Dehydroepiandrostenedione Research Articles

Sex differences in addiction: gonadal hormones and substance use effects in women

Abstract Substance use disorders (SUD) affect differentially women and men. Although the prevalence has been reported higher in men, those women with addictive disorders present a more vulnerable profile and are less likely to enter treatment than men. The aim of this presentation is to present an overview of how gonadal hormones may influence in response to substances, clinical differences in the addictive disorders and implications in treatment response.Ovarian steroid hormones (estrogen, progesterone), the metabolites of progesterone, and negative allosteric modulators of the gamma-aminobutyric acid A (GABA-A) receptor, such as dehydroepiandrostenedione (DHEA) may influence the behavioral effects of drugs.Disclosure of InterestNone Declared

Psychosocial aspects of sports medicine in pediatric athletes: Current concepts in the 21st century

Behavioral aspects of organized sports activity for pediatric athletes are considered in a world consumed with winning at all costs. In the first part of this treatise, we deal with a number of themes faced by our children in their sports play. These concepts include the lure of sports, sports attrition, the mental health of pediatric athletes (i.e., effects of stress, anxiety, depression, suicide in athletes, ADHD and stimulants, coping with injuries, drug use, and eating disorders), violence in sports (i.e., concepts of the abused athlete including sexual abuse), dealing with supervisors (i.e., coaches, parents), peers, the talented athlete, early sports specialization and sports clubs.In the second part of this discussion, we cover ergolytic agents consumed by young athletes in attempts to win at all costs. Sports doping agents covered include anabolic steroids (anabolic-androgenic steroids or AAS), androstenedione, dehydroepiandrostenedione (DHEA), human growth hormone (hGH; also its human recombinant homologue: rhGH), clenbuterol, creatine, gamma hydroxybutyrate (GHB), amphetamines, caffeine and ephedrine. Also considered are blood doping that includes erythropoietin (EPO) and concepts of gene doping.In the last section of this discussion, we look at disabled pediatric athletes that include such concepts as athletes with spinal cord injuries (SCIs), myelomeningocele, cerebral palsy, wheelchair athletes, and amputee athletes; also covered are pediatric athletes with visual impairment, deafness, and those with intellectual disability including Down syndrome. In addition, concepts of autonomic dysreflexia, boosting and atlantoaxial instability are emphasized.We conclude that clinicians and society should protect our precious pediatric athletes who face many challenges in their involvement with organized sports in a world obsessed with winning. There is much we can do to help our young athletes find benefit from sports play while avoiding or blunting negative consequences of organized sport activities.

Evaluation of Laboratory Productivity Commission

Amaç: Bu araştırmada amacımız, Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi (SÜEAH) laboratuvar verimlilik komisyon (LVK) çalışmalarının, laboratuvar maliyet analizi açısından değerlendirilmesidir. Materyal ve Metod: Laboratuvar verimlilik analizi için metodumuz, LVK’nın kuruluş tarihinden altı ay öncesi ve altı ay sonrası verileri otomasyon üzerinden geriye dönük tarayarak, komisyon çalışmalarını maliyet analizi açısından istatistiksel olarak değerlendirmektir. Çalışmada incelenecek olan testler şu şekilde belirlenmiştir; Alfa feto protein (AFP), anti tiroglobulin, anti tiroid peroksidaz (Anti TPO), beta hCG, C-peptid, CA 125, CA 15-3, CA 19-9, karsino embriyonik antijen (CEA), dehidro-epi androstenedion sulfat (DHEA-sülfat), Folat, Estradiol, Ferritin, folikül stimülan hormon (FSH), Progesteron, Prolaktin, total prostatik antijen (Total PSA), tiroksin 3 (T3), tiroksin 4 (T4), tiroid stimülan hormon (TSH), seks hormonu bağlayıcı globülin (SHBG), Vit B12. Bulgular: Çalışılan tüm testlerin istem sayılarında azalma olduğu görülmüştür. Ancak bazı testlerdeki azalma dikkat çekici bulunmuştur. Bu testlerden en fazla istem sayısı azalan %42,19 oranı ile T3 testidir. En az istem sayısı azalan ise, %3,22 oranı ile C-peptid olmuştur. Sonuç: LVK çalışmalarından elde edilen veriler göstermektedir ki; hastanelerde önemli miktarda gereksiz ve test istemleri hastane bilgi yönetim sisteminde (HBYS) mevcuttur. Bu durum kurulacak LVK’ları tarafından düzeltilebilir niteliktedir.

Possible Metabolic Alterations among Autistic Male Children: Clinical and Biochemical Approaches.

The present cross-sectional, hospital-based study was carried out on 146 Egyptian male children, 73 males with autism who were comparable with another 73 healthy age- and sex-matched children, recruited from the outpatients' psychiatric clinics of the Neuropsychiatric and Pediatric Departments of South Valley and Assiut University Hospitals, Egypt. Neuropsychological assessments of autistic males were done using CARS, short sensory profile and intelligent quotients. Serum markers of mitochondrial dysfunction (lactate, pyruvate, and lactate to pyruvate ratio, creatine kinase (CK), L-carnitine, ammonia, lactate dehydrogenase, pyruvate kinase, alanine transaminase and aspartate transaminase), oxidative stress and blood levels of heavy metals (mercury, lead and aluminium) were measured. Serum cholesterol, cortisol, free testosterone, estradiol, dehydroepiandrostenedione, adenosine deaminase and Helicobacter pylori antigen in stool were also performed. There was evidence of mitochondrial dysfunction among autistic children. Additionally, there were significantly lower serum total cholesterol, cortisol and estradiol as well as significantly higher dehydroepiandrostenedione (DHEA) and free testosterone (p < 0.05 for all markers). Twenty-eight (38%) cases were positive for H. pylori antigen in their stool with significant higher serum ammonia and lower adenosine deaminase than in H. pylori-negative autistic children. Mitochondrial dysfunction, H. pylori infection and low cholesterol were prevalent among autistic male children, which should be targeted during autism management.

Absence of a correlation between intra-follicular androgen and AMH levels and the oocyte count in poor responder patients undergoing in vitro fertilization

Androgens are male hormones and precursors of female hormones. Testosterone (T), dehydroepiandrostenedione (DHEA), and anti-mullerian hormone (AMH) enhance follicular recruitment and promote follicular growth and development. Clinical reports have demonstrated that co-treatment with androgens, such as DHEA and Androderm (transdermal testosterone) may increase both quantity and quality of oocytes and embryos and improve pregnancy outcomes in women with diminished ovarian function or premature ovarian failure. This study was designed to find correlations between intra-follicular androgen and AMH levels and the amount of oocytes retrieved from ovarian responders and poor-responders. We enrolled 40 patients undergoing in vitro fertilization (IVF) and tested their follicular fluid for testosterone, DHEA, and AMH levels. AMH levels were significantly different between the groups. However, no correlations were observed between the levels of testosterone, DHEA, or AMH and the amounts of retrieved oocytes. No correlations were observed between androgens and AMH levels with the amount of oocytes in either group. Thus, there is no correlation between intra-follicular androgen and AMH levels and the amount of oocytes in both responders and poor responders. A larger sample size and multi-center study design is needed to confirm this.

Hyperactivity of the Sympatho-Adrenomedullary System Without Any Modification of the Hypothalamic-Pituitary-Adrenal Axis After Food Restriction Among High-Level Weightlifters.

Durguerian, A, Filaire, E, Drogou, C, Sauvet, F, Bougard, C, and Chennaoui, M. Hyperactivity of the sympatho-adrenomedullary system without any modification of the hypothalamic-pituitary-adrenal axis after food restriction among high-level weightlifters. J Strength Cond Res 32(6): 1643-1655, 2018-We examined the effects of 6 days of food restriction on salivary α-amylase (sAA), cortisol and dehydroepiandrostenedione (DHEA) awakening responses, psychological parameters and performance among 11 international weightlifters. Assessments were made at baseline (T1) and 6 days after a normal period of training while maintaining body weight (T2). Then, participants were assigned to 2 groups depending on whether they lost (Diet group) or maintained (Control group) their body mass. Anthropometric, psychological, physical, and physiological assessments were also realized 6 days (T3) after the restricted dietary period for the Diet group. Food restriction (T3) induced a significant rise of sAA awakening response (364.6%, p ≤ 0.05), whereas no significant variations were observed among the hypothalamic-pituitary-adrenal axis (cortisol and DHEA). Significant alterations of the general Recovery Score and General stress Score, evaluated through the Recovery-Stress Questionnaire for athletes, were noted after food restriction. Weightlifting performance, evaluated during a simulated weightlifting competition, was maintained after the 6-day food restriction; we even noted an increased weightlifting performance related to body mass (Sinclair coefficient). Our findings support the hypothesis that food restriction induces a challenging situation to the organism, resulting in an asymmetry between the 2 stress systems activation. These results reinforce the necessity to cautiously plan and monitor the weight regulation process before competition to avoid potential negative outcomes on psychophysiological parameters. In this regard, the psychobiological approach, especially the awakening responses, seems a useful tool.

Quantification of dehydroepiandrosterone in human serum on a routine basis: development and validation of a tandem mass spectrometry method based on a surrogate analyte.

In the clinical laboratories, dehydroepiandrostenedione (DHEA) is usually quantified by immunoassay-based methods, which are often affected by cross-reactivity with endogenous interferences, such as 4-androsten-3β-ol-17-one. The interfering compounds lead to a poor accuracy of the measurements, mainly at a low concentration level. The present paper describes a validated method based on tandem mass spectrometry coupled to liquid chromatography, for the accurate quantification of DHEA in serum. The peculiarity of this method is the use of calibrators and quality controls prepared by adding measured amounts of DHEA-D5, a stable isotope-labeled analogue of DHEA, to real serum from healthy subjects. DHEA-D5 is used in place of DHEA, which is usually present in unstripped serum at physiological levels, as it has the same basic structure, provides an equivalent instrumental response, and can be easily distinguish by DHEA by mass spectrometry due to its different m/z value. The method proved to be sensitive, with a LLOD of 0.09ng/mL and a LLOQ of 0.23ng/mL, and selective, with overall performances that allow its use on a routine basis.

Molecular assessment, characterization, and differentiation of theca stem cells imply the presence of mesenchymal and pluripotent stem cells in sheep ovarian theca layer

The ability of ovarian theca stem cells to differentiate into oocyte and theca cells may lead to a major advancement in reproductive biology and infertility treatments. However, there is little information about function, growth and differentiation potential of these immature cells. In this study adult sheep theca stem cells (TSCs) characteristics, and differentiation potential into osteocyte-like cells (OSLCs), adipocyte-like cells (ALCs), theca progenitor-like cells (TPCs), and oocyte-like cells (OLCs) were investigated. TSCs were isolated, cultured, and compared with mesenchymal stem cells (MSCs), fibroblast cells (FCs), and pluripotent embryonic ovarian cells (EO). Adherent TSCs were morphologically similar to FCs. Cell cycle analysis showed high proliferation capacity of TSCs. TSCs were positive for the mesenchymal cells surface markers, and also expressed POU5F1. Differentiation potential of TSCs into OSLCs and ALCs were confirmed by alizarin red and oil red staining respectively. OSTEOCALCIN and COL1 were expressed in OSLCs. ALCs were positive for PPARα and LPL. TPCs expressed theca specific genes (GLI2, GLI3, PTCH1, CYP17A1, 3β-HSD and LHR) and secreted testosterone, dehydroepiandrostenedione (DHEA), androstenedione, progesterone and estradiol. Lipid droplets in these steroid cells were viewed by oil red staining. OLCs expressed oocyte-specific marker genes including, ZP3, ZP2, GDF9, SYCP3, PRDM1, STELLA, FRAGILIS, DAZL, as well as POU5F1, and showed separated sphere structure. Our results indicated that TSCs derived from ovarian follicles contain MSCs and pluripotent stem cells (PSCs) that can be differentiated into lineages of mesenchymal origin and are capable of differentiation into TPCs and OLCs under in vitro conditions.

The effect of Melatonin on histological changes of ovary in induced polycystic ovary syndrome model in mice

Abstract Background Antioxidants can be used as adjuvant treatment of polycystic ovary syndrome (PCOS). Melatonin (MT) is one of the antioxidant that is used nowadays. Objective In this study, the effect of MT on the histological changes of ovary in the experimental model of polycystic ovary syndrome is investigated. Methods In this study 30 immature female NMRI mice were divided into 5 groups including: (1) control group received distilled water, (2) received a dose of 10 mg/kg MT for 5 days, (3) received Dehydroepiandrostenedione (DHEA) at a dose of 6 mg/kg for 20 days to induce PCOS, (4) after induction of PCOS received MT at a dose of 10 mg/kg for 5 days, and (5) received 6 mg/kg DHEA and 10 mg/kg MT for 20 days simultaneously. Results The evaluation of ovarian tissue characteristics such as the granulosa layer, theca, number and diameter of cysts and follicles was performed. PCOS caused a significant reduction in the number of antral follicles and corpus luteum and an increase in the number of primordial, primary, pre-antral and cystic follicles in comparison with the control group (P Conclusion These findings indicate that MT have a protective effects on polycystic ovary damages induced by DHEA, although the mechanism is unclear. It is likely that this is happening by reducing oxidative damage.

The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression.

Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARγ and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARγ dependent PTEN/p-Akt expression in the granulosa cells.

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome.

Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. Prospective case-control study. Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E1), estradiol (E2), estriol (E3)) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. At 20 weeks of gestation: T (P=0.019) and ADION (P=0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E1, E2, and E3 were not different. Maternal concentration at birth: T (P=0.004) and ADION (P=0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E1, E2 and E3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E2, E3, and AMH between the PCOS mothers and the controls respectively. E1 was lower in girls from PCOS mothers (P=0.007). Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

The effects of Ramadan fasting on the level of sex hormones in pre-menarche girls in Mashhad, Iran

The present study aimed to evaluate the effects of Ramadan fasting on the level of sex hormones in girls between 9-13 years before age at menarche. This study was conducted on a sample of 58 subjects (age range: 9-13 years), who were divided into two groups of fasting (N=31) and non-fasting (N=27). The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone and estradiol were measured in all the subjects before and after Ramadan. Measurements were carried out three days before the start of Ramadan, and one day afterwards. In this study, FSH levels significantly increased in the non-fasting group (P=0.01), and the level of Dehydroepiandrostenedione (DHEA) had a significant decrease during the time of study in both groups (P=0.001, P=0.006). In addition, serum levels of LH significantly increased in the non-fasting group after Ramadan (P=0.006), and estradiol significantly increased in both groups (P=0.008, P=0.004). Given the similar changes in the levels of DHEA, progesterone and estradiol in both study groups, it could be concluded that fasting has no effects on these parameters, and the changes in LH and FSH levels could be due to other contributing factors.

Ovarian rejuvenation with dehydroepiandrostenedione prior to a modified natural in vitro fertilization cycle: A new hope in premature ovarian insufficiency

Patients with primary ovarian insufficiency (POI) are classically oriented to egg donation due to the lack of currently available efficient treatments. In response to this shortcoming, modified natural in vitro fertilization cycle (mnIVF) combined with dehydroepiandrostenedione (DHEA) neoadjuvant treatment is an original therapeutic tool at our disposal. A 33-year-old patient with idiopathic POI was prescribed DHEA neoadjuvant treatment. She rapidly recovered her menstrual cycle and after 3 months of DHEA, basal follicle-stimulating hormone has decreased drastically. Then, a mnIVF was performed. The patient got pregnant and gave birth to a healthy girl. She became pregnant a second time under DHEA only. Coupled with DHEA neoadjuvant treatment, a mnIVF could be a useful therapeutic tool for extremely poor prognosis patients with POI.

Adrenal disorders in human immunodeficiency virus (HIV) infected patients

Human Immunodeficiency Virus (HIV) infection is associated with adrenal disorders, which must not be underestimated. Adrenal morphologic changes are primarily related to opportunistic infections, mostly by cytomegalovirus and mycobacteria, and malignant tumours such as non-Hodgkin's lymphoma and Kaposi's sarcoma. The most frequent biological alteration reported to date is the increases in cortisol concentrations which results from a decrease in cortisol metabolism and hyperactivity of the hypothalamo-pituitary-adrenal axis commonly referred to as pseudo-Cushing's syndrome. These modifications can be a consequence of antiretroviral therapy and do not require any investigation or specific treatment. Conversely, adrenal insufficiency, either iatrogenic or secondary to glandular infiltration by neoplasms or infections, needs long-term substitution with hydrocortisone, but at present occurs more rarely and usually at late stages of disease progression. The impact of HIV infection on the other adrenocortical functions has been less reported in the literature although several studies show low levels of adrenal androgens, especially dehydroepiandrostenedione (DHEA). Impairment in mineralocorticoid function appears occasional and remains a subject of debate.

Griseofulvin increases steroid hormone levels in the supernatant of adrenocortical cells in vitro

It has been shown that griseofulvin, which is an antifungal drug, inhibits growth of adrenocortical cancer cells in vitro. The inhibition of growth is caused by interactions with the microtubule apparatus. Interestingly, the microtubule apparatus is also involved in the regulation of steroidogenesis. Therefore we posed the question if griseofulvin also affects steroid hormone secretion. We have applied the NCI-H295R adrenocortical cancer cell line for the analysis of the effects of griseofulvin on adrenocortical steroid hormone secretion. Cells were incubated with or without griseofulvin at concentrations of 0.1µM, 1µM, 10µM, 40µM and 100µM for 24 hours. Concentrations of aldosterone, cortisol and dehydroepiandrostenedione (DHEA) were analyzed in the supernatants using Enzyme Linked Immunosorbent Assays (ELISAs). In addition, we measured concentrations of potassium levels to rule out that increased steroid hormone levels were a consequence of changed electrolyte concentrations. The incubation with griseofulvin leads to a dose dependent increase of Aldosterone-(approximately 2.3-fold), Cortisol-(approximately 1.3-fold) and DHEA-(approximately 4.3 fold) concentrations. The effects were, at least in part, independent from the concentration of potassium. Griseofulvin interfere with the microtubule apparatus and may disrupt regular trafficking of intracellular steroidal compounds. Apoptosis of adrenocortical cells may contribute to the release of steroid hormones. However, the exact mechanism how griseofulvin leads to increased concentrations of steroid hormones in the supernatant of adrenocortical cells is still unclear.

Can dehydroepiandrostenedione (DHEA) target PRL-3 to prevent colon cancer metastasis?

Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients. Metastasis caused by CRC is mainly responsible for this cancer-related deaths. Despite recent advancements in the treatment methods, prognosis remains poor. Therefore, effective treatment strategies need to be designed for successful management of this disease. Dehydroepiandrostenedione (DHEA), a 17-ketosteroid hormone produced by adrenal glands, gonads and including gastrointestinal tract is required for several physiological processes. Deregulation of DHEA levels leads to various disease conditions including cancer. In fact, several experimental studies strongly suggest that DHEA could be used as a chemopreventive agent against colon cancer. Prenlyation of certain membrane proteins such as phosphatase of regenerating liver-3 (PRL-3) is crucial for metastatic progression of colon cancer cells. The ability of DHEA to target prenylation pathway could be utilized to inhibit PRL-3 prenylation for successful prevention of CRC metastases. As DHEA is a widely consumed drug for various ailments, incorporation of DHEA in the treatment regimen may be beneficial to prevent or delay the occurrence of metastasis resulting from CRC.

Abstract 3635: Association of reduction in serum androgens and change in serum PSA in patients treated with abiraterone acetate (AA): A subset analysis of the COU-AA-301 phase 3 randomized trial

Abstract Objective In study COU-AA-301 the androgen biosynthesis inhibitor AA significantly increased overall survival vs placebo in mCRPC post-docetaxel (HR=0.74) (Scher, ASCO 2011). The objective of the current study was to determine the activity of AA in decreasing androgens in a subset of patients in COU-AA-301 using an ultrasensitive assay that measured serum testosterone (T), androstenedione (A4), and dehydroepiandrostenedione (DHEA) below concentrations detectable with commercially available methods, to determine the ability of AA + prednisone (P), compared to placebo + P, to reduce androgen levels below the lower limits of quantification (LLOQ), and to correlate decreases in androgen levels with PSA response. Methods COU-AA-301 is a randomized double blind study of AA (1000 mg QD + prednisone [P] 5 mg po BID) vs placebo + P. Serum androgen levels were measured at baseline and week 12 in the AA + P and placebo + P arms by an ultrasensitive assay using LC/MS/MS. The LLOQs were: T, &amp;lt;0.05 ng/dL; A4, &amp;lt;0.10 ng/dL; DHEA, &amp;lt;0.10 µg/dL. In this post hoc exploratory analysis, the reduction in androgen levels from baseline to week 12 was compared between treatment arms using the t-test. Also evaluated was the androgen response, defined as the proportion of patients with week 12 androgen concentration below the respective LLOQ. The association between PSA response (PSA Δ50% baseline) and androgen response was analyzed by logistic regression. Results AA + P treatment led to significant reductions in T, A4, and DHEA levels from baseline to week 12 (T: –5.46 vs –2.74 ng/dL, P=0.0002; A4: –26.33 vs –8.81 ng/dL, P=0.0007; DHEA: –22.59 vs –10.40 µg/dL, P=0.0179; AA + P vs placebo + P, respectively). The number of patients with an androgen response at week 12 was substantially greater for AA + P compared with placebo + P (T: 34/72 [47%] vs 0/37; A4: 19/63 [30%] vs 0/31; DHEA: 46/80 [58%] vs 1/38 [3%]; AA + P vs placebo + P, respectively). Eleven patients showed androgen response on all three androgens, 2 patients on A4 and T only, 4 patients on A4 and DHEA only, and 14 patients on T and DHEA only. There was a positive association between PSA response and androgen response, adjusted for treatment effect, in favor of androgen responders (T: OR=1.54 [95% CI, 0.546, 4.347]; A4: OR=3.06 [95% CI, 0.975, 9.604]; DHEA: OR=1.08 [95% CI, 0.401, 2.899]). Conclusions: In study COU-AA-301, AA + P potently inhibited the production of serum androgens T, A4, and DHEA as measured by an ultrasensitive assay. Reduction in T and A4 appears to correlate with PSA response, providing further evidence that mCRPC remains dependent on androgen-mediated signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3635. doi:1538-7445.AM2012-3635

Endogenous Sex Hormones and Glucose Tolerance Status in Postmenopausal Women

In postmenopausal women, endogenous estradiol (E2) and free testosterone (T) have been positively associated with glucose intolerance and type 2 diabetes. Most studies have not examined these associations in a large group of postmenopausal women. The objective was to examine the association between endogenous sex hormones and glucose tolerance in postmenopausal women. This was a cross-sectional study of 1973 postmenopausal women ages 45-84 yr, not taking hormone replacement therapy, in the Multi-Ethnic Study of Atherosclerosis baseline examination. Impaired fasting glucose (IFG) and diabetes were defined based on fasting blood sugar and/or treatment for diabetes. In women with normal glucose tolerance, insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). Increasing quartiles of bioavailable T and E2 and decreasing quartiles of SHBG were associated with significantly increased odds of IFG and diabetes (all P for trend<0.001). Except for the association of bioavailable T with diabetes, the other associations persisted after multivariable adjustment. Although higher dehydroepiandrostenedione (DHEA) was associated with greater odds of IFG (P for trend=0.02), it was not associated with diabetes. Of 1100 women with normal glucose tolerance, E2 and DHEA were positively associated, and SHBG was inversely associated with HOMA-IR (all P<0.001) after multivariable adjustment. Bioavailable T was associated with HOMA-IR (P<0.001), but not fasting glucose. Of postmenopausal women, endogenous bioavailable T, E2, and DHEA were positively associated and SHBG was negatively associated with insulin resistance.

The impact of physical activity in a case of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) affects 5–10% of women of fertile age and most women are diagnosed with the syndrome because of gynecologic symptoms, that is infertility, menstrual disturbances or symptoms of hyperandrogenism such as acne or excess hair growth. Since the report by Burghen et al. (1) in 1980 that PCOS was associated with hyperinsulinemia, it has become clear that women with PCOS are more insulin resistant than weight-matched women without the syndrome (2). PCOS has several features in common with the metabolic syndrome, including dyslipi-demia, abdominal obesity and insulin resistance. In both syndromes, there are also signs of enhanced activity in neuroendocrine stress axes (3, 4), and blood pressure has been found to be higher in PCOS than in controls (5). Metformin, an insulin sensitizing agent, is used for treatment of type 2 diabetes mellitus and also increasingly for PCOS. Other treatments for insulin resistance are physical activity and weight loss (6–8). Motivation is crucial for lifestyle changes (7). Most doctors have experienced that it is difficult to motivate a patient to lose weight and become more physically active and that patient adherence is much easier to achieve to medical treatment than to a change in lifestyle. The following case report illustrates both the effect of physical activity on PCOS and the importance of motivation. A 24-year-old nurse student referred because of oligo-menorrhea and elevated plasma testosterone was enrolled in a double-blind, randomized study of the effect of metformin on PCOS. The study was designed as a crossover study with treatment periods of 6 months separated by a 3-month washout period. Before entering the study, she received general information about PCOS and the importance of being physically active and losing weight was emphasized. Before and after each treatment period, blood pressure and waist-hip (w/h) ratio were measured and body mass index (BMI) calculated. After an overnight fast of 8h, venous plasma levels of glucose (FBG), total cholesterol (chol), triglycerides (TGL), dehydroepiandrostenedione (DHAS), gonadotropins, total testosterone (T) and sex hormone binding globulin (SHBG) were measured. Testosterone index (T index) was calculated as testosterone divided with SHBG. Her periods became regular during the first treatment period and remained so during the remaining study period. She lost weight during the first period, but gained a little again during the second period. Testosterone normalized during both periods. As SHBG rose during the second period, the testosterone index fell. FBG fell continuously during the study (Table 1). An oral glucose tolerance test performed after the study period was normal. When the code was broken, it appeared that she had received metformin during the first treatment period. As the investigator performing the study expressed some surprise over the improving values during the placebo period despite the increasing weight, she explained that she had had a boyfriend for the past 6months. He was a keen sportsman and because of that she had become considerably more physically active. She now took a 1-hour walk each evening, played badminton once a week and went to her job by bike 8 km each day. In the DPP (Diabetes Prevention Program) study (8), physical activity was shown to be more effective than metformin in treating insulin resistance. It is not known how metformin changes insulin sensitivity, but it is thought to increase peripheral glucose uptake in response to insulin, and to reduce hepatic glucose output to some extent. Exercise may enhance insulin sensitivity by affecting the oxidative capacity of skeletal muscle, but it has also been shown that exercise reduces sympathetic nerve activity, which may be exaggerated in insulin resistance (9). The presented case history illustrates that this may also be the case in PCOS, a condition strongly related to insulin resistance. It also shows the importance of social support in changes of lifestyle, and the impact of love as a motivating factor considerably stronger than the advice of doctors.

Supplementation with DHEA: Effect on Muscle Size, Strength, Quality of Life, and Lipids

To evaluate the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women. Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes. Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function. Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL.