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Objective: To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic)., Design: Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29)., Materials and Methods: Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes., Results: Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001)., Conclusions: In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: No prior study to our knowledge has examined the joint contribution of a polygenic risk score (PRS), mammographic density (MD), and postmenopausal endogenous hormone levels-all well-confirmed risk factors for invasive breast cancer-to existing breast cancer risk prediction models., Methods and Findings: We conducted a nested case-control study within the prospective Nurses' Health Study and Nurses' Health Study II including 4,006 cases and 7,874 controls ages 34-70 years up to 1 June 2010. We added a breast cancer PRS using 67 single nucleotide polymorphisms, MD, and circulating testosterone, estrone sulfate, and prolactin levels to existing risk models. We calculated area under the curve (AUC), controlling for age and stratified by menopausal status, for the 5-year absolute risk of invasive breast cancer. We estimated the population distribution of 5-year predicted risks for models with and without biomarkers. For the Gail model, the AUC improved (p-values < 0.001) from 55.9 to 64.1 (8.2 units) in premenopausal women (Gail + PRS + MD), from 55.5 to 66.0 (10.5 units) in postmenopausal women not using hormone therapy (HT) (Gail + PRS + MD + all hormones), and from 58.0 to 64.9 (6.9 units) in postmenopausal women using HT (Gail + PRS + MD + prolactin). For the Rosner-Colditz model, the corresponding AUCs improved (p-values < 0.001) by 5.7, 6.2, and 6.5 units. For estrogen-receptor-positive tumors, among postmenopausal women not using HT, the AUCs improved (p-values < 0.001) by 14.3 units for the Gail model and 7.3 units for the Rosner-Colditz model. Additionally, the percentage of 50-year-old women predicted to be at more than twice 5-year average risk (≥2.27%) was 0.2% for the Gail model alone and 6.6% for the Gail + PRS + MD + all hormones model. Limitations of our study included the limited racial/ethnic diversity of our cohort, and that general population exposure distributions were unavailable for some risk factors., Conclusions: In this study, the addition of PRS, MD, and endogenous hormones substantially improved existing breast cancer risk prediction models. Further studies will be needed to confirm these findings and to determine whether improved risk prediction models have practical value in identifying women at higher risk who would most benefit from chemoprevention, screening, and other risk-reducing strategies., Competing Interests: The authors declare that they have no conflicts of interest.

Background: The molecular mechanisms linking environmental exposures to earlier pubertal development are not well characterized. Epigenetics may play an important role, but data on the relationship between epigenetic marks and puberty, particularly in humans, is limited., Methods: We used pyrosequencing to measure Alu and long interspersed nucleotide elements (LINE-1) methylation in DNA isolated from whole blood samples collected from newborns and 9-y-old children (n = 266). Tanner staging was completed six times between ages 9 and 12 y to determine pubertal status, and hormone levels were measured in 12-y-old boys., Results: Among girls, we observed a suggestive trend of increased odds of breast and pubic hair development with higher Alu and LINE-1 methylation in 9-y-old blood, respectively. The strongest association identified was an inverse association of LINE-1 methylation in 9-y-old girls with odds of experiencing menarche by age 12 (OR (95% CI): 0.63 (0.46, 0.87); P = 0.005). We observed a consistent inverse relationship for Alu and LINE-1 methylation at 9 y with luteinizing hormone (LH), testosterone and follicle-stimulating hormone levels in boys but it was only significant between LINE-1 and LH., Conclusion: DNA methylation of Alu and LINE-1 may be involved in puberty initiation and development. This relationship should be confirmed in future studies.

Background and Objectives: Calcium and phosphorus regulatory hormones may contribute to the pathogenesis of calcium nephrolithiasis. However, there has been no prospective study to date of plasma hormone levels and risk of kidney stones. This study aimed to examine independent associations between plasma levels of 1,25-dihydroxyvitamin D (1,25[OH]2D), 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, fibroblast growth factor 23 (FGF23), parathyroid hormone, calcium, phosphate, and creatinine and the subsequent risk of incident kidney stones., Design, Setting, Participants, & Measurements: This study was a prospective, nested case-control study of men in the Health Professionals Follow-Up Study who were free of diagnosed nephrolithiasis at blood draw. During 12 years of follow-up, 356 men developed an incident symptomatic kidney stone. Using risk set sampling, controls were selected in a 2:1 ratio (n=712 controls) and matched for age, race, and year, month, and time of day of blood collection., Results: Baseline plasma levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, parathyroid hormone, calcium, phosphate, and creatinine were similar in cases and controls. Mean 1,25(OH)2D and median FGF23 levels were higher in cases than controls but differences were small and statistically nonsignificant (45.7 versus 44.2 pg/ml, P=0.07 for 1,25[OH]2D; 47.6 versus 45.1 pg/ml, P=0.08 for FGF23). However, after adjusting for body mass index, diet, plasma factors, and other covariates, the odds ratios of incident symptomatic kidney stones in the highest compared with lowest quartiles were 1.73 (95% confidence interval, 1.11 to 2.71; P for trend 0.01) for 1,25(OH)2D and 1.45 (95% confidence interval, 0.96 to 2.19; P for trend 0.03) for FGF23. There were no significant associations between other plasma factors and kidney stone risk., Conclusions: Higher plasma 1,25(OH)2D, even in ranges considered normal, is independently associated with higher risk of symptomatic kidney stones. Although of borderline statistical significance, these findings also suggest that higher FGF23 may be associated with risk., (Copyright © 2015 by the American Society of Nephrology.)

Objective: To test relationships between adipokines, adiposity, and vasomotor symptoms (VMS), including how these associations vary by menopause stage., Design: A subcohort of the longitudinal cohort Study of Women's Health Across the Nation completed questionnaires, physical measures, and a fasting blood draw annually for 8 years. Associations between a poorer adipokine profile (lower adiponectin, lower high-molecular-weight [HMW] adiponectin, higher leptin, lower soluble leptin receptor, higher monocyte chemoattractant protein 1 [MCP-1]) and VMS were tested with the use of generalized estimating equations adjusting for potential confounders. Interactions by menopause stage (pre-/early perimenopause, late peri-/postmenopause) were tested., Setting: Community., Patient(s): A total of 536 women ages 42-52 at baseline., Intervention(s): None., Main Outcome Measure(s) Vms Result(s): Associations between adipokines and hot flashes varied by menopause stage, with a poorer adipokine profile associated with higher odds of hot flashes early in the transition (adiponectin(log): odds ratio [OR] 0.68, 95% confidence interval [CI] 0.51-0.90; HMW adiponectin(log): OR 0.70, 95% CI 0.58-0.85; leptin(log): OR 1.23, 95% CI 0.99-1.54; multivariable models including body mass index [BMI]), but not later in the transition. The direction of associations between BMI and VMS also varied by menopausal stage. Higher MCP-1 was associated with more night sweats (OR 1.37, 95% CI 1.06-1.76) across menopausal stages., Conclusion(s): An adverse adipokine profile was associated with more VMS, particularly early in the menopause transition., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Over the last decade, gender and age-related hormonal status of trauma patients have been increasingly recognized as outcome factors. In the present study, we examine a large cohort of trauma patients to better appraise the effects of gender and age on patient outcome after blunt and penetrating trauma. We hypothesize that adult females are at lower risk for complications and mortality relative to adult males after both blunt and penetrating trauma. A retrospective analysis was conducted of the National Trauma Data Bank examining hormonally active females for advantages in survival and outcome after blunt and/or penetrating trauma. Over 1.4 million incident trauma cases were identified between 2002 and 2006. Multiple logistic regressions were calculated for associations between gender and outcome, stratified by injury type, age, comorbidity, Injury Severity Score (ISS), and complications. Risk factors associated with mortality in our multiple logistic regression analyses included: penetrating trauma (odds ratio [OR, 2.31; 95% confidence interval [CI], 2.27 to 2.36); adult male (OR, 1.45; 95% CI, 1.41 to 1.49); and ISS 15 or greater (OR, 14.68; 95% CI, 14.38 to 14.98). Adult females demonstrated a survival advantage over adult males (OR, 0.69; 95% CI, 0.67 to 0.71). Adult females with ISS less than 15 demonstrated a distinct survival advantage compared with adult males after both blunt and penetrating trauma. These results warrant further investigation into the role of sex hormones in trauma.

Context: Factors influencing the outcome of surgical treatment of pediatric Cushing's disease (CD) have not been fully established., Objective: The aim of this study was to examine features influencing the outcome of surgery for pediatric CD., Design: In this prospective observational study, the clinical, imaging, endocrinological, and operative outcomes were analyzed in consecutive patients treated at the National Institutes of Health (NIH) from 1982 through 2010., Setting: The study was conducted in a tertiary referral center., Results: Two hundred CD patients (106 females, 94 males) were included. Mean age at symptom development was 10.6 ± 3.6 years (range, 4.0 to 19.0 y). Mean age at NIH operation was 13.7 ± 3.7 years. Twenty-seven patients (13%) had prior surgery at another institution. Magnetic resonance imaging identified adenomas in 97 patients (50%). When positive, magnetic resonance imaging accurately defined a discrete adenoma in 96 of the 97 patients (99%), which was more accurate than the use of ACTH ratios during inferior petrosal sinus sampling to determine adenoma lateralization (accurate in 72% of patients without prior surgery). A total of 195 of the 200 patients (98%) achieved remission after surgery (189 [97%] were hypocortisolemic; 6 [3%] were eucortisolemic postoperatively). Factors associated with initial remission (P < .05) included identification of an adenoma at surgery, immunohistochemical ACTH-producing adenoma, and noninvasive ACTH adenoma. Younger age, smaller adenoma, and absence of cavernous sinus wall or other dural invasion were associated with long-term remission (P < .05). A minimum morning serum cortisol of less than 1 μg/dl after surgery had a positive predictive value for lasting remission of 96%., Conclusions: With rare disorders, such as pediatric CD, enhanced outcomes are obtained by evaluation and treatment at centers with substantial experience. Resection of pituitary adenomas in pediatric CD in that setting can be safe, effective, and durable. Early postoperative endocrine testing predicts lasting remission. Because lasting remission is associated with younger age at surgery, smaller adenomas, and lack of dural invasion, early diagnosis should improve surgical outcome.

Background: Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury., Methods and Results: In 3127 stroke-free Framingham offspring (age, 59±10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function (homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995-1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999-2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume. During a median follow-up of 9.2 years, 130 participants experienced incident stroke/transient ischemic attack. In multivariable analyses adjusted for stroke risk factors, the biomarker panel was associated with incident stroke/transient ischemic attack and with total cerebral brain volume (P<0.05 for both) but not with covert brain infarcts or white-matter hyperintensity volume (P>0.05). In backward elimination analyses, higher log-B-type natriuretic peptide (hazard ratio, 1.39 per 1-SD increment; P=0.002) and log-urinary albumin/creatinine ratio (hazard ratio, 1.31 per 1-SD increment; P=0.004) were associated with increased risk of stroke/transient ischemic attack and improved risk prediction compared with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15% 10-year risk category was used, the net reclassification index was 0.109 (P=0.037). Higher C-reactive protein (β=-0.21 per 1-SD increment; P=0.008), D-dimer (β=-0.18 per 1-SD increment; P=0.041), total homocysteine (β=-0.21 per 1-SD increment; P=0.005), and urinary albumin/creatinine ratio (β=-0.15 per 1-SD increment; P=0.042) were associated with lower total cerebral brain volume., Conclusion: In a middle-aged community sample, we identified multiple biomarkers that were associated with clinical and subclinical vascular brain injury and could improve risk stratification.

Women are twice as likely as men to suffer from depressive symptoms/disorder. Research has focused on physiologic and psychosocial differences between men and women; an important target of study has been periods of reproductive changes. Controversy has existed regarding the extent to which the menopausal transition or postmenopause increases the risk for depressive symptoms/disorders. This paper presents findings from analyses of data from the SWAN study and an ancillary study on mental health. We found that risk for high depressive symptoms and disorder is greater during and possibly after the menopausal transition. Other factors contribute to risk for depression.

Is there evidence for a perimenopausal sleep disorder? We address this question in our presentation of the Study of Women's Health Across the Nation (SWAN) "sleep story," in which we summarize and discuss data addressing sleep quality, objective measures of sleep patterns, and sleep disorders that have been published to date by the SWAN and the ancillary SWAN Sleep Study. We describe what has been learned about sleep during the perimenopause. Analyses exploring racial/ethnic diversity and the role of hot flashes and mood disturbance in sleep-perimenopause associations are described. Implications for clinical practice are considered.

The hormonal correlates of reproductive aging and the menopause transition reflect an initial loss of the follicle cohort, while a responsive ovary remains, and an eventual complete loss of follicle response, with persistent hypergonadotropic amenorrhea. The physiology of the process is described, along with key findings of relevant studies, with an emphasis on the Study of Women's Health Across the Nation. A clinical framework is provided to help clinicians to forecast the major milestones of the menopausal transition and to predict potential symptoms or disease.

Background: Breast cancer is less common in China than in the United States and perinatal characteristics predict breast cancer risk in the offspring. We determined levels of pregnancy hormones in Boston and Shanghai to identify those possibly involved in the intrauterine origin of breast cancer., Participants and Methods: We compared maternal and cord blood levels of estradiol, estriol, testosterone, progesterone, prolactin, insulin-like growth factors (IGF) 1 and 2, insulin-like growth factor-binding protein 3, adiponectin and sex hormone-binding globulin (SHBG) in 241 Caucasian and 295 Chinese women., Results: In both centers, hormone levels at the 16th were predictive of those at the 27th gestational week, but there was little correlation between maternal and cord blood levels. In cord blood, we found significantly (P < 0.01) higher levels of estradiol (44.2%), testosterone (54.5%), IGF-2 (22.7%) and strikingly SHBG (104.6%) in Shanghai women, whereas the opposite was true for IGF-1 (-36.8%)., Conclusions: Taking into account the current understanding of the plausible biological role of the examined endocrine factors, those likely to be involved in the intrauterine origin of breast cancer are SHBG and IGF-2, with higher cord blood levels among Chinese, and IGF-1, with higher cord blood levels among Caucasian women.

Exercise has the potential to impact disease by altering circulating anabolic and catabolic factors. It was the goal of this study to determine how different regimens of low-intensity and moderate-intensity exercise affected circulating levels of these anabolic and catabolic factors in HIV-infected men. Exercise-naive, HIV-infected men, medically cleared for study participation, were randomized into one of the following groups: a moderate-intensity group (MOD, who completed 30 min of moderate-intensity aerobic training followed by 30 min of moderate-intensity resistance training; a low-intensity group (LOW), who completed 60 min of treadmill walking; or a control group (CON), who attended the clinic but participated in no activity. Blood and saliva samples were collected at selected time points before, during, and after each of the 3 required sessions. Compared with baseline, the MOD group (n=14) had a 135% increase in growth hormone (GH) (p<0.05) and a 34% decrease in cortisol (CORT) (p<0.05) at the post time point, a 31% increase in interleukin-6 (IL-6) (p<0.05) at 30-min post exercise, and a 23% increase in IL-6 (p<0.05) and a 13% decrease in soluble tumor necrosis factor receptor 2 (sTNFrII) (p<0.05) at 60-min post exercise. The LOW (n=11) group had a 3.5% decrease in sTNFrII (<0.05) at 30-min post exercise compared with baseline and a 49% decrease (p<0.05) in GH at 60-min post exercise. The CON group (n=13) had a decrease in GH at 30-min (62%, p<0.05) and 60-min (61%, p<0.05) post exercise compared with baseline. The increase in GH from baseline to post was greater in the MOD group (p<0.05) and the decrease in CORT from pre to post was greater in the MOD group (p<0.05) than in the other groups. These data suggest that individual sessions of both low-intensity and moderate-intensity exercise can alter circulating anabolic and catabolic factors in HIV-infected men. The changes in the MOD group present potential mechanisms for the increases in lean tissue mass seen with resistance exercise training.

The hormonal and cardiovascular responses to atropine and low-intensity exercise were examined in 7 young men. Subjects completed 3 trials in a single blind crossover design. During the first trial (T1), subjects received 2.0 mg of atropine intramuscularly at rest. Subsequently in trial 2 (T2), subjects received a saline placebo before 90 minutes of intermittent exercise, and during trial 3 (T3), they received atropine before 90 min of intermittent exercise [3 x (25-minute cycle/5-minute rest) @ 40% VO2 peak]. Venous blood samples and physiological data were collected before, during, and post exercise. Growth hormone (GH) was significantly increased in T2 but unchanged in T1 and T3. Cortisol (CORT) was unchanged in T1 and T2, but in T3 significantly increased (p <0.05) from 45 to 90 minutes compared to T2. Plasma luteinizing hormone (LH) was unaffected in all trials. Plasma prolactin (PRO) significantly increased in T3 from 45 to 90 minutes in comparison to T2. Norepinephrine (NE) was unaffected in T1, but significantly increased in both T2 and T3 (5 to 90 minutes). NE in T3 was also significantly higher compared to T2 (30 to 90 minutes). The heart rate (HR) and rate pressure product (RPP) significantly increased in all trials (15 to 90 minutes) and T3 was significantly elevated in comparison to T2. The administration of atropine before 90 minutes of low-intensity exercise significantly increased cortisol, prolactin, and norepinephrine, decreased growth hormone, and significantly increased cardiovascular stress.

Purpose/objectives: To review strategies to optimize the management of chronic pain in patients with cancer, with an emphasis on the role of opioid analgesics., Data Sources: Published research, articles from a literature review, and U. S. statistics., Data Synthesis: Treatment for cancer pain remains suboptimal. With the therapies currently available, as much as 90% of cancer pain can be controlled. Opioid analgesics are an important component of pain management in patients with cancer., Conclusions: The management of cancer pain is a challenging endeavor that requires an understanding of the etiologies of cancer and the types of pain they can produce. Opioid analgesics are a mainstay of treatment for cancer pain. New drug formulations, delivery systems, and strategies, particularly opioid rotation, are available to optimize cancer pain management., Implications for Nursing: Opioid rotation may be useful for opening the therapeutic window and establishing a more advantageous analgesic-to-toxicity ratio in patients with cancer.

The purpose of this study was to examine relationships among lactational status, naturalistic stress, mood, and levels of serum cortisol and prolactin and plasma adrenocorticotropic hormone (ACTH). Eighty-four exclusively breastfeeding, 99 exclusively formula-feeding, and 33 nonpostpartum healthy control women were studied. The postpartum mothers were studied cross-sectionally once between 4 and 6 weeks after the birth. Stress was measured using the Perceived Stress Scale, the Tennessee Postpartum Stress Scale, and the Inventory of Small Life Events. Mood was measured using the Profile of Mood States. Serum prolactin, plasma ACTH, and serum cortisol levels were measured by commercial ELISA (enzyme-linked immunosorbent assay) kits. Results indicate that breastfeeding mothers had more positive moods, reported more positive events, and perceived less stress than formula-feeders. Reports of stressful life events were generally equivalent in the two groups. Serum prolactin was inversely related to stress and mood in formula-feeders. When breast and formula-feeders were compared to controls, they had higher serum cortisol, lower stress, and lower anxiety. Breastfeeders had lower perceived stress than controls. Breastfeeders had lower depression and anger and more positive life events reported than formula-feeders. However, there were few correlations among stress, mood, and the hormones in postpartum mothers, and those only in formula-feeders, whereas strong relationships were found between serum ACTH and a number of stress and mood variables in controls. Postpartum mothers reported a range of stress and negative moods at 4 to 6 weeks, and in formula-feeders, serum prolactin was related to some of the stress and mood variables. Breastfeeding appears to be somewhat protective of negative moods and stress.

Intrauterine and perinatal factors have been linked to risk of childhood leukemia, testicular cancer, and breast cancer in the offspring. The pool of stem cells in target tissue has been suggested as a critical factor linking early life exposures to cancer. We examined the relation between intrauterine hormone levels and measurements of stem cell potential in umbilical cord blood. Cord blood donors were 40 women, ages >/=18 years, who delivered, from August 2002 to June 2003, a singleton birth after a gestation of at least 37 weeks. We assayed plasma concentrations of estradiol, unconjugated estriol, testosterone, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), and IGF binding protein-3. For stem cell potential, we measured concentrations of CD34(+) and CD34(+)CD38(-) cells and granulocyte-macrophage colony-forming unit (CFU-GM). We applied linear regression analysis and controlled for maternal and neonatal characteristics. We found strong positive associations between IGF-I and stem cell measures, 1 SD increase in IGF-I being associated with a 41% increase in CD34(+) (P = 0.008), a 109% increase in CD34(+)CD38(-) (P = 0.005), and a 94% increase in CFU-GM (P = 0.01). Similar associations were observed for IGF binding protein-3. Among steroid hormones, estriol and testosterone were significantly positively associated with CD34(+) and CFU-GM. These findings indicate that levels of growth factors and hormones are strongly associated with stem cell potential in human umbilical cord blood and point to a potential mechanism that may mediate the relationship between in utero exposure to hormones and cancer risk in the offspring.

It has been proposed that both hypercortisolism and low sympathetic nervous system (SNS) activity contribute to obesity. Because glucocorticoids inhibit SNS activity, we hypothesized that hypercortisolism and low SNS activity may be found in association in Pima Indians, a population with a high prevalence of obesity. We therefore measured indices of hypothalamic-pituitary-adrenal (HPA) axis and SNS activities in 39 nondiabetic men, 20 Pimas (age, 30+/-5 years; weight, 94+/-26 kg; 35%+/-8% body fat [mean +/- SD]) and 19 Caucasians (33+/-9 years, 91+/-23 kg, 28%+/-11% body fat). HPA axis activity was assessed by measurements of morning fasting plasma corticotropin (ACTH) and cortisol concentrations and 24-hour urinary free cortisol (UFC) excretion. SNS activity was assessed as muscle sympathetic nerve activity (MSNA) by microneurography and by measurement of catecholamines (fasting plasma concentration and 24-hour urinary excretion). Plasma ACTH and cortisol and UFC were similar in Pimas and Caucasians. MSNA was positively correlated with percent body fat (r = .49, P = .002) and was lower in Pimas compared with Caucasians after adjustment for percent body fat (24+/-9 v 31+/-10 bursts/min, P = .04). We conclude that Pima Indians, a population with a high prevalence of obesity, have lower SNS activity but normal HPA axis activity compared with Caucasians.

The role of calcium in clinical hypertension can be best understood by a hierarchical model in which the blood pressure effects of a dietary signal depend on alterations of hormonal systems specific for that signal. These alterations mediate both the cellular recognition of these signals as well as the resultant clinical responses to them. In the case of both dietary calcium and dietary salt, these systems appear to include calcium regulating hormones having direct, calcium-dependent vasoactive properties, and which are linked to the activity of the renin-angiotensin system. Altered salt and calcium intake exert reciprocal linked effects on these hormone systems and on blood pressure. These reflect altered cellular calcium uptake from the extracellular space, salt-induced calcium hormones stimulating and calcium-induced suppression of these hormones inhibiting extracellular calcium uptake. Among normotensive individuals, this is associated with a reciprocal calcium-dependent suppression or stimulation of renin secretion, respectively, resulting in an offsetting decreased or increased angiotensin II-mediated release of calcium into the cytoplasm from intracellular stores. Hence, no significant change in cytosolic free calcium or, consequently, in blood pressure usually results from increasing or decreasing dietary salt or calcium intake. However, whether due to genetic or other environmental factors as yet undefined, the metabolic "set point" of plasma renin activity in some subjects is already suppressed, or, alternatively, is unresponsive to the above hormonally mediated dietary mineral variations. Under these circumstances, increases in dietary salt will cause cytosolic free calcium and thus blood pressure to rise, whereas increased dietary calcium in these very same "salt-sensitive" subjects will offset the effect of salt, and lower pressure in these individuals. This analysis suggests that although increasing oral calcium intake to achieve at least current nutritional standards is entirely appropriate, uniform recommendations for all hypertensives to further increase or decrease dietary calcium or salt may be inappropriate and will obscure those for whom these maneuvers are particularly relevant.

Recently, a major topic of discussion has been the impact of synthetic chemicals that possess the capacity to alter hormonal activity, the so-called "endocrine modulators," with potentially the capacity to alter the reproductive capability of humans. Particularly, various synthetic pesticides and industrial chemicals that persist in the environment and/or bioaccumulate have been implicated. Further, it has been alleged that the standard tests for pesticide registration as required by the U.S. Environmental Protection Agency (EPA) and other regulatory agencies may be inadequate to detect endocrine modulating effects. To address these shortcomings, it has been proposed that very specific tests for estrogen receptor binding, or in vitro cell response to chemicals, be used to identify potential endocrine modulators. However, such approaches have certain flaws that limit their application as screens. First, very specific tests, like receptor binding, evaluate only a single chemical event per test. Such tests do not measure toxicity or biological response. Isolated systems are very important for studying mechanisms of action or structure activity relationships, but can only provide a preliminary screen for a single mechanism of toxicity. Isolated systems can not be used to regulate a chemical without additional information. Second, they fail to test many other parts of the neuroendocrine control of the reproductive system. Testing for adverse effects in highly specific in vitro systems failed to replace whole-animal models in carcinogenesis and will also fail in reproductive toxicology because this system is too complicated for such as in vitro approach to be accurately predictive. Advanced tests, such as the EPA multigeneration study, are more effective, and reliable means for evaluation than any specific and narrowly focused screening tests. Experience has shown that a better approach to testing chemicals is to evaluate their effects on the whole animal. When one part of the system is adversely affected, various processes may be indirectly affected and can be detected in the animal model. For example, a modulation of testosterone synthesis could lead to (1) altered accessory sex organ morphology, size, and function; (2) decreased sperm counts; and (3) even decreased fertility. These and many other effects would be noted in toxicity studies that are already required for the registration of crop protection chemicals. The developmental and reproductive toxicity guidelines were recently reviewed in a hearing that included the representatives from the EPA, the public, and the Scientific Advisory Panel. The EPA kept the basic study design the same, but added a few new endpoints to further assess chemical-induced effects on reproductive development and function. The review presented herein concentrates on the required Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) testing for pesticides, and demonstrates how the massive arrays of sensitive endocrine endpoints that are delineated in FIFRA Subdivision F have been successfully used to detect both weak and potent hormonally modulating chemicals. For example, (1) diethyl-stilbestrol (DES), which is a potent synthetic therapeutic estrogen, (2) DDT, which is weakly estrogenic but persistent and bioaccumulating, and (3) dioxins, which have antiestrogenic properties, were all found as being hormonally active in tests similar or identical to FIFRA tests. All food-use pesticides have been evaluated using a comprehensive multigeneration reproduction test. Hence, the FIFRA testing procedures have been demonstrated to identify endocrine modulators of sufficient potency to represent a concern to human health.

Microgravity is known to have a substantial effect on fluid homeostasis. The research described here was planned as part of the first joint Russian-U.S. science program carried out during a Shuttle flight. The aim of the program was to study the nature of the changes in fluid homeostasis induced by microgravity, as well as to determine the possible mechanisms underlying the regulation of fluid balance under conditions of spaceflight. To determine the effects of spaceflight on the homeostasis of fluid and electrolytes, measurements were taken of total body water, extracellular fluid plasma volumes, levels of regulatory hormones, and nutrient consumption before, during, and after a nine-day flight. Changes in renal function were studied before and after the flight. In these 2 subjects, weightlessness was not associated with a decreased extracellular fluid volume. However, there were the characteristic decreases in plasma atrial natriuretic peptide concentrations, and increases in plasma and urinary cortisol. Results indicated decreased urine volume, even through the first 48 hours of flight. Fluid volumes and glomerular filtration rate were increased after landing, probably related to the saline-loading countermeasure used by Shuttle crewmembers. The information obtained as a result of this research will facilitate the development of future research programs, as well as preventive measures for future long-duration spaceflights.

Hormonal imbalances in utero may render males more vulnerable to neurodevelopmental disorder (ND) than females. Since hormonal activity can be influenced by photoperiod, the relationship between season of conception and incidence of ND in offspring was examined within 11,578 mother/child pairs. Fall conception significantly elevated the odds for mental retardation, reading, arithmetic disability, or performance aptitude deficits (but not seizures, articulation disorder, cerebral palsy, or verbal aptitude deficits), and decreased the odds for reading talent (even when socioeconomic class, prenatal visits, infections, fever, vomiting, edema, anemia, and weight loss were covaried). Since the seasonality effect was not stronger in males, and was not specific to those NDs caused by left hemisphere dysfunction, the predictions of Geschwind and Galaburda (1985a, 1985b, 1985c) were not confirmed.

Objectives: The aim of this study was to determine the differences in neurohumoral responses between patients with pulmonary congestion with and without impaired left ventricular ejection fraction., Background: Previous studies have established the presence of neurohumoral activation in patients with congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to the impairment in systolic contractility., Methods: The 898 patients recruited into the Studies of Left Ventricular Dysfunction (SOLVD) Registry substudy were examined to identify those patients with pulmonary congestion on chest X-ray film who had either impaired (< or = 45%, group I) or preserved (> 45%, group II) left ventricular ejection fraction. Plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were measured in these two groups of patients and compared with values in matched control subjects., Results: Distribution of the New York Heart Association symptom classification was the same in the two groups of patients. Compared with control subjects, patients in group II with pulmonary congestion and preserved ejection fraction had no activation of the neurohumoral mechanisms, except for a small but statistically significant increase in arginine vasopressin and plasma renin activity. Compared with patients in group II, those in group I with pulmonary congestion and impaired ejection fraction had significant increases in plasma norepinephrine (p < 0.002), plasma renin activity (p < 0.02) and atrial natriuretic peptide levels (p < 0.0007). When we controlled for baseline differences between groups I and II, the between-group differences in plasma norepinephrine (p < 0.02) and atrial natriuretic peptide (p < 0.002) remained significant. However, plasma renin activity was not significantly different between groups I and II. When the effects of diuretic agents and angiotensin-converting enzyme inhibitors were adjusted, patients with lower ejection fraction were found to have significantly higher plasma norepinephrine and atrial natriuretic peptide levels., Conclusions: The results point to the importance of the decrease in left ventricular ejection fraction as one of the mechanisms for activation of neurohormones in patients with heart failure.

The rapid growth of the neurosciences in the past decade has served to blur the differences and enhance the similarities between research in medicine and in psychiatry. As the number of relevant biological variables and the questions asked in relation to them has expanded, so has the number of medical disorders of interest to the clinical researcher in psychiatry. In addition to these new areas of common interest, consultation-liaison psychiatry and clinical psychiatric research share a common conceptual foundation based upon model development and testing. It is proposed, therefore, that research at the interface between medicine and psychiatry represents a new frontier for both consultation-liaison psychiatry and clinical psychiatric research. Goals and strategies for research at the interface are discussed with specific reference to current research efforts at the National Institutes of Health.

Venous blood was drawn from the eight crewmembers of Space Shuttle flights STS-1 through STS-4 three times before lift-off and twice after landing, and the characteristics of biochemical blood components were evaluated. Twenty-four-hour urine pools were collected 30 d before flight and on landing day or day 4 after landing, and electrolytes, selected hormones and other components were measured. The results indicated that, although fluid and electrolyte loss occur during space flight, conservation of these substances is begun almost immediately upon cessation of weightlessness. Enzyme and hormone measurements indicated that landing may have caused some stress on crewmembers.

The major macronutrient associated with increased breast cancer risk is dietary fat. Evidence for this association is based on epidemiologic, clinical, and laboratory animal studies. In addition, there is suggestive epidemiologic evidence that differences in postmastectomy survival rates in Japan and the United States may be attributable to differences in dietary fat intake. The importance of the type of fat consumed, as well as its amount, has emerged as an issue of major importance. Some oils, including those rich in monounsaturates, medium chain fatty acids, or omega-3 (n-3) fatty acids appear to lack tumor-promoting effects despite their presence in the diet at high levels. Possible mechanisms by which dietary fat may exert its effects could be either direct or indirect. Direct mechanisms involve dietary modification of membrane structure and function; indirect mechanisms involve alterations in the endocrine system, and/or the metabolism of essential fatty acids to biologically active eicosanoids such as prostaglandins, and suppression of immune responses. Dietary guidelines and dietary intervention trials for the primary and secondary prevention of breast cancer are discussed.

Nine commonly performed radioligand analyses were studied for periods of four to seven years in terms of change in level of precision. Consistent improvement in precision is generally observed, except in specific instances when pool characteristics are altered to study sensitivity and crossreactivity.

During the period January, 1978 to June, 1979, a total of 900 college students was seen in a university student health center. Among these, 14.6% (131/900) had menstrual disorders. Oligomenorrhea or secondary amenorrhea, the chief complaint in 72.5% (95/131) students, accounted for 10.6% (95/900) of the total population. When a selected group of students with oligomenorrhea/amenorrhea was investigated, most had elevated levels of luteinizing hormone (LH) and normal/low levels of follicle-stimulating hormone (FSH) suggestive of polycystic ovary syndrome (PCO). The significance of these findings in the development of oligomenorrhea/amenorrhea and PCO under stress is discussed.

Epidemiologic data reveal that the incidence rate of prostate gland carcinoma among the black population in the United States (US) is several times higher than among Nigerians. A collaborative study between the two countries was undertaken, and blood hormone (testosterone [T], dihydrotestosterone [DHT], estrone [E1], estradiol [E2], and prolactin [P1]), total acid phosphatase (TP), and prostatic acid phosphatase (PAP) profiles in the two population groups were compared. In the US groups (patients and controls) there were significantly higher levels of T (P less than 0.01) and E1 (P less than 0.05) compared with the Nigerians. Also, the US patients had significantly higher levels of T (P less than 0.05) and E1 (P less than 0.01) compared with their matched controls. In the Nigerians T but not E1 levels were significantly lower (P less than 0.05) in patients compared with controls. DHT, E2, and P1 were not significantly different in patients and controls between and within the populations. Nigerian patients had higher levels (P less than 0.001) of TP and PAP compared with US patients. It is concluded that differences in blood hormone profiles in the two population groups are based on factors other than the genetic makeup of the populations.