Androstenedione does not stimulate muscle protein anabolism in young healthy men

Androstenedione is the immediate precursor of testosterone. Androstenedione intake has been speculated to increase plasma testosterone levels and muscle anabolism. Thus, androstenedione supplements have become widely popular in the sport community to improve performance. This study was designed to determine whether 5 days of oral androstenedione (100 mg/day) supplementation increases skeletal muscle anabolism. Six healthy young men were studied before the treatment period and after 5 days of oral androstenedione supplementation. Muscle protein turnover parameters were compared to those of a control group studied twice as well and receiving no treatment. We measured muscle protein kinetics using a three-compartment model involving infusion of L-[ring-2H5]phenylalanine, blood sampling from femoral artery and vein, and muscle biopsies. Plasma testosterone, androstenedione, LH, and estradiol concentrations were determined by RIA. After ingestion of oral androstenedione, plasma testosterone and LH concentrations did not change from basal, whereas plasma androstenedione and estradiol concentrations were significantly increased (P<0.05). Compared to a control group, androstenedione did not affect muscle protein synthesis and breakdown, or phenylalanine net balance across the leg. We conclude that oral androstenedione does not increase plasma testosterone concentrations and has no anabolic effect on muscle protein metabolism in young eugonadal men.     

Exogenous oestradiol and progesterone administration does not cause oedema in healthy young women

OBJECTIVE: Oedema is an increase in the extravascular component of extracellular fluid volume (ECFV). Fluid movement across the ECF is controlled by hydrostatic and oncotic pressures, which are influenced by oestradiol and progesterone. Thus we hypothesized that oestradiol decreases, while combined oestradiol + progesterone increases, protein and fluid movement out of the vasculature. SUBJECTS: Subjects were eight healthy women (22 +/- 2 years). DESIGN: Oestrogens and progesterone were suppressed with a gonadotropin-releasing hormone antagonist for 16 days; oestradiol (2 x 0.1 mg/day patches) was added for days 5-16 (E(2)) and progesterone (200 mg/day) was added for days 13-16 (E(2)-P(4)). MEASUREMENTS: We estimated intravascular (plasma) volume (PV), transcapillary albumin escape rate (TER(alb)), and Starling forces (hydrostatic pressures of plasma and interstitium, plasma colloid pressure, capillary filtration coefficient) in the forearm on days 2 (GnRH antagonist), 9 (E(2)) and 16 (E(2)-P(4)). RESULTS: In E(2), P([E2]) increased from 85 +/- 26 to 984 +/- 136 pmol/ml (P < 0.05), with no change in P([P4]). In E(2)-P(4), P([E2]) increased to 775 +/- 195 pmol/ml and P([P4]) increased from 6.4 +/- 3.2 to 43.8 +/- 16.2 nmol/l, P < 0.05). TER(alb) was lower during E(2) (5.1 +/- 0.9) and E(2)-P(4) (5.0 +/- 1.1) compared to GnRH antagonist (5.8 +/- 0.9%/h, P < 0.05). Plasma volume was unchanged by E(2), and showed a trend (P = 0.07) for an increase during E(2)-P(4) (48.2 +/- 2.9, 49.0 +/- 3.0 and 53.9 +/- 3.5 ml/kg for GnRH antagonist, E(2), E(2)-P(4), respectively). Starling forces were unaffected by hormone treatments. Plasma renin activity and serum aldosterone concentration increased during E(2)-P(4). CONCLUSIONS: Neither E(2) nor E(2)-P(4) altered TER(alb) sufficiently to impact Starling forces indicating neither E(2) nor P(4) administration at these levels would likely cause oedema.     

Short-term oxandrolone administration stimulates net muscle protein synthesis in young men.

Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone [Oxandrin (OX)], a synthetic analog of testosterone, would improve net muscle protein synthesis and transport of amino acids across the leg. Six healthy men [22+/-1 (+/-SE) yr] were studied in the postabsorptive state before and after 5 days of oral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femoral arterio-venous sampling and muscle biopsy. The precursor-product method was used to determine muscle protein fractional synthetic rates. Fractional breakdown rates were also directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I and androgen receptor (AR) were determined using RT-PCR. Model-derived muscle protein synthesis increased from 53.5+/-3 to 68.3+/-5 (mean+/-SE) nmol/min.100 mL/leg (P < 0.05), whereas protein breakdown was unchanged. Inward transport of amino acids remained unchanged with OX, whereas outward transport decreased (P < 0.05). The fractional synthetic rate increased 44% (P < 0.05) after OX administration, with no change in fractional breakdown rate. Therefore, the net balance between synthesis and breakdown became more positive with both methodologies (P < 0.05) and was not different from zero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like growth factor I mRNA concentrations. We conclude that short term OX administration stimulated an increase in skeletal muscle protein synthesis and improved intracellular reutilization of amino acids. The mechanism for this stimulation may be related to an OX-induced increase in AR expression in skeletal muscle.     

Partial enterectomy in the rat does not diminish muscle glutamine production.

The hypothesis was posed that consumption of the amino acid glutamine by the splanchnic tissues is an important regulating mechanism for its production in muscle. Therefore, glutamine consumption or production in portal-drained viscera (PDV), liver, and hindquarter was measured by determining fluxes and intracellular concentrations after 80% enterectomy or SHAM operation in rats. Moreover, fluxes and intracellular concentrations of several other amino acids, ammonia, and liver urea production were determined concomitantly. After enterectomy, arterial glutamine concentration was increased, PDV glutamine consumption was decreased by 77%, and liver glutamine consumption was unchanged compared with values in SHAM-operated rats. Although hindquarter glutamine production remained unchanged after enterectomy, intracellular glutamate concentration (glutamine precursor) was lower, suggesting that enterectomy induces changes in muscle metabolism without changing the flux of glutamine. For the remaining gut, it was calculated that after enterectomy glutamine consumption per gram remaining gut tissue increased. These results cast doubt on the hypothesis that diminished splanchnic glutamine uptake can reduce muscle glutamine production.     

Short-term increase of plasma free fatty acids does not interfere with intrinsic mitochondrial function in healthy young men

Free fatty acid (FFA)– and obesity-induced insulin resistance has been associated with disturbed mitochondrial function. Elevated plasma FFA can impair insulin-induced increase of adenosine triphosphate synthesis and downregulate the expression of genes important in the biogenesis of mitochondria in human skeletal muscle. Whether FAs have a direct effect on intrinsic mitochondrial capacity remains to be established. Therefore, we measured ex vivo mitochondrial respiratory capacity in human skeletal muscle after exposure to hyperinsulinemia and high levels of plasma FFA. Nine healthy lean men were studied during a 6-hour hyperinsulinemic (600 pmol/L) euglycemic clamp with concomitant infusion of Intralipid (Fresensius Kabi Nederland, Den Bosch, the Netherlands) (FFA clamped at 0.5 mmol/L) or saline. Mitochondrial respiratory capacity was measured by high-resolution respirometry in permeabilized muscle fibers using an Oxygraph (OROBOROS Instruments, Innsbruck, Austria). Each participant served as his own control. Peripheral glucose uptake (rate of disappearance) was significantly lower during infusion of the lipid emulsion compared with the control saline infusion (68 μmol/kg·min [saline] vs 40 μmol/kg·min [lipid], P = .008). However, adenosine diphosphate–stimulated and maximal carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone–stimulated uncoupled respiration rates were not different in permeabilized skeletal muscle fibers after exposure to high levels of FFA compared with the control condition. We conclude that short-term elevation of FFA within the physiological range induces insulin resistance but does not affect intrinsic mitochondrial capacity in skeletal muscle in humans.     

Orthostatic heart rates and blood pressures in healthy young women and men

Orthostatic heart rate, systolic and diastolic blood pressure responses to standing were measured in 50 young healthy men and women. The responses of the men and women were the same. Heart rate stabilized after 45 seconds of standing, systolic blood pressure after 2 minutes, and diastolic blood pressure immediately on standing. There was considerable variability in the responses of these normal subjects, raising concerns about the validity of commonly accepted normal values.     

Greater oxidative stress in healthy young men compared with premenopausal women

Coronary risk factors, including age, hypertension, diabetes mellitus, hyperlipidemia, and smoking, are associated with enhanced oxidative stress, which is implicated as a potential mechanism for atherogenesis and atherosclerotic cardiovascular diseases. Male sex is one of the well-known cardiovascular risk factors. We tested the hypothesis that oxidative stress is greater in men than in women. Plasma thiobarbituric acid-reactive substances (TBARS) and urinary 8-isoprostaglandin F2alpha (8-iso-PGF2alpha) were measured in 52 young men and 51 age-matched women. The subjects were healthy, were not smokers, and were not taking any medications or vitamins. Age, blood pressure, plasma cholesterol, and glucose did not differ between the groups. Baseline TBARS (2.32 +/- 0.11 [men] versus 1.87 +/- 0.09 [women] nmol/mL, P<0.01) and 8-iso-PGF2alpha (292 +/- 56 [men] versus 164 +/- 25 [women] pg/mg creatinine, P<0.05) were higher in men than in women. Supplementation of antioxidant vitamins for 4 weeks in men produced a significant reduction in TBARS and 8-iso-PGF2alpha by 34% (P<0.01) and 48% (P<0.05), respectively. Plasma superoxide dismutase, catalase, and vitamin E levels were comparable between the groups. Enhanced oxidative stress in men may provide a biochemical link between male sex and atherosclerotic diseases related to oxidative stress.     

Acute moderate elevation of TNF-alpha does not affect systemic and skeletal muscle protein turnover in healthy humans

CONTEXT: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. OBJECTIVE: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover via a 4-h recombinant human (rh) TNF-alpha infusion. We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibits synthesis. SUBJECTS AND METHODS: Using a randomized, controlled, crossover design, postabsorptive healthy young males (n = 8) were studied 2 h under basal conditions followed by a 4-h infusion of either rhTNF-alpha (700 ng . m(-2) . h(-1)) or 20% human albumin (control), which was the vehicle of rhTNF-alpha. Systemic and skeletal muscle protein turnover was estimated by a combination of tracer dilution methodology (primed continuous infusion of l-[ring-(2)H(5)]phenylalanine and l-[(15)N-leucine], with prime of l-[ring-(2)H(4)]tyrosine) and femoral arterial-venous differences over the leg and muscle biopsies. RESULTS: Plasma TNF-alpha concentration rapidly increased from basal levels of approximately 0.7 to 17 pg . ml(-1) with rhTNF-alpha infusion. Whole body protein synthesis, breakdown, and net degradation were similar after the basal and infusion period of the control and rhTNF-alpha trials. Skeletal muscle, musculus vastus lateralis, protein fractional synthetic rate was not different over 4 h of control or rhTNF-alpha (rate of incorporation of (15)N-leucine). Muscle protein turnover determined with the phenylalanine three-compartment model showed similar muscle synthesis, breakdown, and net muscle degradation after 2-h basal and after 4-h control or rhTNF-alpha infusion. CONCLUSION: This study is the first to show in humans that TNF-alpha does not affect systemic and skeletal muscle protein turnover, when acutely elevated for 4 h to moderate levels not causing adverse effects.     

Platelet-derived growth factor does not stimulate prostacyclin synthesis by cultured endothelial cells

We examined the effect of highly purified platelet-derived growth factor (PDGF) on prostacyclin (PGI2) release by cultured human umbilical vein and bovine aortic endothelial cells. PDGF tested at concentrations equal to or exceeding those observed in serum did not increase endothelial cell PGI2 synthesis as measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. In contrast, cells incubated with 20% human whole blood serum (WBS) demonstrated significantly increased PGI2 production (fivefold stimulation). Addition of anti-PDGF antibody to the 20% WBS did not attenuate the increased synthesis of PGI2. Incubation with 20% plasma-derived serum (PDS) that was deficient in PDGF produced stimulation of PGI2 release similar to 20% WBS. These results demonstrate that PDGF does not cause increased PGI2 synthesis in cultured human endothelial cells of human or bovine origin, and further suggest that the stimulation observed with serum is not due to a platelet-release product.     

The muscle protein synthetic response to the combined ingestion of protein and carbohydrate is not impaired in healthy older men

Aging is associated with a progressive decline in skeletal muscle mass. It has been hypothesized that an attenuated muscle protein synthetic response to the main anabolic stimuli may contribute to the age-related loss of muscle tissue. The aim of the present study was to compare the muscle protein synthetic response following ingestion of a meal-like amount of dietary protein plus carbohydrate between healthy young and older men. Twelve young (21 ± 1 years) and 12 older (75 ± 1 years) men consumed 20 g of intrinsically l-[1-¹³C]phenylalanine-labeled protein with 40 g of carbohydrate. Ingestion of specifically produced intrinsically l-[1-¹³C]phenylalanine-labeled protein allowed us to assess the subsequent incorporation of casein-derived amino acids into muscle protein. Blood samples were collected at regular intervals, with muscle biopsies obtained prior to and 2 and 6 h after protein plus carbohydrate ingestion. The acute post-prandial rise in plasma glucose and insulin concentrations was significantly greater in the older compared with the younger males. Plasma amino acid concentrations increased rapidly following drink ingestion in both groups. However, plasma leucine concentrations were significantly lower at t = 90 min in the older when compared with the young group (P < 0.05). Muscle protein-bound l-[1-¹³C]phenylalanine enrichments increased to 0.0071 ± 0.0016 and 0.0072 ± 0.0013 mole percent excess (MPE) at 2 h and 0.0229 ± 0.0016 and 0.0213 ± 0.0024 MPE at 6 h following ingestion of the intrinsically labeled protein in the young and older males, respectively, with no differences between groups (P > 0.05). We conclude that the use of dietary protein-derived amino acids for muscle protein synthesis is not impaired in healthy older men following intake of protein plus carbohydrate.     

Association between C-reactive protein and hypertension in healthy middle-aged men and women

OBJECTIVE: To ascertain whether C-reactive protein (CRP), an inflammatory marker related to increased cardiovascular risk, is associated with blood pressure in a sample of healthy, middle-aged people. METHODS AND RESULTS: A case-control study among 904 participants, 39-50 years old, from a cardiovascular risk screening study. Participants with systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg (n=120) were considered as case participants and all others as control participants (n=784). Exposure was defined using quintiles of high-sensitivity CRP among control participants. A continuous increase in blood pressure was observed across CRP quintiles. Systolic blood pressure increased 1.17 mmHg [95% confidence interval (CI), 0.60-1.74] and diastolic blood pressure 1.04 mmHg (95% CI, 0.64-1.45) from one quintile to the next. The prevalence of hypertension was 13.3% and it increased with CRP exposure: Q1, 8.9%; Q2, 11.9%; Q3, 12.2%; Q4, 14.3%; and Q5, 18.6%. After adjustment for sex, obesity, race, serum insulin level and family history of coronary heart disease, odds ratios for hypertension increased progressively across CRP quintiles. Participants in the highest CRP quintile were 2.35 times more likely to have hypertension than those in the lowest quintile (P=0.03, trend test P=0.04). CONCLUSION: These results are consistent with a continuous, independent association between serum CRP and elevated blood pressure.     

Cholecystokinin does not stimulate prosomatostatin-derived peptides in man

In man, plasma cholecystokinin (CCK) and somatostatin-28 (S-28) levels increase after ingestion of a mixed meal. Both peptides originate from the gastrointestinal tract. In supra- and periphysiological doses, CCK stimulates the release of somatostatin-14 from in vitro pancreatic islets and gastric cells and increases circulating somatostatin-like immunoreactivity in dogs, leading to the conjecture that CCK regulates somatostatin-like immunoreactivity secretion. Nonetheless, whether CCK is responsible in part for the meal-induced rise in S-28 in man has not been established. Therefore, the present study was designed to determine if CCK, at both physiological and supraphysiological concentrations, increases the circulating levels of prosomatostatin (proS)-derived peptides in humans. On 3 separate days, five healthy men ate a mixed liquid meal or received iv infusions of CCK at rates of 18 or 38 pmol/kg.h. Plasma levels of pro-S-derived peptides, including pro-S, S-14, S-13, S-28, and CCK, were measured. Basal CCK levels averaged 0.9 +/- 0.1 pmol/L and increased after the meal to a peak level of 5.4 +/- 1.5 pmol/L and averaged 3.1 +/- 1.2 pmol/L over 90 min. The mean basal levels of pro-S, S-14, and S-13, measured collectively, was 6.1 +/- 0.4 pmol/L eq S14 and was unaltered by food intake. The S-28 level was 6.7 +/- 0.6 pmol/L and rose to a zenith of 13.1 +/- 3.3 pmol/L by 90 min. Infusion of CCK at 18 and 38 pmol/kg.h produced steady state plasma CCK levels of 4.1 +/- 1.1 and 9.9 +/- 1.5 pmol/L, respectively. Basal levels of pro-S-derived peptides were unaltered during the infusion of either the low or high dose of CCK. We conclude that CCK by itself is not a physiological signal to the release of pro-S-derived peptides in man.     

Soy protein isolates of varied isoflavone content do not influence serum thyroid hormones in healthy young men.

OBJECTIVE: The ability of soy isoflavones to inhibit thyroid peroxidase and induce goiter in animals has generated concern regarding their potential antithyroid effects in humans. The purpose of this study was to determine the effects of soy protein isolates of varied isoflavone content on circulating thyroid hormones in healthy young men. DESIGN: Thirty-five healthy men (27.9 +/- 5.7 years old) supplemented their habitual diets with milk protein isolate (MPI), low-isoflavone soy protein isolate (low-iso SPI; 1.64 +/- 0.19 mg iso/day), and high-isoflavone SPI (high-iso SPI; 61.7 +/- 7.4 mg iso/day) for 57 days each, separated by 4-week washouts in a randomized crossover design. Blood was collected on days 1, 29, and 57 of each treatment for analysis of total triiodothyronine (T3), free T3, total thyroxine (T4), free T4, thyroid stimulating hormone (TSH), and thyroid binding globulin (TBG). Twenty-four hour urines were collected at the end of each treatment for analysis of isoflavones. MAIN OUTCOME: Results revealed no significant effects of the low-iso or high-iso SPIs on serum total T3, free T3, total T4, free T4, TSH, or TBG when compared with the MPI on either study days 29 or 57. Urinary data revealed that isoflavones were significantly increased by the high-iso SPI relative to the low-iso SPI and MPI. CONCLUSIONS: Results of this study demonstrate that soy isoflavones in a protein matrix do not significantly influence circulating thyroid hormones in healthy young men.     

Serum from type IIA hyperlipoproteinemic patients does not stimulate proliferation of and collagen synthesis in human fetal aortic smooth muscle cells in culture

The effect of serum from type IIA hyperlipoproteinemic patients on the proliferation and synthesis of collagen and other proteins of human fetal aortic smooth muscle cells (SMC) was studied. The activity of lysyl oxidase secreted into the culture medium was also measured. Type IIA hyperlipoproteinemic sera did not affect the proliferation of human aortic SMC as compared to normolipidemic sera, regardless of incubation time. The findings were similar for 3 different human fetal aortic SMC lines and one fibroblast line from adult human skin. The synthesis of collagen and other proteins was inhibited rather than stimulated in the presence of type IIA hyperlipoproteinemic sera. The activity of lysyl oxidase was not affected by type IIA hyperlipoproteinemic sera. The atherogenicity of hypercholesterolemia cannot be explained either by its direct effect on the proliferation of arterial SMC, as has been suggested by animal cell studies, or by its direct effect on the fibrogenicity of these cells.     

Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women

Background and aimsPre-clinical studies suggest that sesame and its lignans induce beneficial changes in risk factors related to cardiovascular disease and increase the bioavailability of mammalian lignans. However, only very few intervention trials have investigated the potential bioactivities of sesame in humans. We aimed to investigate the effects of sesame supplementation in humans on blood lipids, blood pressure, systemic oxidative stress, inflammatory biomarkers and mammalian lignan metabolism.Methods and resultsWe conducted a randomized, placebo-controlled cross-over intervention trial at a university research centre. Overweight or obese men and women (n = 33) consumed 25 g/d of sesame (∼50 mg/d of sesame lignan) and an iso-caloric placebo matched for macronutrient composition for 5 wks each. Each intervention period was preceded by a 4-wk washout period. Blood lipid profiles, day time ambulatory blood pressure, oxidative stress and inflammatory biomarkers and urinary mammalian lignans were measured before and after each intervention. Results are presented as the effect of sesame supplementation relative to placebo. Urinary excretion of the mammalian lignans, enterolactone and enterodiol, increased by approximately 8-fold (P < 0.001). Blood lipids and blood pressure were not altered. In addition, markers of systemic inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α) and lipid peroxidation (F₂-isoprostanes) were not affected.ConclusionSupplementation with 25 g/d of sesame can significantly increase the exposure to mammalian lignans. However, this did not cause any improvement in markers of cardiovascular disease risk in overweight or obese men and women.     

Glottic dimensions in healthy men and women

Glottic aperture is important in modulating respiratory system resistance. Male patients with obstructive sleep apnea (OSA) have a smaller glottic cross-sectional area compared to controls. Since OSA has a strong male predominance, we reasoned that glottic dimensions may differ between healthy men and women. Therefore, we utilized the acoustic reflection to measure glottic cross-sectional area in 44 non-smoking, non-obese, healthy subjects, 25 men and 19 women. Glottic area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared glottic areas in men and women at three lung volumes: TLC, 50% of vital capacity (VC), and RV. We found that in all but 2 subjects, glottic areas at TLC was greater than at 50% VC or RV. At any given lung volume, there was no significant difference in glottic area between men and women. The reduction in glottic area between TLC and RV was also similar between men and women (36 +/- 24% and 33 +/- 21%, respectively). However, this reduction in glottic area occurred mainly at low lung volumes in women, and more uniformly throughout the vital capacity range in men. We conclude that changes in glottic dimensions are dependent on lung volume, that healthy men and women have similar glottic areas, and that the glottic aperture shows similar variation with lung volume among both sexes.     

Alanine administration does not stimulate gluconeogenesis in preterm infants

Gluconeogenesis partially depends on sufficient precursor supply, and plasma alanine concentrations are generally low in preterm infants. Stimulation of gluconeogenesis may contribute to the prevention of hypoglycemia, an important clinical problem in these infants. In this study we evaluated the effect of extra precursor supply on gluconeogenesis in preterm infants. In 11 infants, gestational age < or = 32 weeks, glucose production rate (GPR) and gluconeogenesis were measured using the [6,6-(2)H(2)]glucose dilution technique and mass isotopomer distribution analysis with [2-(13)C]glycerol, respectively. Unlabeled glucose was administered throughout the study period at a rate of 22 micromol. kg(-1). min(-1). Five infants received alanine (1.5 mg. kg(-1). min(-1)) during the last 3 hours of the study protocol, and 6 infants served as controls. In the control group the rate of gluconeogenesis and GPR remained constant at 4.0 +/- 0.3 micromol. kg(-1). min(-1) and 8.3 +/- 0.6 micromol. kg(-1). min(-1), respectively. In the alanine group plasma alanine concentrations increased from 45 +/- 23 to 829 +/- 115 micromol/L (P =.001); gluconeogenesis and GPR did not differ from control: 3.8 +/- 0.2 micromol. kg(-1). min(-1) and 6.4 +/- 2.0 micromol. kg(-1). min(-1), respectively. We conclude that administration of the gluconeogenic precursor alanine does not stimulate gluconeogenesis in preterm infants, despite a sharp increase in plasma alanine concentrations. We speculate either a restricted capacity of the enzymes involved in the gluconeogenic pathway or a low secretion rate of glucoregulatory hormones as causative mechanisms involved in the gluconeogenic pathway in the preterm neonate.     

Acute inhibition of oestrogen biosynthesis does not affect serum leptin levels in young men

OBJECTIVE: Leptin plays an important role in the regulation of reproduction. To explore the contribution of oestradiol to serum leptin levels in men, we measured the concentrations of serum leptin and insulin after inhibition of oestrogen biosynthesis by selective blockade of the aromatase enzyme. DESIGN: The study had a double-blind parallel group design. METHODS: The aromatase inhibitor, MPV 2213ad, was given to eight healthy male volunteers as a single dose of 100mg. Eight men received placebo. Serum leptin and insulin were determined from blood samples collected at 0800h, 1600h and 2000h both on the actual test day (day 0) and on the previous day (day -1), and from single blood samples taken in the morning of days 1, 2, 4 and 7. Changes in serum leptin were correlated with those seen in serum oestradiol, testosterone, LH, FSH, cortisol and aldosterone, which were determined earlier. RESULTS: After the aromatase inhibitor administration, mean serum oestradiol concentration was reduced by 74% from the baseline compared with a 19% reduction in the placebo group (P for difference <0.001), and returned to pre-treatment levels within four days. Despite marked changes in serum oestradiol and sustained elevations in serum testosterone, LH and FSH concentrations, serum leptin concentrations were similar in the group receiving the aromatase inhibitor and in the placebo group. We found a weak correlation between serum oestradiol and leptin, which could not be reproduced when the percentage changes in these variables were analysed. CONCLUSION: Marked short-term reduction in serum oestradiol concentration has no effect on serum leptin levels in young men.