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Plasma androgen concentrations in diabetic women.

Diabetes (UNITED STATES) Dec 1977, 26 (12) p1125-9

Plasma androgen levels were determined in women assigned to the following groups: idiopathically hirsute, diabetic, both idiopathically hirsute and diabetic, and normal. The androgens examined were androstenedione (AD), dihydrotestosterone (DHT), testosterone (T), and dehydroepiandrosterone (DHEA). We find statistical differences between young (less than 38 years) and older (larger than or equal to 38 years) controls at confidence levels of p less than or equal to 0.01 for AD, DHT, and T and of p less than or equal to 0.05 for DHEA. The results indicate that peak circulating androgen levels occur prior to age 30-35 years for women. There are no significant differences between the young controls and young idiopathically hirsute subjects, but a statistical difference exists between older hirsute and older controls for all four androgens (p less than or equal to 0.05). When a comparison is made among the diabetic, hirsute diabetic, and older control groups (all groups larger than or equal to 38 years), the diabetic group is significantly higher than the control in plasma AD (p less than or equal to 0.01) and DHEA (p less than or equal to 0.05). These same two steroids are also higher in the diabetic group than in the hirsute diabetic group (p less than or equal to 0.05), while the latter differs from controls only in testosterone levels (p less than or equal to 0.05). DHT levels are similar for all three groups.

The connective tissue diseases and the overall influence of gender

Int J of Fertility and Menopausal Studies (USA), 1996, 41/2

The autoimmune diseases are more common in women than men. The actual prevalence ranges from the high of 10 to 15 females for each male for systemic lupus erythematosus to four females for every male with rheumatoid arthritis. Though these diseases are found in the very young and the aged, the high prevalence is observed after puberty in most patients. These diseases vary with regard to severity, and most investigators suspect that the signs and symptoms of these diseases vary with menstrual cycle and change severity during pregnancy. The collagen diseases are devastating to the health of young women. Rheumatoid arthritis occurring at a mean age of 40 years results in debilitating erosive changes in bone with morning stiffness and eventual crippling. Systemic lupus erythematosus, Sjogren's syndrome and others, common to women of the childbearing years, act in several ways to destroy organ systems of the body. Virtually any organ system of the female anatomy can be affected by these illnesses. In the case of lupus, the disease has protean manifestations, such as procoagulation, renal destruction, skin disease, unrelenting arthroparhy and arthritis, and encephalopathy (to name only a few). The underlying mechanisms are not known: however, the immune system acts to destroy tissue via immune complex deposition and through the action of cytotoxic lymphocytic activity. There is an association of both clinical signs and autoantibody subpopulations with markers of the HLA-D or MHC II locus on chromosome 6. No constitutive gene for any of the collagen vascular diseases has been identified in the human. Evidence exists to support an altered metabolism of estrogens and androgens in patients with these diseases. Recent data also indicate that increased estrogen levels might initiate autoimmune diseases in many women and men. Estrogen hydroxylation is increased in both men and women with autoimmune diseases like lupus. The mechanisms are unknown, although estrogene metabolites have been shown to increase B cell differentiation and activate T cells. Moreover, isolated cases of hyperprolactinemia have been observed in association with these hyperestrogenic states, and treatment of hyperprolactinemia has been shown to ameliorate diseases like lupus. Androgen oxidation is also increased in patients with autoimmune disease, but this abnormality has been observed only in patients with lupus, and only women at that. The result is that women with autoimmune diseases like lupus and rheumatoid arthritis have lower plasma androgens than control cases. These data have supported the use of weak androgens, e.g., DHEA, for the treatment of lupus.

Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE)

Clinical and Experimental Immunology (United Kingdom), 1995, 99/2

The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly upregulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.

Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men.

J Clin Endocrinol Metab (UNITED STATES) Oct 1994, 79 (4) p1086-90

It is well recognized that aging in men is accompanied by a decline in the serum levels of some adrenal and testicular steroids, but little or no attention has focused on the multiple steroid metabolites that are formed by steroid-converting enzymes in target tissues. In the present study, we have examined in detail the serum concentrations of a large series of adrenal and testicular steroids and their most significant metabolites produced in intracrine peripheral tissues. The serum concentrations of 26 conjugated and unconjugated C21-, C19-, and C18-steroids were measured in 2423 men aged 40-80 yr. The serum concentrations of the major circulating adrenal C19-steroids, namely dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), androst-5-ene-3 beta, 17 beta-diol and its sulfate, and androstenedione, decreased by about 60% between the ages of 40-80 yr. The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging. In addition to a marked decline in the serum concentrations of adrenal C19-steroids, a smaller, but significant, decrease occurred in serum testosterone. However, serum dihydrotestosterone levels remained constant, but the glucuronidated derivatives of dihydrotestosterone metabolites (androstane-3 alpha, 17 beta-diol glucuronide, androstane-3 beta, 17 beta-diol glucuronide, and androsterone glucuronide) were reduced by 45-50%,suggesting that 5 alpha-reductase activity in peripheral tissues may show a compensatory increase during aging. Analysis of the fatty acid esters of DHEA (DHEA-FA) also revealed that these nonpolar steroids markedly decrease between 40-80 yr of age, although such a decrease in DHEA-FA levels was smaller than that in DHEA and DHEA-S, suggesting that the formation of DHEA-FA may be specifically increased during aging. In summary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small decrease in the testis, the activity of the steroid-converting enzymes present in peripheral tissues does not decrease during aging. In fact, the marked decrease in DHEA formation by the adrenals leads to a decrease of about 50% in total androgens in men between the ages of 40-80 yr. Such a decrease probably affects many physiological processes during aging.

Ovarian suppression with triptorelin and adrenal stimulation with adrenocorticotropin in functional hyperadrogenism: role of adrenal and ovarian cytochrome P450c17 alpha.

Fertil Steril (UNITED STATES) Sep 1994, 62 (3) p521-30

OBJECTIVES: To validate combined ovarian suppression with triptorelin and adrenal stimulation with ACTH in the diagnosis of female hyperandrogenism and to provide new insights into the adrenal-ovarian relationship present in this disorder. DESIGN: Comparison of sexual steroids and basal and ACTH-stimulated steroid levels before and after ovarian suppression induced by triptorelin. SETTING: Department of Endocrinology, Hospital Ramon y Cajal, Madrid, Spain. PARTICIPANTS: Thirty-nine nonselected women with hyperandrogenism. MAIN OUTCOME MEASURES: Serum levels of T, 17-hydroxyprogesterone (17-OHP), 17-hydroxy-pregnenolone, DHEA and DHEAS, androstenedione (delta 4-A), 11-deoxycortisol, and cortisol. RESULTS: Elevated T independent of ovarian suppression pointed to an adrenal disorder in six patients (one with an androgen-producing adenoma, two with late-onset 21-hydroxylase deficiency, three with functional adrenal hyperandrogenism). Nineteen patients had functional ovarian hyperandrogenism as elevated T normalized after ovarian suppression and were subdivided into ovDHEAS+ (n = 7) and ovDHEAS = (n = 12)subgroups depending on the presence of DHEAS hypersecretion. Finally, 14 patients had idiopathic hirsutism according to normal T before and after ovarian suppression. Comparisons of initial hormonal values between groups and with reference values obtained from normal women (n = 11) disclosed in functional adrenal hyperandrogenism an elevation of T and basal and stimulated DHEAS, delta 4-A, and 17-OHP with respect to normal women. These abnormalities were also present in ovDHEAS+ except for basal delta 4-A,which was normal, whereas only T and stimulated 17-OHP were elevated in ovDHEAS =. In the idiopathic group all steroids were normal with the exception of a mild elevation in stimulated DHEAS. CONCLUSIONS: These results show a continuum of abnormalities in hyperandrogenic women, suggesting an enhanced cytochrome P450c17 alpha activity in the adrenal and the ovary as the shared mechanism between functional adrenal hyperandrogenism and functional ovarian hyperandrogenism.

Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it.

Proc Natl Acad Sci U S A (UNITED STATES) Mar 1 1992, 89 (5) p1567-71

Immediate post-training intracerebroventricular administration to male mice of pregnenolone (P), pregnenolone sulfate (PS), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, or aldosterone caused improvement of retention for footshock active avoidance training, while estrone, estradiol, progesterone, or 16 beta-bromoepiandrosterone did not. Dose-response curves were obtained for P, PS, DHEA, and testosterone. P and PS were the most potent, PS showing significant effects at 3.5 fmol per mouse. The active steroids did not show discernible structural features or known membrane or biochemical effects that correlated with their memory-enhancing capacity. The above, together with the findings that DHEA acted even when given at 1 hr after training and that P, PS, and DHEA improved retention over a much wider dose range than do excitatory memory enhancers, led to the suggestion that the effects of the active steroids converge at the facilitatio

Effects of dehydroepiandrosterone on proliferation of human aortic smooth muscle cells

Life Sciences (USA), 1997, 60/11 (833-838)

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) have ession of coronary atherosclerosis in clinical and in vivo studies. However, the mechanisms responsible for the association have not been determined. In the present study, we found that DHEA influences the in vitro growth of vascular smooth muscle cells obtained from the human aorta (hASMC). The concentrations of DHEA ranging from 10-8 M to 10-6 M significantly stimulated the mitogenesis of hASMC in serum-free culture. On the other hand, 4 hrs of pretreatment with DHEA attenuated the fetal calf serum induced proliferative effect in a dose-dependent manner. However, the in vitro effects of DHEA on the mitogenesis observed in hASMC were not seen in rat-derived aortic smooth muscle cell lines (A10 cells). With respect to DHEAS, the hormone, at concentrations up to 10-5 M did not affect the growth of either hASMC orA10 cells in vitro. The growth response of hASMC to DHEA in vitro was markedly affected by the culture conditions. The differential proliferative effects of DHEA on smooth muscle cells between rat and human are of interest. We conclude that the effects of DHEA on mitogenesis of hASMC may, at least in part, explain the association between DHEA and atherosclerosis.

Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer's amyloid precursor protein.

Life Sci (ENGLAND) 1996, 59 (19) p1651-7

Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal cortex, significantly declines with advanced age. We have previously demonstrated that DHEA prevents the reduction in non-amyloidogenic APP processing, following prolonged stimulation of the muscarinic receptor, in PC12 cells that express the ml acetylcholine-receptor. The present study examined whether this effect may be mediated via modulation of APP metabolism. It was found that DHEA treatment increases the content of membrane-associated APP holoprotein by 24%, and the accumulation of secreted APP in the medium by 63%. No increase in viable cell number nor in nonspecific protein production was observed in DHEA-treated cells. Thus, DHEA seems to increase specifically both APP synthesis and secretion. We propose that the age-associated decline in DHEA levels may be related to the pathological APP metabolism observed in Alzheimer's disease.

[Change of serum amyloid P component concentrations in women]

Nippon Sanka Fujinka Gakkai Zasshi (JAPAN) Jul 1996, 48 (7) p481-7

Serum amyloid P component (SAP) is a glycoprotein which was shown to be deposited in periarterial tissues and the glomerular basement membrane. It plays a part in aging, and the onset of amyloidosis and Alzheimer's disease. In order to investigate the effects of sex steroids on the SAP level in menopausal women, SAP was purified. Anti-SAP was raised through the immunization of rabbits. The SAP level was assayed by micro single radial immunodiffusion. The SAP levels increased with aging from 1.1 +/- 0.8mg/dl (mean +/- S.D.) to 5.08 +/- 1.31mg/dl in women. And the SAP level in males was significantly higher in the 15 to 50 year age group than in females of similar ages (p < 0.001). And in the menstrual cycle, the SAP concentrations were significantly higher in the menstrual period (p < 0.05). During hormonal therapy in climacteric women, the SAP levels decreased significantly (p < 0.001) after Premarin treatment (from 5.66 +/- 1.45mg/dl to 4.15 +/- 0.94 mg/dl) and increased (p < 0.001) after dehydroepiandrosterone therapy (from 4.00 +/- 0.74mg/dl to 6.07 +/- 1.14mg/dl). From these findings, the SAP levels in human were concluded to be age dependently increased, and higher in the menstrual period. And it is suggested that a sex difference in SAP is concerned with the effect of estrogen fluctuation.

Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in Alzheimer's disease and in cerebrovascular dementia.

Endocr J (JAPAN) Feb 1996, 43 (1) p119-23

A decreased concentration of dehydroepiandrosterone sulfate (DHEA-S) in patients with Alzheimer's disease (AD) has been reported but is still controversial. In the present study, serum concentrations of DHEA and DHEA-S were determined in 19 patients with AD, 21 patients with cerebrovascular dementia (CVD) and 45 age- and gender matched elderly control individuals from the Japanese community at large. Serum concentration of DHEA among controls, patients with AD and patients with CVD did not significantly differ from one another. However, patients with AD and patients with CVD were found to have lower concentration of serum DHEA-S and a lower DHEA-S/DHEA ration compared to normal control individuals. No significant difference was observed in the concentration of serum DHEA-S or the DHEA-S/DHEA ratio between patients with AD and those with CVD. These results suggest that reduced concentrations of serum DHEA-S may not be unique to AD, but instead reflect a common phenomenon in dementing diseases. However, since serum concentration of DHEA in these patients remained unchanged, the significance of DHEA in dementia remains unclear.

Natural products and their derivatives as cancer chemopreventive agents

Progress in Drug Research (Switzerland), 1997, 48/- (147-171) :

This review summarizes currently available data on the chemopreventive efficacies, proposed mechanisms of action and relationships between activities and structures of natural products like vitamin D, calcium, dehydroepidandrosterone, coenzyme Q10, celery seed oil, parsley leaf oil, sulforaphane, isoflavonoids, lignans, protease inhibitors, tea polyphenols, curcumin, and polysaccharides from Acanthopanax genus.

New agents for cancer chemoprevention

Nation996, 63/SUPPL. 26 (1-28)

Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids (e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid), calcium, betacarotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylomithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3- carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs.Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin inhibitor). Combinations are also being considered, such as vitamin E with l-selenomethionine. Analysis of signal transduction pathways is beginning to yield classes of potentially active and selective chemopreventive drugs. Examples are ras isoprenylation and epidermal growth factor receptor inhibitors.

Neuronal actions of dehydroepiandrosterone. Possible roles in brain development, aging, memory, and affect.

Ann N Y Acad Sci (UNITED STATES) Dec 29 1995, 774 p111-20

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment..

Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism

European Journal of Endocrinology (Norway), 1997, 136/3 (277-281)

Postmenopausal women with endogenous subclinical hyperthyroidism seem to have reduced bone mass, which does not correlate with serum thyroid hormone levels. Relative insufficiencies of IGF-I and dehydroepiandrosterone sulphate (DHEAS) might be additional risk factors for low bone density in these patients. We measured IGF-I, IGF-binding protein-3 (IGFBP-3) and DHEAS levels together with bone mineral density (BMD) of the femoral neck and lumbar spine in women with an autonomously functioning thyroid nodule. Sixty-three women were classified as subclinical hyperthyroid (31 - and 32 postmenopausal) and 39 as overt hyperthyroid (16 - and 23 postmenopausal) and results were compared with data obtained from 41age- matched euthyroid healthy women. In premenopausal women BMD was reduced only in the overt hyperthyroid group, and only in the spine, to 92% (P < 0.05). Serum IGF-I as well as IGFBP-3 were increased in the manifest hyperthyroid group, to 157% (P < 0.001) and 129% (P < 0.05) respectively, whereas DHEAS levels did not change in either premenopausal patient group. In postmenopausal women BMD was significantly reduced both in the subclinical hyperthyroid group (spine to 90% and femoral neck to 88%; P < 0.05), as well as in the hyperthyroid group (spine to 78% and femoral neck to 86%; P < 0.01). In contrast to premenopausal women, serum IGF-I and IGFBP-3 did not change in the two groups who were postmenopausal and serum DHEAS levels were reduced to 58% (P < 0.001) in both postmenopausal groups with subclinical as well as overt hyperthyroidism. In the same two groups of patients, serum IGF-I and DHEAS levels correlated with BMD (femoral neck; both r = 0.50, P < 0.05). In conclusion, women with a solitary autonomous thyroid nodule with subclinical hyperthyroidism have reduced BMD only if they are postmenopausal. This is probably due to the effect of subtle increases in thyroid hormone production together with lack of oestrogen protection of the skeleton. But additional risk factors for the development of enhancd bone loss might be a state of relative IGF-I and DHEAS insufficiency in these patients as well as in postmenopausal women with overt hyperthyroidism.

Dehydroepiandrosterone sulphate as a source of steroids in menopause

Acta Ginecologica (Spain), 1995, 52/9 (279-284)

In the present work, we address the study of pregnenolone-derived hormones focusing on dehydroepiandrosterone sulphate (DHEA-SO4), as the basis of a potential application in the pharmacology of post-menopausal women. The aim is to know whether rejuvenating action of DHEA-S is due to the intrinsic properties of this steroid with a very low androgenic activity or if by contrast, the beneficial effects of this hormone are linked to the therapeutic effects of those steroids into which it converts peripherally: estradiol and estrone. We have restricted our study to the analysis of 182 post-menopausal women 75.8% of which reached their menopause in a natural way and 24.2% underwent bilateral oophorectomy. Levels of DHEA-S04, estrone (E1), estradiol (E2), androstenedione (A2) and testosterone (T) on the basis of patient age, stored fat, body mass index (BMI), total muscle content, and total organic calcium (TOCa) are studied in both groups. We describe the techniques used in the study (bone densitometry, total body composition, hormone blood levels by RIA, BMI, weight and height and compare the results as a function of patient age and BMI, as well as of bone mineral content (BMC), and TOCa.

Relationship between sex steroid hormone levels and CD4 lymphocytes in HIV infected men

Experimental and Clinical Endocrinology and Diabetes (Germany),1996,104

The serum concentrations of the steroid, androgens and estrogens, in the HIV-positive male patients were studied. These men belonged to one of the three main behaviour groups: heterosexual (He), drug addicts (DA) and homosexual (He) at early stages (II and III) or at advanced stage of AIDS (IVC), classified according to the Centers for Disease Control (CDC). The circulating concentrations of sex steroids were then analysed with reference to the risk factors, absolute CD4 cell count and the progression of HIV infection. Regardless of risk factors, the stage II and III HIV-infected patients had serum dehydro-epiandrosterone sulfate (DHEAs) (+37%, p < 0.03), testosterone (T) (+24%, p < 0.006) and estrone (E1) (+170%, p < 0.0001) levels higher than those of controls. The patients IVC stage had low serum DHEAs (-48%, p < 0.0001) and elevated estradiol (E2) (+200%, p < 0.0001). According to risk factors, thew were no significant differences in androgen and estrogen concentrations between the behaviour groups. There were significant positive correlations between the CD4 cell count and the serum concentrations of DHEAs (p < 0.0001), DHEA (p < 0.01) and E1 (p < 0.006). This suggests that thew is a relationship between the circulating sex hormone levels, particularly DHEAs, and the progression of immune depression in HIV, whatever the risk factor. The observed association between DHEAs and the progression of HIV infection suggests that this androgen may play a role in the normal function of the immune system.

Urinary steroids at time of surgery in postmenopausal women with breast cancer

Breast Cancer Research and Treatment (USA), 1997, 44/1 (83-89)

Urinary steroid metabolites were measured by capillary gas chromatography in 22 postmenopausal women with operable breast cancer on day before the tumour excision and in 20 hospitalised control who were before an operation from other cause than cancer. Serum dehydroepiandrosterone-sulphat (DHEAS) and testosterone (T) level were measured by radioimmunassay in the same groups and same time. There was no significant difference in the level of urinary androgen metabolites. Pregnanediol level was significantly lower (P < 0.05) in cancer patients. In the 5 patients with positive axillary nodes the tetrahydrocortisol and alpha-cortolone levels were significantly (P < 0.05) higher than in node negative ones. There was no significant differences in the serum DHEAS and T levels. These results indicate that metabolic changes are existing in postmenopausal patients which may be a cause or a consequence of the disease.

Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women

American Journal of Epidemiology (USA), 1997, 145/11 (1030-1038)

The authors examined the relation between postmenopausal serum levels of testosterone and dehydroepiandrosterone sulfate (DHEAS) and subsequent risk of breast cancer in a case-control study nested within the New York University Women's Health Study cohort. A specific objective of their analysis was to examine whether androgens had an effect on breast cancer risk independent of their effect on the biologic availability of estrogen. A total of 130 cases of breast cancer were diagnosed prior to 1991 in a cohort of 7,054 postmenopausal women who had donated blood and completed questionnaires at a breast cancer screening clinic in New York City between 1985 and 1991. For each case, two controls were selected, matching the case on age at blood donation and length of storage of serum specimens. Biochemical analyses were performed on sere that had been stored at -80degreeC since sampling. The present report includes a subset of 85 matched sets, for whom at least 6 months had elapsed between blood donation and diagnosis of the case. In univariate analysis, testosterone was positively associated with breast cancer risk (odds ratio (OR) for the highest quartile = 2.7, 95% confidence interval (CI) 1.1-6.8, p < 0.05, test for trend). However, after including % estradiol bound to sex hormone-binding globulin (SHBG) and total estradiol in the statistical model, the odds ratios associated with higher levels of testosterone were considerably reduced, and there was no longer a significant trend (OR for the highest quartile = 1.2, 95% CI 0.4-3.5). Conversely, breast cancer risk remained positively associated with total estradiol levels (OR for the highest quartile = 2.9, 95% CI 1.0-8.3) and negatively associated with % estradiol bound to SHBG (OR for the highest quartile = 0.05, 95% CI 0.01-0.19) after adjustment for serum testosterone levels. These results are consistent with the hypothesis that testosterone has an indirect effect on breast cancer risk, via its influence on the amount of bioavailable estrogen. No evidence was found of an association between DHEAS and risk of breast cancer in postmenopausal women.

Sex hormones and DHEA-SO4 in relation to ischemic heart disease mortality in diabetic subjects: The Wisconsin Epidemiologic Study of Diabetic Retinopathy

Diabetes Care (USA), 1996, 19/10 (1045-1050)

OBJECTIVE - Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD. RESEARCH DESIGN AND METHODS - We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older- onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject). RESULTS - In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may he associated with worse IHD risk factors. CONCLUSIONS - This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.

Differences in substrate metabolism between self-perceived 'large-eating' and 'small-eating' women.

Int J Obes Relat Metab Disord (ENGLAND) Apr 1995, 19 (4) p245-52

OBJECTIVE: To compare different aspects of intermediary metabolism in self perceived 'small-eating' females and self-perceived near normal weight 'large-eating' females and relate the data to those reported for Pima Indians who have the world's highest prevalence of non-insulin dependent diabetes mellitus and obesity. DESIGN: Make repeat measurements of rates of oxygen consumption, carbon dioxide production and blood metabolites in 'large-' and 'small-eating' females at rest, during different activities and after ingestion of a standardised liquid meal. SUBJECTS: Nine self perceived, 'large-eating' females and nine self perceived 'small-eating' females. MEASUREMENTS: Resting metabolic rates (RMR), respiratory quotient (RQ) values and plasma insulin, glucagon insulin-like growth factor (IGF-1), dehydroepiandrosterone sulphate (DHEA-SO4) and glucose. RESULTS: RMR (adjusted for FFM) averaged 3891 +/- 93 J/min in the 'small-eaters' and 3375 +/- 107 J/min in the 'large-eaters' for ten consecutive measurements conducted at 30 min intervals during the control period for the measurement of the thermic effect of food. Over this period the average RQ for the 'small-eating' women (0.81) was significantly greater than that of the 'large-eating' women (0.78). The two groups responded similarly to an oral glucose tolerance test but the concentration of DHEA-SO4 in plasma was 35% higher in the 'small-eaters'. CONCLUSION: The 'small-eating' women may have a greater risk of weight gain but they counteract this tendency by maintaining high activity levels.

Differential expression of hepatic oestrogen, phenol and dehydroepiandrosterone sulphotransferases in genetically obese diabetic (ob/ob) male and female mice.

J Endocrinol (ENGLAND) Jan 1995, 144 (1) p31-7

Sulphotransferases (STs) are a family of closely related enzymes playing a key role in regulation of the bioavailability and activity of important endogenous molecules such as steroid hormones. A relationship between the expression of steroid STs and the diabetic state has been demonstrated in various laboratory animal models, and steroid sulphates such as dehydroepiandrosterone sulphate are known to have anti-diabetic properties. In order to further our understanding of the molecular basis for the association of steroid hormone sulphation and diabetes, we have examined the expression of oestrogen, phenol and dehydroepiandrosterone (DHEA) STs in mice carrying the obesity mutation (ob), which in the homozygous state (ob/ob) produces mice which are obese and diabetic. Our data show that, in male mice, ST activities towards oestrone (E1), oestriol (E3), DHEA and the xenobiotic 1-naphthol are elevated in ob/ob mice, whereas in female mice, only the oestrogen ST activities were elevated, with the DHEA and 1-naphthol ST activities reduced. Using antibodies directed against oestrogen ST, it was demonstrated that the induction of E1 and E3 ST activity in ob/ob mice correlated with the expression of an ST isoenzyme not constitutively expressed in control mouse liver.

Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentrations in nondiabetic men.

Metabolism (UNITED STATES) May 1994, 43 (5) p599-603

Although many studies indicate that increased androgenicity is associated with insulin resistance and hyperinsulinemia in both premenopausal and postmenopausal women, relatively few data are available on this relationship in men. We examined the association of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol to glucose and insulin concentrations before and during an oral glucose tolerance test in 178 men from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Total and free testosterone and DHEA-SO4 were significantly inversely associated with insulin concentrations. Free testosterone and DHEA-SO4 were also significantly inversely correlated with glucose concentrations. SHBG was weakly positively associated with glucose concentrations. Estradiol was not related to glucose or insulin concentrations. After adjustment for age, obesity, and body fat distribution, insulin concentrations remained significantly inversely correlated with free testosterone (r = -.23), total testosterone (r = -.21), and DHEA-SO4 (r = -.21; all P < .01). In conclusion, we observed that increased testosterone and DHEA-SO4 are associated with lower insulin concentrations in men. This is in striking contrast to women, where increased androgenicity is associated with insulin resistance and hyperinsulinemia.

Obesity, body fat distribution and sex hormones in men.

Int J Obes Relat Metab Disord (ENGLAND) Nov 1993, 17 (11) p643-9

An unfavourable body fat distribution may cause metabolic abnormalities including diabetes and dyslipidemia. These effects may be mediated by alterations in sex hormones. In women the available data suggest that upper body adiposity is related to increased androgenicity (especially as indicated by low concentrations of sex hormone binding globulin). Few data, however, are available on these relationships in men. We therefore examined the association of total testosterone, free testosterone, oestradiol, dehydroepiandrosterone sulphate (DHEA-SO4) and sex hormone binding globulin (SHBG) to waist-to-hip ratio (WHR) and conicity index in 178 men from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. The conicity index is equal to the abdominal circumference divided by 0.109 x the square root of (weight/height). The conicity index and WHR were significantly inversely related to DHEA-SO4 and free testosterone. SHBG was only weakly associated with body mass index (r = -0.18, P < 0.05). After adjustment for age and body mass index, DHEA-SO4 remained inversely correlated with WHR (r = -0.22, P < 0.01) and conicity index (r = -0.31, P < 0.001) and free testosterone remained inversely associated with conicity index (r = -0.21, P < 0.01). Thus, in men, the association between unfavourable body fat distribution and increased androgenicity is inverse in contrast to the situation in women.

Relationship of sex hormones to lipids and lipoproteins in nondiabetic men.

J Clin Endocrinol Metab (UNITED STATES) Dec 1993, 77 (6) p1610-5

Although many studies show that increased androgenicity is associated with increased triglyceride (TG) and decreased high density lipoprotein cholesterol in both - and postmenopausal women, relatively few data are available on the association of sex hormones to lipids and lipoproteins in men. We examined the association of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol with lipids and lipoproteins in 178 nondiabetic men from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. The TG concentration was significantly inversely related to SHBG (r = -0.22), free testosterone (r = -0.15), total testosterone (r = -0.22), and DHEA-SO4 (r = -0.16). High density lipoprotein (HDL) cholesterol was significantly positively correlated to SHBG (r = 0.21), free testosterone (r = 0.15), total testosterone (r = 0.17), and DHEA-SO4 (r = 0.16). Total testosterone was significantly related to total cholesterol (r = -0.17) and low density lipoprotein cholesterol (r = -0.15). After adjustment for age, body mass index, waist to hip ratio, and glucose and insulin concentrations, TG concentrations remained significantly related to SHBG (r = -0.20), free testosterone (r = -0.15), and DHEA-SO4 (r = -0.18), and HDL cholesterol remained significantly associated with SHBG (r = 0.17), free testosterone (r = 0.15), total testosterone (r = 0.14), and DHEA-SO4 (r = 0.16). In conclusion, we observed a less atherogenic lipid and lipoprotein profile with increased testosterone concentrations. This was not explained by differences in glucose or insulin concentrations. However, sex hormones explained only a small percentage of the variation in total TG and HDL cholesterol concentrations. These findings are in striking contrast to data from women, in whom increased androgenicity is strongly associated with increased TG and decreased HDL cholesterol levels.

Excess androgenicity only partially explains the relationship between obesity and bone density in premenopausal women.

Int J Obes Relat Metab Disord (ENGLAND) Nov 1992, 16 (11) p869-74

Obese subjects have increased bone density relative to non-obese subjects yet this relationship is not fully understood. We examined whether alterations in sex hormones or binding proteins might explain the effect of obesity on osteoporosis in 83 premenopausal women from the San Antonio Heart Study, a population-based study of diabetes. We measured total testosterone, oestradiol, oestrone, sex hormone binding globulin (SHBG), and serum dehydroepiandrosterone sulphate (DHEA-SO4). Bone density was assessed by a Hologic dual photon absorptometer. Lumbar spine and femoral neck density were positively correlated with body mass index (BMI). In addition, femoral neck density was positively correlated with DHEA-SO4. BMI was negatively correlated with SHBG. After adjustment for sex hormones by multiple linear regression a positive association between bone density and obesity still exists suggesting that the association between obesity and bone density is at least partially independent of sex steroids in premenopausal women.

Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus

Ann Intern Med (UNITED STATES) Nov 15 1992, 117 (10) p807-11

OBJECTIVE: To compare plasma androgen levels in diabetic and nondiabetic men and to determine their relation to diabetic dyslipidemia. DESIGN: A population-based, case-control study. SETTING: Community. PARTICIPANTS: Men 53 to 88 years of age from the Rancho Bernardo, California, cohort who were screened for diabetes using an oral glucose tolerance test. MEASUREMENTS: Plasma androgen levels were compared in 44 men with untreated non-insulin-dependent diabetes mellitus and 88 age-matched men who had a normal glucose tolerance test. The relation of lipid and lipoprotein levels to androgen level and diabetic status was assessed before and after adjusting for covariates. RESULTS: Men with diabetes had significantly lower plasma levels of free (4.96 nmol/L compared with 5.58 nmol/L) and total testosterone (14.7 nmol/L compared with 17.4 nmol/L), dihydrotestosterone (428 pg/mL compared with 533 pg/mL), and dehydroepiandrosterone sulfate (DHEA-S) (1.92 mumol/L compared with 2.42 mumol/L) than nondiabetic men. They also had significantly lower high-density lipoprotein (HDL) cholesterol and significantly higher triglyceride levels. Differences were not explained by obesity, alcohol use, or cigarette habit. Overall, the total testosterone level, but not the free testosterone level, was positively correlated with the HDL cholesterol level (P = 0.009) and negatively correlated with the triglyceride level (P = 0.0001). Similar associations were seen in analyses restricted to the men without diabetes. CONCLUSIONS: Lower levels of endogenous androgens are seen in older diabetic men, and low androgen levels are associated with diabetic dyslipidemia.

Increased testosterone in type I diabetic subjects with severe retinopathy.

Ophthalmology (UNITED STATES) Oct 1990, 97 (10) p1270-4

Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured serum testosterone, estradiol, DHEA-S, and sex hormone binding globulin levels in 26 men and 22 women with type I diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic complications. The mean age was 23 years and the mean duration of diabetes was 14 years. Subjects with proliferative or preproliferative retinopathy (greater than or equal to retinopathy level 51-80) were matched by duration of diabetes (+/- 2 years) and sex to subjects with minimal or no retinopathy (less than or equal to retinopathy level 21). Seven stereoscopic retinal photographs of each eye were obtained and photographs were read by the University of Wisconsin Reading Center. Serum testosterone concentrations were significantly higher in male diabetic subjects with proliferative retinopathy (648 +/- 36 ng/dl) than in male diabetic subjects with minimal or no retinopathy (512 +/- 43 ng/dl) (P = 0.017). No other statistically significant differences in sex hormones between subjects with and without proliferative retinopathy were observed. Although these results should be regarded as preliminary because of the small number of subjects, they support the hypothesis that testosterone concentrations may be associated with the development of retinopathy in type I diabetic patients.

Increase in plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide as a marker of peripheral androgen action in hirsutism: a side-effect induced by cyclosporine A.

J Steroid Biochem (ENGLAND) Jan 1990, 35 (1) p133-7

Dose-dependent hypertrichosis is a common dermatological side-effect affecting the majority of patients treated with cyclosporine A (CSA). Previous studies have not demonstrated the influence of CSA on specific sex hormone levels. The aim of this study is to investigate whether CSA increases the activity of 5 alpha-reductase, an enzyme which transforms androgens into dihydrotestosterone in peripheral tissues. The metabolite which best reflects this activity is 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (Adiol G). The study was carried out on 49 insulin-dependent diabetes patients participating in the double-blind "Cyclosporine-Diabete-France" clinical trial, of which 28 were treated with CSA (16 males and 12 females), and 21 received only placebo (10 males and 11 females). All patients underwent extensive clinical and laboratory evaluations prior to and during the present study. In addition to Adiol G, testosterone (T), dehydroepiandrosterone sulfate (DHEA S) and sex hormone-binding globulin (SHBG) were assayed. Levels of Adiol G increased significantly in CSA-treated groups: males, 11.86 +/- 2.58 vs 7.83 +/- 2.30 nmol/l; females, 4.48 +/- 2.70 vs 2.10 +/- 1.22 nmol/l; P less than 0.02 (comparison of means). There were no significant differences in this parameter before and during treatment in either the male or female placebo groups (paired t-test). During the treatment period, T, DHEA S, SHBG and the T/SHBG ratio did not significantly change with respect to their baseline values in any of the groups studied (comparison of means). Comparison (using paired t-test) showed a significant increase of DHEA S in CSA-treated groups: males, delta = 3.08 +/- 3.33 nmol/l, P less than 0.01; females, delta = 0.98 +/- 1.13 nmol/l, P less than 0.05. In conclusion, it is possible that CSA induces hypertrichosis or hirsutism by increasing 5 alpha-reductase activity in peripheral tissues. Nevertheless the role of increased DHEA S as a possible Adiol G precursor cannot be excluded.

Peculiarities of the endocrine time structure in noninsulin-dependent adult-onset (type II) diabetes mellitus.

Prog Clin Biol Res (UNITED STATES) 1987, 227A p467-82

Twenty noninsulin-dependent elderly diabetic patients, ten of whom were treated by oral hypoglycemic agents and ten of whom were regulated by diet alone, and 20 clinically healthy subjects matched for age, sex, height, and weight were examined with six blood and six urine samples at 4-hr intervals over a 24-hr span. Plasma ACTH, cortisol, aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were determined by radioimmunoassay (RIA); epinephrine, norepinephrine, and dopamine in urine were determined by high-pressure liquid chromatography (HPLC); and magnesium in urine was determined colorimetrically on a DuPont ACA. There were a number of changes in some of these functions in type II diabetic patients with and without oral hypoglycemic agents that appear to be of interest. The circadian mean in plasma ACTH concentration in diabetic patients with and without oral hypoglycemic agents is significantly higher than in matched nondiabetic controls. The plasma aldosterone concentration is similar in type II diabetics treated by diet only and in matched controls but is statistically significantly elevated in patients on oral hypoglycemic agents. Correspondingly, the urinary excretion of sodium in type II diabetic patients on oral hypoglycemic agents is lower than in matched controls. The plasma cortisol concentration is unchanged in type II diabetic patients treated by diet alone but shows a slight increase in patients on oral hypoglycemic agents. The circadian means of plasma DHEA-S concentration is slightly higher in diabetic patients with and without oral hypoglycemic agents than in matched controls. This elevation, however, does not quite reach the 95% level of statistical significance. Urinary norepinephrine excretion in type II diabetic patients is similar to that in matched controls. The urinary epinephrine excretion in diabetics with and without oral hypoglycemic agents, however, was lower than in controls, and the urinary excretion of dopamine was higher in the diabetics. The urinary magnesium excretion in type II diabetic patients was lower than in matched controls.

Circadian time structure of endocrine and biochemical parameters in adult onset (type II) diabetic patients.

Endocrinologie (ROMANIA) Oct-Dec 1984, 22 (4) p227-43

Forty-one endocrine and biochemical serum parameters were studied over a 24-hour span with 6 samples at 4-hour intervals in 20 non-insulin dependent (Type II) diabetics and in 20 non-diabetic subjects matched for sex, age, height and weight. Circadian rhythms were verified by cosinor analysis. Group-synchronized circadian rhythms were detected in diabetic and non-diabetic subjects with no statistically significant difference in any of the rhythm parameters (rhythm adjusted mean, amplitude and acrophase) in: Aldosterone, cortisol, insulin, 17-OH progesterone, prolactin, testosterone, TSH, and in serum albumin, creatine phosphokinase (CPK), serum iron, inorganic phosphate and total protein. Statistically significant (p less than .05) circadian rhythms in both groups with a difference in some parameters between the diabetic and the non-diabetic subjects, which were verified by the Bingham Test (p less than .05) were found with a difference in the mesor in cholesterol, glucose, urea nitrogen (BUN), in the amplitude in C-peptide and in the acrophase in triglycerides, globulin and reverse T3 (rT3). Statistically significant circadian rhythms were detected as a group phenomenon for the diabetics only in progesterone, free and total T4, chloride, calcium, bilirubin and LDH and in the non-diabetic subjects only in ACTH, LH, total T3, alkaline phosphatase, uric acid and potassium. In the remainder of the functions studied, acircadian rhythm was detectable with statistical significance by cosinor analysis as a group phenomenon neither in the diabetics nor in the matched non-diabetic controls (DHEA-S, estradiol, FSH, GH, glucagon, free T3, sodium, GOT and gamma GT). In the absence of a detectable circadian rhythmas group phenomenon, the circadian mean was different between the diabetics and the non-diabetic subjects in sodium, chloride and calcium which were higher in the diabetic patients and serum LDH which was lower. In a comparison of endocrine determinations in the two groups, the circadian mean or mesor in T3 was lower in the diabetics and ACTH higher, without corresponding changes in TSH or in corticosteroids. The circadian time structure of Type II diabetic patients thus seems to be very similar to that seen in non-diabetic subjects of the same sex, age, weight and height.The minor differences found in some rhythm parameters will have to be confirmed or excluded in larger numbers of subjects. The higher circadian mean ACTH concentrations without change in steroid rhythm parameters observed in this group is interesting but will also require confirmation. (ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic fluid beta-endorphin and beta-lipotropin concentrations during the second and third trimesters.

Am J Obstet Gynecol (UNITED STATES) Jul 15 1983, 146 (6) p644-51

Amniotic fluid beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were measured by radioimmunoassay after silicic acid extraction and gelchromatographic separation of the two peptides in uncomplicatedsecond-trimester and term pregnancies, in diabetic patients at term, and inpregnancies complicated by Rh-isoimmunization, premature labor, and intrauterine growth retardation. Furthermore, the lecithin/sphingomyelin (L/S) ratios as well as the dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels were determined in most of the amniotic fluid specimens. Both the mean (+/- SE) beta-EP (65.3 +/- 9.1 fmol/ml) and beta-LPH (150 +/-15.8 fmol/ml) concentrations were significantly higher in the 20 patients with normal pregnancies of 16 to 21 weeks' duration than those found in 21 patients with uncomplicated term pregnancies of 38 weeks' gestation, averaging 42.6 +/- 6.0 and 80.1 +/- 10.7 fmol/ml, respectively. The mean amniotic fluid beta-EP and beta-LPH concentrations measured in the latter subjects were similar to those observed in 23 diabetic patients with otherwise uncomplicated term pregnancies. The mean amniotic fluid beta-EP and beta-LPH levels found in the limited number of patients with Rh-isoimmunization (N = 9), premature labor (n = 8), and intrauterine growth retardation (n = 5) with pregnancies of 24 to 36, 24 to 36, and 34 to 38 weeks' gestation, respectively, were not significantly different from the mean amniotic fluid beta-EP and beta-LPH concentrations of uncomplicated term pregnancies. In all patients but those with Rh-isoimmunization, beta-EP concentrations exhibited a positive correlation with beta-LPH levels. However, the molar beta-LPH:beta-EP ratio was significantly lower at term than during the early second trimester. Neither beta-EP nor beta-LPH correlated with the amniotic fluid L/S ratio and only beta-LPH exhibited a significant inverse correlation with amniotic fluid DHEA-S. The latter was significantly higher in uncomplicated term than second-trimester pregnancies. These results confirm that immunoassayable beta-EP is present in amniotic fluid and declines toward term. These data demonstrate that immunoassayable beta-LPH is present in amniotic fluid and show a more pronounced decrease toward the end of pregnancy than beta-EP. Neither peptide, at least on account of the amniotic fluid levels, appears to be associated with fetal maturation. The physiologic significance of amniotic fluid beta-EP and beta-LPH and their possible role as markers of fetal response to stress remain to be elucidated.

Androgen and progesterone levels in females with rheumatoid arthritis

REUMATISMO (Italy), 1994, 46/2 (65-69)

A relationship between sex hormones and autoimmunity has been recognized. Androgens seem to play a protective role against autoimmune diseases such as rheumatoid arthritis (RA) and an inhibitory role of progesterone (P) in IL1 secretion from human monocytes has been demonstrated. Furthermore androgen levels were related to RA activity and low dehydroepiandrosterone sulphate (DHEAS) levels were related to low bone mineral content in postmenopausal (PostM) women with RA. Serum testosterone (T), HDEAS, IL1(beta) and bone-GLA protein (BGP) levels were measured in 22 premenopausal (PreM) and in 23 PostM female RA patients. PreM and PostM patients were divided in two groups according to disease activity. In the PostM patients serum progesterone (P) levels were also determined. DHEAS was lower in PreM RA women (p < 0.001) than in healthy female subjects age-matched to the RA patients. IL1(beta) and BGP were higher in RA patients, namely in active RA patients, than in controls. These data reveal an altered androgen status in female RA patients. Although no direct correlation was found between DHEAS and IL1(beta), an inhibitory role of the cytokine on DHEAS synthesis could be hypothesized. Furthermore P could play a role in the pathogenesis of RA.

Blood dehydroepiandrosterone sulphate (DHEAS) levels in pemphigoid/pemphigus and psoriasis

Clinical and Experimental Rheumatology (Italy), 1995, 13/3

Serum dehydroepiandrosterone sulphate (DHEAS) levels and diagnostic autoantibody titers were measured in patients with pemphigoid/pemphigus (n = 46/4; 21 men and 29 women, 42 to 93 years of age (mean 79)). Twenty-four patients were either on peroral Prednisolone (n = 11), or topical treatment with betamethasone (n = 13), and the other 26 were either receiving non- steroidal drugs or were untreated. Their DHEAS levels were compared to those of 20 patients with psoriasis, and to 23 patients with secondary osteoarthritis (OA). Assessing the patients by group, the mean DHEAS level was markedly lower in the pemphigoid/pemphigus than in the psoriasis and OA patients (geometric mean 600 vs. 2130 and 2100 nmol/l, respectively; p < 0.001). This difference was independent of steroid treatment. No correlation was found between the DHEAS levels and antibody titers. The low levels found in pemphigoid/pemphigus are concordant with those reported for systemic lupus erythematosus, rheumatoid arthritis and polymyalgia rheumatica/giant cell arteritis. DHEAS deficiency is a permanent feature in these autoimmune diseases, and may contribute to their etiology and/or pathophysiology.

Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production.

J Clin Endocrinol Metab (UNITED STATES) Sep 1978, 47 (3) p572-7

Plasma levels of dehydroepiandrosterone sulfate (DHAS) were measured in 513 normal full term newborns, infants, children, adolescents, and adults and the results were expressed in micrograms per dl. In infancy and childhood, DHAS levels were similar in both sexes. In 74 neonates, mixed cord blood mean values /+- SD were 134.6 +/- 64. During the first day of life, plasma DHAS levels were 140 +/- 125 in 33 neonates. During the first month of life, DHAS decreased drastically, then more progressively until the 6th month of life. Between 1-6 months of age, mean levels were 5.9 +/- 4.7 in 40 children. DHAS was very low between 1-6 yr of life (2.3 +/- 1.6) and rose abruptly at the 7th year of life. Thereafter, DHAS continued to increase correlatively with age and pubertal stages in both sexes, a further increase after age 16 or pubertal stage P5 was noted only in male subjects. In adults, DHAS was significantly higher in male (224 +/- 93) than in female (138.3 +/- 51) subjects. DHAS levels were compared to those of dehydroepiandrosterone; at two periods of life, early infancy and adulthood, their patterns differed. After long term hCG stimulation, DHAS increased significantly in 45 normal prepubertal boys and in 2 boys with adrenal insufficiency. These data would suggest a direct testicular production of DHAS.

The neurosteroid dehydroepiandrosterone sulfate (DHEAS) enhances hippocampal primed burst, but not long-term, potentiation.

Neurosci Lett (IRELAND) Jan 5 1996, 202 (3) p204-8

Dehydroepiandrosterone sulfate (DHEAS), which is synthesized in the brain and in the periphery, is known to affect the excitability of hippocampal neurons. However, its influence on electrophysiological plasticity has not been addressed. We have studied the effects of DHEAS on primed burst (PB) and long-term (LTP) potentiation, two electrophysiological models of memory. PB potentiation is a lasting increase in the amplitude of the CA1 population spike produced by minimal (threshold) electrical stimulation; LTP is produced by more extensive (supra-threshold) stimulation. Whereas intermediate doses (24 and 48 mg/kg, s.c.) of DHEAS given to rats enhanced PB potentiation, low (6 mg/kg) and high (96 mg/kg) doses were ineffective. LTP was not affected by any dose of DHEAS. The inverted-U relationship between DHEAS and PB potentiation is consistent with previous work demonstrating an inverted-U dose-dependent enhancement of memory by DHEAS. The present findings suggest that DHEAS could enhance memory by facilitating the induction of neural plasticity.