazone, rosiglitazone (202; 203), and metformin (204; 203) decreased serum DHEA-S in women with polycystic ovarian syndrome (PCOS). In animal research, metformin prevented DHEA-induced embryonic resorption (256). In obese individuals, metformin with a hypocaloric meal lacked a significant effect on DHEA-S levels (400), although in combination with insulin, it resulted in an increased rate of metabolic clearance of DHEA in men (401; 402); however, changes were lacking in the rate of metabolic clearance of DHEA in women (402). In other human research, DHEA and DHEA-S supplementation improved insulin sensitivity (310; 188; 311; 301; 339; 314; 159; 403) and reduced levels of insulin, fasting insulin resistance index, and glucose (115; 159). AntiestrogensAntiestrogens: In vitro, estrogen receptor-positive and estrogen receptor-negative breast cancer cells pretreated with fulvestrant and DHEA-S resulted in a lack of inhibition of estrogen receptor-positive and progesterone receptor-positive cells (127). Thus, the authors concluded that DHEA-S prevents fulvestrant inhibition and competes with fulvestrant in binding to the estrogen receptor. Similarly, in other laboratory research, DHEA-S in combination with tamoxifen resulted in tamoxifen resistance and breast cancer progression (404). AntihypertensivesAntihypertensives: In human research, DHEA-S decreased both systolic and diastolic blood pressure (159), although a lack of effect was seen with DHEA (161). Anti-inflammatoriesAnti-inflammatories: In human research, DHEA upregulated various parameters involved in the NF-kappaB inflammation pathway, including the percent change of activated NF-kappaB, p105, p65, p65 protein, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta RNA, between fasting and glucose-challenged states (249). Other human research has demonstrated favorable changes in the serum concentration of TNF-alpha and IL-6 following DHEA supplementation (161). AntilipemicsAntilipemics: In human research, DHEA and DHEA-S supplementation reduced total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels (192; 115; 159; 158; 160; 161). However, some available human studies have reported a decline in high-density lipoprotein (HDL; "good") cholesterol levels and an increase in triglycerides (155; 405; 153; 154; 156; 157; 137; 158). AntineoplasticsAntineoplastics: In vitro, estrogen receptor-positive and estrogen receptor-negative breast cancer cells pretreated with fulvestrant and DHEA-S resulted in a lack of inhibition of estrogen receptor-positive and progesterone receptor-positive cells (127). Thus, the authors concluded that DHEA-S prevents fulvestrant inhibition and competes with fulvestrant in binding to the estrogen receptor. Similarly, in other laboratory research, DHEA-S concomitant with tamoxifen resulted in tamoxifen resistance and breast cancer progression (404). Antiobesity agentsAntiobesity agents: In human research, DHEA and DHEA-S increased total and lean body mass, and reduced body mass index (BMI), body fat, body weight, and hip and waist circumference (187; 188; 189; 190; 191; 192; 275; 159; 406; 161). In middle-aged and elderly men, benfluorex increased serum DHEA and DHEA-S concentrations (225). AntipsychoticsAntipsychotics: In humans, antipsychotic drugs reduced DHEA and DHEA-S levels, particularly in men (205; 206). In other human research, chlorpromazine and phenothiazine lacked an effect on DHEA-S levels (407). DHEA-induced mania has been reported in humans (194; 251; 252; 253). Analysis of case reports has also noted that DHEA levels are reportedly higher in patients with severe psychosis (254). Clinical studies have also reported anxiety, nervousness, irritability, emotional change, and depression in patients receiving DHEA (173; 175; 193; 183). AntisepticsAntiseptics: DHEA improved survival and reduced complications in septic animals, as demonstrated by observed alterations in their immune system (79; 80; 81; 82; 83). AntiviralsAntivirals: In vitro, DHEA and/or DHEA-S has demonstrated antiviral activity, particularly against adenovirus (19), Trichomonas vaginalis (20), Junin virus (408), and vesicular stomatitis virus (409), with effects similar to those of cidofovir (19). AphrodisiacsAphrodisiacs: In human research, DHEA increased the frequency of sexual intercourse and subjective sexuality ratings of postmenopausal women (328). However, in premenopausal women, DHEA lacked an effect on subjective sexual arousal ratings and vaginal blood flow response following exposure to erotic stimuli (346). Aromatase inhibitorsAromatase inhibitors: In boys with pubertal gynecomastia, treatment with anastrozole resulted in increased levels of DHEA-S (224). However, in postmenopausal women with advanced breast cancer, anastrozole lacked significant effect on DHEA and DHEA-S levels (410). In animal breast cancer models, a lack of effect on DHEA and DHEA-S concentrations has also been noted (411; 412). Bacillus Calmette-Gu?rinBacillus Calmette-Gu?rin: In animals, low doses of DHEA coadministered with Bacillus Calmette-Gu?rin (BCG), a vaccine against tuberculosis, reduced the development of airway hypersensitivity; however, high doses of DHEA reduced the efficacy of BCG (25). BenzodiazepinesBenzodiazepines: In human, animal, and laboratory research, DHEA acted as a negative modulator of the GABA receptor (240; 237; 238; 239; 54). In humans, alprazolam increased DHEA concentrations, although the same effect on DHEA-S concentrations was lacking (240). In other human research, acute coadministration of alprazolam and DHEA before high-intensity exercise resulted in enhanced release of growth hormone induced by exercise (385). In other human research, DHEA decreased triazolam clearance and increased levels of triazolam, reportedly by inhibition of CYP3A by DHEA-S (198). Beta-blockers (beta-adrenergic antagonists)Beta-blockers (beta-adrenergic antagonists): In human research, propranolol increased serum DHEA-S, and the molar ratio of cortisol:17OHP, cortisol:DHEA, and DHEA-S:DHEA in males and females via beta-adrenergic influence (223). BronchodilatorsBronchodilators: In human research, DHEA increased lung capacity for diffusing carbon monoxide, decreased mean arterial pulmonary pressure, and reduced vascular pulmonary resistance (289). BupropionBupropion: In boys with ADHD, bupropion reduced DHEA-S levels (28). Calcium channel blockersCalcium channel blockers: In obese and hypertensive men, calcium channel blockers (amlodipine, nitrendipine, manidipine, and cilnidipine) increased serum DHEA and DHEA-S levels (226; 227; 228; 229). However, non-dihydropyridine (non-DHP) calcium channel blockers, such as diltiazem, reportedly lacked an effect on DHEA or DHEA-S levels (413). Calcium saltsCalcium salts: In humans, DHEA coadministered with calcium and vitamin D improved bone mineral density (116). CanrenoateCanrenoate: In young and elderly subjects, intravenous canrenoate increased DHEA levels (230). Cardiac glycosidesCardiac glycosides: In humans, DHEA-S had digitalis-like activity, similar to that of digitalis-like factors (166; 167). Cardiovascular agentsCardiovascular agents: A review has suggested an association between high levels of DHEA and DHEA-S and cardiovascular disease, metabolic syndrome, and increased risk of myocardial infarction (149; 150; 151; 152). Incidences of arrhythmia (376; 137), chest pain (135; 136), palpitations (135; 136), hypertension, and transient ischemic attacks (162; 163; 181) have been reported. DHEA has also been found to decrease high-density lipoprotein (HDL) levels (153; 154; 156; 157; 155; 158) and increase triglycerides (137). CocaineCocaine: In humans, cocaine stimulated the release of DHEA (414). Discontinuation of cocaine use in cocaine addicts resulted in significant reductions in plasma DHEA-S (415). In cocaine-dependent individuals, DHEA reduced levels of urinary cocaine metabolites, with fewer days in treatment on average compared to placebo, although differences for cocaine craving and adverse experiences were lacking (316). Cognitive improvement agentsCognitive improvement agents: In human research, DHEA demonstrated some beneficial effects on measures of visual spatial performance (296), but lacked an effect on measures of short-term memory and recall (295; 298). ContraceptivesContraceptives: In humans, oral contraceptives (norethindrone and ethinyl estradiol [Ortho Novum? 1/35, Ovcon? 35], norelgestromin, and ethinyl estradiol) reduced serum concentrations of DHEA-S (207; 208; 209) and reduced urinary excretion of DHEA (210). In anorexic women, coadministration of DHEA and oral contraceptives preserved both spinal and whole-body bone mineral density (416). CorticosteroidsCorticosteroids: Experts have noted that DHEA may protect against stress-induced immune system suppression, which may lead to infection (243). In human research and review, corticosteroids (particularly glucocorticoids such as fluticasone and budesonide) suppressed the production of DHEA and DHEA-S (417; 418; 419). Specifically, in human research, corticosteroids (dexamethasone, hydrocortisone, and prednisone) reduced DHEA-S concentrations (211; 212; 213; 214). However, in other human research, alteration of the pharmacokinetics of prednisolone was lacking with the administration of oral prasterone (DHEA) (420). In animals, DHEA prevented dexamethasone-induced hypertension (421). In patients with systemic lupus erythematosus (SLE), DHEA reduced the need for corticosteroids (352) and enabled prednisone reduction to physiologic levels (in women) (355). Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In laboratory research, troleandomycin inhibited DHEA metabolism in human liver microsomal fractions but was less effective in rat liver microsomal fractions, suggesting that hydroxylation of DHEA is primarily mediated by CYP3A (197). In rat liver microsomes, other isoforms are reportedly involved in DHEA metabolism, including CYP1A, CYP2D, and CYP2E1 (197; 199; 200). In other human research, DHEA decreased triazolam clearance and increased levels of triazolam, reportedly by inhibition of CYP3A by DHEA-S (198). DanazolDanazol: Increases in DHEA-S with danazol therapy have been reported in human research (231; 232). Drugs that affect GABADrugs that affect GABA: In human, animal, and laboratory research, DHEA acted as a negative modulator of the GABA receptor (240; 422; 237; 238; 239; 54) and may interfere with binding at the receptor site (239). Drugs that may lower seizure thresholdDrugs that may lower seizure threshold: DHEA-associated seizure has been noted in a case report (186). Drugs used for osteoporosisDrugs used for osteoporosis: In humans, DHEA supplementation in aging adults increased bone mineral density (117; 162; 122; 135; 116; 288). EstrogensEstrogens: DHEA is converted into androgens and estrogens, and in human research, supplementation increased estrogen levels (111; 112; 113; 114; 115; 116; 117; 118; 122). Theoretically, dose adjustments (i.e., reducing the dose) of estrogen therapy may be needed. In humans, estrogen-progestin oral contraceptives and conjugated estrogens reduced serum and plasma concentrations of DHEA and DHEA-S (423; 424; 207; 208; 209). In postmenopausal women, DHEA coadministered with hormone replacement therapy (HRT) resulted in higher elevations of testosterone and estradiol, less of an increase in allopregnanolone and beta-endorphin levels, and less of a decrease in cortisol levels, compared to HRT alone (425). Fertility agentsFertility agents: In human research, DHEA has demonstrated fertility-promoting effects (178; 323; 182). In healthy human males, the gonadotropin-releasing hormone (GnRH) antagonist acyline suppressed intratesticular DHEA; serum DHEA lacked evidence of significant reductions (378). In poor ovarian responders, DHEA in combination with in vitro fertilization (IVF) (with human menopausal gonadotropin [HMG], recombinant follicle-stimulating hormone [r-FSH], and cetrorelix [a GnRH antagonist]) resulted in enhanced ovarian response, reduced cycle cancellation rates, and improved embryo quality (321). Similarly, DHEA in combination with other IVF treatment (with triptorelin acetate [a GnRH agonist], rFSH and recombinant luteinizing hormone [rLH], and human chorionic gonadotropin [hCG]) resulted in higher birth rates and improved embryo quality compared to IVF treatment alone (320). GefitinibGefitinib: In women, treatment with gefitinib lowered DHEA levels (in men and women) and DHEA-S levels (215). Genitourinary tract agentsGenitourinary tract agents: In older adults, elevated and severe urinary symptoms (as evidenced by scores of more than 20, using the American Urological Association Symptom Index for Benign Prostatic Hyperplasia [International Prostate Symptom Score]) and urinary tract infections were reported (162). Gonadotropin-releasing hormone (GnRH) antagonistsGonadotropin-releasing hormone (GnRH) antagonists: In healthy human males, the GnRH antagonist acyline suppressed intratesticular DHEA; serum DHEA lacked evidence of significant reductions (378). In poor ovarian responders, DHEA in combination with HMG, r-FSH, and cetrorelix (a GnRH antagonist) resulted in enhanced ovarian response, reduced cycle cancellation rates, and improved embryo quality (321). Similarly, DHEA in combination with other IVF treatment (with triptorelin acetate [a GnRH agonist], rFSH and rLH, and hCG) resulted in higher birth rates and improved embryo quality compared to IVF treatment alone (320). Growth hormonesGrowth hormones: In humans, DHEA supplementation lacked an enhancing effect on growth hormones (426). In short, small-for-gestational-age children, growth hormone therapy for six months increased DHEA-S levels (427); however, the research is lacking consistency. In a different study using similar children, growth hormone therapy for one year did not produce changes in DHEA-S levels, particularly before the age of nine (428). HepatotoxinsHepatotoxins: In rats and rainbow trout, DHEA induced hepatocarcinogenesis, particularly with long-term use (139; 140; 371; 134; 141; 142; 143). In these studies, various mechanisms underlying this tumor-promoting effect have been described: peroxisome proliferation (139; 140; 371; 134), basophilic cell focus (BCF) growth stimulation (141), and DNA damage by reactive oxygen species (ROS) during DHEA treatment (142). Conversely, other animal research has reported anticancer activity in the liver (429; 430; 431; 432; 40). Hormonal agentsHormonal agents: In human research, DHEA (e.g., GNC? LiveWell) increased serum levels of estradiol, the free estradiol index, estrone, testosterone, androstenedione, 17-hydroxyprogesterone, progesterone, beta-endorphin, and sex hormone-binding globulin (SHBG) (295; 296; 160; 328; 161). However, findings differ among studies, with no or opposing effects being reported for testosterone, SHGB, allopregnanolone, antim?llerian hormone (AMH), FSH, and insulin-like growth factor (IGF)-1 (328; 182; 161; 160). DHEA has also decreased levels of leptin, adiponectin, and ghrelin (159). Breast cancer survivors using DHEA were less likely to experience hormone-related symptoms of hot flashes compared to nonusers of estrogenic botanical supplements (433). Hormone replacement therapy (HRT)Hormone replacement therapy (HRT): In postmenopausal women, DHEA coadministered with hormone replacement therapy (HRT) resulted in higher elevations of testosterone and estradiol, less of an increase in allopregnanolone and beta-endorphin levels, and less of a decrease in cortisol levels, compared to HRT alone (425). Human chorionic gonadotropinHuman chorionic gonadotropin: In healthy human males, hCG treatment increased intratesticular DHEA; however, DHEA in serum was unchanged (378). In poor ovarian responders, DHEA in combination with in vitro fertilization (with HMG, r-FSH, and cetrorelix [a GnRH antagonist]) enhanced ovarian response, reduced cycle cancellation rates, and improved embryo quality (321). Similarly, DHEA in combination with other IVF treatment (with triptorelin acetate [a GnRH agonist], rFSH and rLH, and hCG) resulted in higher birth rates and improved embryo quality compared to IVF treatment alone (320). ImmunosuppressantsImmunosuppressants: Several textbooks, review articles, and animal studies have reported a stimulatory effect of DHEA on immune function (33; 241; 242; 243; 244; 83; 245; 246; 247; 248). Theoretically, DHEA may reduce or interfere with the effects of immunosuppressant agents. MethylphenidateMethylphenidate: In humans, methylphenidate may increase low levels of DHEA in individuals with ADHD (27; 434; 28). MetyraponeMetyrapone: In normal and hirsute women, plasma levels of DHEA were elevated before, during, and after treatment with metyrapone in both groups (222). MorphineMorphine: DHEA levels were significantly lower in chronic morphine-treated animals (216). Neurologic agentsNeurologic agents: In mice models of Alzheimer's disease, DHEA protected the growth and survival of hypoplastic neurites in newborn neurons, but did not inhibit the overproliferation of progenitor cells (386). In humans, dizziness, fatigue, malaise, sleep disturbances, increased dreaming, night sweats, restlessness, "painful spots," and a crawling scalp sensation have been reported (278; 179; 163; 275). In patients receiving 7-Keto, vertigo was reported (187). There is a case of seizure associated with DHEA use in a patient (a 30 year-old female with fragile X syndrome with no history of convulsive disorder) trying to improve ovarian production (186). Clinical studies have also reported anxiety, nervousness, irritability, emotional change, and depression in patients receiving DHEA (173; 175; 193; 183). NMDA receptor antagonistsNMDA receptor antagonists: According to a review, DHEA and DHEA-S act as modulators of N-methyl-D-aspartate (NMDA) receptors (422). Theoretically, DHEA may interfere with the effects of NMDA antagonists like amantadine and memantine. Opiate antagonistsOpiate antagonists: In animals, naltrexone (an opioid antagonist) blocked the antianxiety and antidepressive effects of DHEA via mu-receptor blocking activity (21). OxytocicsOxytocics: Preliminary evidence from clinical trials has suggested that DHEA may shorten labor duration (258; 367; 365). StimulantsStimulants: According to secondary sources, DHEA may interact with stimulants.Tadalafil: In healthy men, a single dose of tadalafil (a phosphodiesterase [PDE] inhibitor) after exercise lacked a significant effect on salivary DHEA-S concentrations; however, DHEA-S:cortisol ratios significantly decreased (435). Thyroid hormonesThyroid hormones: In animals, DHEA treatment altered thyroid hormone status (144). In rats, increased thyroxine (T4) and triiodothyronine (T3) levels were noted following DHEA-S administration, particularly after repeated cold exposure (145; 146; 147). In healthy men, transdermal 7-oxo-DHEA resulted in a slight and temporary elevation in thyroid-stimulating hormone (TSH), T3, and T4 (148). In postmenopausal women, high oral doses of DHEA (1,600mg daily) decreased thyroid-binding globulin concentrations (114). In overweight adults, T3 levels increased in the 7-Keto group (189) and the 7-oxo-DHEA group (191). VaccinesVaccines: In aged mice, coadministration of DHEA and influenza vaccine enhanced immunization (436; 437). In elderly subjects, coadministration of DHEA and influenza vaccine (50mg of DHEA daily for four days, starting two days before vaccination) decreased immune response (against H1N1 and H3N2) (438). However, in other human research, DHEA-S administration (an oral, two-day dose or a single subcutaneous injection) prior to influenza vaccine enhanced immune response (439; 43). In animals, low doses of DHEA coadministered with BCG reduced the development of airway hypersensitivity; however, high doses of DHEA reduced the efficacy of BCG (25). VasodilatorsVasodilators: In vitro, DHEA acted as a vasodilator (164). In pregnant women, DHEA-S exerted vasodilatory effects and increased blood flow to the ophthalmic artery (165). Vitamin D analogsVitamin D analogs: In humans, DHEA coadministered with calcium and vitamin D improved bone mineral density (116). In vitro, DHEA coadministered with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) enhanced alkaline phosphatase activity and osteocalcin production (440). DHEA/Herb/Supplement Interactions:
Alzheimer's agentsAlzheimer's agents: In mice models of Alzheimer's disease, DHEA protected the growth and survival of hypoplastic neurites in newborn neurons, but did not inhibit the overproliferation of progenitor cells (386). In patients with mild-to-moderate Alzheimer's disease, DHEA-S increased VEGF, a neuroprotective growth factor typically reduced in patients with the disease (47). AntiarthriticsAntiarthritics: According to laboratory research, there is a link between DHEA levels and effects (degenerative and protective) on articular cartilage (389; 390; 60; 391; 392; 393; 394). Low levels of DHEA and DHEA-S have been associated with rheumatoid arthritis and juvenile rheumatoid arthritis (389; 390; 391; 392; 393; 394). According to research in premenopausal women, basal levels of DHEA-S may serve as a marker for disease activity (395). However, available research lacks consistency (396), and only a weak relationship has been noted between DHEA and DHEA-S levels and osteoarthritis (397; 398). In addition, it is also unclear whether DHEA-S levels correlate with disease activity and severity (389; 399). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In vitro and in vivo, DHEA and DHEA-S inhibited platelet aggregation (6; 7). In humans, DHEA supplementation reduced plasminogen activator inhibitor type 1 (PAI-1) (8). AntidepressantsAntidepressants: According to a case report, the use of selective serotonin reuptake inhibitors (SSRIs) with DHEA increased the risk of psychiatric disturbances (194). In depressed patients, mirtazapine reduced DHEA-S concentrations, which also correlated with reductions in the Hamilton Depression Rating Scale (195; 196). Similar reductions of DHEA-S were also reported with venlafaxine use (196). In boys with attention-deficit hyperactivity disorder (ADHD), bupropion reduced DHEA-S levels (28). AntihypertensivesAntihypertensives: In human research, DHEA-S decreased both systolic and diastolic blood pressure (159), although a lack of effect was seen with DHEA (161). Anti-inflammatoriesAnti-inflammatories: In human research, DHEA upregulated various parameters involved in the NF-kappaB inflammation pathway, including the percent change of activated NF-kappaB, p105, p65, p65 protein, TNF-alpha, and IL-1beta RNA, between fasting and glucose-challenged states (249). Other human research has demonstrated favorable changes in the serum concentration of TNF-alpha and IL-6 following DHEA supplementation (161). AntilipemicsAntilipemics: In human research, DHEA and DHEA-S supplementation reduced total cholesterol, LDL cholesterol, and triglyceride levels (192; 115; 159; 158; 160; 161). However, some available human studies have reported a decline in HDL ("good") cholesterol levels and an increase in triglycerides (155; 405; 153; 154; 156; 157; 137; 158). AntineoplasticsAntineoplastics: In vitro, estrogen receptor-positive and estrogen receptor-negative breast cancer cells pretreated with fulvestrant and DHEA-S resulted in a lack of inhibition of estrogen receptor-positive and progesterone receptor-positive cells (127). Thus, the authors concluded that DHEA-S prevents fulvestrant inhibition and competes with fulvestrant in binding to the estrogen receptor. Similarly, in other laboratory research, DHEA-S concomitant with tamoxifen resulted in tamoxifen resistance and breast cancer progression (404). Antiobesity agentsAntiobesity agents: In human research, DHEA and DHEA-S increased total and lean body mass, and reduced body mass index (BMI), body fat, body weight, and hip and waist circumference (187; 188; 189; 190; 191; 192; 275; 159; 406; 161). AntioxidantsAntioxidants: In human and laboratory research, DHEA has demonstrated both antioxidant and pro-oxidant effects (15; 16; 17; 18). AntipsychoticsAntipsychotics: In humans, antipsychotic drugs reduced DHEA and DHEA-S levels, particularly in men (205; 206). DHEA-induced mania has been reported in humans (194; 251; 252; 253). Analysis of case reports has also noted that DHEA levels are reportedly higher in patients with severe psychosis (254). Clinical studies have also reported anxiety, nervousness, irritability, emotional change, and depression in patients receiving DHEA (173; 175; 193; 183). AntisepticsAntiseptics: DHEA improved survival and reduced complications in septic animals, as demonstrated by observed alterations in their immune system (79; 80; 81; 82; 83). AntiviralsAntivirals: In vitro, DHEA and/or DHEA-S has demonstrated antiviral activity, particularly against adenovirus (19), Trichomonas vaginalis (20), Junin virus (408), and vesicular stomatitis virus (409), with effects similar to those of cidofovir (19). AphrodisiacsAphrodisiacs: In human research, DHEA increased the frequency of sexual intercourse and subjective sexuality ratings of postmenopausal women (328). However, in premenopausal women, DHEA lacked an effect on subjective sexual arousal ratings and vaginal blood flow response following exposure to erotic stimuli (346). BronchodilatorsBronchodilators: In human research, DHEA increased lung capacity for diffusing carbon monoxide, decreased mean arterial pulmonary pressure, and reduced vascular pulmonary resistance (289). CalciumCalcium: In humans, DHEA coadministered with calcium and vitamin D improved bone mineral density (116). Cardiac glycosidesCardiac glycosides: In humans, DHEA-S had digitalis-like activity, similar to that of digitalis-like factors (166; 167). Cardiovascular agentsCardiovascular agents: A review has suggested an association between high levels of DHEA and DHEA-S and cardiovascular disease, metabolic syndrome, and increased risk of myocardial infarction (149; 150; 151; 152). Incidences of arrhythmia (376; 137), chest pain (135; 136), palpitations (135; 136), hypertension, and transient ischemic attacks (162; 163; 181) have been reported. DHEA has also been found to decrease high-density lipoprotein (HDL) levels (153; 154; 156; 157; 155; 158) and increase triglycerides (137). CarnitineCarnitine: In in vitro research, combined use of DHEA and carnitine may have additive effects on age-related bone loss (441). ChromiumChromium: In human research and review, chromium picolinate increased DHEA-S levels, particularly in postmenopausal women (442; 443). Cognitive improvement agentsCognitive improvement agents: In human research, DHEA demonstrated some beneficial effects on measures of visual spatial performance (296), but lacked an effect on measures of short-term memory and recall (295; 298). ContraceptivesContraceptives: In humans, conventional oral contraceptives reduced serum concentrations of DHEA-S (207; 208; 209) and reduced urinary excretion of DHEA (210). In anorexic women, coadministration of DHEA and oral contraceptives preserved both spinal and whole-body bone mineral density (416). Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In laboratory research, troleandomycin inhibited DHEA metabolism in human liver microsomal fractions but was less effective in rat liver microsomal fractions, suggesting that hydroxylation of DHEA is primarily mediated by CYP3A (197). In rat liver microsomes, other isoforms are reportedly involved in DHEA metabolism, including CYP1A, CYP2D, and CYP2E1 (197; 199; 200). DigitalisDigitalis: In humans, DHEA-S had digitalis-like activity, similar to that of digitalis-like factors (166; 167). Fertility agentsFertility agents: In human research, DHEA has demonstrated fertility-promoting effects (178; 323; 182). In humans, DHEA in combination with IVF resulted in improved embryo quality, enhanced ovarian response, and higher birth rates (321; 320). FiberFiber: In humans, there is an inverse relationship between DHEA and dietary fiber intake (217). Human studies evaluating the effects of a high fiber, low-fat diet have noted decreased levels of plasma and serum DHEA-S (218; 219). FlavonoidsFlavonoids: In laboratory research, flavonoids (kaempferol, quercetin, genistein and daidzein) inhibited DHEA sulfotransferase (SULT2A1) activity regulating the conversion of DHEA to DHEA-S (444). Studies in older men and postmenopausal women have noted a decrease in DHEA following the use or consumption of soy isoflavones (220; 221), while other studies have noted a lack of effect on DHEA-S concentrations (445). Flaxseed and flaxseed oilFlaxseed and flaxseed oil: In pre and postmenopausal women, ingestion of flaxseed lacked an effect on DHEA-S concentrations (446; 447). Genitourinary tract agentsGenitourinary tract agents: In older adults, elevated and severe urinary symptoms (as evidenced by scores of more than 20, using the American Urological Association Symptom Index for Benign Prostatic Hyperplasia [International Prostate Symptom Score]) and urinary tract infection were reported (162). HepatotoxinsHepatotoxins: In rats and rainbow trout, DHEA induced hepatocarcinogenesis, particularly with long-term use (139; 140; 371; 134; 141; 142; 143). In these studies, various mechanisms underlying this tumor-promoting effect have been described: peroxisome proliferation (139; 140; 371; 134), basophilic cell focus (BCF) growth stimulation (141), and DNA damage by reactive oxygen species (ROS) during DHEA treatment (142). Conversely, other animal research reported anticancer activity in the liver (429; 430; 431; 432; 40). Herbs or supplements that affect GABA receptorsHerbs or supplements that affect GABA receptors: In human, animal, and laboratory research, DHEA acted as a negative modulator of the GABA receptor (240; 237; 238; 239; 54) and may interfere with binding at the receptor site (239). Hormonal agentsHormonal agents: In human research, DHEA (e.g., GNC? LiveWell) increased serum levels of estradiol, the free estradiol index, estrone, testosterone, androstenedione, 17-hydroxyprogesterone, progesterone, beta-endorphin, and SHBG (295; 296; 160; 328; 161). However, findings differ among studies, with no or opposing effects being reported for testosterone, SHGB, allopregnanolone, AMH, FSH, and IGF-1 (328; 182; 161; 160). DHEA has also decreased levels of leptin, adiponectin, and ghrelin (159). Breast cancer survivors using DHEA were less likely to experience hormone-related symptoms of hot flashes compared to nonusers of estrogenic botanical supplements (433). Hyperglycemics and hypoglycemicsHyperglycemics and hypoglycemics: In human research, DHEA and DHEA-S supplementation improved insulin sensitivity (310; 188; 311; 301; 339; 314; 159; 403) and reduced levels of insulin, fasting insulin resistance index, and glucose (115; 159). ImmunomodulatorsImmunomodulators: Several textbooks, review articles, and animal studies have reported a stimulatory effect of DHEA on immune function (33; 241; 242; 243; 244; 83; 245; 246; 247; 248). IsoflavonesIsoflavones: In laboratory research, soy isoflavones (genistein and daidzein) inhibited DHEA sulfotransferase (SULT2A1) activity regulating the conversion of DHEA to DHEA-S (444). Studies in older men and postmenopausal women have noted a decrease in DHEA with soy consumption (220; 221), while other studies have noted a lack of effect on DHEA-S concentrations (445). LicoriceLicorice: In vivo and in vitro, licorice and glycyrrhetinic acid increased DHEA levels by inhibiting SULT2A1 activity in the adrenal gland (250). MelatoninMelatonin: During murine retrovirus infection-induced vitamin E deficiency, coadministration of DHEA and melatonin resulted in synergistic effects, more effectively increasing vitamin E levels and enhancing immune function compared to either agent alone (448). Neurologic agentsNeurologic agents: In mice models of Alzheimer's disease, DHEA protected the growth and survival of hypoplastic neurites in newborn neurons, but did not inhibit the overproliferation of progenitor cells (386). In humans, dizziness, fatigue, malaise, sleep disturbances, increased dreaming, night sweats, restlessness, "painful spots," and a crawling scalp sensation have been reported (278; 179; 163; 275). In patients receiving 7-Keto, vertigo was reported (187). There is a case of seizure associated with DHEA use in a patient (a 30 year-old female with fragile X syndrome with no history of convulsive disorder) trying to improve ovarian production (186). Clinical studies have also reported anxiety, nervousness, irritability, emotional change, and depression in patients receiving DHEA (173; 175; 193; 183). Opiate antagonistsOpiate antagonists: In animals, naltrexone (an opioid antagonist) blocked the antianxiety and antidepressive effects of DHEA via mu-receptor blocking activity (21). Osteoporosis agentsOsteoporosis agents: In humans, DHEA supplementation in aging adults increased bone mineral density (117; 162; 122; 135; 116; 288). OxytocicsOxytocics: Preliminary evidence from clinical trials has suggested that DHEA may shorten labor duration (258; 367; 365). PhytoestrogensPhytoestrogens: DHEA is converted into androgens and estrogens, and in human research, supplementation increased estrogen (estrone and estradiol) levels (111; 112; 113; 114; 115; 116; 117; 118). Theoretically, dose adjustments (i.e., reducing the dose) of estrogen therapy may be needed. In humans, estrogen-progestin oral contraceptives and conjugated estrogens reduced serum and plasma concentrations of DHEA and DHEA-S (423; 424; 207; 208; 209). In postmenopausal women, DHEA coadministered with HRT resulted in higher elevations of testosterone and estradiol, less of an increase in allopregnanolone and beta-endorphin levels, and less of a decrease in cortisol levels, compared to HRT alone (425). Polyunsaturated fatty acidsPolyunsaturated fatty acids: In women with polycystic ovarian syndrome (PCOS), a polyunsaturated fatty acid (PUFA)-rich diet lacked an effect on plasma DHEA-S concentrations (449). In other human research, DHEA-S supplementation decreased levels of total fatty acids and increased levels of certain n-6 PUFAs, although results were inconsistent among individual fatty acids (339). ProbioticsProbiotics: In premenopausal women, use of the probiotics Lactobacillus acidophilus and Bifidobacterium longum lacked an effect on DHEA-S concentrations (217). Seizure threshold-lowering agentsSeizure threshold-lowering agents: DHEA-associated seizure has been noted in a case report (186). SoySoy: According to secondary sources, soy reduced the effectiveness of DHEA. Studies in older men and postmenopausal women have noted a decrease in DHEA with soy consumption (220; 221), while other studies have noted a lack of effect on DHEA-S concentrations (445; 450). In laboratory research, soy isoflavones (genistein and daidzein) inhibited DHEA sulfotransferase (SULT2A1) activity regulating the conversion of DHEA to DHEA-S (444). Steroidal agentsSteroidal agents: Experts have noted that DHEA may protect against stress-induced immune system suppression, which may lead to infection (243). In human research and review, corticosteroids (particularly glucocorticoids such as fluticasone and budesonide) suppressed the production of DHEA and DHEA-S (417; 418; 419). Specifically, in human research, corticosteroids (dexamethasone, hydrocortisone, and prednisone) reduced DHEA-S concentrations (211; 212; 213; 214). However, in other human research, alteration of the pharmacokinetics of prednisolone was lacking with the administration of oral prasterone (DHEA) (420). In animals, DHEA prevented dexamethasone-induced hypertension (421). In patients with systemic lupus erythematosus (SLE), DHEA reduced the need for corticosteroids (352) and enabled prednisone reduction to physiologic levels (in women) (355). StimulantsStimulants: According to secondary sources, DHEA may interact with stimulants.Thyroid agentsThyroid agents: In animals, DHEA treatment altered thyroid hormone status (144). In rats, increased T3 and T4 levels were noted following DHEA-S administration, particularly after repeated cold exposure (145; 146; 147). In healthy men, transdermal 7-oxo-DHEA resulted in a slight and temporary elevation in TSH, T3, and T4 (148). In postmenopausal women, high oral doses of DHEA (1,600mg daily) decreased thyroid-binding globulin concentrations (114). In overweight adults, T3 levels increased in the 7-Keto group (189) and the 7-oxo-DHEA group (191). VasodilatorsVasodilators: In vitro, DHEA acted as a vasodilator (164). In pregnant women, DHEA-S exerted vasodilatory effects and increased blood flow to the ophthalmic artery (165). Vitamin DVitamin D: In humans, DHEA coadministered with calcium and vitamin D improved bone mineral density (116). In vitro, DHEA coadministered with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) enhanced alkaline phosphatase activity and osteocalcin production (440). Vitamin EVitamin E: In humans, vitamin E supplementation lacked an effect on serum DHEA or DHEA-S levels (451; 452). In animals, vitamin E masked the antioxidant properties of DHEA; however, in vitamin E deficiency, the antioxidant activity was present (16). Additionally, during murine retrovirus infection-induced vitamin E deficiency, DHEA coadministered with melatonin more effectively increased vitamin E levels and enhanced immune function compared to either agent alone (448). In rat liver microsomes, vitamin E protected against oxidative damage and lipid peroxidation by DHEA (453; 454). YamYam: In postmenopausal women, yam ingestion lacked an effect on serum concentrations of DHEA-S (455). DHEA/Food Interactions:
AlcoholAlcohol: In humans, levels of DHEA-S were increased by moderate and heavy alcohol consumption (233; 234; 235). In other human research, acute alcohol consumption increased DHEA concentrations (236). Additionally, according to secondary sources, high doses of DHEA may cause liver damage. Theoretically, concurrent use with alcohol may increase the risk of adverse effects to the liver. Calcium-containing foodsCalcium-containing foods: In humans, DHEA coadministered with calcium and vitamin D improved bone mineral density (116). Fatty acid estersFatty acid esters: In vitro, DHEA-fatty acyl ester (FAE)-enriched HDL resulted in stronger vasodilation compared to HDL alone, reportedly mediated by nitric oxide synthase (NOS) (164). FiberFiber: In humans, there is an inverse relationship between DHEA and dietary fiber intake (217). Human studies evaluating the effects of a high fiber, low-fat diet have noted decreased levels of plasma and serum DHEA-S (218; 219). FlavonoidsFlavonoids: In laboratory research, flavonoids (kaempferol, quercetin, genistein and daidzein) inhibited DHEA sulfotransferase (SULT2A1) activity regulating the conversion of DHEA to DHEA-S (444). Studies in older men and postmenopausal women have noted a decrease in DHEA following the use or consumption of soy isoflavones (220; 221), while other studies have noted a lack of effect on DHEA-S concentrations (445). Flaxseed and flaxseed oilFlaxseed and flaxseed oil: In pre and postmenopausal women, ingestion of flaxseed lacked an effect on concentrations of DHEA-S (446; 447). IsoflavonesIsoflavones: In laboratory research, soy isoflavones (genistein and daidzein) inhibited DHEA sulfotransferase (SULT2A1) activity regulating the conversion of DHEA to DHEA-S (444). Studies in older men and postmenopausal women have noted a decrease in DHEA with soy consumption (220; 221), while other studies have noted a lack of effect on DHEA-S concentrations (445). LicoriceLicorice: In vivo and in vitro, licorice and glycyrrhetinic acid increased DHEA levels by inhibiting SULT2A1 activity in the adrenal gland (250). Polyunsaturated fatty acidsPolyunsaturated fatty acids: In women with PCOS, a PUFA-rich diet lacked an effect on plasma DHEA-S concentrations (449). In other human research, DHEA-S supplementation decreased levels of total fatty acids and increased levels of certain n-6 PUFAs, although results were inconsistent among individual fatty acids (339). ProbioticsProbiotics: In premenopausal women, probiotic use of Lactobacillus acidophilus and Bifidobacterium longum lacked an effect on DHEA-S concentrations (217). SoySoy: According to secondary sources, soy reduced the effectiveness of DHEA. Studies in older men and postmenopausal women have noted a decrease in DHEA with soy consumption (220; 221), while other studies have noted a lack of effect on DHEA-S concentrations (445; 450). In laboratory research, soy isoflavones (genistein and daidzein) inhibited DHEA sulfotransferase (SULT2A1) activity regulating the conversion of DHEA to DHEA-S (444). Vitamin D-containing foodsVitamin D-containing foods: In humans, DHEA coadministered with calcium and vitamin D improved bone mineral density (116). In vitro, DHEA coadministered with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) enhanced alkaline phosphatase activity and osteocalcin production (440). Vitamin E-containing foodsVitamin E-containing foods: In humans, vitamin E supplementation lacked an effect on serum DHEA or DHEA-S levels (451; 452). In animals, vitamin E masked the antioxidant properties of DHEA; however, in vitamin E deficiency, the antioxidant activity was present (16). Additionally, during murine retrovirus infection-induced vitamin E deficiency, DHEA coadministered with melatonin more effectively increased vitamin E levels and enhanced immune function compared to either agent alone (448). In rat liver microsomes, vitamin E protected against oxidative damaged and lipid peroxidation by DHEA (453; 454). YamYam: In postmenopausal women, yam ingestion lacked an effect on serum concentrations of DHEA-S (455). DHEA/Lab Interactions:
ACTH testACTH test: It is well known that DHEA is secreted in response to adrenocorticotropic hormone (ACTH). In humans, a low-dose ACTH test increased DHEA levels (456; 457). AndrogensAndrogens: DHEA is converted into androgens and estrogens, and in human research, DHEA supplementation increased levels of total androgens, testosterone, dihydrotestosterone, and androstenedione, and testosterone:epitestosterone and testosterone:creatinine ratios (116; 119; 117; 118; 120; 121; 122; 99; 123; 124; 125; 126; 458; 459; 460), although 50mg of DHEA daily lacked an effect on testosterone (387). Antidiuretic hormone (ADH; also known as vasopressin, arginine vasopressin [AVP])Antidiuretic hormone (ADH; also known as vasopressin, arginine vasopressin [AVP]): In response to exercise, DHEA increased AVP response (385). Beta-endorphinBeta-endorphin: In aging males with partial androgen deficiency, DHEA supplementation increased beta-endorphin levels compared to baseline (126). Blood pressureBlood pressure: In human research, DHEA-S decreased both systolic and diastolic blood pressure (159), although a lack of effect was seen with DHEA (161). Body fatBody fat: In older men and women, DHEA supplementation reduced visceral fat area, subcutaneous fat (188), and body mass index (BMI) (190). In other research, DHEA reduced body mass in men but increased it in women (336). The combination of 7-oxo-DHEA plus exercise reduced percentage of body fat in older adults (189). Body weightBody weight: In overweight adults, 7-oxo-DHEA plus exercise reduced body weight (189; 191).Bone mineral densityBone mineral density: In humans, DHEA supplementation increased bone mineral density (117; 162; 122; 135; 116; 119; 288). Carotid artery thickness and flowCarotid artery thickness and flow: Using ultrasonography, an inverse association between DHEA-S and sex-dependent diverse carotid atherosclerosis was noted, as evidenced by increased maximum intima-media thickness (IMT) and mean IMT in males and decreased blood flow volume in the common carotid arteries (CCA-BFV) (461). Coagulation panelCoagulation panel: In vitro and in vivo, DHEA and DHEA-S inhibited platelet aggregation (6; 7). In humans, DHEA supplementation reduced plasminogen activator inhibitor type 1 (PAI-1) (8). CortisolCortisol: DHEA and cortisol are known to have an inverse relationship (462; 84). In humans, DHEA supplementation reduced cortisol levels (463; 464; 112). However, in other human research, inhibition of cortisol secretion was lacking with the administration of oral prasterone (DHEA) (420). CreatinineCreatinine: In human research, cases of increased serum creatinine concentration have been reported with prasterone (181). E-selectin(endothelial leukocyte adhesion molecule-1 [ELAM-1])E-selectin(endothelial leukocyte adhesion molecule-1 [ELAM-1]): In vitro, DHEA decreased the expression of adhesion molecule, E-selectin, in human umbilical vein endothelial cells (HUVECs) (465). EstrogensEstrogens: DHEA is converted into androgens and estrogens, and in human research, supplementation increased estrogen (estrone and estradiol) levels (111; 112; 113; 114; 115; 116; 117; 118). Fatty acidsFatty acids: In patients with X-linked adrenoleukodystrophy, following supplementation of DHEA, decreases in saturated and mono- and polyunsaturated fatty acids (C16:0, C18:0, C20:4omega-6, C22:5omega-6, C18:1omega-9, C20:1omega-9, and C20:3omega-9) in plasma and erythrocytes were noted; however, lowered elevated plasma levels of saturated very long-chain fatty acids were lacking (466). Only in plasma were a decrease in unsaturated fatty acid and oleic acid (syn. olefinic acid C18:1omega 9) and an increase in eicosanoic acid (C20:1omega 9) noted. In human research, DHEA-S supplementation decreased levels of total fatty acids and increased levels of certain n-6 PUFAs, although results were inconsistent among individual fatty acids (339). Flow-mediated dilation (FMD)Flow-mediated dilation (FMD): In postmenopausal women, plasma DHEA-S levels correlated with percent of flow-mediated dilation (FMD) of the brachial artery (467). In older men, DHEA supplementation increased FMD (301). GlucagonGlucagon: In hypoadrenal women, DHEA supplementation reduced plasma glucagon (468). GlucoseGlucose: In men with age-related disorders, including cardiovascular disease, DHEA supplementation reduced glucose levels (301; 115). In middle-aged women, administration of DHEA before exercise improved glucose tolerance tests (469); however 50mg of DHEA daily lacked an effect on serum glucose (387). Growth hormoneGrowth hormone: In aging men with partial androgen deficiency, DHEA supplementation increased growth hormone levels (126). Hemagglutination inhibition (HAI) antibody titersHemagglutination inhibition (HAI) antibody titers: In aging adults, DHEA-S supplementation prior to the influenza vaccine enhanced immune response, as evidenced by an increase in HAI titers (439). In elderly humans given a tetanus vaccination after four days of ingesting DHEA-S (100mg daily), changes were lacking in protective antibody levels vs. the placebo group (44). Hormone panelHormone panel: In human research, DHEA (e.g., GNC? LiveWell) increased serum levels of estradiol, the free estradiol index, estrone, testosterone, androstenedione, 17-hydroxyprogesterone, progesterone, beta-endorphin, and SHBG (295; 296; 160; 328; 161). However, findings differ among studies, with no or opposing effects being reported for testosterone, SHGB, allopregnanolone, AMH, FSH, and IGF-1 (328; 182; 161; 160). DHEA has also decreased levels of leptin, adiponectin, and ghrelin (159). Immune panelImmune panel: In older men, DHEA supplementation increased monocytes, the number of B cells and B cell activity, T cell activity (excluding the total number of T cells), IL-2, and the number of natural killer (NK) cells and NK activity (10). In postmenopausal women, DHEA enhanced NK cell activity (470). In human and laboratory research, DHEA increased IL-2 (10; 471) and suppressed levels of IL-6 (11). DHEA has been suggested to inhibit, or stimulate, production of IL-2 and IL-3 in vitro (472; 473). Alterations in IL-4 and interferon (IFN) have also been noted in vitro (474). In vitro, DHEA reduced the expression of chemokine receptor type 2 (CCR2), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4) in U937 cells (465). InsulinInsulin: In human research, DHEA and DHEA-S supplementation improved insulin sensitivity (310; 188; 311; 301; 339; 314; 159; 403) and reduced levels of insulin, fasting insulin resistance index, and glucose (115; 159). Insulin-like growth factor (IGF-1)Insulin-like growth factor (IGF-1): In humans, DHEA and DHEA-S increased IGF-1 (47; 116; 119; 336; 117; 288). Intercellular adhesion molecule-1 (ICAM-1)Intercellular adhesion molecule-1 (ICAM-1): In vitro, DHEA decreased the expression of the adhesion molecule ICAM-1 in HUVECs (465). Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)Luteinizing hormone (LH) and follicle-stimulating hormone (FSH): In aging men with partial androgen deficiency, DHEA supplementation decreased levels of LH and FSH (126). Reduced levels were also noted in postmenopausal women (475; 112). In men, transdermal 7-oxo-DHEA increased levels of LH and FSH (476). Lipid profileLipid profile: In humans, DHEA supplementation decreased HDL cholesterol, LDL cholesterol, very-low-density lipoprotein (VLDL) cholesterol, total cholesterol, and apolipoprotein A-I levels (468; 405; 153; 192; 155; 115; 156; 157; 269); however, other research has noted a lack of effect (387; 477). In other research evaluating topical 7-oxo-DHEA, an increase in HDL cholesterol, apolipoprotein A-I, apolipoprotein B, and lipoprotein (a) was noted along with a decrease in total cholesterol levels (476). Liver function test (LFTs)Liver function test (LFTs): In animal research, DHEA supplementation reduced liver damage, as evidenced by a decrease in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin (40; 478). Also, in rats and rainbow trout, DHEA induced hepatocarcinogenesis, particularly with long-term use (139; 140; 371; 134; 141; 142; 143). However, in human research, elevated liver enzymes have been reported following DHEA supplementation (181; 182). N-telopeptidesN-telopeptides: In women with anorexia nervosa, DHEA supplementation reduced levels of urinary N-telopeptides (NTx), a marker of bone resorption (283). OsteocalcinOsteocalcin: In humans, osteocalcin increased after treatment with DHEA (479; 480; 481; 482; 283; 483; 271). In other research, a decrease in osteocalcin was noted after DHEA supplementation (125; 484). Plasminogen activator inhibitor type 1 (PAI-1)Plasminogen activator inhibitor type 1 (PAI-1): In humans, DHEA supplementation reduced plasminogen activator inhibitor type 1 (PAI-1) (8). ProlactinProlactin: In postpartum women, supplementation with DHEA-S lacked significant effects on serum prolactin levels (111). Prostate-specific antigen (PSA)Prostate-specific antigen (PSA): In human prostate carcinoma cell lines (LNCaP cells), DHEA increased the expression of prostate-specific antigen (PSA) (485; 138). However, in other research in healthy males, supplementation lacked effects on PSA concentrations (387; 486; 487). Pulmonary function testsPulmonary function tests: In human research, DHEA increased lung capacity for diffusing carbon monoxide, decreased mean arterial pulmonary pressure, and reduced vascular pulmonary resistance (289). eizure thresholdSeizure threshold: DHEA-associated seizure has been noted in a case report (186). Sex hormone-binding globulin (SHBG)Sex hormone-binding globulin (SHBG): In aging men with partial androgen deficiency, DHEA supplementation decreased levels of SHBG (126). Reduced levels were also noted in postmenopausal women (112). In men, transdermal 7-oxo-DHEA increased in levels of SHBG, but nonsignificantly (476). TelomereTelomere: In humans, DHEA supplementation increased normal cell telomeres, thereby reducing pain (64). Thyroid hormoneThyroid hormone: In animals, DHEA treatment altered thyroid hormone status (144). In rats, increased T3 and T4 levels were noted following DHEA-S administration, particularly after repeated cold exposure (145; 146; 147). In healthy men, transdermal 7-oxo-DHEA slightly and temporarily elevated TSH, T3, and T4 (148). In postmenopausal women, high oral doses of DHEA (1,600mg daily) decreased thyroid-binding globulin concentrations (114). In overweight adults, T3 levels were increased in the 7-Keto group (189) and the 7-oxo-DHEA group (191). Tissue plasminogen activator (tPA) antigenTissue plasminogen activator (tPA) antigen: In humans, DHEA supplementation reduced tPA antigen (8). Transforming growth factor-beta1 (TGF-beta1)Transforming growth factor-beta1 (TGF-beta1): In patients with mild-to-moderate Alzheimer's disease, DHEA-S increased TGF-beta1, a neuroprotective growth factor typically reduced in patients with the disease (47). Vascular cell adhesion molecules (VCAM-1)Vascular cell adhesion molecules (VCAM-1): In vitro, DHEA decreased the expression of the adhesion molecule VCAM-1 in HUVECs (465). Vascular endothelial growth factor (VEGF)Vascular endothelial growth factor (VEGF): In patients with mild-to-moderate Alzheimer's disease, DHEA-S increased VEGF, a neuroprotective growth factor typically reduced in patients with the disease (47).