Medically reviewed by Drugs.com. Last updated on Oct 22, 2019.
Common Name(s): Dehydroepiandrosterone, Dehydroepiandrosterone sulfate, DHEA, DHEAS, Prasterone
Adequately powered, long-term clinical trials are lacking to support therapeutic use of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) supplementation (hereafter jointly referred to as DHEA/S). Reviews of clinical trials found no convincing evidence to support a place in therapy for DHEA in improving cognitive function or physical strength in elderly patients, or in treating postmenopausal symptoms in women, hyperlipidemia or insulin resistance, schizophrenia, or cancer. Some evidence exists to support the use of DHEA/S supplementation in women with diminished ovarian reserves, in subpopulations of elderly women with osteoporosis, and in mild systemic lupus erythematosus. DHEA is recommended as third-line monotherapy or adjunctive therapy for treatment of major depressive disorder (MDD) by Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines, and limited data suggest a potential role for DHEA as an anxiolytic.
Adrenal insufficiency: 50 mg/day for 3 months is considered a replacement dose, while 200 mg/day achieves supraphysiological circulating levels and is considered a pharmacological dose.
Anorexia nervosa: 100 mg/day for 6 months was used in a pilot study.
Diminished ovarian reserve: DHEA 50 to 75 mg/day (in divided doses) has been used in clinical studies of assisted reproduction.
Exercise training–induced muscle damage: 100 mg/day of DHEA supplementation was administered over 5 days in a study in young men undergoing exercise training.
Major depressive disorder: DHEA doses ranging from 30 to 450 mg/day for 6 to 8 weeks have been used in clinical studies.
Metabolic syndrome: DHEAS 100 mg/day for 3 months has been used in a study evaluating effects against metabolic syndrome in pre- and postmenopausal women.
Postmenopausal women: DHEA 25 mg/day has been suggested because this dose minimizes androgenic adverse effects; however, only studies in which at least 50 mg/day was used demonstrated positive outcomes as hormonal replacement therapy.
Use of DHEA or DHEAS is not recommended in breast or prostate cancer.
Information regarding safety and efficacy in pregnancy and lactation is lacking. DHEA supplementation has been evaluated for use in improving oocyte production in infertility.
Supraphysiologic serum DHEAS levels due to DHEA supplementation have been documented to interfere with commercially available progesterone assays, yielding false-positive increases in serum progesterone.
Studies in adrenal insufficiency suggest DHEA is generally well tolerated. However, data from long-term studies are lacking. Observed adverse effects include mania and hypomania, acne, hirsutism, gynecomastia, testicular changes, increased blood pressure, and decreased high-density lipoprotein (HDL) levels.
Use caution in individuals with psychiatric disorders; agitation, confusion, anxiety, paranoia, and suicidal thoughts have been reported. Use of hormones like DHEA may cause erythrocytosis. Use caution in individuals with diabetes, as DHEA may increase insulin resistance or sensitivity. Use caution in individuals with liver dysfunction, as DHEA may exacerbate this condition. Use caution in individuals with polycystic ovarian syndrome, as DHEA may worsen this condition.
Many nonprescription preparations of DHEA are developed in China and are likely to contain DHEA derived from diosgenin that has been extracted from the root of wild yam (Dioscorea villosa). Other commercial preparations contain synthetically derived DHEA. These supplements are not regulated by the US Food and Drug Administration (FDA) and are exempt from pharmaceutical quality standards; wide variations in DHEA content among products have been described.Olech 2005, Webb 2006
DHEA was first isolated by the German biochemist Adolf Butenandt in the 1930s. Claims of supplementary DHEA being the "fountain of youth" hormone have arisen largely from the observation that endogenous levels of the hormone decline with age and from anecdotal descriptions of enhanced energy and well-being in patients treated with DHEA for adrenal insufficiency. Although its use is prohibited under the World Anti-Doping Code and the National Collegiate Athletic Association, several high-profile athletes have tested positive for DHEA.Maninger 2009, Webb 2006 The FDA banned over-the-counter sales of DHEA in 1985; however, since the passage of the Dietary Supplement Health and Education Act of 1994, DHEA has been widely available and marketed as a dietary supplement.Webb 2006
DHEA is a precursor in the production of sex hormones.Olech 2005 It is produced endogenously in the adrenal gland from cholesterol, but can also be synthesized in neurons, glial cells, and the ovaries.Fouany 2013, Grimley 2006, Maninger 2009 Both DHEA and its main metabolite DHEAS are major circulating hormones in the body. Levels vary according to age, peaking in early adulthood and generally declining to 10% to 20% between 70 and 80 years of age, although there is great individual variability in these changes.Genazzani 2007, Maninger 2009, Mazat 2001 In women, exogenous DHEA results in greater increases in systemic androgens, while in men, DHEA use results in increases in both systemic estrogens and androgens, with greater influence on estrogens.Samaras 2013 Factors that influence circulating DHEA/S levels include alcohol intake, body mass index (BMI), ethnicity, nutritional status, gender, smoking status, thyroid function, and use of concomitant medications such as corticosteroids.Olech 2005 Autoregulation mechanisms and local tissue requirements can result in sex hormone levels in peripheral tissues that differ considerably from what would be expected based on circulating levels.Samaras 2013
Uses and Pharmacology
The sulfate derivative of DHEA has been shown to act as a noncompetitive antagonist of gamma-aminobutyric acid (GABA) receptors, as well as a positive allosteric modulator of N-methyl-D-aspartate receptors. In humans, neuroprotective, antioxidant, antihypertensive, and anti-inflammatory effects have also been reported. Serum DHEA levels peak in 60 to 480 minutes after administration.Fouany 2013
Note: Studies conducted in nonprimate animals have limited applicability in humans because the levels of circulating DHEA/S are different; rodents have very little circulating DHEA.Bovenberg 2005, Genazzani 2007, Maninger 2009
Limited clinical studies have been conducted in women with diminished ovarian reserves. Reviews of the studies have concluded that DHEA supplementation increases the number of oocytes produced, hence increasing the chance of pregnancy. The rate of miscarriage has also been found to be diminished, possibly by reducing aneuploidy. Reported adverse events are androgenic in nature, but also include 1 case report of seizure. One study suggests that most babies born after maternal DHEA treatment are male, possibly related to increases in intrafollicular testosterone or other androgen levels in women taking DHEA; however, corroboration of more studies is needed.Gleicher 2011, Mamas 2009, Narkwichean 2013, Wiser 2010 A small controlled study in women with primary ovarian insufficiency found increases in antral follicle count and ovarian volume but no changes in follicle-stimulating hormone on anti-Mullerian hormone.Yeung 2013 However, a 2016 meta-analysis that pooled data from 2 studiesNarkwichean 2013, Wiser 2010 found adjuvant use of DHEA supplementation had no effect on the number of oocytes and clinical pregnancy rates in women who were poor responders to ovarian stimulation.Jeve 2016 Another systematic review and meta-analysis sought to explore data from a larger sample of patients, specifically those in whom in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) failed due to diminished ovarian reserve or poor response. The systematic review (8 studies [N=647]) found that DHEA did not increase the number of oocytes retrieved compared with controls; however, a significant increase in pregnancy rate was observed (P=0.02). Significance remained (P<0.001) for the increase in clinical pregnancy rate after removal of the study with the highest relative heterogeneity. DHEA was not found to have a significant effect on implantation or abortion rates.Li 2015 Reports of increased progesterone subsequent to DHEA administration in women with low ovarian reserveStrauss 2014 should be interpreted cautiously, as the resulting serum DHEAS level has been demonstrated to cross-react with 3 commercially available progesterone assays (Immulite 2000, eCobas, Centaur), yielding false-positive increases in serum progesterone.Forman 2015, Franasiak 2016 The British Fertility Society Policy and Practice Committee 2015 evidence-based guidelines and recommendations for good clinical practice do not support the routine use of DHEA as an adjuvant in IVF cycles based on a lack of robust evidence of benefit.Nardo 2015
Circulating DHEA/S levels are lower among patients with asthma.Kasperska-Zajac 2010 When nebulized DHEAS (70 mg/day) was evaluated in a study of patients with moderate to severe asthma, no effect on forced expiratory volume at 1 second or peak expiratory flow rate was demonstrated; however, a difference over placebo was shown using the Asthma Control Questionnaire.Wenzel 2010
DHEA is a weak androgen, and adrenal androgens are associated with an increased risk of cancer, especially of the breast and prostate. Until rigorous laboratory and clinical studies have been conducted, the use of DHEA/S in cancer prevention is not supported.Arnold 2009, Matsuzaki 2006
Animal and in vitro data
The relevance of effects of DHEA in rodent models of cancer is unclear.Arnold 2005, Arnold 2009 Epidemiological data are inconclusive regarding the role of DHEA and DHEAS in cancer. Some studies suggest that the age-related decline in DHEA/S, testosterone, and estrogen is protective for hormone-sensitive cancers. Other studies correlate elevated DHEA/S with decreased rates of cancer.Arnold 2005, Arnold 2009, Matsuzaki 2006
DHEA supplementation may be of benefit in posttraumatic stress disorder and in addiction by improving abstinence.Maninger 2009, Yadid 2010 The role of exogenous DHEA in depression remains unclear. A correlation between low DHEA levels and increased symptoms of depression in elderly women has been suggested; 2 well-designed studies found modest effects.Olech 2005
CANMAT clinical guidelines for the management of MDD in adults (2016) recommend DHEA as third-line monotherapy in mild to moderate MDD based on level 2 evidence (at least 1 randomized controlled trial with adequate sample size and/or meta-analysis with wide confidence intervals) and as adjunctive therapy based on level 3 evidence (small-sample randomized clinical trials or nonrandomized, controlled prospective studies or case series or high-quality retrospective studies).Ravindran 2009, Ravindran 2016
One small randomized, placebo-controlled, 6-month pilot study (N=21 evaluable) evaluated the effects of DHEA 100 mg/day in community-dwelling anorexia nervosa patients. Beck Depression Inventory score at 3 and 6 months and BMI at month 4 were improved in the treatment group compared with placebo. There were no differences between treatment groups for Eating Disorders Inventory and Clinical Global Improvement Scale scores.Bloch 2012
A small double-blind, randomized, placebo-controlled trial (N=29) investigated the effect of DHEA on neural regulation of emotions. A single 400 mg oral dose of DHEA was administered 120 minutes prior to neuroimaging in right-handed healthy young males (18 to 34 years of age). Memory accuracy for emotional stimuli was significantly reduced with DHEA compared with placebo (P=0.029), suggesting a reduction in emotional reactivity encoding; this effect was negatively correlated with serum DHEA (P=0.005). Additionally, magnetic resonance imaging (MRI) results revealed that activity was reduced in regions of the brain associated with negative emotion and increased in regions linked to emotion regulatory control in the DHEA group compared with controls. These results suggest a possible role for DHEA in anxiety and depressive disorders.Sripada 2013 In a behavioral and electrophysiological study in 21 healthy women 18 to 26 years of age with normal anxiety levels, DHEA/S levels were shown to be related to brain processing under negative emotional contexts.do Vale 2015
Circulating DHEA levels in the elderly population are only 10% to 20% of those in young adults, and some but not all observational studies suggest patients diagnosed with dementia have lower circulating DHEA/S levels.Genazzani 2007, Grimley 2006, Maninger 2009, Olech 2005 This observation has led to the suggestion that DHEA supplementation might prevent or slow the decline in cognitive function with age; however, there is currently no positive evidence to support this.Bovenberg 2005, Grimley 2006, Maninger 2009, Merritt 2012, Sorwell 2010
In a study of DHEA treatment (50 mg orally for 6 months) of erectile dysfunction in patients with different organic etiologies, results suggest oral DHEA may be beneficial in patients with erectile dysfunction who have hypertension or without organic etiology. DHEA treatment had no impact on erectile dysfunction patients with diabetes mellitus or with neurological disorders.Reiter 2001
Correlations between reduced circulating DHEA/S levels and urticaria and other immune-related disorders have led to proposals for DHEA supplementation. However, clinical trials are largely lacking.Buford 2008, Kasperska-Zajac 2008, Kasperska-Zajac 2011 In a review of clinical trials, no effect of DHEA supplementation was found in well-established rheumatoid arthritis in one study; however, decreased disease activity was observed in another study of patients with inflammatory bowel disease, although the study was not placebo controlled.Hazeldine 2010 In animal studies of experimental sepsis and trauma, DHEA decreased splenocyte proliferation and increased circulating NK cells and CD8+ lymphocytes; as a result, a role in managing critical illness has been suggested.Oberbeck 2010
Metabolic effects (lipids/insulin)
Studies evaluating the effect of DHEA supplementation on lipid profiles have produced equivocal results. Dosages used in trials vary from 25 to 1,600 mg/day and include heterogenous populations, making meta-analysis difficult. Some studies report decreases in total cholesterol as well as decreased HDL cholesterol; other studies report no effect. While it is possible that certain subpopulations may experience greater metabolic benefit with DHEA supplementation, specific populations have not been identified.Davis 2011, Olech 2005, Panjari 2010, Tchernof 2004 Similarly, results for body composition and body fat distribution outcomes are inconsistent.Olech 2005, Tchernof 2004 The role of exogenous DHEA in insulin sensitivity is unclear. Some studies report a modest effect, while a greater number show no effect.Talaei 2010, Tchernof 2004 In one study, DHEAS supplementation did not improve insulin response in hypopituitary hypoadrenalism.McHenry 2012 In a study in obese pre- and postmenopausal women, DHEAS produced reductions in both obesity parameters (weight, BMI, body fat, leptin) and in metabolic syndrome parameters (waist circumference, blood glucose, blood pressure) in postmenopausal women; in premenopausal women, the effects of DHEAS were limited to decreases in obesity parameters.Gómez-Santos 2012
Data regarding the effect of supplemental DHEA on muscle strength or physical function in elderly patients are inconclusive.Baker 2011 A meta-analysis of DHEA/S use in elderly men found a small reduction in body fat that was dependent on DHEA conversion to testosterone and estradiol.Corona 2013 A small controlled trial in young healthy men found that DHEA supplementation reduced muscle soreness and serum creatine kinase levels during 5 days of exercise training.Liao 2013
A small double-blind, randomized, placebo-controlled, crossover trial (N=16) investigated the effect of oral DHEA supplementation (50 mg) on testosterone levels in young and middle-aged men after high-intensity interval training. Baseline free testosterone was approximately 75% lower in middle-aged men (mean age, 49 years) compared with young men (mean age, 21 years). Compared with placebo, mean free testosterone levels after the exercise challenge increased significantly with DHEA supplementation in both middle-aged and young men from 2.76 pg/mL to 9.99 pg/mL and from 9.22 pg/mL to 19.4 pg/mL, respectively (P<0.05 for each). Likewise, the free testosterone to cortisol ratio was significantly increased during the recovery period with DHEA compared with placebo. Little to no effect on levels of cortisol, total testosterone, or luteinizing hormone was observed with DHEA.Liu 2013
Reviews of clinical trials and 2 meta-analyses of DHEA supplementation found no convincing evidence to support use for treatment of postmenopausal symptoms in women with intact adrenal function. The quality of evidence for the majority of studies was low due to imprecision and risk of bias.Alkatib 2009, Bovenberg 2005, Elraiyah 2014, Genazzani 2010, Grimley 2006, Olech 2005, Panjari 2010 Sexual function, well-being, quality-of-life measures, depressed mood, anxiety and distress, metabolic parameters (lipid profile, carbohydrate metabolism), body weight, BMI, and cognition were among the outcomes measured. DHEAS has been shown to stimulate osteoblasts; however, results for improvements in bone density are equivocal, with only a small effect demonstrated in some studies. In a meta-analysis of data of 23 trials (N=1,188), subgroup analyses were conducted based on study design (parallel vs crossover) and duration of follow-up (less than 12 months vs 12 months or longer; range: 1.5 to 24 months) to explain between-study heterogeneity; no significant subgroup interactions were found. The most commonly used DHEA dose was 50 mg and ranged from 25 mg to 1,600 mg. A benefit from DHEAS supplementation may be seen in elderly women with low circulating DHEA, but not in elderly men. Fracture rates were not reported in the studies.Christiansen 2011, Elraiyah 2014, Grimley 2006, Olech 2005 Limited studies suggest transvaginal DHEA may have potential benefit in vaginal atrophy; however, further studies are required.Panjari 2011 A pilot study in 7 healthy, nonobese, postmenopausal women showed positive correlations between DHEAS, estrone, and androstanediol glucuronide after daily administration of DHEA 50 mg supplementation for 3 weeks. Increases were also seen in testosterone and estradiol but were highly variable. Oral DHEA supplementation disrupted preexisting androgen/estrogen balance, causing an unpredictable hyperandrogenism compared with placebo. Effects on sleep appeared to depend on the relative conversion of DHEA to estradiol versus testosterone; therefore, supplementation may result in either sleep inhibition or sleep stimulation. Little to no effect was observed on growth hormone secretion, prolactin, thyroid function, adrenocorticotropic hormone, and cortisol profiles.Caufriez 2013
Vaginal preparations of DHEA 0.25% to 1% have shown efficacy in reducing pain due to vaginal atrophy. A prasterone 0.5% vaginal insert is approved for treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause.Intrarosa April 2017
Uncontrolled studies conducted in patients with schizophrenia in the 1950s reported an improved sense of well-being (ie, improvement in energy, insight, self-confidence, emotionality, vitality, adjustments to environment, school and occupational performance, anxiety, depression, apathy, withdrawal) with DHEA supplementation; however, data from recent clinical trials are limited and equivocal.Maninger 2009 Some evidence exists of altered DHEA/S circulating levels in patients with schizophrenia; it is possible that differences in baseline levels between schizophrenic and healthy matched controls may account for equivocal results of clinical studies.Ritsner 2011 In one study, DHEA dosages of 150 mg/day over 12 weeks improved negative symptoms (loss of interest, energy, and humor), with no effect on hallucinations or delirium.Ritsner 2011 Another study used DHEA 200 mg/day for 6 weeks and found no superiority over placebo.Maninger 2009
Systemic lupus erythematosus
The use of DHEA in systemic lupus erythematosus is controversial and based on the observed effects of DHEA and DHEAS on the immune system and enhanced autoantibody production by estrogen and suppression by androgens.Bovenberg 2005, Olech 2005
A Cochrane review of 7 studies evaluating the use of DHEA in mild to moderate systemic lupus erythematosus found little clinical effect, with only one study showing stabilization or improvement over placebo (8% more patients). The review showed modest, clinically relevant increases in health-related quality-of-life measures, but the long-term effect (longer than 1 year) of DHEA supplementation is unknown.Crosbie 2007, Hazeldine 2010 The use of DHEA in more severe lupus is not supported because it exerts DHEA antiglucocorticoid effects.Olech 2005
DHEA is available as oral preparations, intraoral sprays, and transdermal creams and gels.Olech 2005
Orally administered DHEA has a low bioavailability (less than 10%), and intravenous DHEA is subject to rapid hepatic clearance. Transdermal and subcutaneous routes offer greater bioavailability. Oral DHEA is converted to inactive DHEAS, which can then act as a reservoir for the body to utilize. DHEA 200 mg/day given to healthy men for 1 week resulted in a DHEA level of 1 mcg/dL and a DHEAS level of 400 mcg/dL.Olech 2005
Adrenal insufficiency: 50 mg/day for 3 months is considered a replacement dose, while 200 mg/day achieves supraphysiological circulating levels and is considered a pharmacological dose.Genazzani 2007
Anorexia nervosa: 100 mg/day for 6 months was used in a pilot study.Bloch 2012
Exercise training–induced muscle damage: 100 mg/day of DHEA supplementation was administered over 5 days in a study in young men undergoing exercise training.Liao 2013
Major depressive disorder: DHEA doses ranging from 30 to 450 mg/day for 6 to 8 weeks have been used in clinical studies.Ravindran 2016
Metabolic syndrome: DHEAS 100 mg/day for 3 months has been used in a study evaluating effects against metabolic syndrome in pre- and postmenopausal women.Gómez-Santos 2012
Postmenopausal women: DHEA 25 mg/day has been suggested because this dose minimizes androgenic adverse effectsBovenberg 2005; however, only studies in which at least 50 mg/day was used demonstrated positive outcomes as hormonal replacement therapy.Genazzani 2007, Olech 2005, Panjari 2010
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. DHEA supplementation has been evaluated for use in improving oocyte production in infertility.Gleicher 2011, Mamas 2009, Wiser 2010
Subsequent to DHEA supplementation, the resulting supraphysiologic serum DHEAS level has been demonstrated to cross-react with 3 commercially available progesterone assays (Immulite 2000, eCobas, Centaur), yielding false-positive increases in serum progesterone. This interference with progesterone immunoassays may impact clinical decision making for IVF.Forman 2015, Franasiak 2016
Estrogen derivatives: Avoid combination. Dehydroepiandrosterone may enhance the adverse/toxic effect of estrogen derivatives.Corona 2013, Davis 2011, Labrie 1997, Legrain 2003, Merritt 2012, Morales 1994, Mortola 1990
Progesterone: Subsequent to DHEA supplementation, the resulting supraphysiologic serum DHEAS level has been demonstrated to cross-react with 3 commercially available progesterone assays (Immulite 2000, eCobas, Centaur), yielding false-positive increases in serum progesterone. This interference with progesterone immunoassays may impact clinical decision making for IVF.Forman 2015, Franasiak 2016
Testosterone: Avoid combination. Dehydroepiandrosterone may enhance the adverse/toxic effect of testosterone.Bosy 1998, Bowers 1999, Corona 2013, Davis 2011, Kicman 1990, Labrie 1997, Legrain 2003, Morales 1994, Mortola 1990
Studies in adrenal insufficiency suggest DHEA is generally well tolerated. However, data from long-term studies are lacking.Bovenberg 2005, Crosbie 2007, Elraiyah 2014, Grimley 2006 Many observed adverse effects are predictably hormonal in nature: acne and hirsutism in women, gynecomastia and testicular wasting in men, and unfavorable effects on lipid metabolism (decreased HDL levels) and blood pressure in both genders.Crosbie 2007, Olech 2005, Ravindran 2016 Mania and hypomania have occurred in patients both with and without a psychiatric history. These reactions appear to be related to higher doses.Dean 2000, Kline 1999 DHEA supplementation should not be used in hormone-dependent breast and prostate cancers.Olech 2005 Higher doses have been associated with worsening of prostatitis and increased breast cancer risk.Ravindran 2016 A single case report of seizure in a woman taking DHEA to increase oocyte production exists.Gleicher 2011, Mamas 2009
Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements; of the 217 supplement products implicated in liver injury, dehydroepiandrosterone was among the 22% (116) of non-bodybuilding single-ingredient products identified.Navarro 2014
Information in humans is limited. Although DHEA has been demonstrated to be carcinogenic (ie, hepatic tumors) in rodents, relevance in humans has been debated due to hepatic and biliary mechanisms that eliminate the suggested causative peroxisome buildup. Protective effects of DHEA on other cancers have also been demonstrated in rodents.Matsuzaki 2006, Webb 2006
- Dioscorea villosa
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