Plasma steroid profiles in male and female mudpuppies, Necturus maculosus (Rafinesque).

Plasma steroid profiles of healthy adult male and female mudpuppies, Necturus maculosus Rafinesque, were measured in animals sampled from November–June. Steroids in ether extracted plasma were analyzed directly by radioimmunoassay (RIA) for progesterone (P), total androgens, and total estrogens, or after Celite-ethylene glycol column chromatography for P, dihydrotestosterone (DHT), testosterone (T), estrone (E₁), and estradiol-17β (E₂). Steroid levels in both sexes were high compared to other vertebrates (10- to 100-fold greater), and highly variable at all times of the year. Comparison of the steroid profiles of males and females showed no qualitative differences; howeve, titers of all steroids (in ng/ml) were higher in males. Progesterone (P) ranged from 2.0–64.0, dihydrotestosterone (DHT) from 2.0–133, testosterone (T) from 4.0–202, estrone (E₁) from N.D. to 1.87, and estradiol (E₂) from 2.0–9.85 in adult males. In adult female Necturus, P ranged from N.D. to 15.5, DHT from 2.9–11.4, T from 1.5–8.3, and E₂ from −0.4–6.35. E₁ was not detectable. No clear seasonal variations in steroid titers or gonadal structure were observed although holding conditions at 5–8° did not approximate those in nature.     

Relationship of plasma sex hormones to different parameters of obesity in male subjects

Relationships between plasma sex hormones and different parameters of obesity (weight, ideal body weight [IBW], overweight, fat mass, and body surface) were investigated in 70 healthy nonobese and obese males, 20–40 yr of age and with a body weight of 85%–245% of IBW. Plasma sex hormones remained unaffected by weight up to approximately 160% of the IBW. Only in the massively obese subjects was plasma testosterone decreased to 40% of controls (from 6.2 to 2.5 ng/ml), whereas free testosterone remained almost constant. On the other hand, plasma estrone and estradiol exhibited significant increases in obese subjects, ranging from 31.5 ± 5.3 to 52.3 ± 5.8 pg/ml for estrone, and 25.4 ± 5.4 increasing to 44.7 ± 5.0 pg/ml for estradiol. Similarly, free estradiol was shown to significantly increase with obesity in men from 505 ± 118 to 991 ± 123 fg/ml (p < 0.001). The ratios of testosterone/androstenedione, as well as of estradiol/estrone, were not affected by obesity, suggesting that reduction of the 17-oxo-group of the steroids is not influenced by the amount of fat tissue. A significant (p < 0.001) correlation was found between IBW and estrone (r = 0.80) and estradiol (r = 0.75), as well as the ratios of estrone/androstenedione (r = 0.62) and estradiol/testosterone (r = 0.86). This is consistent in its evidence indicating that fat tissue may be able to aromatize androgens. In the obese subjects, there were significant correlations between plasma sex hormones (testosterone, estrone, estradiol, and free estradiol) and the parameters of obesity used. Among these, correlations were best with IBW, overweight, and fat mass (r = 0.74–0.89; p < 0.001); body weight and body surface were less favorable.     

Correlation of serum testosterone with insulin resistance in elderly male type 2 diabetes mellitus patients with osteoporosis

Aims/Introduction

The present study was designed to investigate the correlations between the serum testosterone level and insulin sensitivity in elderly male type 2 diabetes patients with osteoporosis.

Materials and Methods

A total of 35 elderly male patients with type 2 diabetes (type 2 diabetes group), 30 elderly male type 2 diabetes patients combined with osteoporosis (DO group) and 30 healthy elderly men (normal control group) participated in the present study. The fasting plasma glucose, fasting insulin, testosterone (T) and estradiol (E₂) were measured. The insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR) and E₂/T were calculated. Then, the correlations of serum testosterone level with ISI and HOMA-IR were analyzed by statistical methods.

Results

The HOMA-IR, E₂ and E₂/T of the type 2 diabetes group and DO group were significantly increased, whereas the bone mineral density, ISI, T and sex hormone binding globulin were decreased compared with those of the normal control group. Serum testosterone levels of the type 2 diabetes group and DO group were negatively correlated to the HOMA-IR (r = −0.496, −0.506; P < 0.05), whereas they were positively correlated to the fasting insulin (r = 0.281, 0.292; P < 0.05) and ISI (r = 0.364, 0.403; P < 0.05).

Conclusions

The reduced level of serum testosterone in elderly male type 2 diabetes patients with osteoporosis might promote insulin resistance.     

Sex hormone binding globulin binding capacity, testosterone, 5alpha-dihydrotestosterone, oestradiol and prolactin in plasma of patients with prostatic carcinoma under various types of hormonal treatment.

Sex hormone binding globulin (SHBG) binding capacity, the concentrations of testosterone (T), of 5alpha-dihydrotestosterone (DHT), of oestradiol-17beta (Oe2), of oestrone (Oe1), of prolactin (hPr) and the percentual specific binding of T to SHBG (%TB) were measured in plasma of patients suffering from prostatic carcinoma and of a control group of similar age. No significant differences in any of the investigated parameters were found between the control group and the carcinoma patients before treatment although 15% of the latter showed distinctly elevated hPr values. Treatment of carcinoma patients with 1) Antiandrogen (cyproterone acetate, Androcur) resulted in a significant decrease of T, Oe2 and SHBG. The DHT/T-ratio increased. n=5. 2) Orchidectomy caused an even more pronounced fall in T, DHT, Oe1 and Oe2 blood levels. SHBG was not altered. DHT/T-ratio increased. n=32. 3) Cyproterone acetate after orchidectomy led to elevated hPr values. n=5. 4) Oestrogen (diethylstiboestrol-diphosphate, Honvan) after orchidectomy increased SHBG and hPr. n=6. 5) Corticosteroid (Prednisone, Decortin) after orchidectomy decreased T and SHBG below the levels found after orchidectomy alone. n=5. 6) Diureticum (Mefruside, Baycaron) (n=5) or 7) a placebo (n=7) did not alter any of the parameters measured. 8) Treatment with HCG (Primogonyl) of patients suffering from oligozoospermia resulted in a significant increase of T, DHT and Oe2. SHBG was not altered. DHT/T-ratio decreased. n=7.     

Androgen inhibition of basal and estrogen-stimulated prolactin binding in rat liver

Estradiol (E₂ 0.25 μg) administered twice a day for 7 days to rats ovariectomized 2 weeks previously caused a 4.5-fold increase in [¹²⁵I]ovine prolactin (PRL) binding to a rat liver crude plasma membrane fraction. Testosterone (T, 500 μug) injected in combination with E₂ caused a 75% reduction in PRL binding. In male rats (both intact and castrated) injected once daily with E₂-benzoate (EB, 10 μg/100 g body wt), T-propionate (TP, 100 μg/100 g body wt.) caused a 62–73% decrease in E₂-induced binding without affecting the high levels of plasma PRL induced by EB. DHT led to a significant inhibition of PRL binding at the relatively low doses of 10 and 2.5 μg/100 g body wt. in control and E₂-treated ovariectomized rats, respectively. T was slightly less effective than DHT in reducing PRL binding. DHT was also found to be effective in reducing PRL binding to rat liver in rats hypophysectomized bearing a pituitary homotransplant, the level of binding decreasing from 10.7 ± 0.8% to 7.4 ± 0.7% (P < 0.01) in animals injected twice a day for 7 days (100 μug/100 g body wt.). A single injection of DHT caused a 24% reduction (P < 0.01) in PRL binding 12 h after its injection in E₂-treated animals, the stimulatory effect of the estrogen being completely inhibited within 3–5 days of DHT treatment. These data indicate that androgens can effectively reduce prolactin binding to rat liver independently of their effect on plasma PRL.     

Indications of Low Sex Hormone Binding Globulin (SHBG) in Young Females with Type 1 Diabetes,and an Independent Association to Microalbuminuria

Sex hormone binding globulin (SHBG) is normally decreased during puberty and inversely related to insulin resistance. Microalbuminuria is rare before puberty in Type 1 diabetes implicating that sex hormones may contribute to its development. We investigated SHBG levels in young females with >5 years of Type 1 diabetes, and the association to microalbuminuria. Ten diabetic females with, and 15 without microalbuminuria, and 17 healthy controls in pubertal stage 4–5 were compared regarding anthropometric data, fasting serum levels of SHBG, testosterone, insulin, insulin-like growth factor-1 (IGF-1), lipids and lipoproteins. Multiple regression analyses were performed to study variables with independent influences on SHBG and albumin excretion rate (AER), respectively, in Type 1 diabetes. SHBG was lower and testosterone/SHBG ratio higher in normoalbuminuric females with diabetes than in controls. This was further emphasized in diabetic patients with microalbuminuria. IGF-1 was lower in Type 1 diabetes than in controls, and significantly decreased in microalbuminuric as compared to normoalbuminuric diabetic patients. IGF-1 was only correlated to SHBG in healthy controls. In Type 1 diabetes, applying stepwise multiple regression analysis, insulin dose, BMI, and HbA_1c had a significant and independent inverse influence on SHBG (r² = 0.77, p < 0.001). With log AER as the dependent variable, low SHBG, low IGF-1, HbA_1c, and age added to the regression (r² = 0.65, p = 0.004), whereas BMI, insulin dose and blood pressure did not. In conclusion, SHBG is decreased in young females with Type 1 diabetes, influenced by increased insulin requirements, BMI and HbA_1c. In turn, low SHBG seems to be independently associated to elevated AER in these patients. Prospective studies are necessary to confirm our results.     

EFFECTS OF ETHINYLOESTRADIOL ON PLASMA LEVELS OF PITUITARY GONADOTROPHINS, TESTICULAR STERIODS AND SEX HORMONE BINDING GLOBULIN IN NORMAL MEN

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17β-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE₂) in a dose of 30 μg/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17β-oestradiol during EE₂ administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE₂ in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE₂ doses in such studies may be less ‘physiologic’ than is often assumed.     

Testosterone-binding protein in a seasonally breeding amphibian

The concentration of testosterone and dihydrotestosterone (DHT) in the plasma of Taricha granulosa rises markedly during the season when androgen-dependent epigamic structures and behaviors recrudesce. During this season (June–October), the physiological characteristics of the testosterone-binding globulin (TeBG) remain unchanged. Competitive binding studies indicate that TeBG binds fairly specifically to testosterone and DHT. The dissociation constant (5 × 10^?8M) and binding capacities (ranging from 6 to 12 ng androgen bound/ml plasma) were determined using the charcoal adsorption procedures. Because the binding capacity of TeBG remains unchanged when the concentrations of androgens increase, the proportion of testosterone and DHT bound to TeBG is drastically lower during the breeding season, compared to the nonbreeding season. Furthermore, bilateral castration of male newts apparently reduces the binding capacity of TeBG, but Silastic implants of androgen fail to restore the binding capacity.     

Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle-aged men

OBJECTIVE Administration of testosterone has been reported to increase serum levels of IGF-I in men with isolated hypogonadotrophic hypogonadism. An inverse relation between serum IGF-I and sex hormone binding globulin (SHBG) is seen in GH deficient children. The biological action of IGF-I is thought to be influenced by binding proteins, one of which is insulin-like growth factor-binding protein-1 (IGFBP-1), which is not only a carrier protein but also actively regulates the cellular actions of IGF-I. These observations suggest associations between IGF-I, IGFBP-1, testosterone and SHBG in serum. The aim of the present study was to investigate these associations in normal healthy men. DESIGN AND PATIENTS The associations between the serum levels of IGF-I and IGFBP-1 on one hand, and testosterone and SHBG on the other were investigated in 38 normal healthy young and middle-aged men. RESULTS Serum levels of IGF-I decreased both with increasing age (r = ? 0.66, P < 0.001) and increasing SHBG levels (r = ? 0.46, P = 0.002), but increased with increasing free testosterone (f-testosterone) (r = 0.42, P = 0.005). These associations remained after mutual simultaneous adjustments in a multiple regression analysis. IGFBP-1 did not display any significant univariate correlation with age (r = ? 0.25, P = 0.06) or SHBG (r = 0.18, P = 0.14), but showed a significant positive correlation with both f-testosterone (r = 0.42, P = 0.004), and total testosterone (t-testosterone) (r = 0.39, P = 0.008). In a multiple regression analysis IGFBP-1 was positively correlated with both SHBG and f-testosterone, but not with t-testosterone. CONCLUSION The present study suggests that among healthy young and middle-aged men, there is an association between serum levels of free-testosterone and SHBG on the one hand, and serum IGF-I and IGFBP-1 on the other.     

Serum androgen levels in adolescents with type 1 diabetes: relationship to pubertal stage and metabolic control

Delayed sexual maturation is still frequently seen in adolescents with type 1 diabetes. A close relationship between insulin and androgen metabolism has been found in a number of studies. Our study was designed to investigate whether or not abnormalities in androgen secretion could play a role in the onset of sexual maturation in adolescents with type 1 diabetes. We have asked whether or not there was a correlation between daily insulin dosage, duration of diabetes, metabolic control, age, pubertal stage, and body mass index (BMI) versus serum androgen concentrations. Basal total and free testosterone, dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha diol-G) plasma concentrations were measured in 36 pubertal boys and 31 pubertal girls with type 1 diabetes and in 59 sex- and pubertal stage-matched control subjects without diabetes. Significantly higher serum total testosterone (p<0.01) and free testosterone (p<0.05) levels were found in females and males with type 1 diabetes than in controls at pubertal stage 5. DHEA-S, SHBG, DHT and 3alpha diol G concentrations in patients with diabetes were not significantly different from those in controls. There was no correlation between daily insulin requirements and serum androgen levels. These data suggest that adolescents with diabetes have similar serum levels of DHEA-S, SHBG, DHT and 3alpha diol G as healthy subjects at all stages of puberty. However, there are significant differences in serum testosterone and free testosterone levels in adolescents with diabetes when compared to healthy, sex- and pubertal stage-matched controls in late puberty. We hypothesize that the increased testosterone levels in patients with diabetes could relate to reduced fertility in females, disorders of sexual maturation and an increased risk for cardiovascular complications later in life.     

Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins

We have observed that familial factors have a decided influence on the plasma content of sex steroids in men both in the general population and in men of families with prostatic cancer. The contribution of genetic and nongenetic familial factors on the variation of plasma sex steroid content and action has now been investigated in 75 pairs of normal male monozygotic (MZ) twins and 88 pairs of dizygotic (DZ) twins. Zygosity was determined by measuring ten blood proteins and enzymes. The mean plasma values for testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and 3 alpha-androstanediol glucuronide (3 alpha-diol G), free T, LH, FSH, SHBG, age, and degree of adiposity were all similar between the groups of twins. Familial factors (P less than 0.01) accounted for 50% or more of the variation in plasma hormone levels in MZ twins (3 alpha-diol G, 84%; T/DHT, 70%; T, 63%; E1, 63%; free T, 61%; E2, 57%; DHT, 56%; LH, 55%; and FSH, 54%) except for SHBG, which was 30%. The familial influence was greater in MZ twins than in DZ twins for all measurements except for SHBG. The heritability of the variation of hormone levels in plasma was determined from the equation: 2[rMZ(intraclass correlation) - rDZ]. Genes regulate 25% to 76% of the total variation of plasma content of the hormones except for DHT (12%) and SHBG (less than 1%). Genetic regulation of tissue DHT formation was suggested by observing a 48% genetic effect on the plasma content of 3 alpha-diol G.(ABSTRACT TRUNCATED AT 250 WORDS)     

MEASUREMENT OF SEX HORMONE BINDING GLOBULIN IN HUMAN AMNIOTIC FLUID: ITS RELATIONSHIP TO PROTEIN AND TESTOSTERONE CONCENTRATIONS, AND FETAL SEX

Sex hormone binding globulin (SHBG) has been identified and quantified in human amniotic fluid. Identification was based on its electrophoretic mobility on polyacrylamide gels and its steroid binding characteristics, which were identical to those attributed to SHBG in pregnancy serum. Amniotic fluid SHBG binding capacity was measured by competitive saturation analysis using [³H]-5α-dihydrotestosterone as the labelled ligand, after removal of endogenous steroids with dextran-coated charcoal. Similar amniotic fluid SHBG binding capacities were found in samples taken during early (13–20 weeks, 8.5 ± 5.1 (SD) nmol/l, n= 10) and late (36–37 weeks, 8.7 ± 3.0 nmol/l, n= 28) pregnancy. In comparison with pregnancy serum SHBG levels (390 ± 140 nmol/l, n= 5), amniotic fluid SHBG was not enriched in relation to the relative concentrations of total proteins, albumin or transferrin. Amniotic fluid is therefore not a better source for the purification of SHBG than pregnancy serum. There were no differences in amniotic fluid SHBG levels with respect to fetal sex, but positive correlations were observed between SHBG binding capacities and testosterone concentrations in amniotic fluid from both male (r= 0.68, P < 0.001) and female (r= 0.53, P < 0.05) fetuses. It is suggested that SHBG may sequester free testosterone in amniotic fluid, and that measurements of SHBG in amniotic fluid may help to more accurately identify fetal sex in cases where borderline amniotic fluid testosterone concentrations are found.     

High affinity binding of adrenocortical and gonadal steroids by plasma proteins of Australian marsupials.

High affinity binding of cortisol, progesterone, testosterone, and estradiol by plasma proteins was examined in 29 marsupial species by equilibrium dialysis and/or polyacrylamide gel electrophoresis. The association constant (K_a, 36°) and binding capacity ([Σ_ϱ]) for cortisol and testosterone were measured by microdialysis and found to be 3.2 to 9.6 × 10⁷M⁻¹ and 0.3 to 3.7 × 10⁻⁷M respectively, for cortisol and 1.6 to 8.3 × 10⁸M⁻¹ and 0.3 – 4.0 × 10⁻⁷M for testosterone. High-affinity binding of cortisol was detected in all 25 species studied by this method but testosterone was bound in 9 only. Steroid-binding proteins were further characterized by polyacrylamide gel electrophoresis of plasma equilibrated with radioactive steroid at 4°. Two types of non-albumin binding proteins were identified, one with a mobility like human corticosteroid-binding globulin (CBG) and an affinity for both cortisol and progesterone and a second protein with a mobility like human sex hormone-binding globulin (SHBG) and an affinity for testosterone. High affinity binding of estradiol was not detected, and a second CBG was found in four species.     

Mental wellbeing and quality of sexual life in women with primary Sjögren's syndrome are related to circulating dehydroepiandrosterone sulphate

Objectives: To evaluate the possible effect of androgen status on sexuality and mental wellbeing in patients with primary Sjögren''s syndrome (pSS). Methods: Serum levels of dehydroepiandrosterone sulphate (DHEA-S), testosterone (T), androstenedione, sex hormone binding globulin (SHBG), and the SHBG/T ratio were measured in 21 women with pSS. Sexual life was assessed by a Swedish version of the McCoy scale, which covers sexual experience and responsiveness during the past 30 days. A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine quality of life and psychological symptoms in patients with pSS. Results: Positive correlations were found between DHEA-S serum levels and the total McCoy score (r_s=0.62; p<0.01), as well as the subscales of this score reflecting arousal (0.59; p<0.05), desire (r_s=0.52; p<0.05), and satisfaction (r_s=0.66; p<0.01). Serum DHEA-S concentrations were also related to the total PGWB score (r_s=0.60; p<0.01) and subscales of this score: depression (r_s=0.62; p<0.01), wellbeing (r_s=0.64; p<0.01), general health (r_s=0.67; p<0.01), and self control (r_s=0.67; p<0.01). Total McCoy and PGWB scores and their subscales were not related to the serum levels of testosterone and androstenedione or the T/SHBG ratio. Conclusions: Circulating levels of the weak androgen DHEA-S are positively related to the quality of sexual life and mental wellbeing in women with pSS.     

Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings

Objective Sex steroid concentrations in men are related to body composition and both are determined by genetic and environmental factors. This study investigates heritability estimates of sex steroid serum concentrations and body composition as well as the genetic and environmental components of their interrelation. Patients Six hundred and seventy‐four men (25–45 years) were included in this study with 274 independent pairs of brothers. Measurements Body composition and regional fat mass estimates were determined using dual‐energy X‐ray absorptiometry. Serum testosterone (T), SHBG, oestradiol (E₂) and LH levels were determined by immunoassay; free T and E₂ levels were calculated. Results Both sex steroid hormone concentrations and indices of body composition exhibited significant heritability estimates. Among sex steroid hormones, T had the highest heritability (h² = 0·65), followed by free T (h² = 0·54). A heritability of 0·73 was observed for SHBG; a heritability estimate of 0·83 was obtained for body weight. Significant genetic correlations were found between whole body fat mass and serum T (ρ_G = –0·46), free T (ρ_G = –0·27) and SHBG (ρ_G = –0·48) concentrations. No genetic relationship was observed between total (F) E₂ or LH concentrations, respectively, and body composition. Conclusion Both sex steroid serum levels and body composition are under strong genetic control. Their interrelation is in part underlied by a genetic correlation, indicative of the action of shared genes.     

Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men

Although triiodothyronine (T₃) exerts major regulatory actions in both animals and humans, most clinical studies of T₃ administration have been relatively short-term. The present study examined the effects of more than 2 months (63 days) of low-dose T₃ treatment on overnight pulsatile growth hormone (GH) secretion, short-term insulin secretion, and of sex steroid levels in seven healthy, lean men studied at an inpatient metabolic unit. At baseline, there were strong correlations between sex hormone—binding globulin (SHBG) and several measures of GH production, including total GH production (r = .99), GH interburst interval (r = −.75, and GH mass (r = .82). SHGB was also inversely correlated with basal insulin secretion (r = −.74). There was a 42% increase in serum levels of total testosterone (18.5 ± 1.3 to 26.3 ± 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 ± 2.2 to 44.9 ± 7.0 nmol/L, P = .008) following T₃ treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 ± 18.4 to 137.3 ± 19.5 pmol/L. T₃ treatment significantly reduced the GH interburst interval (P < .05) and produced slight increases in the measures of GH secretion. There were no statistically significant effects of T₃ treatment on insulin secretion, although insulin peak amplitude, mass secreted per burst, and total production all decreased. We conclude that experimentally induced T₃ excess in healthy men produces significant and sustained changes in sex hormone levels and GH secretion. Furthermore, there are strong associations between SHBG and both GH and insulin secretion independent of thyroid hormone excess that require additional study.     

Evaluation of exercise capacity using wave intensity in chronic heart failure with normal ejection fraction

Impaired exercise capacity has been found in patients with diastolic dysfunction with preserved systolic function. Although conventional transthoracic echocardiography (TTE) provides useful clinical information about systolic and diastolic cardiac function, its capability to evaluate exercise capacity has been controversial. The inertia force of late systolic aortic flow is known to have a tight relationship with left ventricular (LV) performance during the period from near end-systole to isovolumic relaxation. The inertia force and the time constant of LV pressure decay during isovolumic relaxation can be estimated noninvasively using the second peak (W₂) of wave intensity (WI), which is measured with an echo-Doppler system. We sought to determine whether W₂ is associated with exercise capacity in patients with chronic heart failure with normal ejection fraction (HFNEF) and to compare its ability to predict exercise capacity with parameters obtained by conventional TTE including tissue Doppler imaging. Sixteen consecutive patients with chronic HFNEF were enrolled in this study. Wave intensity was obtained with a color Doppler system for measurement of blood velocity combined with an echo-tracking system for detecting changes in vessel diameter. Concerning conventional TTE, we measured LV ejection fraction (EF), peak velocities of early (E) and late (A) mitral inflow using pulse-wave Doppler, and early (Ea) and late (Aa) diastolic velocities using tissue Doppler imaging. Left ventricular EF, E/A ratio, Ea, and E/Ea ratio did not correlate with exercise capacity, whereas W₂ significantly correlated with peak VO₂ (r = 0.54, p = 0.03), VE/VCO₂ slope (r = ?0.53, p = 0.03), and ΔVO₂/ΔWR (r = 0.56, p = 0.02). W₂ was associated with exercise capacity in patients with chronic HFNEF. In conclusion, W₂ is considered to be clinically more useful than conventional TTE indices for evaluating exercise capacity in patients with chronic HFNEF.     

Hypertriglyceridemia and hypoalphalipoproteinemia in azoospermic and oligospermic young men: Relationships of endogenous testosterone to triglyceride and high density lipoprotein cholesterol metabolism

Based upon the hypothesis that endogenous testosterone plays a significant role in triglyceride and high density lipoprotein cholesterol metabolism, the specific aim of this study in 9 azoospermic and 10 oligospermic subjects (compared to 20 fertile men) was to examine potential relationships between endogenous testosterone, luteinizing hormone, follicle stimulating hormone, lipids-lipoproteins, and lipoprotein lipases. The azoospermic and oligospermic men had much higher fasting plasma triglyceride levels (mean ± SD; 479 ± 258, 295 ± 119) than did normal controls (105 ± 31 mg/dl, p < 0.001, p < 0.001). The azoospermic and oligospermic subjects also had much lower mean high density lipoprotein cholesterol levels (C-HDL) than normals (27 ± 8 and 29 ± 7 versus 44 ± 7 mg/dl, p < 0.001, p < 0.001). Very low density lipoprotein's (VLDL) in vitro potency to activate lipoprotein lipase (U/mg of VLDL protein) was about one-third normal in the azoospermic subjects (57 ± 26 U/mg), and about one-half normal in the oligospermic subjects (86 ± 27), with values in the normals being 167 ± 58, p < 0.001, p < 0.001. Mean plasma testosterone levels were 3.4 ± 0.7 ng/ml in the azoospermic subjects, considerably lower than mean levels in normals (6.6 ± 2.0, p < 0.001), with intermediate levels in the oligospermic men (5.2 ± 1.7 ng/ml). Pooling the data for the azoospermic, oligospermic, and normal men, plasma testosterone levels were positively correlated with C-HDL (r = .42, p < 0.01) and inversely correlated with triglyceride (r = ?.50, p < 0.001) and very low density lipoprotein cholesterol (r = ?.37, p < 0.02). Plasma testosterone was also positively correlated with lipoprotein lipase activator potency, (r = .45, p < 0.01). These findings suggest that endogenous physiologic testosterone levels may play a role relative to regulation of triglyceride and C-HDL levels in men, and may also affect the hydrolytic susceptability of very low density lipoprotein molecules. Hypertriglyceridemia and low C-HDL levels in azoospermic and oligospermic men mandate quantitation of lipid-lipoprotein levels in infertility clinics to identify men at putatively increased risk for future coronary heart disease.     

Relationship of sex steroid hormones with bone mineral density (BMD) in a nationally representative sample of men

Objective Sex steroid hormones influence bone mineral density (BMD) in women, but are less well‐studied in men. We evaluated the association of serum total and free sex steroid hormones and SHBG with osteopaenia in a nationally representative sample of men aged 20–90 years. Design BMD and sex steroid hormones were measured among participants in NHANES III, a cross‐sectional study of the US population. Population A total of 1185 adult men in morning examination session of Phase I of NHANES III (1988–91). Measurements Relation of oestradiol (E₂), testosterone, and SHBG concentrations with BMD. Osteopaenia was defined as 1–2·5   SD below the mean for white men aged 20–29 years. Results Men in the lowest quartile of free E₂ had 70% increased odds (OR = 1·69, 95% CI 0·95–2·98) of osteopaenia compared with men in the highest quartile. Men in the lowest quartile of free testosterone had nearly four times the odds of osteopaenia than those in the highest quartile (OR = 3·82, 95% CI 1·87–7·78). Lower concentrations of SHBG appeared protective against osteopaenia (P‐trend = 0·01). Neither total testosterone nor total E₂ was associated with BMD, although men with clinically low E₂ (< 20 ng/l) had lower BMD (0·930 g/cm², 95% CI 0·88–0·98) than men with normal‐range E₂ (1·024 g/cm², 95% CI 1·01–1·04; P = 0·004). Findings for free E₂ were most pronounced among elderly men, while the findings for free testosterone were most pronounced among younger men. Conclusions In this nationally representative study, men with lower free E₂, lower free testosterone, and higher SHBG concentrations in circulation were more likely to have low BMD.     

Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy

Background: We aimed to investigate the associations between androgen status and markers of liver disease severity and to determine the effect of interferon‐α (IFN‐α) treatment on sex hormone levels in the context of hepatitis C infection. Methods: We audited liver biopsy and sex hormone data from 35 men with chronic hepatitis C and a separate group of 11 men with hepatitis C who received IFN‐α treatment at Fremantle Hospital. Results: We found that men with low fibrosis scores (0–2) on the modified Knodell histological activity index were more likely to have lower sex hormone–binding globulin (SHBG) levels (38.2 ± 13.2 vs 66.6 ± 43.3 nmol/L, P < 0.001) and higher free testosterone levels (380.4 ± 102.0 vs 255.9 ±83.0 pmol/L, P = 0.01) than those with higher fibrosis scores (3–6). SHBG directly correlated with fibrosis scores (r = 0.37, P = 0.032). Free testosterone levels inversely correlated with liver fibrosis scores (r = ?0.43, P = 0.011). A transient reduction in total testosterone of 5.7 ± 4.2 nmol/L (P = 0.014) occurred within the first 6 months of IFN‐α therapy although free testosterone was unaffected. Conclusion: More severe liver disease was associated with lower free testosterone and higher SHBG. IFN‐α therapy reduced total testosterone but not to hypogonadal levels, with no decline in free testosterone. These data suggest that liver disease in hepatitis C infection modulates androgen status indirectly via increased SHBG. Screening for androgen deficiency in the context of hepatitis C infection should selectively target men with more severe liver disease or documented higher grade fibrosis.