Effets secondaires des androgènes

Androgens, when used in medical replacement dosages, are well tolerated with no major side effects. In contrast, the illegal use by athletes of doses of androgens 10 to 100 fold higher than therapeutical doses can be responsible for a number of health hazards, all the more so since they are not medically controled. In addition, new usages of androgens at high doses are now emerging such as male contraception and hormone replacement therapy for andropause. Androgen side effects can be classified in 4 categories: il all cases they depend on the dose and the molecule used. 1) Androgenic side-effects are constant. In men, they include testicular atrophy and azoospermia leading to sterility. They are readily reversible in 2 to 3 months after cessation of treatment. However, potential long term effects on prostate should be evaluated. In women and adolescents, high doses of androgens will also produce androgenic side effects (increase of body mass, acne, deepening of the voice, hirsutism, balding) and in adolescents, premature epiphyseal fusion. These effects are often irreversible and should preclude high dose androgen administration in these subjects. 2) Toxic side-effects, especially due to the use of 17α-alkylated derivatives, bear mainly on liver function; they involves pathological liver function tests and jaundice but can also include more serious hepatic complications such aspeliosis hepatitis or hepatoma. 3) Effects on the cardiovascular system: blood lipids and lipoproteins change toward values promoting atherosclerosis are constant and an increased thrombogenic risk has also been reported. 4) Behavioural side-effects: Androgens are supposed to develop aggressivity and mental strength; psychotic manifestations have been reported, but in the human these effects are poorly documented and there seemingly exists a strongplacebo effect. In conclusion, in adult man at least, high doses of androgens seem to result in essentially reversible effects and androgen abuse do not involve major risks. However further studies are necessary to evaluate potential longterm effects such as liver toxic effects, significance of the cardiovascular changes and moreover, the potential development of an androgen-dependent prostate pathology.     

Cryoconservation de spermatozo?des avant vasectomie: utilité et paradoxes à travers l’activité des CECOS

Sperm banking when consulting for vasectomy can appear as a paradox. Around 12% of the men who decide to have a vasectomy consult in a CECOS for sperm cryopreservation before surgery. Among these men, less than 5% will use their frozen sperm. In about 10 years, artificial insemination has been quite abandoned and in vitro fertilization is now widely used by these patients when they desire a child in a new couple. It is thus time to ask wether cryopreservation of sperm is still to be proposed before vasectomy.     

Effet d'ammonium quaternaire halogène sur des cultures de cellules tumorales

This work reports the action of one halogenic quaternary ammonium compound on the in-vitro proliferation of different lines of human cancer cells. IC 50 inhibition growth was observed at a concentration of 2.10⁻⁶ mol and T1 growth at 3.10⁻⁶–5.10⁻⁵ mol. These results seem to indicate that halogenic quaternary ammoniums present a potent growth inhibitory activity on different cancer cells lines. The presence of a quaternary ammonium group, responsible for some alkylating effect, could explain such a result.     

Androgènes et sexualité masculine

Testosteron is known to be critical for the right maintenance of masculin sexuality. It acts on all components of sexuality: libido, erection and ejaculation. As far as erection is concerned, one has to emphasize on the fact that only spontaneous nocturnal erections are androgen-dependent unlike erectile responses to visual erotic stimuliThe T can act, at the level of target organes, either as unchanged or as more often observed after reduction to DHT or aromatisation to E2. It is essencially as DHT that the male hormone seems to act on the sexuality at both the central and peripherical levels. The oestrogens even if now shown to have no peripherical action, are still subject to controversy as far as their central action is concerned. Therefore an action at the cerebral level of the oestrogens produced locally can not be definitively eliminated.The concentrations of T required for the re-establishment of the sexual function in case of hypogonadism are closer to the lower limits of normal values. The upper treshold of the action of T on the sexuality, if any, would be at supra-physiological levels.Androgenotherapy of sexual dysfonctionnalities is wittnissing a constant evolution. New and more performing products, as well as novel and less astreignant ways of administration, are already disponible or under evaluation. Moreover, the improvement of plasmic androgen exploration (dosage of free and non-sex hormone-binding globulin bound testosterone) associated to a better understanding of side effects of the androgenic therapeutics may allow in the near futur to reach a consensus on the androgenotherapy indications. As a matter of fact among the population of patients considered eugonadic (based on normal levels of T) and showing a sexual dysfonctionality, two subgroups might be interested: That of elderly patients displaying either an increase of the hormone-binding globulin (SHBG) or a decrease of the non-sex hormone-binding globulin bound testosterone levels and that of young patients suffering from idiopathic impotence. It should be, however, pointed at that the recent character of the different physiopathologic and therapeutic acquisitions requires a validation through larger series and long term studies.     

Diagnostic et traitement du déficit en androgènes des patients infectés par le virus de l’immunodéficience humaine

Androgen deficiency is frequent among men infected by the human immune deficiency virus (HIV), with an estimated prevalence of between 35% and 50%. Primary testicular damage has been described, either due to the virus itself, opportunistic agents such as CMV,Toxoplasma gondii orMycobacterium avium intracellulare, or less frequently neoplastic invasion by lymphoma or in a context of Kaposi’s sarcoma. However, secondary hypogonadism remains a more frequent cause. Hypogonadotropic hypogonadism can be secondary to opportunistic infections, malnutrition, and sometimes even certain therapeutic agents. Since the introduction of highly active antiretroviral therapies, the prevalence of hypogonadism has substantially decreased. However, it remains a significant clinical problem, particularly among patients suffering from wasting, as androgen deficiency may aggravate the loss of lean body mass observed in the wasting syndrome of HIV patients. Screening for androgen deficiency is therefore indicated in HIV patients suffering from wasting, even in the absence of specific symptoms. Androgen replacement therapy is justified in symptomatic (loss of libido, impotence) and asymptomatic patients with documented hypogonadism. We recommend replacement therapy with testosterone by subcutaneous or intramuscular injection. In the absence of specific symptoms, it should be remembered that testosterone replacement therapy of HIV-infected hypogonadic patients is associated with improvements in body composition and muscle strength, bone densitometry, quality of life and mood. Similar improvements have also been demonstrated in hypogonadic patients with wasting syndrome. Synthetic testosterone analogues such as oxandrolone or nandrolone do not seem to be more powerful than testosterone at replacement doses, and may be associated with more side effects, particularly severe hepatic dysfunction. In contrast, there is no proven benefit of androgen treatment of eugonadic HIV-infected patients, and the treatment of such patients with androgens, even in the presence of wasting, cannot be recommended.     

Place des troubles de la spermatogenèse dans l’hypofertilité masculine

According to Thonneauet al., (1991), 14% of couples are subfertile. In at least 59% of the cases, a male factor was involved. This indicates that 8% (14% × 59%) of men are hypofertile. Since several causes can induce male infertility and because of the heterogeneous criteria and classifications used in the literature, the percentage of each etiologic factor has not been very precisely established. In a population of 2072 consecutive patients we identified an alteration of spermatogenesis in 52% of the cases. This indicates that about 4% of men might have a spermatogenic problem. The spermatogenic insufficiency was isolated in 43% of the cases (i.e. 23% of the total population) or associated with post-testicular causes of male infertility (infectious/inflammatory; autoimmune; obstructive) in 57% of the cases (i.e. 30% of the total population studied). An etiologic factor is clinically identified for 64% of the patients presenting with a spermatogenic insufficiency. The most relevant risk factors linked to spermatogenic alteration were history of mumps orchitis (OR [IC95%]=14,6 [3,4–62,3]), history of radiotherapy-chemotherapy (OR=14,7 [3,4–63,2]). These situations were found with a low frequency (1,4% and 1,3% of the cases respectively) but provoked a spermatogenic alteration in a large majority of cases (92,9% and 92,3% respectively). On the other hand, varicoceles (OR=3,7 [2,9–4,8]) and troubles in testicular descend (OR=2,9 [2,3–3,7]), were more frequent (20,6% and 20,1% of the cases respectively), but less frequently associated with spermatogenic insufficiency (in 73,7 and 69,6% of the cases).     

Polymorphisme du gène du récepteur des androgènes: recherche de mosaïques tissulaires et relation avec l'infertilité masculine

Androgens are male steroid hormones necessary for initiation and maintenance of spermatogenesis. They act via a specific receptor which belongs to the nuclear receptor superfamily. The transactivation N-terminal domain of this receptor is characterized by a CAG repeat polymorphism in the first exon of the gene coding for polyglutamines. An increased CAG repeat length is involved in Kennedy's disease, a neurodegenerative disease associated with infertility and impaired virilization. Some recent studies have shown a correlation between the number of CAG repeats and male fertility. The aim of this study was to define this correlation and to determine whether or not infertile men presented a tissue mosaicism between blood and sperm, as described in several diseases involving CAG repeats. The length of CAG repeats of blood and testicular cells was measured in 36 oligospermic or azoospermic patients and 15 controls. An inverse correlation was found between CAG repeat length and total number of ejaculated spermatozoa. However, no tissue mosaicism between blood and sperm was observed in our population.     

Spécificité des hyphomycètes entomopathogènes pour les larves de lepidoptèresNoctuidae

Résumé L'étude de la sensibilité des 4 espèces de noctuelles,Mamestra brassicae L.,Spodoptera littoralis Boisduval,Spodoptera frugiperda Smith etScotia ipsilon Hübner, aux hyphomycètes a été conduite avec 10 souches dePaecilomyces fumoro-roseus (Wize) Brown & Smith, 6 deNomuraea rileyi (Farlow) Samson, 1 deBeauveria bassiana (Bals.) Vuill. et 1 deMetarhizium anisopliae (Metsch.) Sor. Les chenilles nouvelles-nées agées de moins de 16 h ont été exposées pendant 24 h sur des rondelles de feuilles contaminées par aspersion des inoculums, puis élevées individuellement à 25±1°C. A la dose de 3.10⁵ conidiospores/cm², l'activité pathogène des germes sur les chenilles varie dans de larges proportions suivant l'espèce-h?te et suivant l'isolat considérés. L'espèce la plus sensible à la plupart des souches estM. brassicae et la plus résistanteS. littoralis. Les germes les plus performants présentent des temps létaux 50% compris entre 2 et 3,5 j (à la dose de 3.10⁵ spores/cm²) et des doses létales 50% de 10³ à 10⁴ conidiospores/cm² (mortalités cumulées le 6e j après traitement); ce sont les isolats:P. fumoso-roseus n^o 13, 32, 39, 40 et 45 pourM. brassicae, N. rileyi n^o 5 pourS. littoralis; P. fumoso-roseus n^o 32 pourS. frugiperda etM. anisopliae n^o 139 pourS. ipsilon. La virulence élevée du pathotypeN. rileyi n^o 5 pourS. littoralis et son agressivité à l'égard des 3 autres noctuelles, confirment l'intérêt de cet hyphomycète en dehors de son aire d'origine (Sud-Est des Etats-Unis). Par ailleurs, les aptitudes des souches européennes deP. fumoso-roseus montrent que cette espèce présente des potentialités pour la lutte biologique contre divers noctuides.

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Summary Bioassays were carried out on 1st instar larvae to determine the relative susceptibility of 4 noctuid species,Mamestra brassicae L.,Spodoptera littoralis Boisduval,Spodoptera exigua Smith andScotia ipsilon Hübner to 10Paecilomyces fumoso-roseus, 6Nomuraea rileyi, 1Metarhizium anisopliae and 1Beauveria bassiana isolates. Neonate larvae, 2 to 16 h old, were exposed for 24 h to leaf pieces treated with conidial suspensions of each fungal strain and then transferred to untreated foliage at 25±1°C. When tested at 3×10⁵ conidia/cm², pathogenic activity of hyphomycetes towards noctuids showed high variability depending on both host-species and fungal isolate.M. brassicae was more susceptible to tested isolates than the other 3 noctuids. In contrast,S. littoralis was the most resistant species. The most active pathotypes had LT 50 values ranging from 2 to 3,5 days at the concentration of 3×10⁵ conidia/cm² and LD 50 values ranging from 10³ to 10⁴ conidia/cm² (mortality recorded at 6 days post exposure). According to these data, there were 5P. fumoso-roseus isolates (nos 13, 32, 39, 40 and 45) highly active againstM. brassicae, oneN. rileyi isolate (n^o 5) againstS. littoralis, oneP. fumoso-roseus isolate (n^o 32) againstS. frugiperda and oneM. anisopliae isolate (n^o 139) againstS. ipsilon. Bioassays establishing the high virulence of the FloridaN. rileyi isolate (n^o 5) to the Egyptian cottonworm and its pathogenic activity against the other tested noctuids, confirmed the interest for this fungal entomopathogen which has been demonstrated on noctuid populations in the southeastern United States. Moreover results of the host range assays of European isolates ofP. fumoso-roseus showed that this species appears to be an other potentially valuable microbial control agent against noctuid pests.

     

Estrogènes et spermatozoïdes

Aromatase is the terminal enzyme responsible for estrogen biosynthesis; it is present in the endoplasmic reticulum membrane of steroidogenic cells in vertebrates. This enzyme functions with the ubiquitous reductase as the electron donor. The aromatase gene is unique and its expression is regulated in a tissue and more precisely in a cell-specific fashion via the alternative use of several promoters located in the first exons. This enzymatic complex is generally involved in development, reproduction, sexual differentiation and behaviour, but also in bone and lipid metabolism, brain functions and diseases such as breast and testicular tumors. The aromatase gene expression and its transduction in a fully active protein in testicular somatic cells and germ cells together with the widespread distribution of estrogen receptors (ERα & β) in the testis and the genital tract of the male, are clearly in favor of a physiological role for estrogens in the spermatogenesis processings especialy in sperm maturation. Therefore, we begin to understand the physiopathological roles of the estrogens in males indeed, the aromatase deficiency is associated, with severe bone maturation problems and sterility in man. Conversely, it is also obvious that estrogens in excess are responsible of the impaired spermatogenesis. These female hormones (or the ratio androgens/estrogens) do play a physiological role in the development and maintenance of male gonadal functions and obviously, several steps are concerned especially the sperm production and maturation.     

Contraception hormonale masculine par les androgènes seuls. Acquis et perspectives

There is in France a demand for male contraception. It is possible to respond it using steroids (androgens, progestins). Studies in several countries, including France, have confirmed the contraceptive efficacy of these treatments ?? equivalent to female contraception. Androgens may be indicated, in defined conditions, to couples for which traditional methods of contraception are not suitable. Two obstacles limit widespread use of androgens: risk of a prolonged state of hyperandrogenism and mode of administration by injection. The combination of progestins to low doses of androgens should reduce these drawbacks.     

Données sur la distribution des éléments biogènes dans l'estuaire du Tamar, à Plymouth

Résumé Le Tamar possède un estuaire à circulation d'eau typique (pas de mélange des eaux) mais présentant encore à ce point de vue, certaines particularités qu'il convient d'approfondir.Les quelques facteurs écologiques (température, transparence, salinité, phosphates et silicates) étudiés dans la zone la plus salée (de eu- à mésohaline) de l'estuaire montrent des variations importantes qui se réfléteront probablement dans la distribution du phytoplancton. La distribution des phosphates pose un certain nombre de problèmes et notamment celui de leur plus faible teneur en surface. Il conviendra de compléter cette étude préliminaire par des recherches sur la distribution des nitrates et l'exploration des zones oligohaline et limnétique.

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Summary A typical water circulation pattern (no mixing of fresh and sea waters) is demonstrated in the Tamar estuary, however a few particular points still are to be elucidated.The ecological factors (temperature, transparence, salinity, inorganic phosphate and silicate) studied in the lower reaches of the estuary show some important variations.It is emphasized that an exceptionally low amount of inorganic phosphate is found at the surface or the subsurface.

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Assistant au Laboratoire de Botanique systématique et Ecologie de l'Université Libre de Bruxelles. Boursier de l'U.N.E.S.C.O., stagiaire au Laboratoire de la Marine Biological Association of the U.K., Plymouth.     

L’insémination intrautérine dans l’éjaculation rétrograde. Importance du pH et de l’osmolarité sur la mobilité des spermatozoïdes

The effect of pH and osmolarity on motility of human spermatozoa in retrograde ejaculation was studied in a freshly voided urine specimen. The maximum rate of motility is obtained when the pH ranged from 7.0 to 7.5 and osmolarity from 300 to 400 m.osmol/Kg. Thus the control of these two parameters allowed us to improve sperm motility and to perform intrauterine insemination with ovarian hyperstimulation. The different causes of retrograde ejaculation in this study are diabetes, surgical injury and idiopathic. Fifty-one intrauterine insemination cycles were realized in twenty-three patients, and eleven pregnancies are obtained (21.5% per cycle).