Normal Healthy Men Research Articles

SPAG5 mRNA is over-expressed in peripheral blood leukocytes of patients with Down’s syndrome and cryptorchidism

Men with Down's syndrome (DS) have an increased risk of cryptorchidism, but the mechanisms causing its onset are not clear. Cryptorchidism causes a primary testiculopathy responsible for infertility. SPAG5 mRNA is predominantly expressed in testis in pachytene spermatocytes. This observation prompted us to evaluate the expression of SPAG5 gene in five DS men with cryptorchidism and five normal healthy men (controls) by quantitative real-time PCR in peripheral blood leukocytes. We found that SPAG5 is over expressed in the five men with DS and cryptorchidism compared with five age- and sex-matched normal controls. This finding suggests that the increased expression of this gene may play a pathogenic role durin testicular development in subjects with DS and cryptorchidism.

An Evidence-Based Review of Exercise and Metabolic Syndrome

An Evidence-Based Review of Exercise and Metabolic Syndrome

Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma?

Prostate is an immunocompetent and not an immunoprivileged organ. It has an active immunologic armamentarium. There are three major prostate abnormalities namely, prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer. In all these abnormalities, infection/inflammation has been implicated. As infection/inflammation of the male genital tract can also be involved in induction of antisperm antibodies (ASA), this study was conducted to examine if these prostate abnormalities lead to the formation of ASA. Sera were obtained from normal healthy men (n = 20), men with chronic prostatitis (n = 20), men with BPH (n = 25), men with prostate cancer (n = 25) and immunoinfertile men (n = 10). The presence of antisperm antibodies against lithium diiodosalicylate (LIS)-solubilized human sperm extract (HSE), seminal plasma and synthetic peptides based upon sperm-specific antigens namely fertilization antigen (FA-1) and YLP(12), were analysed using the sperm immobilization technique (SIT), tray agglutination technique (TAT), enzyme-linked immunosorbent assay (ELISA) and indirect immunobead binding technique (IBT). All the sera from normal men and men with prostate abnormalities (chronic prostatitis/BPH/prostate cancer) were found to be negative in SIT and TAT. In ELISA, a few sera from men having prostate abnormalities (4-24%) showed a weak positive immunoreactivity (2-3 SD units) with some of the spermatozoa/seminal plasma antigens. Majority of the samples did not show any immunoreactivity (<2 SD units) in ELISA. Even the samples that showed a weak positive immunoreactivity in ELISA did not bind to live human sperm in IBT, indicating lack of sperm binding antibodies in these sera. In all these assays, the sera from immunoinfertile men were positive. Our findings indicate that chronic prostatitis, BPH and prostate cancer do not induce antibodies to spermatozoa, sperm-specific antigens and seminal plasma components. Although prostate is an immunologically competent organ, and its abnormalities cause a rise in circulating prostate-specific antigen (PSA), it appears that there is no concomitant induction of immunity to spermatozoa/seminal components including sperm-specific fertility-related antigens, thus not causing ASA-induced immunoinfertlity. This is the first study to our knowledge reporting the absence of ASA in men with BPH and prostate cancer.

Expression of STRBP mRNA in patients with cryptorchidism and Down’s syndrome

The most frequent defect of the male urogenital tract at birth is cryptorchidism. Cryptorchidism causes primitive testicular pathology responsible for infertility. Men with Down's syndrome (DS) have an increased risk of cryptorchidism. The spermatid perinuclear RNA-binding protein (STRBP) gene codifies a microtubule-associated RNA-binding protein and it is highly expressed in the testis as well as in the brain. At both levels, this gene seems to play a relevant role in the regular development of these organs. These observations prompted us to evaluate the expression of STRBP mRNA in 5 DS men with cryptorchidism and 5 normal healthy men (controls) by quantitative Real Time PCR in peripheral blood leukocytes. We found a decreased expression of the STRBP gene in men with DS and cryptorchidism compared with controls. This finding suggests that the impaired expression of this gene in DS may play a pathogenetic role in the altered brain and testicular development in subjects with DS and cryptorchidism.

Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal and subfertile men.

Various frequencies of sperm aneuploidy are reported in sperms of subfertile patients compared to normal individuals. Moreover, sperm DNA damage is shown to be associated with male infertility. In this study, the rate of DNA damage and frequencies of aneuploidy in sperms of subfertile patients was investigated. Semen samples were obtained from healthy normal and subfertile (oligozoospermia, asthenozoospermia, and oligoasthenozoospermia) men. The frequency of aneuploidy was assessed using primed in situ labeling (PRINS) analysis with specific primers for chromosomes 18, 21, X, and Y. Sperm DNA damage was assessed using alkaline comet assay. The mean frequencies of disomy for the patients were significantly higher than normal for all chromosomes (P < 0.01). The extent of DNA damage in sperms of subfertiles was significantly higher than in normal individuals (P < 0.001). The obtained results indicated that higher rate of DNA damages led to higher frequency of chromosomal disomy except for asthenozoospermia samples which exhibited higher rate of DNA damage and lower frequency of chromosomal disomy. These results demonstrate that men with oligozoospermia and oligoasthenozoospermia have an elevated risk for chromosome abnormalities in their sperm, particularly sex chromosomes. DNA damage might be involved in the process of malsegregation of chromosomes.

(18)F-FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy.

The purpose of this study was to evaluate glucose metabolism of normal human testis on (18)F-FDG PET/CT and to assess possible correlations among age, the serum levels of sex hormones, and vasectomy. (18)F-FDG PET/CT was performed in 66 normal healthy men (50.8 ± 13.6years, range 22-81), and mean standard uptake values (SUV) of (18)F-FDG in testis and adductor muscle were measured. Testis-muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex-hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. (18)F-FDG PET/CT was also performed in 32 vasectomized men (55.7 ± 7.8years, range 38-71) and 52 nonvasectomized men (55.4 ± 11.6years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age-related decline was found in T/M ratio (r = -0.509, p < 0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r = 0.427, p = 0.0003; r = 0.435, p = 0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p < 0.0378 and p = 0.0001, respectively). Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular (18)F-FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular (18)F-FDG uptake in the normal adult population.

Oxytocin does not modify GH, ACTH, cortisol and prolactin responses to Ghrelin in normal men

In order to test the possible effect of Oxytocin (OT) on Ghrelin-stimulated GH, PRL, ACTH and cortisol, ten healthy normal men were studied. Ghrelin (0.2 μg/kg body weight (BW)) as an iv bolus; Ghrelin plus OT (2 IU as bolus plus 0.07 IU/min administered for 90 min). The administration of OT did not change GH, PRL, ACTH and cortisol release induced by Ghrelin. The data suggests that in humans OT did not modulate the GH, PRL, ACTH and cortisol response to Ghrelin.

Bone mineral density, bone mineral content, gingival crevicular fluid (matrix metalloproteinases, cathepsin K, osteocalcin), and salivary and serum osteocalcin levels in human mandible and alveolar bone under conditions of simulated microgravity

In astronauts and cosmonauts, exposure to microgravity has been associated with several physiological changes, including an osteoporosis like loss of bone mass. It has been reported that head-down tilt bed-rest studies mimic many of the observations seen in space flights. There has been no study of the effects of mandibular bone and alveolar bone loss in both sexes under conditions of simulated microgravity. This study was designed to investigate bone mineral density; bone mineral content; matrix metalloproteinase (MMP)-8, MMP-9, cathepsin K, and osteocalcin levels in gingival crevicular fluid (GCF); and salivary and serum osteocalcin levels in normal healthy men and women under conditions of simulated microgravity, namely, -6° head-down-tilt (HDT) bed rest. The subjects of this investigation were 10 male and 10 female volunteers who were exposed to 3 weeks of -6° HDT bed rest. Dual-energy X-ray absorptiometry was used to measure bone density and bone mineral content in alveolar bone from the mandibular canine to the third molar, as well as in the mandibular ramus, before, during, and after exposure to conditions of simulated microgravity. GCF (ie, MMP-8, MMP-9, cathepsin K, and osteocalcin) and salivary and serum osteocalcin levels were measured by enzyme-linked immunosorbent assays. Bone mineral density and bone mineral content were significantly lower under conditions of simulated microgravity in both sexes. The decreases were greater in women than in men, but the differences between sexes were not significant. Cathepsin, osteocalcin, MMP-8, and MMP-9 levels were significantly higher under conditions of simulated microgravity than under normal conditions; the increases were greater in women than in men, but the differences were not significant. Additional, more comprehensive, studies with larger sample sizes are now necessary for the investigation of simulated microgravity and microgravity.

Estimation Of The Eyeball And Orbital Volume Using The Cavalieri Principle On Computed Tomography Images

Objective: The volumes of the eyeball and orbit have been the subject of a few studies, yet none of them have used stereological methods to estimate the volume. In the present study, we estimated the volumes of the eyeball and orbita in normal healthy men and women using the stereological method. Material and Methods: We estimated the volume of the eyeball (VE) and the volume of the orbit (VO) in normal men and women using the Cavalieri principle as a combination of a point-counting technique. We used computed tomography scans taken from 31 subjects (12 men and 19 women). Results: The mean (±SD) VO in the female subjects was 18.47±2.52 cm 3 on the right side and 18.16±2.52 cm 3 on the left side. The VE was 7.45±1.19 cm 3 and 7.45±1.25 cm 3 on the right and left sides, respectively. The mean (±SD) VO in the male subjects was 22.35±3.05 cm 3 on the right side and 22.71±2.80 cm 3 on the left side. The VE was 7.32±0.74 cm 3 and 7.61±1.04 cm 3 on the right and left sides, respectively. Conclusion: Measurement by the technique described is an easy, and quick method of assessing the volumes of the eyeball and orbit.

Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males

To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men. Prospective study. Departments of Biochemistry and Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening. High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods. Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured. Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL. The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.

Serum alpha-immunoreactive inhibin in males with renal failure, under haemodialysis and after successful renal transplantation.

Serum alpha-immunoreactive inhibin was evaluated in 16 male renal transplant recipients with stabilized renal function of mean age 38.5 +/- 10.7 years and was compared to that in sex- and age-matched 17 haemodialyzed patients; 10 patients with chronic renal failure and 26 healthy normal men (controls). Serum LH, FSH, prolactin and testosterone were also measured simultaneously, in the same samples. In renal transplant recipients, inhibin was found significantly higher than that in controls (P<0.001), 25% however of the values were in the normal range. In contrast, all haemodialyzed patients showed highly elevated inhibin values of inhibin were also highly elevated compared to those in normals. A negative correlation was noticed between inhibin and FSH only in controls (r(s) = -0.610, P<0.005). In renal transplant recipients, inhibin showed a strong correlation with serum creatinine (sCr) (r(s) = 0.710, P<0.008), while in the case of graft rejection the rise of sCr was immediately followed by a parallel increase of inhibin. In conclusion, the highly elevated inhibin in uraemic men not improved by haemodialysis and persistent after successful renal transplantation, might be implicated in the pronounced hypergonadotropic hypogonadism of haemodialyzed patients and the remaining dysfunction of hypothalamic-pituitary-testicular axis in renal transplant recipients.

Testicular steroid response to continuous and pulsatile intravenous luteinizing hormone-releasing hormone administration in normal men.

In 18 healthy normal men Leydig cell response was examined following intravenous luteinizing hormone-releasing hormone (LH-RH) administration under standardized conditions. The same total amount of LH-RH was administered for 3 hours both in a continuous (1 microgram/min; C (1,1)) and in a pulsatile fashion, by giving a 20 micrograms dose at 20 minutes intervals, P (20, 20), and a 60 micrograms dose at 60 minutes intervals, P (60, 60). Following the different modes of LH-RH administration which all caused 3-4 fold elevations of the mean endogenous luteinizing hormone (LH) concentrations and 1.7-2 fold elevations of the mean follicle-stimulating hormone (FSH) serum levels, an overt increase of the mean testosterone (T) levels was noticed up to 1.5 X the baseline value. No difference was observed in the total amount of T release among the investigated groups. The patterns of the T response, however, clearly differed from one another with a rapid increase, during the C (1, 1) and the P (20, 20) LH-RH administration, and a delayed but persistent T increase in the P (60, 60) experiment. The mean 17-hydroxyprogesterone (17-OHP) concentrations demonstrated a similar course to T in the P (60,60) experiment, while significant increases of the oestradiol (E 2) levels were never observed in all three experiments. In view of the comparable LH and FSH increments in response to LH-RH administration in either experiment the differences in T responses may be explained by assuming a direct effect of LH-RH on Leydig cell steroidogenesis in the men.

Mucuna pruriens improves male fertility by its action on the hypothalamus–pituitary–gonadal axis

To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan

Aging is associated with many changes in sleep, with one of the most prominent being a reduction in slow wave sleep. Traditional measures of this phenomenon rely on spontaneous activity and typically confound the incidence and amplitude of delta waves. The measurement of evoked K-complexes during sleep, enable separate assessment of incidence and amplitude taken from the averaged K-complex waveform. The present study describes data from 70 normal healthy men and women aged between 19 and 78 years. K-Complexes were evoked using short auditory tones and recorded from a midline array of scalp sites. Significant reductions with age were seen in the amplitude of the N550 component of the averaged waveform, which represents the amplitude of the K-complex, with linear regression analysis indicating approximately 50% of the variance was due to age. Smaller, yet still significant reductions were seen in the ability to elicit K-complexes. The data highlight the utility of evoked K-complexes as a sensitive marker of brain aging in men and women.

Prediabetes is associated with abnormal circadian blood pressure variability

Blood pressure (BP) exhibits a circadian variation characterized by a morning increase, followed by a small postprandial valley and a deeper descent during nocturnal rest. Although abnormal 24-h variability (abnormal circadian variability (ACV)) predicts adverse cardiovascular disease (CVD) outcomes, a 7-day automatic ambulatory BP monitoring (ABPM) and subsequent chronobiologic analysis of the gathered data, permits identification of consistency of any abnormal circadian variation. To test whether normal overweight healthy men and women with prediabetes differed from subjects with normoglycemia in having ACV with a 7-day ABPM. Consent for a 7-day ABPM was obtained from subjects with family history of diabetes mellitus, who were participating in the screening phase for a randomized, double blind, placebo-controlled weight loss trial in prediabetics to prevent progression to diabetes mellitus. The automatic 7-day ABPM device recorded BP and heart rate every 30 min during the day and every 60 min during the night. Normoglycemic and prediabetic subjects matched for age, sex, race, BP, BMI, waist circumference and glycemic control, differed statistically significantly only in their fasting and/or 2-h postprandial serum glucose concentrations. Chronobiologically-interpreted 7-day ABPM uncovered no abnormalities in normoglycemics, whereas prediabetics had a statistically significantly higher incidence of high mean BP (MESOR-hypertension), excessive pulse pressure and/or circadian hyper-amplitude-tension (CHAT) (P<0.001). ACV detected with 7-day ABPM may account for the enhanced CVD risk in prediabetes. These findings provide a basis for larger-scale studies to assess the predictive value of 7-day ABPM over the long term.

Effect of Mucuna pruriens on semen profile and biochemical parameters in seminal plasma of infertile men

To investigate the impact of Mucuna pruriens seeds on semen profiles and biochemical levels in seminal plasma of infertile men. Prospective study. Departments of Biochemistry and Obstetrics and Gynecology, King George's Medical University, Lucknow, India. Sixty normal healthy fertile men (controls) and 60 men undergoing infertility screening. High-performance liquid chromatography assay procedure for quantitation of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma, namely lipids, fructose, and vitamin C, were estimated by standard spectrophotometric procedures. Before and after the treatment, seminal plasma lipid profile, lipid peroxide, fructose, and antioxidant vitamin levels were measured. Treatment with M. pruriens significantly inhibited lipid peroxidation, elevated spermatogenesis, and improved sperm motility. Treatment also recovered the levels of total lipids, triglycerides, cholesterol, phospholipids, and vitamin A, C, and E and corrected fructose in seminal plasma of infertile men. Treatment with M. pruriens increased sperm concentration and motility in all the infertile study groups. Oligozoospermic patients recovered sperm concentration significantly, but sperm motility was not restored to normal levels in asthenozoospermic men. Furthermore, in the seminal plasma of all the infertile groups, the levels of lipids, antioxidant vitamins, and corrected fructose were recovered after a decrease in lipid peroxides after treatment. The present study is likely to open new vistas on the possible role of M. pruriens seed powder as a restorative and invigorating agent for infertile men.

Comparison of calcaneal bone density in operative versus non-operative army personnel

Purpose: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels.Methods and Materials: Weekly serum PSA values were determined during radiotherapy (RT)_in nine patients (“treatment group”) without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes fr the rate of change in PSA was determined using model: log PSA = β0 + β1∗week + β2∗week2 + error. These results are compared with 17 normal volunteers (“control group”) who were not exposed to ionizing irradiation. an attempt is made to compare any similarities and differences in subsets of 64 T1–T4NOMO PC patients who received pelvic RT.Results: An elevation in the serum PSA levels were noted in eight of nine patients in the “treatment group” with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for exampel, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50–650%. The median slope was 0.601 week−1 (range 0.192–3.045 week−1). No such increases were seen in the “control group” (median slope = 0.03 week−1; range, 0.18–0.13 week−1). When diffrences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.24). A similar ternd of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were ≤ 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in52.7% of those with ≤ 20 ng/ml preradiotherapy PSA values.Conclusion: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum (PSA) levels are seen in over 50% of prostate cancer patients with ≤ 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e0 Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

Re: Penile duplex pharmaco‐ultrasonography of cavernous arteries in men with erectile dysfunction and generalized atherosclerosis

We thank Carlo Foresta and Nicola Caretta for comments on the paper of Bocchio et al. (2006). The comments and criticisms were expected as the clinical use of penile duplex pharmaco-ultrasonography (PDPU) of cavernous arteries has never been fully substantiated due to the lack of reference values of normal healthy men because of its invasive nature, and because of the large variation of Doppler parameters due to easy error sampling and lack of consensus on modalities of sampling and pharmaco-stimulation. Given this general comment I would like to answer to the points raised by Foresta and Caretta: That ‘atherosclerosis hits small vessels earlier that large vessels, hence P-CDU may point out atherosclerotic lesions developed before carotid lesions’, is based on a fascinating hypothesis (Montorsi et al., 2005) to be demonstrated yet. The formula proposed by Caretta et al. (2006) that incorporates peak systolic velocity of cavernous arteries after pharmaco-stimulation and age to predict carotid atherosclerosis is of interest but needs further validation. Intima-media thickening of common carotid arteries is age-dependent also in the absence of atherosclerosis and is accelerated in men exposed to vascular risk factors (Lakatta & Levy, 2003). It is not clear in the population study of Caretta et al. (2006) which is the predictive value of patient age for carotid atherosclerosis and how much the accuracy of the formula is dependent on the inclusion of age. In conclusion, the clinical relevance of PDPU seems to need further validation in the clinical evaluation of men with erectile dysfunction after defining a consensus on modalities of sampling and on reference values of different parameters.

Estradiol Is Concentrated in Human Platelets and Is Released upon Activation.

Background and Aim: Estrogens are prothrombotic in both normal and atherosclerotic vessels. There is evidence that exogenous estrogen modifies platelet reactivity and signaling pathways, but very little is known about sex hormone metabolism in platelets or whether platelet estrogen stores contribute to atherothrombosis. To begin to characterize the role of sex hormones in platelet biology, we measured estradiol (E2), estrone (E1) and testosterone (T) concentrations within platelets and plasma of normal healthy men and women. Additionally, we tested the hypothesis that platelets have the capacity to release E2 during thrombin-stimulated platelet aggregation and activation.Methods and Results: Platelets and plasma were prepared from platelet-rich plasma (PRP) samples of 16 male (age 24–63), 13 premenopausal female (age 25–34) and 8 menopausal female (age 39–65) donors; no females were using exogenous hormones. E2, E1 and T were determined by Gas Chromatography-Mass Spectrometry. Hormone content in platelets and plasma was expressed per mL of PRP. Plasma E2, E1 and T levels were within the range of values previously reported in the literature. E2 concentrations were significantly higher in platelets compared to plasma in men (p<0.01) but not in women (premenopausal p=0.33; menopausal p=0.16). The geometric mean and 95% CI for platelet and plasma E2 levels were 199 (114–349) and 55 (37–81) pM for men, 360 (154–831) and 235 (158–357) pM for premenopausal women, and 107 (52–224) and 40 (15–118) pM for menopausal women, respectively. Conversely, T concentrations were significantly lower in platelets than in plasma in both men and women (p<0.01). E1 levels in platelets and plasma were not significantly different within men and within women. In a subset of participants, PRP samples were incubated with 0.5 U/mL thrombin for 10 minutes at 37oC and estradiol levels were measured in the non-clotted plasma+platelet releasate. Compared to no thrombin, thrombin-treated PRP from male subjects (n=7) yielded a 1.6 to 6.7 fold increase in E2 levels (p<0.01). The incubation of PRP from premenopausal (n=5) and menopausal women (n=4) with thrombin did not produce a significant change in E2 release.Conclusion: Our results show that platelets have the capacity to concentrate E2 and may serve as a vascular vehicle for the delivery of this prothrombotic factor upon platelet activation.

Androgen Therapy Induces Muscle Protein Anabolism in Older Women

Normal healthy men and women undergo a gradual loss of skeletal muscle mass and strength with advancing age. While androgens are protein anabolic in older men, the metabolic effects in older women are poorly understood. The objective of this study was to determine whether oral administration of a synthetic derivative of testosterone [oxandrolone, Oxandrin (OX)] (7.5 mg orally twice daily for 14 d) to five older women (age, 65 +/- 2 yr) would enhance skeletal muscle anabolic biomarkers including mixed muscle fractional synthetic rate (FSR), net phenylalanine balance, androgen receptor, and IGF-I protein expression at d 0, 5, and 14 of treatment. As a positive control, seven older men were examined after 14 d of OX (10 mg orally twice daily). The study was performed at the General Clinical Research Center. Fourteen days of OX significantly increased skeletal muscle FSR in older women (d 0, 0.073 +/- 0.006 vs. d 5, 0.092 +/- 0.006 vs. d 14, 0.115 +/- 0.007%/h) (P < 0.05, d 0 vs. d 14). Conversely, OX stimulated FSR in older men after only 5 d (d 0, 0.061 +/- 0.003 vs. d 5, 0.101 +/- 0.01 vs. d 14, 0.084 +/- 0.01%/h) (P < 0.05, d 0 vs. d 5). Androgen receptor expression was significantly increased in older men by d 14, but had not increased in older women. No change was noted in IGF-I expression in either group. We conclude that the skeletal muscle of older women and men responds to androgen administration, although the time course of anabolism appears to be gender specific.