Aldo Isidori

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis

Objectives  Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle‐aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile.

Effects of testosterone on sexual function in men: results of a meta‐analysis

Objectives  The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta‐analysis of placebo‐controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life.

Medical treatment to improve sperm quality.

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.

Subjective visual halos after sildenafil (Viagra) administration: Electroretinographic evaluation.

PURPOSE The ophthalmologic and electroretinographic (ERG) findings in one subject with subjective visual disturbances after sildenafil administration are described. DESIGN Interventional case report. METHODS A complete ophthalmologic examination was performed, including best-corrected visual acuity and ERG, repeated 1 and 2 hours after administration of 100 mg of sildenafil. MAIN OUTCOME MEASURES Rod responses were obtained over a range of retinal illuminances from those producing a minimum detectable response to those producing rod saturation. Intensity amplitude function was determined. RESULTS At 2 hours after 100 mg of oral sildenafil, we observed significant variations from baseline in parameters of best-fit Naka-Rushton function; V(max) was notably higher, and K was 0.14 log units lower than baseline. CONCLUSIONS Sildenafil administration resulted in a higher rod response to light stimuli and in a higher rod sensitivity. These findings are consistent with the weak PDE-6 inhibition induced by sildenafil.

Treatment of male infertility

Male factor infertility is a general term that describes a situation in which the inability to conceive is associated with an alteration identified in the male partner. This dysfunction may be associated with low sperm concentration (oligozoospermia), poor sperm motility (asthenozoospermia) or abnormal sperm morphology (teratozoospermia); however, generally, a disturbance of all these variables, oligoasthenoteratozoospermia, is mostly frequent in male subfertility. For many andrological disorders, it is not possible to find a reasonable cause and various uncontrolled treatments have been applied to infertile men, often just on an empirical basis. More recently, after the explosive development of modern assisted reproduction techniques (ARTs), feasible with a single spermatozoon [intracytoplasmic sperm injection (ICSI)], the treatment of male infertility has received new meaning and andrologists are no longer expected to achieve a quantitative increase in sperm number but are instead asked to improve the fertility potential of the single sperm cell in order to achieve better results in both in vitro fertilization and ICSI. Additional prospective studies are needed to better understand the possible role of therapy in ART candidate patients.

Aspirin inhibits androgen response to chorionic gonadotropin in humans

Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17β-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E2 levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17β-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E2levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17β-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E(2) levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E(2) levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17beta-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.

Treatment and Follow-Up of Patients with Infertility due to Spermagglutinins

A therapeutic trial based on pharmacologically induced azoospermia followed by the administration of corticosteroids was carried out in 48 patients with infertility due to spermagglutinins. Three types of responses were observed: type A, no modifications in the blood and spermagglutinating (SA) titer (19 cases); type B, disappearance or significant decrease in SA titer during treatment, with return to normal values upon resumption of spermatogenesis (7 cases); and type C, disappearance or significant decrease in SA titer for at least 1 year after stopping treatment (22 cases). Within the 1st year after stopping therapy only men who responded in type C fashion were able to impregnate partners; three pregnancies ended in abortion and nine in normal births.

Acute electroretinographic changes during sildenafil (Viagra) treatment for erectile dysfunction.

The authors describe their findings on 12 subjects who were treated with 50 mg of Sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after ingestion. The Naka–Rushton equation was used to describe the b-wave luminance-response function of the scotopic ERG. Statistically significant differences were noted in the Vmax and K values. Sildenafil ingestion resulted in an increase in Vmax (higher rod response to light stimuli) and a decrease in K (higher sensitivity).

STIMULATORY ACTION OF ENDOTHELIN-1 ON RAT LEYDIG CELLS: INVOLVEMENT OF ENDOTHELIN-A SUBTYPE RECEPTOR AND PHOSPHOLIPASE A2-ARACHIDONATE METABOLISM SYSTEM

In a previous report we have observed that endothelin-1 (ET-1) is able to stimulate testosterone (T) production by rat Leydig cells revealing an interaction with human chorionic gonadotropin (hCG). The present study was designed to further characterize the stimulatory action of ET on testicular steroidogenesis, to evaluate which subtype of ET receptors is involved in this activity and to examine the role of phospholipase A2 (PLA2)-arachidonate metabolism system in ET-1 transduction mechanism. To this purpose we investigated: i) the interaction of ET-1 with another secretagogue of T, like luteinizing hormone releasing hormone (LHRH); ii) the interference of ET(A) and ET(B) receptor antagonists (BQ-123 and BQ-788, respectively) and of inhibitors of PLA2 (quinacrine) and arachidonate lipoxygenase pathway (nordihydroguaiaretic acid:NDGA) on ET-1-induced T and PGE2 secretion from purified rat Leydig cells. Data obtained indicate that ET-1 amplified T and PGE2 response to LHRH and this secretagogue in turn potentiated testicular steroidogenesis stimulated by endothelin. The ET(A) antagonist, BQ-123, inhibited in a dose-related fashion ET-1-induced T production whereas ET(B) antagonist, BQ-788, failed to affect T response to the peptide. Furthermore, ET(A) antagonist inhibited the stimulatory effect of ET-1 on hCG- or LHRH-induced T secretion and it was able to exert a dose-dependent inhibition of ET-1-stimulated PGE2 output. Moreover, a PLA2 inhibitor quinacrine inhibited the stimulatory action of ET-1 on T production and suppressed basal and ET-1-induced PGE2 release whilst a lipoxygenase blocker NDGA did not modify T response to the peptide. Taken together these findings i) indicate additivity of effects between ET-1 and LHRH in stimulating T and PGE2 production; ii) confirm that ET(A) subtype receptors mediate the stimulatory action of ET-1 on rat Leydig cells; iii) strongly suggest that PLA2-arachidonate metabolism system is involved in endothelin transduction mechanism.

Rotationally invariant slave bosons for strongly correlated superconductors

We extend the rotationally invariant formulation of the slave-boson method to superconducting states. This generalization, building on the recent work by Lechermann et al. [Phys. Rev. B {\bf 76}, 155102 (2007)], allows to study superconductivity in strongly correlated systems. We apply the formalism to a specific case of strongly correlated superconductivity, as that found in a multi-orbital Hubbard model for alkali-doped fullerides, where the superconducting pairing has phonic origin, yet it has been shown to be favored by strong correlation owing to the symmetry of the interaction. The method allows to treat on the same footing the strong correlation effects and the interorbital interactions driving superconductivity, and to capture the physics of strongly correlated superconductivity, in which the proximity to a Mott transition favors the superconducting phenomenon.