The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross-over. The median study length was 3 months (range 1-36 months). Our meta-analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut-off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta-regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta-analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low-normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long-term safety data are not available. The present meta-analysis highlights the need, and pitfalls, for large-scale, long-term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle-aged and elderly men with reduced T levels and ED.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

Superconducting spintronics has emerged in the past decade as a promising new field that seeks to open a new dimension for nanoelectronics by utilizing the internal spin structure of the superconducting Cooper pair as a new degree of freedom 1,2 . Its basic building blocks are spin-triplet Cooper pairs with equally aligned spins, which are promoted by proximity of a conventional superconductor to a ferromagnetic material with inhomogeneous macroscopic magnetization 3 . Using low-energy muon spin-rotation experiments we find an unanticipated e ect, in contradiction with the existing theoretical models of superconductivity and ferromagnetism: the appearance of a magnetization in a thin layer of a non-magnetic metal (gold), separated from a ferromagnetic double layer by a 50-nm-thick superconducting layer of Nb. The e ect can be controlled either by temperature or by using a magnetic field to control the state of the remote ferromagnetic elements, and may act as a basic building block for a new generation of quantum interference devices based on the spin of a Cooper pair.The ability to manipulate the spin degree of freedom of charge carriers is key to realizing future spin-based electronics. Integrating superconductors into spintronic devices can greatly enhance performance 1 and allows the transport of spin over long distances without the dissipation of heat 2 . To achieve the alignment of electron spins, ferromagnetic materials are used. Superconductivity and ferromagnetism are, however, antagonistic states of matter, and the interplay between these two states results in the conversion of conventional spin-singlet into spin-triplet pair correlations 3 . Whereas spin-singlet pairs have spin angular momentum S = 0, spin-triplet pairs have S = 1, with three possible spin projections s z = −1, 0, +1. The realization of such spin-triplet pairs in mesoscopic systems containing interfaces between superconducting (S) and ferromagnetic (F) layers has attracted much interest from both the theoretical and experimental communities. Interaction of spin-singlet superconductivity with collinear ferromagnetism leads to oscillations and suppression of the pair correlation at a short distance ξ f due to the exchange magnetic field in the ferromagnet, which tends to align the spins of electrons parallel 4-7 . However, to create longer-range penetration of spin-triplet superconductivity into the ferromagnet, interaction with a non-collinear magnetism is required [8][9][10] , motivating the discovery of superconducting currents through ferromagnetic metals over distances far longer than the singlet penetration length ξ f (refs 11-13). These long-range triplet components (LRTC) have parallel spin projections (s z = ±1), and are not suppressed by the exchange field. Theory predicts that the conversion into spin-triplet pairs should also give rise to an induced magnetic moment in the superconductor, decaying away from the interface [14][15][16] , often called the inverse or magnetic proximity effect. For diffusive systems this induced m...

Graphite is a model system for the study of three-dimensional electrons and holes in the magnetic quantum limit, in which the charges are confined to the lowest Landau levels. We report magneto-transport measurements in pulsed magnetic fields up to 60 T, which resolve the collapse of two charge density wave states in two, electron and hole, Landau levels at 52.3 and 54.2 T, respectively. We report evidence for a commensurate charge density wave at 47.1 T in the electron Landau level, and discuss the likely nature of the density wave instabilities over the full field range. The theoretical modeling of our results predicts that the ultraquantum limit is entered above 73.5 T. This state is an insulator, and we discuss its correspondence to the "metallic" state reported earlier. We propose that this (interaction-induced) insulating phase supports surface states that carry no charge or spin within the planes, but does, however, support charge transport out of plane.

Approximately 30% of cases of couple infertility are due to a male factor. Several conditions can interfere with spermatogenesis and reduce sperm quality and production. Treatable conditions, such as hypogonadism, varicocele, infections and obstructions, should be diagnosed and corrected, but many aspects of male factor infertility remain unclear. Various agents have been used in the attempt to increase the fertility potential of subjects with idiopathic oligoteratoasthenozoospermia. The rationale of medical treatment to improve sperm quality in these subjects has been questioned by the introduction of assisted reproductive technologies. However, there is now growing awareness of the importance of good quality spermatozoa for embryonic development and higher birth rates. Confounding factors in assessing the efficacy of male infertility treatments have erroneously inflated the superiority of assisted reproductive technologies over conventional approaches. A systematic review is given of relevant randomized controlled trials and effects on semen parameters. The analysis reveals that although results are heterogeneous, gonadotrophins, anti-oestrogens, carnitine and trace elements may be beneficial in improving sperm quality, although their effect on pregnancy rate remains controversial. The most common drug regimens are compared and an estimate of the results expected from these treatments provided.

For patients with worsening levels of consciousness and radiologically evident ventricular enlargement, we recommend external ventricular drainage. We reserve surgical resection of necrotic tissue for patients whose clinical status worsens despite ventriculostomy, those for whom worsening is accompanied by signs of brainstem compression, and those with tight posterior fossae.