Extent In Men Research Articles

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women.

Platelet Inhibition by Aspirin 81 and 325 mg/day in Men Versus Women Without Clinically Apparent Cardiovascular Disease

Compared with men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to that in men. Our objective was to compare inhibition of platelet aggregation in women and men after low- and high-dose aspirin. We enrolled healthy subjects (n=106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and after the 2 aspirin doses. Women had greater baseline platelet activation measurements. After the 2 aspirin doses, men and women had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclo-oxygenase-1 pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after the 2 aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared with men after aspirin 81 mg/day in response to collagen (p=0.016 in whole blood, p=0.037 in PRP), ADP (p<0.001 in whole blood, p=0.012 in PRP), and epinephrine (p=0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydrothromboxane B2) decreased after aspirin to a similar extent in men and women. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin compared with men treated with a lower dose of aspirin.

Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period

We sought to determine whether lipolysis, fatty acid (FA) mobilization, and plasma FA oxidation would remain elevated for hours following isoenergetic exercise bouts of different intensities. Ten men and eight women received a primed-continuous infusion of [1,1,2,3,3-(2)H(5)]glycerol and continuous infusion of [1-(13)C]palmitate to measure glycerol and plasma FA kinetics. On Day 1 (D1), participants were studied under one of three different conditions, assigned in random order: (1) before, during and 3 h after 90 min of exercise at 45% V(O2)peak (E45), (2) before, during and 3 h after 60 min of exercise at 65% V(O2)peak (E65), and (3) in a time-matched sedentary control trial (C). For each condition, participants were studied by indirect calorimetry the following morning as well (D2). Rate of appearance (Ra) of glycerol (Ra(GL)) increased above C during exercise in men and women (P < 0.05), was higher in E45 than E65 in men (P < 0.05), and was not different between exercise intensities in women. During 3 h of postexercise recovery, Ra(GL) remained significantly elevated in men (P < 0.05), but not women. FA Ra (Ra(FA)) increased during exercise in men and women and was higher in E45 than E65 (P < 0.05), and remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05), but with a greater relative increase in men than women (P < 0.05). Plasma FA oxidation (Rox) increased during exercise with no difference between intensities, and it remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05). Total lipid oxidation (Lox) was elevated in both sexes (P < 0.05), but more in men during 3 h of postexercise recovery on D1 (P < 0.05) and remained elevated on D2 in men (P < 0.05), but not in women. There were no differences between E45 and E65 for postexercise energy substrate turnover or oxidation in men and women as energy expenditure of exercise (EEE) was matched between bouts. We conclude that the impact of exercise upon lipid metabolism persists into recovery, but that women depend more on lipid during exercise whereas, during recovery, lipid metabolism is accentuated to a greater extent in men.

Revisiting the effect of posture on high-intensity constant-load cycling performance in men and women

It was recently observed that inclining the body from a supine to upright position improved the performance of high-intensity, constant-load cycling to a larger extent in men than women (Egaña et al. in Eur J Appl Physiol 96:1-9, 2006), although this gender-related effect was based on a small number of men (n = 5) and women (n = 5). To explore this effect further, we studied the effect of body tilt on cycling performance in a larger and different group of men (n = 8) and women (n = 18). Peak power, peak VO2 and the ventilatory threshold (VT) were determined during an upright maximal graded cycle test, and a high-intensity test (80% peak power) was performed to failure in both the upright and supine positions. Performance was significantly longer in the upright compared with supine position in men (17.4 +/- 7.7 vs. 7.6 +/- 3.4 min) and women (14.1 +/- 6.0 vs. 6.0 +/- 3.7 min). The magnitude of this postural effect was not significantly different between men and women; whereas it was significantly correlated with the relative intensity of exercise expressed as a function of VT (r = -0.39). These data demonstrate that the postural effect on high-intensity cycling performance is not influenced by gender; but that it is related to the intensity of exercise relative to the ventilatory threshold.

Medication-Induced Weight Gain and Dyslipidemia in Patients With Schizophrenia

Our friend and colleague Wayne Fenton asked to write this article for the Journal because of his desire to educate other psychiatrists about the treatment of schizophrenia, including what he recognized to be a growing problem with the metabolic syndrome. This lifelong passion, which he pursued from his psychiatry residency at Yale, through his directorship of Chestnut Lodge, to his position at NIMH as Director of the Division of Adult Translational Research and Associate Director for Clinical Affairs, ended tragically with his killing during an evaluation of a psychotic young man. Wayne had worked tirelessly to secure support for new drug discovery in the NIMH programs that he directed. The Journal will be initiating in 2007 a series of articles on the discovery of new mental illness treatments. We will dedicate this series to Wayne's memory and include with it a memorial of his life and contributions to the treatment of mental illness.

The impact of family history of diabetes and lifestyle factors on abnormal glucose regulation in middle-aged Swedish men and women

We investigated associations between abnormal glucose regulation and family history of diabetes, separately and in combination with lifestyle risk factors. This cross-sectional study comprised 3,128 men and 4,821 women, aged 35-56 years, half with a family history of diabetes. Oral glucose tolerance testing identified subjects with previously undiagnosed prediabetes (IFG, IGT) and type 2 diabetes. Information on lifestyle factors was obtained by questionnaire. Biological interaction was measured with the synergy index. A family history of diabetes conferred a higher odds ratio (OR) for type 2 diabetes in men (OR=3.1, 95% CI 1.7-5.6) than in women (OR=1.7, 95% CI 1.0-3.0), and the synergy index was 2.8 (95% CI 0.9-9.0), suggesting interaction between a family history of diabetes and sex. For prediabetes and diabetes combined, the synergy index was 1.7 (1.0-2.8). Exposure to only one lifestyle risk factor (obesity, physical inactivity, smoking or low sense of coherence [a psychosocial index]) increased the risk to a similar extent in men and women. Combined exposure to a family history of diabetes and lifestyle-related risk factors had a greater effect on type 2 diabetes than any of these factors alone, especially in men. However, analysis of interaction between a family history of diabetes and the lifestyle factors did not indicate any interaction for diabetes, but did indicate interaction for a family history of diabetes and obesity in women with prediabetes. Our data suggest a more pronounced effect of a family history of diabetes on the risk of type 2 diabetes in men than in women. While both a family history of diabetes and lifestyle risk factors had effects on type 2 diabetes, irrespective of sex, these effects did not appear to interact.

The Anti-Ischemic Effect of Metoprolol in Patients with Chronic Angina Pectoris Is Gender-Specific

Several gender-specific differences in cardiovascular diseases are known and pharmacokinetics of β-blockers shows relevant sex-specific differences. The plasma levels of metoprolol, for example, are higher in women compared to men. However, randomized studies have shown that metoprolol has little or no greater reduction in the mortality of women following myocardial infarction. We tested the hypothesis that metoprolol might have significant gender-specific effects in patients with chronic angina pectoris. Body weight of women was slightly (–9%) less than that of men and the daily dose of metoprolol was similar in both groups. Thus, according to pharmacokinetics women should have obtained higher plasma levels of this drug and the ensuing pharmacologic effects of metoprolol should have been greater. Our results do not confirm this assumption. Metoprolol reduced the frequency of angina episodes and the consumption of nitroglycerin tablets to a similar extent in both sexes. However, the pretreatment hemodynamic profiles confirmed the existence of gender-specific differences: women had significantly higher heart rate and blood pressure both at rest and during exercise. Since both groups were comparable in age, comorbidities, and medications, the existing difference is likely to be due to gender-specificity. The hemodynamic differences persisted during therapy with metoprolol: resting heart rate, blood pressure and rate pressure product were reduced to a greater extent in men. During cycloergometry, there was a slight difference in the time of onset of ST depression and time of onset of angina, which were slightly higher in men, but probably because of the limited number of cases, the difference between men and women did not reach significance. On the other hand, with metoprolol the duration of exercise and, in parallel, the number of metabolic equivalents was significantly greater in males than in females. Thus in spite of a presumed greater plasma concentration of metoprolol in women, we found a significant difference in anti-ischemic effect in favor of men. We conclude that metoprolol might exert a significantly greater therapeutic effect on stress-induced angina pectoris in men than in women and this difference should be taken into account when prescribing this β-blocker.

Muscle AMPKα2 activity, acidosis, and protein synthesis in men and women following resistance exercise

Basal muscle protein synthesis is not different between men and women. Skeletal muscle AMP-activated protein kinase (AMPKα2) and acidosis have recently been identified as inhibitors of muscle protein synthesis. The purpose of this study was to determine if there were sex-based differences in muscle AMPKα2 activity, acidosis, and protein synthesis in young men and women following a bout of resistance exercise. We report preliminary data obtained in young subjects (4M, 4F) before and after a bout of resistance exercise. Muscle biopsies were collected from the v. lateralis prior to, immediately post exercise, and at 1hr and 2 hr post exercise. We utilized immunoprecipitation methods to measure AMPKα2 activity. Fractional protein synthetic rate was measured using stable isotope techniques. AMPKα2 activity was not different between men and women at any timepoint (P > 0.05). AMPKα2 activity increased by (25 ± 10 %) immediately post exercise, remained elevated at 1hr (33 ± 13%) and 2hr (33 ± 11%) post exercise (P < 0.05). Femoral vein lactate increased to a similar extent in men (0.8 ± 0.2 to 11.9 ± 1.5 mM) and women (0.7 ± 0.1 to 10.1 ± 0.5 mM) during the resistance exercise bout. Blood pH also decreased during exercise (P > 0.05). Lactate and pH returned to baseline similarly in men and women during post exercise recovery (P < 0.05). Muscle protein synthesis was unchanged from baseline following resistance exercise with no sex-based differences (P > 0.05). We conclude that there are no sex-based differences in muscle AMPKα2 activity, acidosis or protein synthesis immediately following a bout of resistance exercise.

Body mass index and waist circumference correlate to the same degree with insulin-mediated glucose uptake

To compare the relationship between insulin-mediated glucose uptake (IMGU) and excess adiposity as determined by measurement of either body mass index (BMI) or waist circumference (WC), IMGU was quantified by determining the steady-state plasma glucose (SSPG) concentration with the insulin suppression test and the relationship between the SSPG concentration and BMI or WC evaluated in a study of 208 healthy individuals (128 women/80 men). The results indicated that BMI and WC were correlated ( P < .001) to a similar degree in both men ( r = 0.90) and women ( r = 0.86). Steady-state plasma glucose and both indices of excess adiposity were also significantly correlated ( P < .001) to an essentially identical extent in men ( r values of 0.71 vs 0.70) and women ( r values of 0.54 vs 0.53). When the population was divided into tertiles on the basis of SSPG concentrations, 96% of those in the most insulin-resistant tertile were identified as being overweight/obese by BMI criteria and 84% as abdominally obese by WC criteria. However, a substantial number of those in the most insulin-sensitive tertile also demonstrated excess adiposity as defined by either BMI (45%) or WC (33%). To summarize, (1) BMI and WC correlate closely within an individual and equally well with IMGU, and (2) BMI is as effective as WC in identifying insulin-resistant individuals.

Advancing Global-and Continental-Scale Hydrometeorology: Contributions of GEWEX Hydrometeorology Panel

Over the past 9 years, the Global Energy and Water Cycle Experiment (GEWEX), under the auspices of the World Climate Research Programme (WCRP), has coordinated the activities of the Continental Scale Experiments (CSEs) and other related research through the GEWEX Hydrometeorology Panel (GHP). The GHP contributes to the WCRP'S objective of “developing the fundamental scientific understanding of the physical climate system and climate processes [that is] needed to determine to what extent climate can be predicted and the extent of man's influence on climate.” It also contributes to more specific GEWEX objectives, such as determining the hydrological cycle and energy fluxes, modeling the global hydrological cycle and its impacts, developing a capability to predict variations in global and regional hydrological processes, and fostering the development of observing techniques, data management and assimilation systems. GHP activities include diagnosis, simulation, and experimental prediction of regional water balances and process and modeling studies aimed at understanding and predicting the variability of the global water cycle, with an emphasis on regional coupled land–atmosphere processes. GHP efforts are central to providing a scientific basis for assessing critical science issues, such as the consequences of climate change for the intensification of the global hydrological cycle and its potential impacts on regional water resources. This article provides an overview of the role and evolution of the GHP and describes scientific issues that the GHP is seeking to address in collaboration with the international science community.

Older Men's Social Participation: The Importance of Masculinity Ideology

The central question was, independent of marital status and health, is the satisfaction that older men derive from their social networks linked to gender ideology? Based on the 135 older men within a larger study of community-based older adults, findings show that masculinity ideology is inversely related to the size of networks and the extent of men's social participation; however, endorsing the traditional masculinity ideology is directly associated with the satisfaction men derived from their social participation. Older men who believe in the traditional masculinity script felt satisfied in their relationships, whereas men who reject this ideology and reported a greater need to discuss private feelings had developed larger networks and increased their involvement in their networks during the year between the T1 and T2 interviews. Discussed in the context of covert and face-to-face intimacy pursuits, abiding by the cultural of hegemony masculinity seems to yield less interaction but greater satisfaction among older men.

Dexamethasone-induced insulin resistance shows no gender difference in healthy humans

Recent reports suggest that lipid-induced insulin resistance is more pronounced in men than in women. Whether such gender difference exists for other factors known to induce insulin resistance in healthy individuals remains unknown. We therefore assessed whether glucocorticoid-induced insulin resistance differs in men and women. The insulin sensitivity and insulin secretion of 8 women and 7 men, all non obese and healthy, were evaluated with or without administration of dexamethasone (2 mg/day during 2 days) by means of a two-step hyperglycemic clamp. Dexamethasone decreased insulin sensitivity to the same extent in men and women. The relative increases in insulin concentration observed after dexamethasone in the basal state, during the first phase of insulin release and at the two steps of hyperglycemia were similar in men and women. The hyperinsulinemia thus attained allowed to fully compensate for insulin resistance in both genders. The effects of glucocorticoids on insulin sensitivity and insulin secretion show no gender difference in healthy humans.

Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women.

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 +/- 0.82 vs. women, 4.70 +/- 0.77 l x min(-1) x Torr(-1); 150 Torr: men, 4.33 +/- 1.15 vs. women, 3.21 +/- 0.58 l x min(-1) x Torr(-1)). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 +/- 1.40 vs. women, 5.97 +/- 0.71 l x min(-1) x Torr(-1); 150 Torr: men, 5.73 +/- 0.81 vs. women, 3.83 +/- 0.56 l x min(-1) x Torr(-1)). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.

Men with acromegaly need higher doses of octreotide than women.

To investigate the effect of gender on the response of GH to short-acting octreotide in patients with acromegaly, and on the GH and IGF-1 levels during long-term treatment with a slow-release formulation of octreotide. Twenty-one men (mean age 54 years; range 26-78) and 15 women (mean age 54 years; range 22-74) with acromegaly were treated with subcutaneous injections of 100 microg short-acting octreotide twice daily. Serum samples for GH were taken before start of treatment, in the morning prior to the injection, and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range 34-78) and 12 women (mean age 64 years; range 28-81) with acromegaly were switched from ongoing treatment with short-acting octreotide to injections of the slow-release formulation. A 4-h GH-profile and morning IGF-1 were taken at start and after 3, 9, 15 and 21 months of treatment. Subcutaneous injections of 100 microg octreotide reduced the mean level of GH during a 7-h period to a similar extent in men and women compared to the GH levels prior to the injections. During long-term treatment with similar doses of the depot formulation of octreotide, the mean IGF-1 level remained significantly higher in the men than in the women, whereas there were no differences in the mean GH levels between the two groups. The responses to short- and long-acting octreotide illustrate an effect of gender, due to different sensitivity to GH in the periphery. Furthermore, the results show that in the treatment of acromegaly, men will need higher doses of octreotide than women to normalize IGF-1.

Sexual dimorphism in counterregulatory responses to hypoglycemia after antecedent exercise.

After antecedent hypoglycemia, counterregulatory responses to subsequent hypoglycemia exhibit greater blunting in men than in women. Because physical exercise and hypoglycemia share multiple counterregulatory mechanisms, we hypothesized that prior exercise may also result in gender-specific blunting of counterregulatory responses to subsequent hypoglycemia. Thirty healthy subjects (15 women and 15 men; age, 28 +/- 3 yr; body mass index, 23 +/- 1 kg/m2) were studied during 2-d experiments. Day 1 consisted of either identical 90-min morning and afternoon cycle exercise at 50% maximum oxygen expenditure or two 2-h episodes of hyperinsulinemic euglycemia. Day 2 consisted of a 2-h morning hyperinsulinemic-hypoglycemic clamp. Endogenous glucose production was measured using [3-(3)H]glucose. Muscle sympathetic nerve activity was measured using microneurography. Day 2 insulin (540 +/- 36 pmol/liter) and plasma glucose (2.9 +/- 0.06 pmol/liter) levels were similar in men and women during the last 30 min of hypoglycemia. Compared with antecedent euglycemia, d 1 exercise produced significant blunting of d 2 counterregulatory responses to hypoglycemia. Several key d 2 counterregulatory responses were blunted to a greater extent in men than in women: glucagon (men, -105 +/- 14; women, -25 +/- 7 ng/liter; P < 0.0001), epinephrine (men, -2625 +/- 257 pmol/liter; women, -212 +/- 573; P < 0.001), norepinephrine (men, -0.50 +/- 0.12 nmol/liter; women, -0 +/- 0.11; P < 0.001), and muscle sympathetic nerve activity (men, -13 +/- 4; women, -4 +/- 4 bursts/min; P < 0.01). Cardiovascular responses (heart rate and systolic and mean arterial blood pressures) were also more blunted by antecedent exercise in men than in women. After d 1 exercise, the amount of glucose infused during d 2 hypoglycemia in men was increased 6-fold compared with that after d 1 euglycemia. This amount was significantly increased (P < 0.01) compared with the 2-fold (P < 0.01) increment in glucose infusion that was required in women after d 1 exercise. Lipolysis was unaffected by d 1 exercise in women, but was significantly blunted during d 2 hypoglycemia in men. In summary, two bouts of prolonged, moderate exercise (90 min at 50% maximum oxygen expenditure) induced a marked sexual dimorphism in key neuroendocrine (glucagon, catecholamines, and muscle sympathetic nerve activity) and metabolic (glucose kinetic, lipolysis) responses to next day hypoglycemia.

Association of plasma viscosity and carotid thickening in a French working cohort

Plasma viscosity and intima-media thickness (IMT) are frequently associated with cardiovascular disease and its risk factors. We evaluated the association of rheologic and vascular factors in asymptomatic subjects. Plasma viscosity (coaxial cylinder viscometry) and both preintrusive and intrusive atherosclerosis in the carotid arteries (ultrasonography) were investigated in 246 men and 337 women aged 17 to 65 years from the AXA study, a prospective cohort of healthy workers. Plasma viscosity was positively related to age-adjusted mean bifurcation carotid artery IMT ( P < .01 for men; P < .04 for women) and maximum carotid artery IMT ( P < .01 for men; P < .02 for women), but not to mean common carotid artery IMT. Multivariate adjustment affected these relations to a greater extent in men than in women. The odds ratio (range) of having intrusive atherosclerosis in relation to 1 SD greater plasma viscosity was 2.27 (1.52 –3.38) in men and 1.63 (1.17–2.26) in women. Adjustment of age, waist-to-hip ratio, smoking, hypercholesterolemia, hypertension, diabetes, and fibrinogen had very little effect on the magnitude of these odds ratios. Thus, plasma viscosity was associated with carotid thickening, suggesting that rheologic factors are involved in the subclinical phase of atherosclerosis.

Workplace Subordination and Men's Avoidance of Housework

Understanding the determinants of men's participation in housework has been the focus of much research in the past two decades. Increasingly, scholars argue that men's reluctance to do family work is because they associate it with “women's work” and thus a threat to their masculinity. The authors extend this idea by considering the link between challenges to men's identities in the workplace and their behavior in the home. Using data collected for the Class Structure and Class Consciousness Survey, it was found that the extent of men's workplace subordination was negatively related to their performance of “feminine” tasks in the home. Moreover, this relationship was stronger in families in which wives' earnings approached those of their husbands'. The theoretical implications of the results are discussed, and a call is made for more longitudinal studies to understand the complex and evolving relationship between work and family.

Effects of Growth Hormone Replacement Therapy on Bone Markers and Bone Mineral Density in Growth Hormone-Deficient Adults

During the 1990s, interest in the effects of growth hormone deficiency (GHD) in adults increased, and several studies were performed to evaluate the effects of growth hormone (GH) substitution therapy in these patients. Because adults with GHD have reduced bone mineral density (BMD) and an increased risk of fractures, the effects of GH replacement therapy on bone metabolism have been evaluated in long-term studies. A universal finding is that the serum and urinary levels of biochemical bone markers increase during GH substitution therapy, and these increases are dose dependent. After years of GH substitution therapy, the levels of biochemical bone markers remain elevated, according to some studies, whereas other studies report that these levels return to baseline. BMD of the spine, hip and forearm increase after 18–24 months of treatment. Bone mineral content (BMC) increases to a greater extent than BMD, because the areal projection of bone also increases. This difference could be caused by increased periosteal bone formation, but a measurement artefact resulting from the use of dual-energy X-ray absorptiometry cannot be excluded as a possible explanation. One study of GH-deficient adults found that, after 33 months of GH treatment, BMD and BMC increased to a greater extent in men with GHD than in women. There is also a gender difference in the increases in serum levels of insulin-like growth factor I and biochemical bone markers during GH treatment. The reason for these findings is unknown, and the role of sex steroids in determining the response to GH therapy remains to be fully elucidated.

Abnormal Testosterone:Epitestosterone Ratios after Dehydroepiandrosterone Supplementation

The interest in supplementation with testosterone precursors rose to new levels after Mark McGwire disclosed the use of androstenedione (and creatine) during his quest to overtake the 37-year-old home run record of Roger Maris. Banned by the National Collegiate Athletic Association (NCAA), the International Olympic Committee (USOC), and the National Football League, androstenedione, an immediate testosterone precursor, is purported to increase testosterone. Studies performed in East Germany in the 1960s demonstrated transient increases in testosterone up to 300% above normal in women and to a lesser extent in men (1). Increased testosterone was so transient that experts questioned whether any anabolic effects could occur. Indeed, there is no research that shows any performance enhancement in those who have used androstenedione, anecdotal reports not withstanding. Similarly, dehydroepiandrosterone (DHEA) has been banned by the NCAA and the USOC because of its physiological role as a testosterone precursor (2). As an adrenal androgen, DHEA acts as a steroid precursor for gonadal and peripheral testosterone and estrogen production. Once again, performance benefits for athletes are neither documented nor proven. DHEA is “guilty” by virtue of its position in the biochemistry of gonadal hormone production. DHEA was first identified in 1934 (3). As a precursor to testosterone and estrogen, DHEA can be converted peripherally to androstenedione, testosterone, and dihydrotestosterone and aromatized to estrogen. The degree of either the …

Single-Dose Pharmacokinetics and Pharmacodynamics of Recombinant Human Follicle-Stimulating Hormone (Org 32489) in Gonadotropin-Deficient Volunteers

Objective: To assess safety, pharmacokinetic, and pharmacodynamic properties of recombinant human follicle-stimulating hormone (FSH; Org 32489, Organon International, Oss, the Netherlands) after a single intramuscular injection in the buttock. Design: In a prospective study, safety variables, serum FSH, luteinizing hormone, inhibin, estradiol (females only), and testosterone (males only) were evaluated up to a maximum of 11 days after injection of 300 IU recombinant FSH. Setting: Four specialist Reproductive Endocrinology and Infertility units. Volunteers: Fifteen men and women exhibiting all pituitary gonadotropin deficiency. Result(s): A single bolus of 300 IU recombinant FSH was well tolerated, and no drug-related adverse effects were noted. Comparison of before and after treatment safety variables, including serum antirecombinant FSH antibodies, showed no changes of clinical relevance. Analysis of serum FSH levels revealed comparable elimination half-lives of 44 ± 14 (mean ± SD) and 32 ± 12 hours in women and men volunteers, respectively. In contrast, peak FSH concentrations were significantly lower in women than in men volunteers (4.3 ± 1.7 versus 7.4 ± 2.8 IU/L), and the time required to reach peak levels of FSH was significantly longer in women than in men (27 ± 5 versus 14 ± 8 hours). The area under the serum level versus time curve tended to be smaller in women than in men volunteers (339 ± 105 versus 452 ± 183 IU/L × hours), but the difference did not reach statistical significance. Together these data suggest that recombinant FSH is absorbed from its intramuscular depot to a lower rate and extent in women than in men. In both sexes a relationship between serum FSH levels and body weight was apparent. During the experimental period, other hormones remained low at baseline levels or were only slightly increased. Conclusion(s): Our findings indicate that recombinant FSH is well tolerated and that it is absorbed from its intramuscular depot to a higher rate and extent in men than in women. After intramuscular administration, its half-life is in good agreement with that previously reported for natural FSH.