Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health.

BACKGROUND: Hyperactivity and hypoactivity of the HPA have been forwarded as of pathophysiological relevance in major depressive disorder and chronic fatigue syndrome (CFS), respectively. METHODS: This study examines cortisol levels in the two disorders, and also assesses levels of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-alpha-hydroxyprogesterone; 15 subjects with CFS diagnosed according to CDC criteria, 15 subjects with DSM III-R major depression and 11 healthy subjects were compared. RESULTS: DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alpha-hydroxyprogesterone did not differ between the three groups. CONCLUSIONS: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.     

Low pregnenolone sulphate plasma concentrations in patients with generalized social phobia

BACKGROUND: Animal studies have shown that neuroactive steroids modulate the activity of the gamma-aminobutyric acid type A/benzodiazepine receptor complex and that these steroids display anxiolytic or anxiogenic activity depending on their positive (e.g. allopregnanolone) or negative allosteric modulation (e.g. dehydroepiandrosterone sulphate) of this receptor. This study compared plasma levels of allopregnanolone, dehydroepiandrosterone sulphate and pregnenolone sulphate in healthy controls and in patients with generalized social phobia, as assessed with the Mini-International Neuropsychiatric Interview. METHODS: Plasma concentrations of allopregnanolone, pregnenolone sulphate, and dehydroepiandrosterone sulphate were measured in 12 unmedicated male patients with generalized social phobia and 12 matched healthy male volunteers. RESULTS: Concentrations of pregnenolone sulphate were significantly lower in patients with generalized social phobia than in healthy controls. No statistically significant differences were found for the concentrations of allopregnanolone and dehydroepiandrosterone sulphate in plasma. CONCLUSIONS: These results are particularly interesting since we also observed lower pregnenolone sulphate concentrations in male patients suffering from generalized anxiety disorder. Their relevance to the pathophysiology of social anxiety disorder remains to be determined.     

Dehydroepiandrosterone and the cerebral functions

Of all steroidal hormones, dehydroepiandrosterone (DHEA) and its sulphate form, DHEAS, are synthesized by the adrenal glands in the biggest quantities. In this review the authors consider the ways of the synthesis of the neurosteroids, possible mechanisms of the regulation of these processes, and their dynamics under stressful conditions. The paper presents analysis of experimental and clinical data on the role of DHEAS in the manifestation of different cerebral functions. The authors pay special attention to the results of substitutive therapy with DHEA(S) in patients with such CNS functional disorders, as Alzheimer's disease, depression, age-relative memory and sleep disturbances, etc.     

Lifetime psychiatric comorbidity rate in Israeli non-help-seeking patients with combat-related post-traumatic stress disorder

BACKGROUND: Most of the data on lifetime psychiatric comorbidity in combat-related posttraumatic stress disorder (CR-PTSD) were collected in help-seeking patients. METHODS: In the present study we used the Schedule for Affective Disorder and Schizophrenia-Lifetime Version to examine a relatively large sample (n=80) of Israeli non-help-seeking CR-PTSD patients. The diagnosis of PTSD was based on the DSM-III-R criteria. RESULTS: We found a low rate of lifetime psychiatric comorbidity, especially drug dependence (2.25%), alcoholism (2.25%) and major depressive disorders (5%). CONCLUSION: It seems that in contrast to help-seeking CR-PTSD, non-help-seeking CR-PTSD is associated with a low frequency of comorbid psychiatric disorders. LIMITATION: Only non-help seeking CR-PTSD patients who agreed to participate in the study were included in this investigation. CLINICAL RELEVANCE: The detection and diagnosis of CR-PTSD comorbidity is important for establishing appropriate psychotherapeutic and pharmacological treatment.     

Dehydroepiandrosterone and brain functioning

The adrenal glands synthesize dehydroepiandrosterone (DHEA) and its sulphate form (DHEAS) more intensively than they do other steroid hormones. Researchers are interested in these hormones for several reasons. Firstly, for some years they have been trying to find the reason for DHEA and DHEAS to be synthesized and present in the organism in such high concentrations. Secondly, their attention have been attracted by age-dependent regression of DHEA, which is strictly determined. Thirdly, despite longstanding efforts of scientists, the physiological role and spectrum of the biological activity of DHEA is still unclear. Evidence of that DHEA and DHEAS can be synthesized in situ in the brain tissue, received in rat experiments, urged researchers to clarify the role of these neurosteroids in the CNS. The presented review covers ways of neurosteroid synthesis, possible mechanisms of the regulation of these processes, and their dynamics under the condition of stress. The authors analyze experimental and clinical observations undertaken with a goal to clarify a possible role of DHEA in the manifestation of various brain functions. Special attention is payed to ambiguous results of modern studies, dedicated to replacement therapy of various disorders of CNS functioning (Alzheimer's disease, depression, age-specific memory impairment, sleep disturbance etc.) with DHEAS.     

High doses of systemic DHEA-sulfate do not affect sleep structure and elicit moderate changes in non-REM sleep EEG in rats

The hormone dehydroepiandrosterone (DHEA) and its metabolite DHEA-sulfate (DHEAS) occur in huge quantities in the plasma as well as in the brain of vertebrates. To investigate whether DHEAS modulates sleep-wake behavior, we assessed the sleep response to three doses (25, 50, and 100 mg/kg) of intraperitoneally administered DHEAS, mixed with oil, in 8 rats. DHEAS injections produced dose-dependent and long-lasting elevations in the plasma levels of both DHEAS and DHEA. DHEAS administration did not affect sleep time and architecture but exerted persistent effects on the electroencephalogram (EEG) within non-rapid eye movement sleep: 50 mg/kg DHEAS significantly augmented EEG power in the frequency range of sleep spindles, and 100 mg/kg DHEAS depressed EEG power in the slow-wave frequency bands. The findings indicate that DHEAS changes the sleep EEG in a dose-dependent way, possibly through a modulation of GABA- and glutamate-induced currents.     

Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder

BACKGROUND: Depressive symptomatology has been connected with an activation of the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. METHODS: We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. RESULTS: Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. CONCLUSIONS: Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.     

Dehydroepiandrosterone and exercise in golden hamsters.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are adrenal androgens that have been associated with a sense of well-being in humans. We describe two experiments done to test the hypothesis that an increase in DHEA or DHEAS secretion is associated with the inclination to exercise using a hamster model. In the first experiment, morning blood samples were obtained from adult male golden hamsters at various intervals after being placed in cages with (EX group) or without (SED group) access to running wheels. The EX group had lower DHEA (6, 12, and 14 weeks; p < 0.05) and DHEAS (13 and 16 weeks; p < 0.01) levels than the SED hamsters. In the second experiment, the number of wheel revolutions was monitored in castrated adult male hamsters implanted with Silastic capsules containing no hormone (blank control group), testosterone, or DHEA. The number of wheel revolutions in the group receiving DHEA was not significantly different than the blank control group, whereas testosterone increased wheel running at 4, 5, and 7 weeks (p < 0.05). These results indicate that DHEA and DHEAS levels decrease with exercise in male golden hamsters and that exogenous DHEA does not enhance the tendency to run on wheels.     

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real‐time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways. In MDD, a significant decrease in mRNA level of cytochrome P450 17A1 (CYP17A1, synthesizing C19 ketosteroids) in the ACC and a significant increase in mRNA levels of hydroxysteroid sulfotransferase 2A1 [SULT2A1, catalyzing the sulfate conjugation of dehydroepiandrosterone (DHEA)] were observed in the DLPFC, suggesting alterations in DHEA and its sulfate metabolite DHEAS levels. Decreased intensity and distribution of CYP17A1 immunohistochemical staining was found in the ACC of MDD patients. Interestingly, there was a significant positive correlation between the mRNA levels of CYP17A1 and tyrosine‐related kinase B (TrkB) full length isoform. In a unique post‐mortem human brain slice culture paradigm, BDNF mRNA expression was found to be significantly increased following incubation with DHEA. Together, these data indicate a close relationship between DHEA and BDNF‐TrkB pathways in depression. Furthermore, in the DLPFC, higher mRNA levels of 11β‐hydroxysteroid dehydrogenase‐1 (HSD11B1, reducing cortisone to the active hormone cortisol) and steroidogenic acute regulatory protein (STAR, facilitating the shuttle of cholesterol through the intermembrane space) were found in the MDD patients and BPD patients, respectively. In conclusion, this study suggests the presence of a disturbance in the endogenous synthesis of DHEA and DHEAS in mood disorders, which has a close relationship with BDNF‐TrkB signaling.     

DHEA for postmenopausal women: A review of the evidence

Background

Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most abundant sex steroids in women and provide a large reservoir of precursors for the intracellular production of androgens and estrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been proposed that restoring the circulating levels of these steroids to those found in young women may have anti-aging effects and improve sexual function and wellbeing in postmenopausal women.

Aim

To review the published literature for the efficacy of DHEA therapy data regarding safety.

Methods

A systematic literature search of MEDLINE (Ovid) and Pub-Med (1966 to November 2009) for original studies that included any of the terms dehydroepiandrosterone, DHEA or DHEAS, sexual function, wellbeing, women and metabolic parameters of interest.

Results

Overall the interpretation of the data was limited by inadequate sample size and short treatment duration of available studies with inconsistent results. The more recent randomized controlled trials however do not support a benefit of oral DHEA therapy for women. A possible benefit that emerged is that vaginally administered DHEA may improve vaginal atrophy with concomitant improvements in sexual function in women who are estrogen deficient due to menopause. The potential value of oral DHEA therapy for postmenopausal women is called into question.     

Impact of overnight dexamethasone suppression on the adrenal androgen response to an oral glucose tolerance test in women with and without polycystic ovary syndrome

In order to test the hypothesis that adrenocortical overactivity, possibly related to the stress of testing, may impact on the measurement of circulating androgen concentrations during glucose- induced hyperinsulinaemia, we prospectively screened 10 patients with the polycystic ovary syndrome (PCOS) and nine healthy control women with an oral glucose tolerance test (OGTT), before and after the administration of dexamethasone. Blood sampling was performed at 0, 30, 60, 90, and 120 min following the oral ingestion of 75 g of glucose, before and after the administration of 1.0 mg dexamethasone on the evening prior to testing. Total and free testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol, glucose and insulin were assessed during the 2 h OGTT. Women with PCOS had increased basal concentrations of free testosterone, total testosterone, androstenedione, and insulin compared to control women. In women with PCOS an acute decline in circulating concentrations of DHEAS occurred during the OGTT. In PCOS women there were no changes in other ovarian or adrenal androgens during OGTT before or following dexamethasone administration. In control women DHEA concentrations declined during the OGTT. Following overnight dexamethasone suppression in control women, circulating concentrations of DHEAS and testosterone also declined. It is concluded that: (i) in PCOS women only the concentration of circulating DHEAS decreased during glucose-induced hyperinsulinaemia and dexamethasone administration did not further alter androgen responses to an OGTT; (ii) it is possible that, in these hyperandrogenic patients, the insulin-related suppression of adrenocortical testosterone and DHEA is negated by their much greater ovarian secretion of these androgens; (iii) in control women DHEA concentrations acutely declined during the OGTT and the administration of dexamethasone resulted in the acute decline of DHEA, DHEAS, and testosterone; (iv) it appears that the stress related to testing impacts on the androgen response to OGTT, at least in healthy women.      

Family and past history of mental illness as predisposing factors in post-traumatic stress disorder

BACKGROUND: Family studies of post-traumatic stress disorder (PTSD) have given inconsistent results to date. Identifying predisposing factors in PTSD compared to anxiety disorders may help to clarify the classification of PTSD as a diagnostic entity. METHOD: Retrospective case note study of 87 PTSD patients who participated in an RCT, and 51 PTSD patients and 87 agoraphobics treated routinely in outpatients. RESULTS: Compared to agoraphobics, PTSD patients had significantly less family history of anxiety disorder but not mental illness in general. They also had significantly less personal history of mental illness prior to the index episode. CONCLUSIONS: Trauma precipitated PTSD in subjects who had significantly fewer premorbid predisposing factors than did agoraphobics. Such factors may predispose agoraphobics to become psychiatrically ill after more minor trauma. Research is needed to systematically compare the events which precipitate PTSD as opposed to agoraphobia and other anxiety disorders.     

The neurosteroids DHEA and DHEAS may influence cognitive performance by altering affective state

The effects of Dehydroepiandrosterone (DHEA) and its sulfate ester, Dehydroepiandrosterone sulfate (DHEAS) on performance in various cognitive and affective tasks were investigated. Ovariectomized rats (n = 48) received 0.0, 3.0, or 7.5 mg/kg s.c. of DHEA or DHEAS suspended in 10% ethanol/sesame oil v/v. For the cognitive tasks (water maze, Y-maze, passive avoidance, and object recognition), subjects were injected after training trials. For the affective tasks (tail flick, open field, and elevated plus-maze), subjects were injected 1 or 24 h prior to testing. DHEA deceased latencies and trials to criterion in the water maze, and decreased motor activity in the open field at 24 h postinjection. DHEAS decreased latencies to the goal arm in the Y-maze and reduced motoricity and the number of entries into the center of a brightly lit open field, both 1 and 24 h after injection. These findings suggest that DHEA and DHEAS may alter performance on cognitive tasks due to motor or anxiety effects.     

Alcoholism and anxiety in bipolar illness: differential lifetime anxiety comorbidity in bipolar I women with and without alcoholism

INTRODUCTION: This study was undertaken to evaluate the prevalence rate of anxiety comorbidity in bipolar subjects with and without alcohol use disorders (AUD). METHODS: Bipolar men and women who entered the Stanley Foundation Bipolar Network (SFBN) underwent a Structured Clinical Interview for DSM-IV (SCID-IV) and were divided into those subjects meeting current or lifetime criteria for an alcohol use disorder (AUD=213) vs. those subjects who did not (non-AUD=137). Lifetime rates of comorbid anxiety disorder were evaluated between groups. RESULTS: Of 350 subjects, 163 (46.5%) met criteria for an anxiety disorder. Panic disorder and OCD were the most common anxiety disorders in the AUD and non-AUD groups. OCD and specific phobia were significantly less prevalent in BP I patients with AUD compared to those without. Bipolar women with AUD had a significantly higher rate of PTSD than those without. CONCLUSION: These data highlight the added liability of anxiety comorbidity in BP disorder. Specifically, the greater amount of PTSD and lesser amount of OCD in bipolar women with alcohol comorbidity may have important diagnostic and treatment implications beyond dual diagnosis. Further study in comorbidity patterns is encouraged to not only better understand illness burden, but to maximize pattern-specific treatment outcomes.     

Vaginal DHEA to treat menopause related atrophy: a review of the evidence

Vaginal atrophy is a common symptom of postmenopausal estrogen deficiency and can present as dryness, irritation, infection and dyspareunia and can affect sexual function and quality of life. Currently vaginal atrophy is treated with the intravaginal application of preparations containing estradiol or estriol, which are both effective and safe. It has been proposed that intravaginally administered dehydroepiandrosterone (DHEA) can be used to treat vaginal atrophy. DHEA and its sulphate DHEAS are the most abundant circulating sex steroid hormones in women, and provide a large precursor reservoir for the intracellular production of androgens and estrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. Although there is some evidence to support the use of intravaginal DHEA for postmenopausal women with symptoms of vaginal atrophy, independent studies are required to confirm this. In addition studies regarding the effects of vaginal DHEA on sexual function in women without vaginal atrophy are needed. Given that the efficacy and long term safety of low dose vaginal estradiol and estriol therapy is well established and that vaginal estrogen requires application of 2-3 times a week, rather than daily dosing; the benefit of daily vaginal DHEA over estrogen also needs to be considered as women may find it unpalatable to adhere to daily dosing with a cream preparation.     

Ovarian and adrenal steroid production: regulatory role of LH/HCG

BACKGROUND: The contribution of the adrenal glands to the total circulating steroid pool in women is not well known. There is evidence that human adrenals express the LH receptor gene and that LH may affect adrenal androgen secretion. METHODS: HCG stimulation tests (a single dose of 5000 IU i.m.) were performed in women at reproductive age (group 1, n = 6, age 21--39 years) before and after treatment with a GnRH agonist for 3 weeks, and in oophorectomized post-menopausal women (group 2, n = 6, 47--59 years) during and after estrogen replacement therapy (ERT). RESULTS: HCG did not stimulate the secretion of cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) in group 2. In contrast, in group 1, the basal concentrations of serum 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone and estradiol (E(2)) were stimulated significantly (17-OHP 105%, androstenedione 31%, testosterone 20%, E(2) 136%) by HCG, and the treatment with GnRH agonist decreased the responses. The basal serum concentrations of these steroids were significantly lower in oophorectomized women (17-OHP 57%, androstenedione 46%, testosterone 25%), and HCG did not increase these levels. It can be approximated that the ovarian contribution to the circulating levels of 17-OHP, androstenedione and testosterone is 25--30%, and that the adrenals are the primary source of cortisol, DHEA and DHEAS. CONCLUSION: LH/HCG does not have a major role in the regulation of adrenal steroid synthesis in endocrinologically healthy women.     

Elevated blood levels of dehydroepiandrosterone sulphate vary with symptom load in posttraumatic stress disorder: findings from a longitudinal study of refugees in Sweden

BACKGROUND: The present study is part of a longitudinal study of recently resettled refugees with the aim of learning which factors in their daily life influence health as measured by self-report and stress-responsive hormones. METHODS: In a group of recently resettled refugees with a high incidence of posttraumatic stress disorder (PTSD), diagnosed by structured interview, self-rated symptoms of PTSD were followed three times over a period of 9 months after inclusion in the study. Eighty-six individuals were included in the study and 58 subjects (67.4%) completed it. Blood samples were drawn at each examination for assessment of hormone levels. RESULTS: After adjustment for age, dehydroepiandrosterone sulphate (DHEA-s) was observed to be higher in non-depressed PTSD cases than in non-PTSD without depression. There was an interaction between PTSD and depression regarding DHEA-s levels. DHEA-s correlated significantly with changes in self-rated symptoms of PTSD at last follow-up; the greater the increase in PTSD symptoms, the greater the increase in plasma DHEA-s. The variation of DHEA-s levels in relation to changes in self-rated health in non-PTSD showed the opposite pattern, although not reaching significance. CONCLUSIONS: The finding of changes in DHEA-s should encourage further studies of the role of altered steroid metabolism in PTSD.     

Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa

OBJECTIVE: Animal data suggest that neuroactive steroids, such as 3alpha,5alpha-tetrahydroprogesterone (3a,5a-THP), dehydroepiandrosterone (DHEA), and its sulfated metabolite (DHEA-S), are involved in the modulation of eating behavior, aggressiveness, mood, and anxiety. Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by abnormal eating patterns, depressive and anxious symptoms, enhanced aggressiveness, and endocrine alterations. Previous studies reported decreased blood levels of DHEA and DHEA-S in small samples of anorexic patients, whereas no study has been performed to evaluate the secretion of these neuroactive steroids in BN as well as the production of 3alpha,5alpha-THP in both AN and BN. Therefore, we measured plasma levels of DHEA, DHEA-S, 3alpha,5alpha-THP and other hormones in patients with AN or BN and explored possible relationships between neuroactive steroids and psychopathology. METHOD: Ninety-two women participated in the study. There were 30 drug-free AN patients, 32 drug-free BN patients, and 30 age-matched, healthy control subjects. Blood samples were collected in the morning for determination of hormone levels. Eating-related psychopathology, depressive symptoms, and aggressiveness were rated by using specific psychopathological scales. RESULTS: Compared with healthy women, both AN and BN patients exhibited increased plasma levels of 3alpha,5alpha-THP, DHEA, DHEA-S, and cortisol but reduced concentrations of 17beta-estradiol. Plasma testosterone levels were decreased in anorexic women but not in bulimic women. Plasma levels of neuroactive steroids were not correlated with any clinical or demographic variable. CONCLUSIONS: These findings demonstrate increased morning plasma levels of peripheral neuroactive steroids in anorexic and bulimic patients. The relevance of such hormonal alterations to the pathophysiology of eating disorders remains to be elucidated.     

Human chorionic gonadotropin does not alter patterns of adrenal androgen secretion in primary human adrenal reticularis and fasciculata cell culture

OBJECTIVE: Controversy surrounds the role of the ovary in maintaining postmenopausal androgen levels. Some postulate that aging ovaries are endocrinologically senescent and that menopausal levels of luteinizing hormone drive the adrenal cortex to secrete increasing amounts of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as prohormones for subsequent peripheral bioconversion to maintain menopausal testosterone levels. We hypothesized that human chorionic gonadotropin (hCG), acting as an luteinizing hormone analog, would thus augment adrenal androgen secretion from primary human adrenocortical zona reticularis and zona fasciculata cell cultures. DESIGN: Human adrenal glands, obtained from a local organ donation program, were separated microscopically into reticularis and fasciculata zones and were cultured to confluence in serum-supplemented media, followed by a further incubation in defined media. They were then exposed to 24 hours of varying hCG doses, followed by an incubation with defined media and pregnenolone. Supernatants were assayed for adrenal androgens and cortisol. Data were expressed as the molar ratio of (DHEA+ DHEAS)/cortisol and the molar ratio of DHEA/DHEAS. For each of the four runs, mean molar ratios were compared by analysis of variance. RESULTS: For each of the four runs, the molar ratio was increased 17- to 157-fold in the reticularis compared with the fasciculata cells, indicating efficient zonal separation. Addition of hCG did not alter the molar ratios of adrenal androgens to cortisol or DHEA/DHEAS for either cell type. CONCLUSIONS: Addition of hCG to human adrenal reticularis or fasciculata cells does not seem to change the pattern of secretion of adrenal androgens or cortisol. It is thus unlikely that luteinizing hormone plays a significant role as an adrenal androgen secretagogue, at least with short-term exposure.     

One-year therapy with 10mg/day DHEA alone or in combination with HRT in postmenopausal women: effects on hormonal milieu

The purpose of this study was to evaluate the effects on hormonal milieu of 1-year therapy with 10 mg/day oral dehydroepiandrosterone (DHEA) or 50 microg transdermal estradiol plus 100 mg/day oral micronized progesterone in a group of 20 healthy postmenopausal women (age=50-58 and years since menopause (ysm)=1-6) and also the effects observed by combining these two therapies in a group of 12 postmenopausal women (age=54-61 and ysm=6-10) characterized by lower baseline DHEA and DHEAS levels (<2.40 and <0.55 microg/ml, respectively). DHEA produced a significant rise in androgens levels, whereas HRT did not. Moreover, DHEA alone induced a significantly lower increase in estrogens and beta-endorphin levels and a higher decrease in cortisol levels than HRT. DHEA and HRT also produced a significant similar increase in allopregnanolone levels. DHEA plus HRT induced a significantly higher increase in testosterone and estradiol and a lower increase in allopregnanolone and beta-endorphin levels and a significantly lower decrease in cortisol levels than HRT alone treated group. A similar increase was observed in progesterone and SHBG levels in all groups. These results suggest that 10-mg DHEA seems to be the proper dose to replace androgen deficiency in subjects with reduced Delta-5 androgens plasma levels. However, the aging process and the number of years since menopause may further modulate the effects of hormone therapy on hormonal milieu.