DHEA Replacement Research Articles

A Review of Adrenal Gland Disorders

Cortisol is a glucocorticoid hormone which is a potent anti-inflammatory that controls the body use of fat, protein and carbohydrates, control sleep-wake cycle, cortisol also regulates blood pressure, increases blood sugar and at times of stress helps to provide energy boost and better handle of stress response. Aldosterone is a mineralocorticoid hormone that mainly regulates blood pressure, and levels of sodium and potassium as well helps in preserving a neutral pH level. Androgens are converted into oestrogen in the ovaries, and into different androgens in the testes, they have weak male hormones effect, DHEA replacement showed some benefit on quality of life in females with Addison disease. Catecholamines (adrenaline and noradrenaline) are hormones which increase the heart rate, cardiac contractility, blood flow to muscles and brain, and major assist to glucose utility and metabolism. Vasoconstriction of blood vessels is mainly controlled by catecholamines, like cortisol to some degree these hormones are essential in stress response. Will discuss presentation and management for common adrenal gland diseases like cortisol excess and deficiency, pheochromocytoma, mineralocorticoid excess, adrenal incidentalomas, and congenital adrenal hyperplasia.

Traiter l’insuffisance surrénale : pour quels enjeux ? Par quels moyens thérapeutiques ?

Quality of life remains altered in the adrenal insufficient patient treated by hydrocortisone and fludrocortisone. Due to its pharmacokinetics properties, hydrocortisone requires 2 to 3 daily doses -including a morning intake of 2/3 or half of the daily dose respectively- while fludrocortisone requires a once morning daily dose. Titration of hydrocortisone and fludrocortisone relies on the clinical symptoms of over- or under-replacement together with biochemical indexes such as plasma sodium, potassium and renin. DHEA replacement may improve quality of life and mood and may increase lean body mass and bone mineral density, especially in women with adrenal insufficiency. The new slow release hydrocortisone formulations may help reproduce a more physiological cortisol plasma profile and thus reduce the impact of over-replacement on cardiovascular risk factors and glucose metabolism. Acute adrenal insufficiency is a life-threatening complication of glucocorticoid and mineralocorticoid under-replacement, which may be prevented by educational programs towards the adrenal insufficient patient.

Effect of DHEA supplementation on serum IGF-1, osteocalcin, and bone mineral density in postmenopausal, glucocorticoid-treated women

DHEA therapy increases bone formation in postmenopausal women. We have found only a few reports of dehydroepiandrosterone replacement therapy in women receiving long-term glucocorticoid medication. The purpose of this study was to establish whether DHEA replacement therapy may be useful in the treatment of steroid-induced osteoporosis in postmenopausal women. Nineteen women, aged 50-78 years, treated at least for three years with average daily doses of more than 7.5 mg prednisone, with T-score L2/L4<-1.5 and bisphosphonates intolerance, were enrolled to the study. For the first year of the study the patients were given calcium, vitamin D3 and thiazide diuretics. For another year the patients received orally micronized DHEA 25-50 mg daily. Before the study, after twelve months of Calcium/D3 therapy, then after six weeks and six months of DHEA therapy, serum concentrations of DHEAS, androstenedione, testosterone, estradiol, FSH, IGF-1 and osteocalcin were assessed. Bone mineral density (BMD) in lumbar spine and femoral neck was measured before the treatment, after a year on Calcium/D3 and after six and twelve months of DHEA replacement therapy. In all treated women, DHEA significantly increased serum DHEAS, androstenedione and testosterone concentrations. A significant elevation of serum IGF-1 and osteocalcin concentrations was found as early as after six weeks of DHEA treatment. A significant increase of bone mineral density in the lumbar spine and femoral neck was observed after six and twelve months of DHEA treatment. Our results suggest a beneficial role of DHEA replacement therapy in the treatment of steroid-induced osteoporosis.

Higher DHEA-S (dehydroepiandrosterone sulfate) levels are associated with depressive symptoms during the menopausal transition: results from the PENN Ovarian Aging Study

The influence of sex hormones on mood during the menopausal transition has been the subject of ongoing investigation. Because dehydroepiandrosterone sulfate (DHEA-S) has been associated with several indicators of healthy aging, we conducted a population-based study of midlife women to determine the relationship between DHEA-S levels and depressive symptoms and major depression during the transition through menopause. Unexpectedly, the original report revealed a positive correlation between DHEA-S levels and depressive symptoms at baseline. The cohort was studied over 11years to determine whether the positive association between DHEA-S levels and depression persists through the menopausal transition. We conducted a longitudinal cohort study with 11 assessments during an 11-year interval in Philadelphia, Pennsylvania, using a randomly identified, population-based sample of 436 African American and Caucasian premenopausal women aged 35 to 47years at enrollment. For outcome measures, we used the Center for Epidemiologic Studies Depression Scale and standardized diagnosis of major depression. In a multivariable model, DHEA-S levels were positively associated with depressive symptoms when adjusted for age, menopausal stage, race, smoking status, and body mass index. There was no association between DHEA-S levels and a diagnosis of major depression. DHEA-S levels were positively associated with depressive symptoms through the menopausal transition. No association with major depression was apparent during the menopausal transition, but results may have limited power due to low prevalence of major depression in this cohort. These findings suggest that taking DHEA supplements may increase depressive symptoms for some women, and women and their physicians should be cautious about instituting DHEA replacement therapy during the menopausal transition.

Redox imbalance influence in the myocardial Akt activation in aged rats treated with DHEA

This study examined, in young and old (3 and 24 month-old, respectively) healthy Wistar rats, the in vivo effect of DHEA (10 mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose — 6-phosphate dehydrogenase (G6PDH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and thioredoxin (Trx) reductase activities, hydrogen peroxide steady-state concentration and Nrf2, GST, Trx-1, Akt and p-Akt expressions were assessed in heart tissue. DHEA treatment significantly increased GST activity in 3 and 24 month-old treated groups. The aging factor diminished hydrogen peroxide concentration and Nrf2 expression, independently of treatment. However, the aging process increased GST, Akt and p-Akt expressions in both 24 month-old groups. The aged group responded differently to DHEA respective to GSSG content, GPx activity and p-Akt concentration. Further studies are needed to form conclusions about the efficacy and safety of DHEA replacement in the elderly, and to better understand DHEA's net effect on oxidative stress parameters and its modulation of signaling cascades.

Effect of DHEA Replacement Therapy on Muscle Strength and Size in Sedentary Older Adults

Effect of DHEA Replacement Therapy on Muscle Strength and Size in Sedentary Older Adults

Trypanosoma cruzi: Orchiectomy and dehydroepiandrosterone therapy in infected rats

The ability of gonadal hormones to influence and induce diverse immunological functions during the course of a number of parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulfate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. The effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA were examined, by comparing blood and cardiac parasitism, macrophage numbers, nitric oxide and IFN-γ levels. Orchiectomy enhanced resistance against infection with elevated numbers of macrophages, enhanced concentrations of NO and IFN-γ and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergistic effect, up-modulating the immune response. Male sex steroids appear to play fundamental role in determining the outcome of disease, through the regulation and modulation of the activity of the immune response.

Anterior pituitary hormone replacement therapy—a clinical review

This clinical review summarizes current approaches to diagnosis and treatment of anterior pituitary hormone deficiency. The diagnostic value of endocrine function tests and replacement strategies for hydrocortisone, thyroxine, sex steroids, and growth hormone replacement are reviewed. Female androgen deficiency syndrome and the current role of DHEA and testosterone replacement in women are also discussed.

Hormone replacement Up-to-date. Adrenopause and DHEA replacement therapy

It is well known that serum levels of DHEA and its sulfate form DHEA-S decline along with aging. This phenomenon is called adrenopause in contrast to menopause. Experimental studies show that DHEA has many beneficial effects such as anti-diabetic, anti-atherosclerosis, and anti-osteoporosis effects. Therefore, DHEA replacement has been performed as anti-aging therapy. Several clinical trials of DHEA replacement demonstrated the improvement of sense of well-being, lipid metabolism, and bone metabolism. We recently reported on the result of short-term administration of DHEA in healthy Japanese volunteer men. It is thought that further accumulation of original data is necessary to promote DHEA replacement therapy in Japan.

Does DHEA Replacement Improve Physical Functional Performance in Older Adults?

Does DHEA Replacement Improve Physical Functional Performance in Older Adults?

Does DHEA Replacement Improve Physical Functional Performance in Older Adults?

Does DHEA Replacement Improve Physical Functional Performance in Older Adults?

Authors’ Response: DHEA Replacement in Adrenal Insufficiency

Authors’ Response: DHEA Replacement in Adrenal Insufficiency

Dhea replacement therapy in female sexual dysfunction: preliminary experience

Dhea replacement therapy in female sexual dysfunction: preliminary experience

Dehydroepiandrosterone (DHEA) supplementation for cognitive function .

In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist. Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis

Hypothalamic-pituitary-adrenal underactivity has been reported in rheumatoid arthritis (RA). This phenomenon has implications with regard to the pathogenesis and treatment of the disease. The present study was designed to evaluate the secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its relation to clinical variables in RA, spondyloarthropathy (Spa), and undifferentiated inflammatory arthritis (UIA). Eighty-seven patients (38 with RA, 29 with Spa, and 20 with UIA) were studied, of whom 54 were women. Only 12 patients (14%) had taken glucocorticoids previously. Age-matched, healthy women (134) and men (149) served as controls. Fasting blood samples were taken for determination of the erythrocyte sedimentation rate (ESR), serum DHEAS and insulin, and plasma glucose. Insulin resistance was estimated by the homeostasis-model assessment (HOMAIR). DHEAS concentrations were significantly decreased in both women and men with inflammatory arthritis (IA) (P < 0.001). In 24 patients (28%), DHEAS levels were below the lower extreme ranges found for controls. Multiple intergroup comparisons revealed similarly decreased concentrations in each disease subset in both women and men. After the ESR, previous glucocorticoid usage, current treatment with nonsteroidal anti-inflammatory drugs, duration of disease and HOMAIR were controlled for, the differences in DHEAS levels between patients and controls were markedly attenuated in women (P = 0.050) and were no longer present in men (P = 0.133). We concluded that low DHEAS concentrations are commonly encountered in IA and, in women, this may not be fully explainable by disease-related parameters. The role of hypoadrenalism in the pathophysiology of IA deserves further elucidation. DHEA replacement may be indicated in many patients with IA, even in those not taking glucocorticoids.

Dhea Replacement in Women with Adrenal Insufficiency—Pharmacokinetics, Bioconversion and Clinical Effects on Well-Being, Sexuality and Cognition

Standard replacement for adrenal insufficiency (AI) consists of glucocorticoids and mineralocorticoids while DHEA deficiency is routinely ignored. Thus, AI represents the ideal pathophysiological model of isolated DHEA deficiency. We investigated the effects of DHEA replacement in 24 women with primary and secondary AI employing a double blind, placebo-controlled, randomized crossover design. A DHEA dose of 50 mg/d was chosen based on preceding single-dose pharmacokinetics and bioconversion studies. Each patient received four months of treatment with DHEA and four months placebo, with a one-month washout period. Measurements included serum steroid hormones, somatotropic parameters and psychometric assessment of well-being, mood, cognition and sexuality. Treatment with DHEA raised the initially low serum concentrations of DHEA, DHEAS, androstenedione, and testosterone into the normal range. DHEA induced a slight increase in serum IGF-I, but only in patients with primary AI, suggesting a growth hormone-mediated effect. DHEA treatment significantly improved overall well-being as well as scores for depression, anxiety, and their physical correlates. Furthermore, DHEA significantly increased both sexual interest and the level of satisfaction with sex. DHEA replacement had no influence on the cognitive performance, which was already on a high level at baseline. In conclusion, DHEA replacement improves well-being and sexuality in women with adrenal insufficiency. If this is due to a direct effect of DHEA on the brain, an indirect effect via increased androgen synthesis, or both, remains to be elucidated. Long-term studies in patients of both sexes are needed to further define the role of DHEA in standard replacement for adrenal insufficiency.

The Effect of DHEA Replacement on the Endocrine and Lipid Profiles of Perimenopausal Women

The Effect of DHEA Replacement on the Endocrine and Lipid Profiles of Perimenopausal Women

DHEA replacement therapy for human aging: a call for perspective.

DHEA replacement therapy for human aging: a call for perspective.

O-081 The effect of DHEA replacement on the endocrine and lipid profiles of perimenopausal women

O-081 The effect of DHEA replacement on the endocrine and lipid profiles of perimenopausal women

F099 metabolic effects of 12-month percutaneous DHEA replacement therapy in postmenopausal women

F099 metabolic effects of 12-month percutaneous DHEA replacement therapy in postmenopausal women