Diagnostic, traitement et surveillance de l’hypogonadisme de survenue tardive chez l’homme: Recommandations officielles de l’International Society for the Study of the Aging Male (ISSAM) et commentaires

There is increasing interest in the subject of hormone changes in the aging male, which is likely to become particularly important with the expected growth in the population of men over 50. The main concerns at present are androgen decline in the aging male (ADAM), or partial androgen deficiency of the aging male (PADAM), commonly known as the andropause. Although progress has been made in our knowledge of androgen deficiency in the aging male, it is still incomplete and sometimes confusing, and some aspects of androgen replacement therapy remain controversial. The International Society for the Study of the Aging Male (ISSAM) therefore felt it was a good time to review the current situation by publishing a series of practical and official guidelines concerning the diagnosis, treatment and monitoring of late-onset hypogonadism in males. The aim of this study is to present and discuss the French translation of these recent international guidelines.     

Infection génitale à chlamydia chez l’homme et retentissement sur la fécondité

Chlamydia trachomatis is responsible for the most common sexually transmitted disease, up to 40% of the non gonococcal urethritis. It is a compulsary intracellular parasite. Its peculiar metabolism makes the bacteria interfere with the host cell immunity. Infection can become chronic and induce inflammation, if not properly treated, by permanent emission of antigens and heat shock proteins, and stimulation of Tcells. Autoimmunization against sperm can occur and impair fertilization and embryo implantation. Thus, Chlamydial infection can be associated with male infertility because of tissue damage, altered movement and antisperm immunization. PCR and LCR are to date the most sensitive detection techniques for c.trachomatis. Our study aim was to determine the prevalence of Chlamydial infection by PCR in 6 groups of men in andrologic practice. The highest prevalences have been found in the infertile men group and in the symptomatic group. No Chlamydia culture was found positive in any group. The association of PCR with anti C. trachomatis seminal IgA and seric IgG are useful tools for andrologic exploration.     

Analyse de l’algorithme décisionnel basé sur la testostérone totale et recommandé pour le diagnostic de l’hypogonadisme acquis

Introduction

The diagnosis of acquired hypogonadism is still an important issue for laboratory medicine. Hypogonadism is defined as a sustained decrease of total testosterone confirmed by the biochemistry laboratory and total testosterone measurement is proposed as the initial step in the investigation of hypogonadism. If TT is over 12 nmol/l, the probability of hypogonadism is considered low and it is suggested that patients be referred to others methods of investigation. Only a small percentage of men aged 50 and over are treated for hypogonadism. Seventy percent of men investigated for hypogonadism have a TT of over 12 nmol/l and there is an unpredictable increase of SHBG during this period, reducing the bioavailability of circulating testosterone. The hypothalamic-pituitary gonadal axis is modified with age and contributes to hypogonadism. The efficacy of biochemical investigation of hypogonadism needs to be reassessed.

Materials and methods

Total testosterone and LH were measured on the Centaur immunoanalyser (Siemens) and SHBG was analysed on the Immulite 2000 (Siemens). Bioavailable testosterone was calculated using the formula provided by ISSAM.

Results

Using the algorithm based on TT, only 27.9% of men would have been investigated for hypogonadism. Of the 638 patients considered as normal, 325 showed an index of hypothalamic-pituitary gonadal axis stimulation and possible hypogonadism, revealed by an elevated LH. In these patients with TT superior to 12 nmol/l and a LH superior to 7 UI/l, SHBG level was at the upper limit of or over the reference range. No correlation was observed between calculated BT and the abnormal LH level found in these patients. Calculated BT was not considered a good marker of hypogonadism for these patients.

Conclusion

Elevated LH is a biochemical marker of hypogonadism and should be interpreted in the context of stimulation of the hypothalamic-pituitary gonadal axis. Based on our data, an initial step in the investigation of hypogonadism based only on TT does not seem suitable for the identification of all patients who might experience hypogonadism. A complete investigation should be offered to all patients with clinical evidence of hypogonadism whatever their TT level. In patients who might benefit from hormonal treatment, calculated BT should be interpreted with caution. A definition of hypogonadism based on TT does not seem appropriate and a new definition based on bioavailable testosterone and the hypothalamopituitary gonadal axis should be considered.     

Développementin vitro de la lignée germinale foetale mâle chez le rat, la souris et l’homme

The key role of the foetal germ cell line in the reproductive capacity of the adult has been known for a long time. More recently, the observed increase in male reproductive disorders such as the decline of sperm count and quality and the increased incidence of testicular cancer has been postulated to be due to alterations of foetal and neonatal testicular development in response to increasing environmental pollution. However, few tools are available to study foetal and neonatal germ cell line development and the effects of physiological or toxic substances on this process. The authors have developed an organ culture system in which foetal or neonatal testis is grown on a filter floating on a synthetic medium free of serum, hormones or biological factors. This study, using rats and mice, first compared the long-term morphological and functional development of Sertoli and germ cells in thisin vivo system. In rats, these cells developed normally over a period of two weeksin vitro. Fewer cells were produced thanin vivo, but a similar level of differentiated function was observed. Germ cells, which are difficult to maintainin vitro, resumed mitosis after a quiescent period, at the same time asin vivo. Similar results were obtained with mouse fetuses, but this model was less efficient. This culture model can be used to study post-natal development of the germ cell lineage in testes derived from foetuses on the last day of foetal life and invalidated for P63, that do not survive after birth. This gene was found to be involved in the regulation of germ apoptosis which resumes after birth in the mouse. Lastly, this model applied to the human species (from 6 to 12 weeks of gestation) showed that testicular architecture and germ cells can be maintained for 4 days with better efficiency at younger stages than at older stages. p]In conclusion, testicular architecture and intercellular communications are sufficiently preserved to sustain gametogenesisin vitro with no added factors. This method is potentially useful to study the effects of various factors, particularly xenobiotics.     

Intérêt de l’utilisation de la scintigraphie osseuse dans le diagnostic et le suivi de l’ostéochondrite primitive de la hanche

Osteochondritis, or Legg-Calvé-Perthes disease (LCP), is a necrosis of the proximal femoral epiphysis. This vascular accident entails on the complex phenomenon of growth of the child's hip and can result in deformations or even a strict destruction of the proximal femoral epiphysis. The aim of this article is to show the interest of the bone scintigraphy (BS) in precocious diagnosis and follow-up of LCP disease. In this aim, we introduced a clinical case of LCP disease where BS allowed a precocious diagnosis and a strigent monitoring. Discussion of case includes a systematic review of literature.     

Dosage de la testostérone plasmatique chez l’homme

The measurement of testosterone in plasma is the main tool to investigate the endocrine function of the testis. Radioimmunoassay of total testosterone using³H-testosterone as tracer, after steroid extraction and chromatography avoids the interactions of steroids and plasma proteins in the assay. It can be considered as a method of reference. Direct methods, without extraction and chromatography, and using non-radioactive tracers have been developped. They are easier and faster to perform but less accurate because of the aforementioned interactions. In the plasma, testosterone is mainly bound with a high affinity to SBP and with a low affinity to albumin. Non-SBP-bound testosterone is considered to represent the fraction of the testosterone available for target cells. Non-SBP-bound testosterone can be measured after precipitation of SBP by ammonium sulfate. This procedure is usefull to investigate androgenicity when plasma SBP concentrations are altered such as in hyperthyroidism, aging and severe exocrine testicular failure. Plasma free testosterone can be mesured by equilibrium dialysis, a procedure not suitable for routine assay or more easily but less accuratly by direct measurement in the plasma with methods using tracer analogs. The interpretation of testosterone measurement must take into account moment-to-moment and nycthemeral variations. The inter-subject variations of plasma testosterone concentrations are large, the decrease with aging is very progressive. Testosterone has a permisive effect on male sexual function with a threshold level above which no relationship between plasma testosterone concentration and sexual “performances” could be demonstrated. Because of the multifactorial control of human sexual function, the threshold value is difficult to determine for a given patient.     

Place de l’embolisation percutanée de la varicocèle dans le traitement de l’infertilité

Objectives

To describe percutaneous embolization of varicocele and to evaluate the effect on fertility disorders.

Materials and methods

One hundred nineteen patients, aged 11 to 48 years, underwent percutaneous embolization for varicocele indicated by a fertility disorder in 23% of cases. Correction of the varicocele and resolution of associated pain, improvement of testicular trophicity and the effect on fertility were studied and a review of the literature was performed.

Results

Percutaneous embolization was performed using neuroleptanalgesia on an outpatient basis. The technique combined venous sclerotherapy and placement of coils in the gonadal vein. The technique was successful in 95% of cases and one complication was observed. At 3 months, the varicocele and related pain had resolved in 98% of treated patients. According to previous reports in the literature, the relations between varicocele and fertility disorders are still unclear, but improvement of fertility (semen quality and conception rates) after varicocele repair has been established.

Conclusion

Although the consequences of varicocele on fertility have not been fully elucidated, treatment of varicocele appears to be beneficial. Percutaneous embolization of varicocele is a safe and effective alternative to surgery. This technique, based on a urological and radiological consensus, is the first-line treatment for varicocele in our institution.     

Le traitement actuel de l’impuissance chez le paraplégique

The author is summing up his 25 years experience in the treatment of paraplegics impotency to account for the present and almost continuous resulting use of self injections of vasoactive drugs. The sexual reeducation, based on the neurological level, that is to say on the physiopathology, has disappeared for 10 years, as the urinary reeducation has been replaced by self catheterism. Nevertheless, there are some education rules left for the paraplegics and the couple in the relationship as well as in the technique. Trying to obtain orgasm for the paraplegics has become a priority, since the erection is obtained easily through drugs. A reference is made to the vasoactive drugs that have been used and their effects. The behaviour is precise somewhat different in the case of the traumatic and total paraplegics as compared to the partial medical paraplegics (cauda equina, spina bifida, multiple sclerosis…) for whom psychology is different. The sensitivity deficiencies which are the same for all of them mustn’t make us forget that there are still reflex erogeneous spots that must be searched for.     

Effets d’une exposition à la Vinclozoline et à la Génistéine de la gestation à l’âge adulte sur la fonction de reproduction du ratWistar mâle: protocole et résultats préliminaires

Current evidence indicates that endocrine disrupters (EDs) can induce adverse effects on the male reproductive tract in various mammalian species. Recent reports indicate deterioration in male reproductive health in several human populations, but the evidence for a causal link with endocrine disruption is still weak. In addition, the experimental conditions of most of the reportedin vivo studies are not representative of environmental exposures (for example, high doses, short-term exposure, a single ED) and the mechanisms by which EDs disrupt the reproductive system are poorly understood. The objective of the present study is to develop an animal model to assess the reproductive effects and study the putative cellular and molecular mechanisms involved after exposure to genistein (phytoestrogen) and vinclozolin (fungicide with a known antiandrogenic potential) alone or in combination. The study will be performed in male Wistar rats, with administration of low and high doses of the compounds from conception to adulthood and a subset of the males in each treatment group will be mated with unexposed females. We plan to assess the level of sperm production, histology of the reproductive organs, motility and morphometry of spermatozoa and hormone levels, as well as DNA fragmentation of spermatozoa and determination of the number of germ cells, Sertoli cells and the diameters of seminiferous tubules. Estrogen, androgen, progesterone and FSH receptors will be detected and quantified and the level of testicular apoptosis and several apoptosis pathways will be studied to determine the putative cellular and molecular mechanisms involved. The preliminary results confirmed the developmental effects previously reported for high doses of vinclozolin. More interestingly, they indicated a number of deleterious effects for male rats exposed to low dosages alone or mixtures of low and high dosages compared to controls and rats exposed to high dosages alone. For example, a number of developmental anomalies of the genitalia were observed and a significant decrease of sperm motility and motion and fertilizing ability were observed. These preliminary results provide evidence that chronic exposure to environmental levels of EDs or mixtures of EDs have a detrimental impact on the male reproductive tract. The next step involves assessment of the anatomical disorders and the study of some of the cellular and molecular mechanisms possibly involved.     

Reactivite thermique de la peau scrotale chez l’homme

Although the existence of heat exchange between the testicular artery and the adjacent veins is well known, it may be insufficient to maintain the lower temperature of the testis. In order to investigate the role of the scrotum in testicular thermoregulation, the dynamics of scrotal and other skin temperatures was studied in relation to thermal stress. The results of this study revealed that the scrotal skin exhibited a greater thermal inertia than did other skin areas. This finding may be due to modifications in scrotal blood flow patterns as temperature increased, as well as changes in the scrotal surface area. Other possible thermoregulatory factors may include the evaporation of sweat from the scrotum. In conclusion, there seems to be a complex collection of mechanisms, rather than a single specific mechanism, regulating testicular temperature.     

Imagerie 3D fonctionnelle de l’articulation de la hanche pour la prévention,le diagnostic,la planification et le suivi chirurgical

In order to reduce the failure rate due to a poor understanding of mechanical causes, the new diagnostics and pretreatments of osteoarticular pathologies are turning increasingly to methods assessing the 3D morphology of the joints, its kinematics and its impact on the adjacent joints. The goal of the TecSan HIPEOS project is to provide, in combination with the EOS? system, a set of clinical tools to better understand the structural and kinematic 3D consequences of musculoskeletal diseases in order to optimize the decision, the surgery and functional recovery. The TecSan HIPEOS project has led to clinically validated applications (sterEOS?), that integrate the 3D approach in clinical practice for the diagnosis, the post-operative control and follow-up of the hip joint based on a static and/or a functional approach of the joint. Other prototype tools have been developed and used to establish proofs of concept and to open interesting perspectives for future applications including surgical planning and pseudokinematic studies. The article summarizes the results obtained both in terms of product innovation and clinical validation.     

Intérêt de la tomoscintigraphie cardiaque à la 123I-mIBG couplée à la perfusion myocardique dans le diagnostic de l’atrophie multisystématisée

ObjectiveThe aim of this prospective study is to assess the pertinence of using ¹²³I-mIBG myocardial tomoscintigraphy coupled with perfusion scintigraphy as a diagnostic tool, to discriminate between multiple system atrophy (MSA) and idiopathic Parkinson's disease (PD) at first guided by clinical data and L-DOPA tests.Material and methodsForty patients, aged from 43 to 78 years (median 62 years) with Parkinson's syndrome were studied. Nineteen had a diagnosis of PD (criteria of brain bank) and 21 AMS (Gibbs criteria). All were given test to acute L-DOPA. Chest-centered planar imaging (128 × 128 matrix, 5 minutes of duration) is performed at 1 hour and 4 hours after injection of 220 MBq of ¹²³I-mIBG, in addition a non-synchronised tomoscintigraphy (64 × 64 matrix, 32 images of 50 seconds , zoom 1.45) was performed after the 4th hour and 15 minutes after injection of 200 to 400 MBq of ^99mTc-tetrofosmin. Besides neurological data, the parameters retained for comparison purposes with ¹²³I-mIBG cardiac tomoscintigraphy were patients’ age, duration of disease and L-DOPA test results. Two regions of interest (ROI) identical in size and in shape are used for ¹²³I-mIBG uptake quantifications (H/M and washout [Wo]). The first one was placed in projection of mediastinum (M) and the other one in projection of heart (H).ResultsWe found an overall decreased uptake of the myocardial ¹²³I-mIBG without perfusion abnormality in 15 of 19 patients with PD and 11 among them were L-DOPA sensitive (L-DOPA test greater than 30%). Normal tracer uptake with ¹²³I-mIBG associated with an almost quite normal perfusion was seen in 15 of 21 patients with MSA and they were little or not L-DOPA sensitive (L-DOPA test less than 30%). Therefore, 10 discordant cases (25%) between cardiac scintigraphy and clinical evolution of disease with also discordant L-DOPA tests were observed. In the PD group, quantification of data enhanced the diagnostic decision with low heart to mediastinum ratio (H/M) (1.32 ± 0.15 at the early stage and 1.25 ± 0.13 at the later stage). In the MSA group, the uptake of ¹²³I-mIBG (1.66 ± 0.43 at the early stage and 1.72 ± 0.42 at the later stage) was comparable to literature data, however, with significant inter-individual variations. The association of data of scintigraphy with L-DOPA test allows to improve sensitivity in 84% and specificity in 90.5%.ConclusionOur prospective study of 40 cases shows the relevance of cardiac sympathetic postganglionic imaging with ¹²³I-mIBG coupled with myocardial perfusion scintigraphy to discriminate between MSA and PD with a higher sensitivity (71.4%) compared to the test with L-DOPA but a lower specificity (78.9%) than the L-DOPA. The difficulty of diagnosis is firstly linked to damage occurring to both the pre- and postganglionic sympathetic systems in patients with MSA and secondly to the integrity of the sympathetic nerve endings in patients with PD. However, the association of data of scintigraphy with L-DOPA test show a significant improvement of sensibility (84%).     

Gene SRY et anomalies de la determination genetique du sexe chez l’homme

Normal sexual development in man is the consequence of a complex process. This review focuses on the translation of genedal sex (XX or XY karyotype) into gonadal sex (testis or ovary). During the last three years attempts to identify and clone the testis determining factor (TDF) have exploited detailed maps of the Y chromosome established by geneticists over the last decade. A candidate gene, named SRY (sex determining region, Y) located at the tip of the short arm of the Y chromosome, shows many characteristics in common with TDF in that it is the sole element of the Y chromosome required for male development. The discovery of TDF led us to analyse sex-reversed individuals, i.e. XX males and XY females, with the aim of constructing a model for the processes regulating the development of an organ as complex as the testis. This SRY gene is now the subject of intense molecular biological effort by various groups, effort which we hope will elucidate the mechanism(s) of sex determination.     

Physiopathologie des troubles de l’érection chez l’homme paraplégique

Peripheral mechanisms responsible for penile erection are dependant upon a complex control by the nervous system, including peripheral nervous pathways, spinally mediated reflex loops and supraspinal nervous structures. Spinal cord injury is accompanied by a partial or a complete modification of these controls. In relation to the reflexogenic or psychogenic origin of penile erection, spinal cord injury does not cause the same effects. Reflexogenic erections sitll occur after spinal cord injury at a suprasacral level. After lesions at a level lower than the thoracolumbar spinal cord, tumescence following psychogenic stimulation has been observed. The hypotheses resulting from clinical and experimental observations and explaining the differences at the origin of these response are detailed. The recent developments in the neurophysiology of penile erection and the role of neurotransmitters allow a more analytical approach of the phenomenous and also bring new insights into possible compensatory pathways following spinal cord injury.     

Stratégies biologiques à l’heure de l’Assistance Médicale à la Procréation chez le blessé médullaire

Most men with spinal cord injury (SCI) men have fertility problems caused by anejaculation and decreased fertility of the ejaculate. There are two main causes for the impaired reproductive potential in SCI men: ejaculatory dysfunction and poor quality semen. However, current treatment techniques allow a large number of SCI males to achieve ejaculation (rectal electro-stimulation, penile vibrator stimulation). Firstly, masturbation and/or penile vibrator are used at home allowing the couple to perform insemination themselves. The semen of men with spinal cord injuries has commonly been characterised by small volume, abnormal count (low or high), decreased sperm mobility, increased formation of reactive oxygen species, sperm autoimmunity, necrospermia. This impairment is thought to be due to insufficient drainage, genitourinary infections and raised scrotal temperature. Testicular biopsy reveals varying degrees of tubule degeneration and decreased spermatogenetic activity. Semen could be used for various assisted reproductive technologies such as intrauterine insemination,in vitro fertilisation (IVF) and microinsemination (ICSI). The literature reports pregnancy rates by intrauterine insemination of about 15 to 20% per couple. Clinical pregnancy rates after IVF and ICSI techniques are 30% per cycle and these results are comparable to the clinical pregnancy rates when these techniques are performed for female infertility. However, semen must be frozen as soon as possible after the injury and the patient must be informed about the various available assisted reproductive technologies.     

Les inhibiteurs spécifiques de la recapture de la sérotonine dans la dépression de l’enfant et de l’adolescent: revue des controverses récentes

European and US drug regulatory authorities have recently warned against the use of selective serotonin reuptake inhibitors (SSRIs) in childhood and adolescent depression. Through an extensive literature review on the use of SSRIs to treat depression in children and adolescents — including psychiatric clinical trials, pharmacology, and drug safety data — we will: i) describe the main arguments justifying various regulatory decisions; ii) present published data and subsequent meta-analyses; iii) discuss how to integrate the recommendations into daily clinical practice, freeing professionals from a Manichean approach. We reach the limits of evidence-based medicine, which provide the basis of the scientific work of the regulatory authorities.