Hyponatremia, hypernatremia and impairment of functional, psychological and sexual domains.

OBJECTIVE: To determine the influence of serum sodium on physical, psychologic and sexual function. METHODS: This is a cross-sectional survey on 3340 community-dwelling men aged 40-79 years from a prospective cohort study in eight European countries, the European Male Ageing Study (EMAS). Participants filled-out the Short Form-36 (SF-36), the Physical Activity Scale for the Elderly (PASE), and the EMAS sexual function questionnaire. For all the analyses, serum sodium corrected for glycaemia ([Na+]G) was used. RESULTS: The relationship between [Na+]G and SF-36 physical function score (F = 3.99; p = 0.01), SF-36 mental health score (F = 7.69; p < 0.001), and PASE score (F = 14.95; p < 0.001) were best described by a quadratic equation, with worse scores for [Na+]G in either the lowest or the highest ends of the range. After dividing the sample into [Na+]G < 136 mmol/L (n = 81), 136-147 mmol/L (n = 3223) and > 147 mmol/L (n = 36), linear regression analyses with linear spline functions adjusted for confounders did not confirm these relationships. Similarly, erectile dysfunction and [Na+]G, were in a quadratic relationship (F = 9.00; p < 0.001). After adjusting for confounders, the linear regression with spline functions denoted a significantly worsened erectile function for increases in serum [Na+]G > 147 mmol/L (B = 0.15 [0.04;0.26], p < 0.01) but no relationship with [Na+]G < 136 mmol/L. Likewise, the relationship of [Na+]G with concerns about sexual dysfunction was confirmed only for men with serum [Na+]G > 147 mmol/L. CONCLUSIONS: This is the first study supporting an association between [Na+]G and sexual function. A worsening of erection and concerns about sexual function were observed for the highest values of [Na+]G, independently of other relevant factors.

Presence of aerobic micro-organisms and their influence on basic semen parameters in infertile men.

Urogenital tract infections in males are one of the significant etiological factors in infertility. In this prospective study, 72 patients with abnormal semen parameters or any other symptoms of urogenital tract infection were examined. Semen analysis according to the WHO 2010 manual was performed together with microbial assessment: aerobic bacteria culture, Chlamydia antigen test, Candida culture, Ureaplasma and Mycoplasma-specific culture. In total, 69.4% of semen samples were positive for at least one micro-organism. Ureaplasma sp. was the most common micro-organism found in 33% of semen samples of infertile patients with suspected male genital tract infection. The 2nd most common micro-organisms were Enterococcus faecalis (12.5%) and Escherichia coli (12.5%), followed by Staphylococcus aureus (7%), Chlamydia trachomatis (7%) and Candida sp. (5.6%). Generally, bacteria were sensitive to at least one of the antibiotics tested. No statistically significant relationship was observed between the presence of aerobic micro-organisms in semen and basic semen parameters: volume, pH, concentration, total count, motility, vitality and morphology.

Testosterone and oestradiol in concert protect seminiferous tubule maturation against inhibition by GnRH-antagonist.

Oestradiol enhances follicle stimulating hormone (FSH) action on seminiferous tubule maturation, but the relative involvement of oestradiol and testosterone remains unclear. This study compares the influences of oestrogen and androgen in FSH and testosterone-deficient rats. Animals were injected daily GnRH-antagonist alone (Ant) or combined with 17ß-oestradiol benzoate (EB), or testosterone propionate (TP), or both from post-natal day (pnd) 5 to 15. Hormone levels, tubule growth, cell numbers, germ cell apoptosis and proliferation, and Sertoli cell maturation were evaluated on pnd 16. Ant decreased serum FSH and testosterone levels to ∼60% and ∼50% of control values, respectively, and decreased tubule growth, Sertoli cell number and maturation. Germ cell number declined by apoptosis. Co-administration of EB stimulated spermatogonia proliferation and maintained FSH levels (86% of control). Tubule growth, Sertoli cell number and spermatocyte apoptosis remained normal after TP co-administration, but Sertoli cell maturation, germ cell number and spermatogonia survival were reduced. Co-administration of EB with TP prevented all inhibitions. In conclusion, administration of oestradiol with testosterone, but neither one alone, protected seminiferous tubule maturation against inhibition caused by Ant-induced disruption. Oestrogen was involved in stimulating germ cell proliferation and the maintenance of Sertoli cell maturation, whereas androgen affected seminiferous tubule growth and spermatocyte survival.

Less advanced testicular dysgenesis is associated by a higher prevalence of germ cell neoplasia.

There is a theory that the more evident clinical signs of testicular dysgenesis, the more frequent the neoplastic lesions are. The aim of this study was to relate the incidence of testicular germ cell neoplastic lesions (overt germ cell tumours--GCT or testicular carcinoma in situ) to the intensity of testicular organogenesis disturbances (dysgenesis). Biopsies were taken from 154 testes of the following patients: 23 patients with GCT in the contralateral gonad (CGCT), 41 patients with undescended testes operated in childhood (UDT), 90 with azoo-/oligozoospermia (A/O) diagnosed because of infertility. Assessment of seminiferous epithelium, number of Leydig cells, areal fraction of intertubular space (IS), morphometric analysis of seminiferous tubules diameter and thickness of tubular wall were performed. Monoclonal antibodies against placental like alkaline phosphatase and cytokeratin 18 were applied. Germ cell neoplastic lesions were detected in 7.1% of testes and were associated with disturbed spermatogenesis. Among testes with disturbed spermatogenesis they were found the most frequently in CGCT (22.2% vs. 11.1% in UDT and 3.8% in A/O), where spermatogenesis had the highest score (5.7 +/- 3.8 points vs. 4.2 +/- 2.7 in UDT and 4.6 +/- 2.9 in A/O). In CGCT, signs of testicular dysgenesis were less advanced: the highest tubular diameter was 164.4 +/- 32.3 microm vs. 163.5 +/- 28.6 in UDT and 161.4 +/- 31.5 in A/O, the lowest thickness of tubular wall was 8.9 +/- 3.2 microm vs. 10.2 +/- 3.6 in UDT and 10.2 +/- 3.2 in A/O, lowest IS was 36.9 +/- 14.9% vs. 47.9 +/- 18.0 in UDT and 46.5 +/- 18.5 in A/O, and the lowest percentage of tubules with immature Sertoli cells was 0.1 +/- 0.4% vs. 4.9 +/- 7.0 in UDT and 5.2 +/- 9.7 in A/O. Results indicate that neoplastic lesions appear only in testes with disturbed spermatogenesis. Worse condition of spermatogenesis is associated by the presence of other dysgenetic features, but neoplastic lesions appear more frequently in testes with the less advanced features of testicular dysgenesis.

The volume of unilaterally undescended testis after hCG therapy compared to orchidopexy and combined methods.

The aim of the study was to compare the effects of human chorionic gonadotropin (hCG) therapy with those of surgical or combined therapy on testicular volume (TV) in boys at different ages with unilateral canalicular undescended testis (UDT). In total, 155 boys aged 1 to 12 years were treated: either surgically (ST), or by 50 IU/kg body weight hCG administration every three days for five weeks (HT), or by a combination of the two. The patients underwent ultrasound examination of TV before the treatment, 9-12 (median 10) and 24-39 months (median 32) after therapy. The testicular atrophy index (TAI) of the affected testicle was calculated. The success rate was 94.7% for ST, 39.2% for HT and 98% for HST patients. The atrophy rate was 5.3% for ST, 0% for HT and 2% for HST. Neither treatment type nor patient age significantly influenced gonadal atrophy. No significant differences in TV of the affected testis were observed after treatment between the groups. The TAI values were significantly the lowest in HT group (p = 0.0006). Both TV and TAI changes from the baseline values did not differ between the treatment groups. At the 24- to 39-month follow-up, no significant differences were observed in the change in baseline TV and baseline TAI between age groups. TV of the affected testis increased significantly (p = 0.0000), and TAI decreased significantly over time (p = 0.01), with no significant differences depending on the age group, treatment type or the interaction of the two factors. The hCG therapy did not impair the development of affected and healthy testes, neither as single nor as neoadjuvant therapy, both during early assessment and after 2-3 years. Patients' age at the initiation of treatment seems irrelevant.

Estradiol enhances the stimulatory effect of FSH on testicular maturation and contributes to precocious initiation of spermatogenesis.

Male rats were daily injected with human FSH (hFSH) or estradiol benzoate (EB) or hFSH+EB between day 5 and 15 of life and autopsied on day 16. hFSH accelerated testicular growth, increased number of spermatogonia and serum level of testosterone. hFSH stimulated also spermatogonia differentiation, which resulted in 5-fold increase of the number of spermatocytes. EB given alone induced adverse, inhibitory effects on spermatogenesis and serum testosterone, did not influence serum FSH and LH but increased 14-fold the level of prolactin. Except from testosterone, EB given with hFSH not only overcame inhibitions, but multiplied hFSH stimulatory effects on spermatogenesis up to 30-times of control values. In addition, after FSH+EB premeiotic germ cell ratio reached adult type value precociously. Estradiol may play regulatory roles in testicular maturation (1) inhibitory, direct one or resulting from decrease in testosterone secretion; (2) stimulatory, by enhancement of FSH action, with a possible involvement of prolactin that may act in concert with FSH.

Testicular pathology in 46,XY dysgenetic male pseudohermaphroditism: an approach to pathogenesis of testis cancer.

Eleven children with dysgenic male pseudohermaphroditism (DMP) and 18 boys with isolated penile hypospadias, all with 46,XY karyotype, were studied. Testicular dysgenesis was associated with significantly lower testosterone response to human chorionic gonadotropin (0.9 +/- 0.2 ng/mL) than it was in hypospadias (3.3 +/- 0.1 ng/mL), and with significantly higher mean serum follicle-stimulating hormone (FSH) levels (8.4 +/- 2.3 IU/L vs 1.5 +/- 0.3 IU/L). Gonadoblastoma, a tumor that arises from the sex cords, was found in more than 1/4 of patients with DMP, whereas testicular carcinoma in situ (CIS) cells were present in all of these patients. Forty-two percent to 98% of CIS cells revealed an aneuploid pattern of nuclear DNA, indicating that most of them are neoplastic cells. In patients with hypospadias, CIS was not seen, and no other abnormalities were detected. In children with DMP, the percentage of tubules populated with germ cells was significantly lower than it was in those with hypospadias (48.3% +/- 10.6% vs 92.4% +/- 4.0%). The total number of germ cells (CIS cells + spermatogonia) did not differ significantly between the 2 groups, but the number of spermatogonia was significantly reduced in children with DMP (0.08 +/- 0.05 vs 3.65 +/- 0.2), suggesting impaired differentiation of gonocytes to spermatogonia. The following significant correlations were present with DMP: 1) the higher the seminiferous tubule cross-section area, the higher the number of CIS cells (r = 0.78); and 2) the higher the serum gonadotropin levels, the higher were tubular diameter (r = 0.93 for FSH and r = 0.75 for luteinizing hormone [LH]), area (r = 0.79 for FSH and r = 0.82 for LH), percentage of tubules populated with germ cells (r = 0.86 for FSH and r = 0.81 for LH), and number of CIS cells (r = 0.87 for FSH and r = 0.79 for LH). The results indicate that in intersex children with 46,XY karyotype, CIS occurs in dysgenetic testes in all cases and is frequently associated with gonadoblastoma. Impaired organogenesis of sex cords, relative inhibition of testosterone secretion, and the associated increased secretion of gonadotropins may create a milieu that induces or is favorable for the formation or maintenance of neoplastic lesions in dysgenetic testes early in childhood.

Nuclear DNA content and proliferative potential of human carcinoma in situ cells in testes of intersex children.

Gonocytes, fetal germ cells, when persisted beyond infantile period of life are considered as preinvasive testicular germ cell cancer (carcinoma in situ--CIS). The aim of the study was to investigate nuclear DNA content and proliferative potential of CIS cells together with the expression of placental-like alkaline phosphatase (PLAP), a marker of CIS and germ cell cancer. In dysgenetic testes of 4 intersex children proliferating cell nuclear antigen (PCNA) and PLAP were examined immunohistochemically. DNA content was assessed by densitometry of nucleus in Feulgen stained histologic sections. High incidence of aneuploidy (95.1-97.6% of CIS cells with 2.6-6.8c) was found with the predominant DNA pattern of tri- and tetraploidy in children aged 1 to 3 years. The incidence of triploidy (65-78.1% of cells) was similar to the incidence of the expression of PCNA (53.4-62%), what indicates that part of hyperploid germ cells might represent phase S of cell cycle, but the rest of hyperploid cells might represent neoplastic transformation. In turn, germ cells of 8-months-old patient were predominantly diploid with low incidence of PCNA positive cells which indicate that proliferation/neoplastic transformation of abnormal germ cells is significant mostly after 1 year of age in intersex children. The frequency of PLAP expression in CIS cells (3.1-27% of cells) was weakly related to the frequency of aneuploidy what limits the usefulness of PLAP reaction for the detection of CIS cells.

Immunohistochemical diagnosis of preinvasive germ cell cancer of the testis.

The aim of the study was to identify testicular carcinoma in situ (CIS), a precursor of germ cell tumours (GCT), in patients from the high risk groups, using classic and alternative immunohistochemical methods. 70 patients with 46,XY karyotype were examined. Whole gonads or biopsy specimens were fixed in Bouin's fluid. In cases with dysgenetic male pseudohermaphroditism (DMP), gross histopathology revealed sex cord tumour gonadoblastoma in 4 and malignant dysgerminoma in 1 out of 23 patients. In all patients, paraffin sections were treated with antibodies against placental-like alkaline phosphatase (PLAP), a classic immunohistochemical marker of GCT and CIS. CIS was detected immunohistochemically in 10 out of 23 cases with DMP (43.5%), in 1 out of 10 cases with androgen insensitivity syndrome (10%), in 3 out of 18 cases operated previously because of already developed GCT in contralateral testis (16.6%) and in 1 out of 3 patients with cryptorchidism in anamnesis (33.3%). CIS was not found in 16 examined adult infertile men with azoospermia. In addition to PLAP investigation, 12 cases with DMP and 6 cases with GCT were examined using M2A and TRA-1-60 antibodies, the alternative immunohistochemical markers of CIS. While in DMP positive reactions for M2A and TRA-1-60 accompanied PLAP reaction in 1/3 of cases, M2A accompanied PLAP in all cases with GCT. The positive reaction for TRA-1-60 accompanied PLAP and M2A in 1 case with GCT. The results indicate that among different risk groups the highest incidence of CIS occurs in DMP. Screening for CIS is of importance also in cryptorchidism, androgen insensitivity syndrome and in men who underwent gonadectomy because of unilateral GCT. The immunostaining for PLAP seems to be more discriminative procedure. The positive staining of CIS cells with M2A and TRA-1-60 antibodies may be indicative for more advanced neoplastic transformation.

[Comparison between the influence of estradiol benzoate, testosterone propionate and human chorionic gonadotropin on initiation of spermatogenesis in the rat]. / Porównanie wplywu róznych dawek benzoesanu estradiolu, propionianu testosteronu oraz ludzkiej gonadotropiny lozyskowej na zapoczatkowanie spermatogenezy u szczura.

Newborn male rats were injected daily from the 5th to 15th day of life with: EB in doses of 6.2 or 12.5 or 25.0 micrograms and TP in doses of 1.2 or 2.5 or 5.0 mg (experiment 1), and with hCG (experiment 2) in doses of 2.0 or 4.0 or 8.0 I.U. Animals were sacrificed on the 16th day of life, testes and seminal vesicles were taken and fixed. The function of seminiferous tubules was examined by quantitative analysis of spermatogenesis. EB increased the mean number of germinal cells. TP stimulated differentiation of spermatogonia, but it decreased the number of all germinal cell types. Only the lowest dose of hCG stimulated the mean number of germ cells in the earliest stages of spermatogenesis, hCG used in the higher doses suppresses maturation of seminal tubules and decreases testicular weight.

[Influence of intratesticular injections of tamoxifen on spermatogenesis and testosterone secretion in the rat]. / Wplyw dojadrowego podawania tamoksyfenu na spermatogeneze i wydzielanie testosteronu u szczura.

Three groups of adult Wistar rats were injected every second day with: 5 or 10 or 20 micrograms of tamoxifen (Tx) to the right testis. Left testis was injected with the same volume of solvent. Control group received the solvent for Tx. Animals were killed after 15 days. Blood samples were taken from heart for testosterone determinations. Both testes were taken for histological examination and quantitative analysis of seminiferous epithelium was performed. Testosterone was analysed with radioimmunoassay method. It was demonstrated that intratesticular supply of Tx caused significant rise in the number of type A spermatogonia and significant increase of testosterone concentration in the blood. It is concluded that Tx influences spermatogenesis in adult rats through stimulation of the earliest steps of gamete formation. Testosterone may or may not mediate this effect.

[Tamoxifen and spermatogenesis in rats subjected to effects of estradiol]. / Tamoksyfen a spermatogeneza u szczurów poddanych dzialaniu estradiolu.

During 14 subsequent days male Wistar rats received subcutaneously 50 micrograms of EB and different doses of tamoxifen intratesticularly. Action of EB was examined by comparison with the group, which received the solvent for EB only. EB caused the reduction in the mean testis weight, degenerative changes of germinal cells and decrease of blood testosterone level to undetectable values. Tamoxifen did not prevent these changes, but revealed a positive influence on the mean numbers of spermatogonia, spermatocytes and spermatids, including spermatozoa. It indicates that tamoxifen may stimulate the whole spermatogenesis in spite of the inhibition of testosterone production.

[Expression of fetal antigens of gonocytes in the investigation of pathogenesis of germinal cell neoplasia]. / Ekspresja antygenów plodowych w gonocytach przy badaniach nad patogeneza nowotworów jadra pochodzenia zarodkowego.

Expression of fetal antigens of germinal cells reacting with antibodies M2A and TRA-1-60 has been studied in fetal germinal cells-gonocytes (G) persisted in gonads of prepubertal boys because of male pseudohermaphroditism (MP) and in germinal carcinoma cells in situ (CIS) of adult men. The presence of G and CIS cells was detected immunohistochemically by identification of placental like alkaline phosphatase (PLAP). CIS cells showed expression of M2A in all adult men and additionally TRA-1-60 in one case. These antigens were present in G cells only in 2 out of 6 G bearing testes of boys with MP (30%). G cells were not found in testes of 3 other older boys with MP. So, in 1/3 cases of children with MP G cells show similar features like CIS cells during the prepubertal period indicating that they are able to enter malignant transformation in early prepubertal testis. Although total frequency of occurrence of G cells in MP boys was 2/3 (60%), their malignant transformation may be lower.

[Sexual differentiation of the human brain]. / Róznicowanie plciowe mózgu czlowieka.

Normal human development requires the compatibility between genetic sex (sex chromosomes), sex of gonades (tests or ovaries), genitalia (external and internal sex organs), somatic features (body characteristics) and psychic sex. The psychic sex, called frequently gender, consist of gender identity (self-estimation), gender role (objective estimation) and sexual orientation (hetero- or homosexual). It was believed that the psychic gender depends only on socio-environmental influences such as rearing, learning and individual choice. Although, the process of sexual differentiation of human brain is not completely elucidated, it has became recently evident that endogenous hormones more then socio-environmental factors influence gender differences. Experimental studies on animals revealed that transient action of sex steroids during perinatal period of life is crucial for the dymorphism of sexual behavior (male or female) in adulthood. It seems, that also in the human male neonates testosterone produced by testes perinatally takes the main role in the irreversible masculinization of the brain i.e. creation of the differences vs. female brain. The evaluation of patients with disturbances of sexual differentiation of external genitalia (the lack of the testosterone transformation into 5-alpha dihydrotestosterone in peripheral tissues of men or the inborn excess of androgens in women with the congenital adrenal hyperplasia) has served as a useful clinical model for understanding factors, affecting the formation of gender. In these individuals the formal sex established according to genetic sex and somatic sex may be incompatible with gender identity and role. However, it has been found that the female gender identity is most frequently associated with the presence of ovaries or the lack of gonads (gonadal dysgenesis), while the male gender identity appear most frequently in the presence of testicular tissue irrespective of female or hermaphrodite (intersex) phenotype. In genetic men with the absence of male genitalia formation, caused by the aberrant function of androgen receptor, the gender identity depends on the severity of the disorder: female gender identity in the complete androgen insensitivity syndrome and female or male gender identity in the complete androgen insensitivity syndrome and female or male in the partial androgen insensitivity. These clinical observations confirm the experimental data indicating androgen role in the male gender identity creation. This knowledge is necessary for the decision of the direction of surgical correction of sex organs in children with ambiguous genitalia, which should not depend on the expected efficiency to perform sexual intercourse, but mostly on the expected or already present individual gender identity.

[Precocious maturation of the testis associated with excessive secretion of estradiol and testosterone by Leydig cells]. / Przedwczesne dojrzewanie jadra przy nadmiernym wydzielaniu estradiolu i testosteronu przez komórki Leydiga.

We present the quantitative description of spermatogenesis in a 4.5-year-old boy with precocious puberty, where Leydig cell hyperplasia was associated with excessive secretion of testosterone (T), but predominantly with estradiol (E). The results were compared with data obtained from an age-matched group and adult men without hormonal abnormalities. We showed, that excessive secretion of T and E with relative deficiency of FSH is sufficient to induce testicular tubule maturation and qualitatively complete spermatogenesis, although with a poorer quantitative aspect.