Human urinary epidermal growth factor: effects of age, sex and pregnancy

Urinary concentrations of immunoreactive human epidermal growth factor (hEGF) were determined by specific homologous radioimmunoassay in 169 healthy men (aged 20-69 years), 275 healthy women (20-8 years). healthy women (20-68 years) and 413 pregnant women (20-39 years). Relative hEGF concentrations in urine (micrograms/g creatinine) decreased significantly in both sexes between 24 and 64 years of age. The relative concentrations of hEGF in urine were significantly higher in women than in men at ages 20-69 years. The mean values of relative urinary hEGF concentrations in pregnant women in their twenties and thirties (30.0 +/- 0.7 micrograms/g creatinine and 29.6 +/- 1.2 micrograms/g creatinine) were significantly higher than those in age-matched nonpregnant women (27.3 +/- 1.8 micrograms/g creatinine and 22.8 +/- 0.7 micrograms/g creatinine). Among the trimesters, it was highest in the 2nd trimester of women in the twenties and thirties (33.4 +/- 1.3 micrograms/g creatinine and 31.7 +/- 1.9 micrograms/g creatinine). The significance of the increased urinary excretion of hEGF (micrograms/g creatinine) in pregnancy is not known. Further studies are required to find a source of hEGF in urine and a possible relation between increased hEGF excretion and fetoplacental growth and development.     

Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians

The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16-75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16-30, 31-45, 46-60 and 61-75 years of age, comprising 20, 20, 15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study.     

Reference values for serum silicon in adults

Silicon is an essential nutrient of fundamental importance to human biology. It has been shown that silicon is required for bone, cartilage, and connective tissue formation. However, the assessment of silicon concentration is difficult as reference values are lacking. The aim of the present study was to establish reference values for apparently healthy individuals. Silicon concentrations were determined in serum of 1325 healthy subjects 18-91 years of age using atomic absorption spectrometry. Medians for serum silicon concentrations showed a statistically significant age and sex dependency. In men 18-59 years of age the median was 9.5 micromol/L and decreased to 8.5 micromol/L at 60-74 years of age. In women there was an increase in the median from age 18-29 years (10.00 micromol/L) to 30-44 years (11.10 micromol/L) followed by a decrease in the age group of 45-59 years (9.23 micromol/L). In subjects aged over 74 years the median serum silicon values were 7.70 micromol/L for men and 8.00 micromol/L for women. The most important findings in this study are the decrease of silicon and the course of the silicon concentrations with age, especially in women. The present study is an important prerequisite for studies that aim to identify the health effects and medical implications of silicon.     

Normative standards of plasma cholesterol and triglyceride concentrations in Canadians of working age.

Fasting plasma cholesterol and triglyceride concentrations were determined for 6407 working Canadian adults aged 20 to 69 years in Toronto and Hamilton. Means, medians and 5th and 95th percentiles were ascertained from the data for men, women taking oral contraceptives or estrogen preparations, and women not taking such medication. Mean plasma cholesterol values (mg/dL) ranged in men from 168.3 at ages 20 to 24 years to 211.5 at ages 45 to 49 years, and in women using hormone preparations from 180.3 at ages 20 to 24 years to 224.2 at ages 50 to 54 years; corresponding values in women not using these preparations were 164.9 and 220.6. Plasma triglyceride means (mg/dL) ranged in men from 108.7 at ages 20 to 24 years to 166.7 at ages 40 to 44 years, in women using hormone preparations from 115.4 at ages 20 to 24 years to 145.3 at ages 45 to 59 years, and in women not using these preparations from 77.5 at ages 20 to 24 years to 112.4 at ages 50 to 54 years.     

Age-related changes of vertebral bone mineral density in Russian population]

Vertebral trabecular bone mineral density (BMD) was measured by quantitative computed tomography (QCT) in 1061 subjects (610 females and 451 males aged from 7 to 91 and from 12 to 89, respectively) with known history of diseases or taking medicines affecting bone metabolism. Peak BMD values in our patients were observed at the age of 20-29 years with further gradual decrement in men and more steep in women. Negative relationship between BMD and age was r = -0.991 for men and r = -0.968 for women. Analyzing BMD changes by decades we observed the largest decrement in men after 60 (13.1% for 60-69 and 14.1% for 70-79 years of age) and in women after 50 (22.5% for 50-59, 22.1% for 60-69 and 20.8% for 70-79 years) which was most probably due to decline in sex hormones production that is known to significantly influence bone metabolism. This was confirmed by BMD values three-phase approximation in women showing the lowest rate of calcium loss by trabecular bone in reproductive period (1.9 mg/cm3/yr) and the highest in perimenopause (3.98 mg/cm3/yr). Annual calcium loss in postmenopause was 2.22 mg/cm3.     

Age-specific reference ranges for prostate-specific antigen among healthy Syrian men

Prostate-specific antigen (PSA) has become the most useful serum tumor marker in adjunct to digital rectal examination (DRE) for the management of prostate cancer (PC). The currently cited reference range of normal PSA levels (between 0 and 4.0 ng/mL) is deficient in terms of both sensitivity and specificity. Age-adjusted PSA have been proposed as an alternative to serum PSA. The primary objective of the present study is to determine the age-specific PSA and the percentage of free PSA (%FPSA) in healthy Syrian men. A total of 3,000 healthy Syrian men over 40 years old participated in this study. All men were asked to have total serum (TPSA) and free PSA (FPSA) tested, a DRE, and, when recommended, a prostate biopsy. Serum TPSA levels correlated with age (r=0.30, p<0.001). The 95th percentile TPSA values ranged from 1.7 ng/mL in the age group 40-49 years to 5.8 ng/mL in the group 70-80 years. The general pattern for medians and the percentile values for FPSA across age groups were similar to those seen for TPSA concentrations (r=0.37, p<0.001). However, the %FPSA was fairly constant across age groups except for the higher ratios in the youngest age group. These findings confirm that the serum TPSA and FPSA levels correlate with age. Interestingly, however, Syrian men have lower PSA values compared with other races. Racial differences of PSA concentrations were observed. Our results may help increasing the sensitivity and specificity of PSA measurements in the diagnosis of prostate cancer in Syria and probably in the surrounding regions.     

Validity of hamstring muscle length assessment during the sit-and-reach test using an inclinometer to measure hip joint angle

The aim of this study was twofold: (i) to describe the criterion-related validity of the sit-and-reach test (SRT) using a hand-held inclinometer when assessing hamstring muscle length (HML) when HML is recorded in degrees of hip joint angle (HJA); and (ii) to describe the effect of gender and age on HML in healthy adults during the performance of a SRT. We examined 212 healthy subjects (106 men and 106 women) whose ages ranged from 20 to 79 years. The Pearson-product moment correlation coefficient (r) described the relationship between HJA at the end-point of the SRT and the criterion, supine passive straight-leg raise (PSLR). We conducted a 6 x 2 analysis of variance, where age was stratified on 6 levels of 10-year increments (20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years of age) and gender was stratified on 2 levels (men and women). There was a statistically significant correlation (r = 0.59, P < 0.01) between performance on the SRT as measured by HJA and the supine PSLR, but the SRT only accounted for 35% of the variability in the PSLR. SRT performance in men (mean +/- SD, 80 +/- 9 degrees) was significantly less (P < 0.001) than in women (mean +/- SD, 92 +/- 10 degrees). Subjects in the 60- to 69- and 70- to 79-year age groups had significantly less (P < 0.05) HJA than those in the 20- to 29-, 30- to 39-, and 40- to 49-year age groups. Using an inclinometer to measure HJA during the SRT is not a valid method for assessing HML in men and women who can independently assume a long-sitting position on a hard surface. Clinicians should recognize there are differences in HML between men and women, and that men and women between 20 to 49 years of age have more HML than their counterparts between ages 60 to 79 years.     

Age diminishes the testicular steroidogenic response to repeated intravenous pulses of recombinant human LH during acute GnRH-receptor blockade in healthy men

Testosterone (Te) concentrations fall gradually in healthy aging men. Postulated mechanisms include relative failure of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and/or gonadal Te secretion. Available methods to test Leydig cell Te production include pharmacological stimulation with human chorionic gonadotropin (hCG). We reasoned that physiological lutropic signaling could be mimicked by pulsatile infusion of recombinant human (rh) LH during acute suppression of LH secretion. To this end, we studied eight young (ages 19-30 yr) and seven older (ages 61-73 yr) men in an experimental paradigm comprising 1) inhibition of overnight LH secretion with a potent selective GnRH-receptor antagonist (ganirelix, 2 mg sc), 2) intravenous infusion of consecutive pulses of rh LH (50 IU every 2 h), and 3) chemiluminometric assay of LH and Te concentrations sampled every 10 min for 26 h. Statistical analyses revealed that 1) ganirelix suppressed LH and Te equally (> 75% median inhibition) in young and older men, 2) infused LH pulse profiles did not differ by age, and 3) successive intravenous pulses of rh LH increased concentrations of free Te (ng/dl) to 4.6 +/- 0.38 (young) and 2.1 +/- 0.14 (older; P < 0.001) and bioavailable Te (ng/dl) to 337 +/- 20 (young) and 209 +/- 16 (older; P = 0.002). Thus controlled pulsatile rh LH drive that emulates physiological LH pulses unmasks significant impairment of short-term Leydig cell steroidogenesis in aging men. Whether more prolonged pulsatile LH stimulation would normalize this inferred defect is unknown.     

Urinary steroid concentrations during natural and gonadotrophin-induced oestrus and pregnancy in the giant panda (Ailuropoda melanoleuca)

Urinary concentrations of conjugated oestrone and pregnanediol-3-glucuronide were measured during and after spontaneous and induced oestrus and during pregnancy. Behavioural oestrus was preceded by a rise in oestrone values from less than 10 ng/mg creatinine (Cr) to peaks of 45 ng/mg Cr. Maximal lordotic response and mating activity coincided with the decline in oestrone levels. After presumed ovulation, urinary pregnanediol glucuronide concentrations increased from less than 5 to 15-30 ng/mg Cr. Further increases in this steroid (to 60-80 ng/mg Cr) occurred 114 days after mating, presumably coincident with implantation. These high levels of pregnanediol glucuronide were maintained for 3 weeks, began to decline 1 week before parturition and fell to a nadir (less than 5 ng/mg Cr) immediately after delivery. When FSH was administered i.m. for 5 days, urinary oestrone values rose markedly and were maximal (580 ng/mg Cr) on Day 7. Mating first occurred on Day 20 and 500 i.u. hCG were given i.m. Urinary pregnanediol glucuronide levels during the next 5 months were similar to those in the previous year during pregnancy with values rising 105-108 days after mating. However, no birth occurred. These results support the suggestion that pandas exhibit delayed implantation and demonstrate that the panda is responsive to exogenous gonadotrophins.     

Sex-specific HDL cholesterol changes with weight loss and their association with anthropometric variables: the LIFE study

Decrease in the level of high-density lipoprotein cholesterol (HDLC) has been observed in women who start dieting, but not in men. Patterns of HDLC change during intentional weight loss through 30-months of follow-up, and their association with changes in anthropometric measurements were examined in obese women (N = 112) and men (N = 100). Missing HDLC values at 6-, 12-, 18-, and 30-month follow-up (N = 16, 34, 55, and 50, respectively) due to dropout were imputed by multiple imputation. Mean ages and BMIs of subjects at baseline were 47.2 years and 34.8 kg/m(2) for women, and 50.4 years and 35.0 kg/m(2) for men. On average, participants lost weight steadily for 12 months, followed by slow regain. During the first 6 months, HDLC decreased significantly in women (-4.1 mg/dl, P = 0.0007), but not in men. Significant HDLC increases were observed in both men and women from 6- to 12-month follow-up. HDLC changes in women were positively associated with changes in hip circumference from baseline to 12-month independent of changes in triglycerides (TG), glucose, and insulin. Rapid decrease of predominantly subcutaneous fat in the femoral and gluteal area might be associated with HDLC decrease in women during initial weight loss.     

High levels of urinary vascular endothelial growth factor in women with severe preeclampsia

Elevated plasma VEGF concentrations in preeclampsia are associated with local placental ischemia and endothelial dysfunction. We investigated the urinary VEGF excretion in women with severe preeclampsia (n=37) and its relation with proteinuria compared to that in healthy pregnant (n=32) and non-pregnant women (n=30). In women with severe preeclampsia VEGF levels were 54.0 (19.9-192.4) ng/mmol creatinine, significantly (p<0.0001) higher than levels in pregnant controls (28.2 (6.7-63.0) ng/mmol creatinine) and non-pregnant controls (29.5 (10.1-59.1) ng/mmol creatinine). Proteinuria was not significantly correlated with urinary VEGF levels. In conclusion, high urinary VEGF concentrations in severe preeclampsia might reflect increased renal production of VEGF rather than elevated VEGF levels in the systemic circulation.     

Age-related differences in lactate distribution kinetics following maximal exercise.

Lactate concentrations were determined at 3, 5, and 7 min of recovery following maximal, continuous, multi-stage treadmill work in 180 men, aged 20-80 years, who were participants of the Baltimore Longitudinal Study of Aging. Each subject was placed into one of six age groups, e.g., 20-29, 30-39, etc. As expected, average concentrations decreased consistently with age. All three sampling times were similar in characterizing maximal lactates for the youngest men. For each older group, except for the oldest, the later values were significantly (p less than 0.01) higher than the 3-min values. For subjects in their 50's and 60's mean concentrations continued to rise through the 7th min. These data suggest that in man there is a progressive, age-related diminution of ability to diffuse lactate from muscle and/or distribute it into its space. This may result in decreased endurance and work capacity and a prolongation of recovery. As an alternative to multiple sampling and analyses for maximal lactate, single blood samples should be obtained no sooner than 5 min of recovery for men up to age 50, and at 7 min for those between 50 and 70 years. Variability among the men over 70 years of age was large enough to preclude single-sample alternatives.     

Maximal oxygen uptake of agricultural men and women in India

The maximal oxygen uptake (VO2 max) of 228 men and 47 women from the Indian agricultural community was measured. The VO2 max in 20-24-year-old men was about 17% less than in the 25-29-year-old group. With advancing age, the VO2 declined gradually to the ages 55-59, excepting the 36-39-year-old group. The loss in VO2 max was 0.65 ml/kg.min per year between 25 and 39 years of age and 0.16 ml/kg.min per year between 40 and 59 years of age. However, 30-39-year-old women had 7% higher VO2 max than the 20-29-year-old age group; and the difference in VO2 max between the group 30-39 and the group 40-49 years of age was 32%. The 20-29-and 40-49-year-old women had VO2 max 24 and 30% less than those of men in the same age range.     

High-performance liquid chromatographic determination of glyoxal and methylglyoxal in urine by prederivatization to lumazinic rings using in serial fast scan fluorimetric and diode array detectors

Glyoxal and methylglyoxal are two important markers of oxidative stress and both are involved in the evaluation of several diseases. A new HPLC method for determining glyoxal and methylglyoxal in urine was developed. The method is based on the reaction of alpha-dialdehydes, glyoxal and methylglyoxal, with 5,6-diamino-2,4-hydroxypyrimidine sulfate in basic medium to form highly fluorescent lumazine derivatives. Creatinine was also included in the method even though it does not react with the reagent. The derivatives and creatinine are separated on a C(18) reversed-phase column with a mobile phase consisting of acetonitrile:citrate buffer, pH 6.0 (3:97 v/v). The flow rate was 1.0mLmin(-1) and the effluent was monitored photometrically at 250 nm for determination of creatinine and fluorimetrically at 500 nm (exciting at 330 nm) for determination of glyoxal and methylglyoxal derivatives. Recording time of the separation is less than 10 min. Determination of the analytes is performed in urine after incubation of the sample, with the reagent in alkaline medium, for 30 min at 60 degrees C. Urinary levels of glyoxal and methylglyoxal, expressed as glyoxal/creatinine and methylglyoxal/creatinine ratios, in healthy young women and men were determined. For women, values of 0.80+/-0.37 and 0.60+/-0.22 microg/mg of creatinine were found for glyoxal and methylglyoxal, respectively. For men, values of 0.63+/-0.15 and 0.49+/-0.05 microg/mg of creatinine were found for glyoxal and methylglyoxal, respectively. These results were also related to the body mass index of each individual.     

Variable sensitivity to the glucocorticoid activity of cortisol in patients with primary adrenal insufficiency: assessment with ACTH profiles

Our aim was to investigate the usefulness of circulating levels of adrenocorticotropic hormone (ACTH) and also salivary cortisol to monitor cortisone substitution in patients with Addison's disease. 13 patients with primary adrenal insufficiency (8 women and 5 men, age 44 ± 11 years) received 12.5 mg cortisone acetate orally at 16:00 h and 25 mg at 07:00 h. Blood samples for cortisol and ACTH analysis were drawn every hour for 24 h, and also every half hour between 07:00 and 12:00 h. Samples for salivary cortisol were collected in parallel. Total ACTH levels showed large inter-individual variations and a diurnal rhythm with a nadir in the early evening at 19:00 (median 19 ng/l, range 2-434 ng/l) and high levels in the early morning, with a peak around 07:30 (median 844 ng/l, range 45-2,249 ng/l). Plasma cortisol concentrations showed 2 peaks distinct in time, but variable in height, 1-2 h after intake of cortisone. Plasma cortisol correlated significantly with ln(ACTH) at 17:00 h (r=-0.56), at 10:00 h (r=-0.51), and at 10.30 h (r=-0.57). When tested at different time points, ln(ACTH) at 10:00 to 12:00 h was negatively correlated with plasma cortisol between 08:30 and 12:00 h. Plasma cortisol was highly correlated to ln(salivary cortisol) most of the time points measured, but 30-60 min after intake of cortisone acetate the correlation disappeared. In conclusion, the large interindividual variation in ACTH levels most likely indicates varying sensitivity to cortisol with a need for individualized dosing schemes. Furthermore ACTH-determinations may be useful for dose titration of cortisol.     

Haematological profile in healthy urban population (8 to 70 years of age)

Haematological profile for 17 constituents of blood were determined in 998 healthy school children (8-19 years old) and 2246 healthy adult persons (20-70 years old) residing permanently or at least 5 years in a defined geographic region of Zagreb, Croatia. Physiological variations corresponding to age and sex were studied as the most important factors affecting biological variation in haematological constituents of blood. In our study erythrocytes, haemoglobin and haematocrit values were not sex dependent until the age of 13 after which the values were higher in men that in women. Sedimentation rate showed sex and age related differences in the adult age with higher values in women especially after 50 years. Total leukocyte count declined with age and in adults the values were slightly lower in women. Segmented neutrophil granulocytes showed the upward trend with age whereas the lymphocyte and monocyte counts declined. Women showed slightly higher platelet count in the adult age. Based on biological variation, we have estimated the reference intervals for 17 haematological constituents of blood in order to provide medically reliable evaluation of haematological laboratory results.     

Reference Values for Serum Magnesium Levels in Young Adult Iranian Subjects

This study aims at determining the reference values for serum magnesium (Mg) concentrations in Iranian adults. Serum Mg level was measured using flame atomic absorption spectrometry in 491 subjects (233 men and 258 women), aged 20-50 years, randomly selected from a population-based study. The International Federation of Clinical Chemistry guidelines and the robust method were used for determining the reference values. The 95% reference values for serum Mg concentration were 1.83-2.49, 1.79-2.48, and 1.83-2.55 mg/dL in men, women, and total population, respectively. The prevalences of hypo- and hypermagnesemia, according to the reference values obtained in the current study, were 2.5% and 4.0%, respectively. In conclusion, this study reports serum Mg reference values based on current standards in a large healthy population of young Iranian adults.     

Determination of urinary 8-epi-prostaglandin F(2alpha) using liquid chromatography-tandem mass spectrometry: increased excretion in diabetics

Liquid chromatography-tandem mass spectrometry (LC/MS-MS) was applied to the quantitative analysis of urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) level. 8-Epi-PGF(2alpha) and its internal standard, [(2)H(4)]-8-epi-PGF(2alpha), were extracted from urine by using a solid phase extraction cartridge and loaded to LC/MS-MS in selected reaction monitoring (SRM) mode. The standard curve showed good linearity in the range of 40 pg to 10 ng (r = 0. 997). The accuracy of the added 8-epi-PGF(2alpha) ranged from 96.8 to 104.9% with a mean +/- SD of 99.5+/-2.5%. The average level +/- SD of urinary 8-epi-PGF(2alpha) in 13 healthy volunteers (five women and eight men, 31+/-7.4 years old) was 429.4+/-149.6 pg/mg creatinine. The level of seven patients with noninsulin dependent diabetes mellitus (two women and five men, 40+/-13.6 years old), 630.9+/-275.6 pg/mg creatinine, was statistically higher than that of healthy volunteers (P<0.05). This finding suggested that diabetics are in a highly oxidative condition. This simple and rapid LC/MS-MS method can be used to elucidate the pathophysiological feature of diabetes or for monitoring the curative effect.     

Correlates of pentraxin 3 serum concentration in men and women with type 2 diabetes

Elevated levels of plasma pentraxin 3 (PTX3), a marker of inflammation, are associated with the risk of developing cardiovascular diseases in the general population, as well as in patients with type 2 diabetes (DM2). In this study, we aimed to determine factors associated with PTX3 serum concentrations in men and women with DM2. The study included 116 consecutive patients (67 men and 49 women) with DM2 from an outpatient diabetic clinic. Men were characterised by lower age and higher uric acid, creatinine and bilirubin concentrations and waist/hip ratio than women. In women, low-density lipoprotein cholesterol (LDL-C) levels were higher than in men. In men, median (interquartile range) values of PTX3 concentration were 4.02 (1.99), and in women they were 4.53 (3.31) ng/ml (NS). In men, PTX3 concentrations correlated with total cholesterol (TC), triglycerides, apolipoprotein (Apo) C3, Apo B48, Glc and creatinine levels. In women, PTX3 correlated significantly with TC and LDL-C and Apo B100. Partial regression analysis revealed that after adjusting for age, PTX3 concentrations in men were significantly associated with TC, LDL-C, triglycerides, creatinine, Apo C3 and Apo B48, while in women they were associated with TC, LDL-C and Apo B100. The results could be of importance in sex-specific prevention of vascular complications in DM2 patients.     

Differential gender responses to hypoglycemia are due to alterations in CNS drive and not glycemic thresholds

The aims of this study were 1) to determine whether differential glycemic thresholds are the mechanism responsible for the sexual dimorphism present in neuroendocrine responses during hypoglycemia and 2) to define the differences in counterregulatory physiological responses that occur over a range of mild to moderate hypoglycemia in healthy men and women. Fifteen (8 male, 7 female) lean healthy adults underwent four separate randomized 2-h hyperinsulinemic (1.5 mU. kg(-1).min(-1)) glucose clamp studies at euglycemia (90 mg/dl) or hypoglycemia of 70, 60, or 50 mg/dl. Plasma insulin levels were similar during euglycemic and hypoglycemic studies (91-96 +/- 8 microU/ml) in men and women. Hypoglycemia of 70, 60, and 50 mg/dl all resulted in significant increases (P < 0.05, P < 0.01) in epinephrine, glucagon, growth hormone, cortisol, and pancreatic polypeptide levels compared with euglycemic studies in men and women. Plasma norepinephrine levels were increased (P < 0.05) only relative to euglycemic studies at a hypoglycemia of 50 mg/dl. Muscle sympathetic nerve activity (MSNA) increased significantly during hyperinsulinemic-euglycemic control studies. Further elevations of MSNA did not occur until hypoglycemia of 60 mg/dl in both men and women. Plasma epinephrine, glucagon, growth hormone, and pancreatic polypeptide were significantly increased in men compared with women during hypoglycemia of 70, 60, and 50 mg/dl. MSNA, heart rate, and systolic blood pressure responses were also significantly increased in men at hypoglycemia of 60 and 50 mg/dl. In summary, these studies have demonstrated that, in healthy men and women, the glycemic thresholds for activation of epinephrine, glucagon, growth hormone, cortisol, and pancreatic polypeptide occur between 70 and 79 mg/dl. Thresholds for activation of MSNA occur between 60 and 69 mg/dl, whereas norepinephrine is not activated until glycemia is between 50 and 59 mg/dl. We conclude that 1) differential glycemic thresholds are not the cause of the sexual dimorphism present in counterregulatory responses to hypoglycemia; 2) reduced central nervous system efferent input appears to be the mechanism responsible for lowered neuroendocrine responses to hypoglycemia in women; and 3) physiological counterregulatory responses (neuroendocrine, cardiovascular, and autonomic nervous system) are reduced across a broad range of hypoglycemia in healthy women compared with healthy men.