CAG repeat length in the androgen receptor gene affects the risk of male infertility.

During recent years several studies have suggested that a slight increase in the number of CAG repeat sequences in exon 1 of the androgen receptor gene causes idiopathic oligozoospermia. We tested whether CAG repeats are more numerous in men with idiopathic infertility compared to those with known causes of oligozoospermia. CAG repeats were analysed in a consecutive sample of 217 infertile men covering a wide range of diagnoses and sperm counts. Data were compared with those of a control group of 131 normozoospermic men including 62 fathers. CAG repeats (x +/- SD) did not differ between idiopathically (21.4 +/- 2.9) and non-idiopathically infertile men (21.6 +/- 2.8) or normozoospermic men of unproven fertility (20.6 +/- 3.0). Only fathers had significantly fewer repeats (19.4 +/- 3.1; p < 0.001). Different from controls, no correlation between CAG repeats and any semen parameter existed in patients. Comparison of our and published studies showed that odds ratios for infertility in men with CAG repeat length in the upper quartile of the normal range increased when the controls were selected by proven fertility. We conclude that more numerous CAG repeats do not directly cause oligozoospermia and propose that men with longer CAG repeats might be more prone to develop infertility in response to any pathogen/epigenetic factors.

Manifestation of Y-chromosomal deletions in the human testis: a morphometrical and immunohistochemical evaluation.

BACKGROUND: Deletions of the AZF (azoospermia factor) subregions on the Y chromosome are accompanied by a diverse spectrum of spermatogenic disturbances ranging from hypospermatogenesis to total depletion of germ cells causing infertility. The AZF region encodes gene products which are candidates for the genetic control of spermatogenesis. Although it is known which genes are involved, a general principle of cause and effect cannot yet be deciphered and the deletion type has non-uniform histological phenotypes. METHODS AND RESULTS: We analysed morphological parameters of testicular biopsies from 17 patients diagnosed for Y chromosome microdeletions. As control groups we analysed testes from patients with idiopathic Sertoli cell-only (SCO) syndrome (n = 11), mixed atrophy (n = 10) and complete spermatogenesis (n = 11). A detailed genetic analysis on the extension of the observed microdeletions revealed similar breakpoints in the distal and proximal region of the AZFc region, indicating a common mechanism of homologous recombination for such deletions, as has been suggested before. Morphometric parameters such as the diameter of the tubules, lumen, thickness of the lamina propria and height of the tubule epithelia were investigated. The diameter of the tubules from patients with microdeletions was found to be significantly smaller compared with patients with mixed atrophy. Considering also the size of the tubules, lumen and epithelia, a Y-chromosomal microdeletion represents an intermediate state between an idiopathic SCO and normal spermatogenesis. The immunohistochemical analysis of six different Sertoli cell markers, cytokeratin 18, vimentin, inhibin alpha subunit, 14-3-3 theta, FSH receptor and androgen receptor, revealed no impact of AZF deletion on the specific expression pattern of these genes. CONCLUSIONS: Our results suggest that, notwithstanding the deletion of a common region in the AZFc region, microdeletions of the Y chromosome lead to an intermediate status between idiopathic SCO and complete spermatogenesis, resulting in a heterogeneous histological profile regardless of the seminiferous activity. The Sertoli cell function seems not to be altered.

Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study.

INTRODUCTION: In healthy men, body weight and total fat content increase with advancing age, while serum testosterone levels decrease. In order to elucidate whether a causal relationship between these phenomena exists, we investigated the influence of testosterone or human chorionic gonadotrophin substitution on body mass index (BMI), total fat mass and serum leptin in testosterone-treated and untreated hypogonadal patients in comparison with ageing eugonadal men. METHODS: In a cross-sectional study, the inter-relationships of body weight, total fat mass, serum sex hormones and leptin were analysed in untreated hypogonadal men (n=24; age 19-65 years), treated hypogonadal men (n=61; age 20-67 years) and healthy eugonadal men (n=60; age 24-78 years). Total fat mass was assessed by bioimpedance measurement. Univariate and multiple linear regression analysis was used to detect possible differences. RESULTS: In eugonadal men, serum testosterone levels decreased with advancing age (correlation coefficients: r=-0.71; P<0.0001), while BMI (r=0.39; P=0.002), total fat content (r=0.51; P<0.0001) and leptin (r=0.48; P<0.0001) increased significantly. In untreated hypogonadal patients, an increase in BMI (r=0.50; P=0.013) and total fat mass (r=0.41; P=0.044) was also observed with advancing age. However, in substituted hypogonadal patients, no age-dependent change in BMI (r=0.067; P=0.606), body fat content (r=-0.083; P=0.522), serum testosterone (r=-0,071; P=0.59) or serum leptin (r=-0.23; P=0.176) was found. CONCLUSION: Since testosterone-substituted older hypogonadal men show BMI and fat mass similar to those of younger eugonadal men and since non-treated hypogonadal men are similar to normal ageing men, testosterone appears to be an important factor contributing to these changes. Thus ageing men should benefit from testosterone substitution as far as body composition is concerned.

Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone.

BACKGROUND: For male hormonal contraception, combined administration of gonadotrophin-releasing hormone (GnRH) antagonists and androgens effectively suppresses spermatogenesis to azoospermia. In non-human primates this suppression can be maintained more easily by androgens alone. METHODS: A clinical trial with six healthy volunteers was performed to test this approach in man. Loading doses of 10 mg/day of the GnRH antagonist cetrorelix were given subcutaneously for 5 days, followed by maintenance doses of 2 mg/day up to week 12. At 2 weeks after the first GnRH antagonist injection, androgen substitution was initiated with a loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP) intramuscularly, followed by injections of 200 mg 19NT-HPP every 3 weeks up to week 26. RESULTS: Serum concentrations of LH, FSH and testosterone were effectively suppressed by cetrorelix administration. Within 12 weeks, azoospermia was achieved in all six volunteers. After cessation of cetrorelix injections in week 12, gonadotrophins and testosterone increased significantly despite continued 19NT-HPP injections. In parallel, spermatogenesis was restimulated in five of six volunteers. CONCLUSIONS: Combined administration of cetrorelix and 19NT-HPP leads to azoospermia within 3 months. However, complete azoospermia cannot be maintained by continued injections of the non-aromatizable 19NT-HPP alone.

The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity.

Genomic effects of T are exerted via the AR. The length of the polymorphic CAG repeat sequence in the AR gene is inversely correlated with the transcriptional regulation of target genes by T. In 110 healthy men (20-50 yr), we investigated the interactions among this polymorphism, serum levels of sex hormones, cardiovascular risk factors, and flow-mediated and nitrate-induced vasodilatation of the brachial artery. The number of CAG repeat had no significant correlations with serum concentrations of total or free T. Stepwise multiple regression analysis revealed positive correlations of the number of CAG repeat with serum levels of high density lipoprotein cholesterol (partial r = 0.44; P < 0.001) and flow-mediated vasodilatation (partial r = 0.37; P < 0.001). The association of CAG repeat with high density lipoprotein (HDL) cholesterol was independent of body fat content and serum levels of free T, which both had significant negative correlations with HDL cholesterol. The association of CAG repeat with flow-mediated vasodilatation was independent of cigarette smoking and serum levels of free T and low density lipoprotein cholesterol, which also were correlated with flow-mediated vasodilatation. We conclude that a low number of CAG repeat in the AR gene implies a greater chance for low levels of HDL cholesterol and reduced endothelial response to ischemia, which are both important risk factors for coronary heart disease.

Sonographic testicular microlithiasis as an indicator of premalignant conditions in normal and infertile men.

Sonographic detection of multiple, small hyperechogenic lesions in the testis (testicular microlithiasis; TM) can indicate germ cell tumors. However, it has not been well established whether this finding signifies a risk factor for development of testicular neoplasm in all cases or whether it indicates premalignant changes only in those men with additional risk factors for germ cell cancer, such as infertility, a history of testicular maldescent, or the presence of an atrophic testis. In a retrospective analysis of 1701 consecutively performed scrotal sonographies of patients with (n = 1399) and without (n = 219) infertility or with contralateral testicular tumors (n = 83), the prevalence of TM was compared with that in 198 healthy men who volunteered for different clinical trials. TM was equally frequent in all groups (2.3% [32/1399] of infertile patients, 2.3% [5/219] of other patients without infertility, and 1.5% [3/198] of healthy men). Results of testicular biopsies were available for a subgroup of infertile men. Carcinoma in situ (CIS) was present only in cases with TM (2/11). In addition, sonographic follow-up examinations were performed in another 14 men with TM. Testicular tumors had developed in 2 patients, one whom was infertile and one in the control group. None of these patients had a history of testicular maldescent but all testes affected either by CIS or tumors were reduced in volume. We conclude that diagnosis of TM, especially if it is present in an atrophic testis, demands a diagnostic biopsy or at least sonographic follow-up examinations.

Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men.

Androgens are essential for the maintenance of normal spermatogenesis. Androgen action is mediated by the androgen receptor (AR), which in the testis is expressed by Leydig, peritubular, and Sertoli cells. The fact that sperm numbers range from 20 up to 300 million/mL in normal men without any indication of changed endocrine parameters led us to assume that genetic variability of transduction of androgen signaling could be important. We therefore compared the variable number of CAG repeats in the AR with sperm concentrations in men with normal ejaculate parameters (62 fathers and 69 volunteers participating in clinical trials). In multivariate analysis CAG repeat length did not differ between the volunteers (19.4 +/- 3.1) and the fathers (20.6 +/- 3.0), but was significantly correlated to sperm concentrations with a coefficient of -0.25. When compared with a group of infertile men with (n = 14) or without (n = 30) a family history of infertility, no such correlation was found. These results indicate that men with short CAG repeats have the highest sperm output within the normal fertile population. Polymorphisms of the AR contribute to the efficiency of spermatogenesis in normal men, but do not play a predominant role in male infertility.

Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception.

Recent trials for hormonal male contraception are based on gestagens or GnRH antagonists combined with oral or injectable testosterone substitution. However, the efficacy of most trials remained disappointing. Norethisterone enanthate (NETE) has been used as a long-acting injectable female contraceptive and has shown sustained suppression of spermatogenesis in male monkeys and prolonged suppression of gonadotropins in men. This study was designed to prove the efficacy of the long-acting testosterone undecanoate ester (TU) alone or in combination with NETE in a phase II clinical trial. Fourteen healthy men received injections of 1000 mg TU in combination with injections of 200 mg NETE every 6 weeks over a period of 24 weeks, followed by a control period of 28 weeks. Another 14 volunteers received TU alone. During the study semen variables, reproductive hormones, clinical chemistry and lipid parameters, well-being, and sexual function were monitored. Scrotal content and prostates were checked sonographically. During the entire treatment period mean testosterone serum concentrations remained within the normal limits. Marked suppression of gonadotropins in both treatment groups resulted in azoospermia in 7 of 14 and 13 of 14 volunteers and in oligozoospermia in 7 of 14 and 1 of 14 in the groups given TU only or TU/NETE, respectively. However, the highest azoospermia rate in the TU/NETE group was achieved 8 weeks after the end of the treatment period, and 1 volunteer with very high initial sperm counts (mean, 190 million/mL at baseline) remained oligozoospermic (10.2 million/mL). From week 20 to week 24 there was a significant, fully reversible maximum weight gain of 3.7 kg, on the average, in the NETE group. In the NETE and TU alone groups there were significant 26.6% and 11.5% maximum decreases in high density lipoprotein cholesterol compared with baseline values during the treatment period. A significant elevation of low density lipoprotein and a decrease in lipoprotein(a) were detected in the TU/NETE group. In conclusion, combination treatment with NETE showed suppression of spermatogenesis comparable with results using testosterone esters in combination with GnRH antagonists or cyproterone acetate, but had more favorable injection intervals and better efficacy. Because of its long-lasting, profound suppression of spermatogenesis and the absence of serious side-effects, the combination of TU and NETE can be considered a first choice for further studies of hormonal male contraception.

Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception.

OBJECTIVE: Approaches to hormonal male contraception are based on injectable testosterone esters alone or in combination with gestagens or GnRH analogs but the short half-life of clinically used testosterone esters have long hindered further development. This study was designed to prove the efficacy of the long-acting testosterone undecanoate ester (TU) alone or in combination with oral levonorgestrel (LNG) in a phase II clinical trial. DESIGN AND SUBJECTS: Twenty-eight healthy men were randomized to receive injections of 1000 mg TU every 6 weeks in combination with daily oral LNG (250 microg) or daily oral placebo treatment over a period of 24 weeks, followed by a control period of 28 weeks. MEASUREMENTS: During the course of the study semen analysis, reproductive hormone analysis, analysis of clinical chemistry and lipid parameters, well-being and sexual function, sonography of scrotal contents and prostate were performed. RESULTS: Marked suppression of gonadotrophins in both treatment groups resulted in azoospermia in 8/14 and 7/14 volunteers and severe oligozoospermia (< 3 x 1012/l) in 4/14 and 7/14 in the placebo and gestagen treated groups, respectively. Time to induction of azoospermia (mean +/- SEM) was not significantly different between the placebo (week 19.5 +/- 2.2) and LNG groups (week 15.4 +/- 2.2). During the whole treatment period mean testosterone serum concentrations remained within normal limits. Although not significant, it was evident that volunteers who became azoospermic had a better suppression of gonadotrophins and lower SHBG levels during treatment compared to non-azoospermic volunteers. Despite better gonadotrophin suppression in the LNG group no significant differences compared to placebo could be observed in the extent and kinetics of suppression of spermatogenesis, thus not demonstrating a major beneficial effect of LNG in the combination with injectable TU. Treatment led in both groups to a decrease of HDL and Lp(a) which was more pronounced in the LNG group (P > 0.05). CONCLUSION: Treatment with 1000 mg testosterone undecanoate injected at 6 weekly intervals or in combination with levonorgestrel showed suppression of spermatogenesis comparable to weekly injections of 200 mg testosterone enanthate. Because of its long half-life and in the absence of severe side-effects, testosterone undecanoate can be considered as first choice testosterone ester in further studies of hormonal male contraception.

Seminal plasma characteristics as indicators of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in men with obstructive azoospermia.

OBJECTIVE: To determine the prognostic value of seminal plasma volume, pH, fructose, and alpha-glucosidase for the detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. DESIGN: Retrospective data analysis. SETTING: University infertility clinic (referral center). PATIENT(S): Fifty-nine men with obstructive azoospermia. INTERVENTION(S): Semen analysis including seminal plasma volume, pH, fructose, alpha-glucosidase, molecular genetic diagnosis of CFTR mutations and FSH measurement. MAIN OUTCOME MEASURE(S): Sensitivity and specificity of seminal plasma markers for the detection of CFTR mutations. RESULT(S): A CFTR mutation was detected in 26 of 59 patients with obstructive azoospermia. Patients carrying a mutation had significantly lower seminal plasma volume (mean +/- SEM: 1.5 +/- 1.4 mL vs. 2.8 +/- 2.2 mL), lower pH levels (25th percentile, median, 75th percentile: 6.5, 6.8, 7.5 vs. 7.7, 7. 9, 7.9) and lower fructose content (1.0, 1.1, 3.7 vs. 5.8, 20.0, 83. 0 micromol/ejaculate) than those without mutations. Diagnostic efficacy for detection of mutations was best (pH 81.4%, fructose 81. 8%) at a cutoff level for pH of 7.4 and fructose of 2 micromol/ejaculate. CONCLUSION(S): Seminal plasma markers provide an effective, noninvasive method to predict CFTR mutations in men with obstructive azoospermia.

Long-term substitution therapy of hypogonadal men with transscrotal testosterone over 7-10 years.

OBJECTIVE: Testosterone (T) substitution of hypogonadal men by conventional intramuscular injection of T esters is not considered optimal because it induces unphysiologically fluctuating serum T levels. In contrast, scrotal T patches produce normal serum (T) levels mimicking diurnal variations. In order to assess the quality of this new form of T substitution we followed hypogonadal men treated by transdermal T up to 10 years. PATIENTS: Eleven men aged 35.9 +/- 9.8 years (mean +/- SD) at the beginning of the study were treated with transscrotal T patches (Testoderm) because of primary (n = 4) or secondary (n = 7) hypogonadism. Clinical examinations were performed every 3 months during the first 5 years and every 6 months thereafter. All 11 patients were seen for 7 years and some for longer periods: eight for 8 years, six for 9 years and four for 10 years. MEASUREMENTS AND RESULTS: With daily application of one patch T levels rose from 5.3 +/- 1.3 nmol/l (mean +/- SE) to 16.7 +/- 2.6 nmol/l at month 3 and remained in the normal range throughout treatment. Serum 5 alpha-dihydrotestosterone (DHT) rose from 1.3 +/- 0.4 nmol/l to 3.9 +/- 1.4 nmol/l and oestradiol from 52.3 +/- 9.3 to 71.3 +/- 9.6 pmol/l and remained stable without significant variations throughout the observation period. Patients reported absence of local side-effects except for occasional itching. No relevant changes occurred in clinical chemistry, including total cholesterol levels and triglycerides. Haemoglobin and erythrocyte counts remained normal. Bone density measured by QCT increased slightly from 113.6 +/- 5.4 to 129.7 +/- 9.3 mg/cm3 during the observation period (P = 0.028). In the nine patients aged < 50 years prostate volumes showed a small but insignificant increase from 16.8 +/- 1.5 to 18.8 +/- 2.1 ml during transscrotal T therapy. In the two older patients prostate volume remained constant or decreased slightly during T therapy after an initial increase in the previously untreated patient. Prostate specific antigen levels were constantly low in all patients. CONCLUSION: Transscrotal testosterone patches are well-accepted and safe in long-term testosterone substitution therapy for male hypogonadism.

Serum inhibin B in combination with serum follicle-stimulating hormone (FSH) is a more sensitive marker than serum FSH alone for impaired spermatogenesis in men, but cannot predict the presence of sperm in testicular tissue samples.

The measurement of serum FSH is useful in the diagnostic workup of the infertile male, but fails to predict the presence of sperm in testicular tissue. We investigated whether inhibin B reflects testicular morphology and the presence of sperm more accurately than FSH. Serum inhibin B and gonadotropin levels were determined in 91 infertile men undergoing diagnostic bilateral testicular biopsy. In 52 of the 91 patients multiple samples were taken for testicular sperm extraction (TESE). Inhibin B levels were (mean +/- SEM) 238+/-32 pg/mL in men with normal spermatogenesis (n = 9), 102+/-18 pg/mL in men with spermatogenetic arrest (n = 15), 98+/-16 pg/mL in hypospermatogenesis (n = 23), 41+/-6 pg/mL in focal Sertoli cell-only syndrome (SCO; n = 26), and 27+/-8 pg/mL in complete SCO (n = 18). The percentage of SCO tubuli was more strongly correlated to serum inhibin B (r = -0.58; P<0.01) than to FSH (r = 0.34; P<0.05). Similarly, the percentage of tubules with elongated spermatids was significantly (P<0.05) more strongly correlated to serum inhibin B (r = 0.65; P<0.01) than to FSH (r = -0.4; P<0.01). Thus, inhibin B is slightly more sensitive than FSH as an index of the spermatogenic status. Neither FSH nor inhibin B alone, however, could predict the type of spermatogenetic damage exactly. The combination of FSH and inhibin B had high diagnostic sensitivity (88%) and specificity (83%) for the presence of elongated spermatids in testicular biopsies. Sperm could be retrieved in 34 (65%) of the TESE patients. The combination of inhibin B and FSH measurement showed a sensitivity of 75% and a specificity of 73% when identifying patients in whom sperm could possibly be retrieved by TESE. We conclude that although the measurement of serum inhibin B improves the sensitivity of predictive tests for the presence of sperm in histology or for TESE, this parameter cannot accurately predict TESE outcome.

Clinical trial of transdermal testosterone and oral levonorgestrel for male contraception.

Approaches to hormonal male contraception are predominantly based on injectable testosterone (T) application. As most users would prefer an injection-independent modality, this study was designed to develop a self-applicable hormonal male contraceptive regimen by combining transdermal T with an oral gestagen. Eleven healthy men (23-40 yr old) were treated with oral levonorgestrel and transdermal T for 24 weeks. T was applied daily as a transdermal patch to be worn on the trunk. Levonorgestrel was taken orally at a dose of 250 microg daily up to week 12, followed by 500 microg to week 24 in those volunteers who had not become azoospermic by that time. Within 24 weeks, 2 of 11 volunteers had become azoospermic, and 3 of 11 showed sperm concentrations below 3 million/mL. The sperm concentrations of the remaining volunteers declined, but failed to reach the limit considered compatible with contraception by WHO. Treatment resulted in suppression of LH, FSH, and sex hormone-binding globulin, whereby the volunteers with lower sperm concentrations showed more pronounced suppression than the others. Mean T concentrations remained within the lower limit of normal and on occasions were below this level. There were no complaints of hypoandrogenism. Although mean levels of low density lipoprotein cholesterol, apolipoprotein B, as well as basal and postprandial insulin increased, high density lipoprotein cholesterol and apolipoprotein A-I decreased during the treatment phase. Changes in lipid parameters were normalized within 3 weeks after cessation of medication. Although only 5 of 11 volunteers reached the target sperm counts (<3 million/mL), the study shows that a self-applicable hormonal male contraceptive could be developed.

[Diagnostic and therapeutic concepts of HPV infection in HIV-positive women]. / Diagnostische und therapeutische Konzepte bei HPV-Infektion HIV-positiver Frauen.

Among HIV-seropositive women there is a high prevalence of anogenital human papillomavirus (HPV) infection. HPV-DNA is more frequent detected in cervicovaginal-lavage specimens from HIV-seropositive women as in those from HIV-seronegative women. We and others suggest that HIV-infection increases the risk to have HPV-associated lesions of the lower female genital tract, especially the risk for developing a squamous intraepithelial lesion of the cervix. In this report we describe the current diagnostic and therapeutic strategies in HIV-seropositive women with HPV-infection. The gynecological examination should be performed at six to twelve month intervals, including the colposcopy and the Pap smear test. We hope to improve the quality of our screening program by doing an additional HPV-test. At last we investigate the CD4+ T-lymphocyte counts because it is observed that women with low CD4+ cell counts (< 200/microliter) were more likely to have persistent HPV-infection as those with higher counts (> 500/microliter). The treatment method is dependent on the development of the HPV-associated lesion and the clinical status of the HIV infected women. In cases with external warts local application of Condylox should be the first line treatment. Probably in about few months we could use other drugs like Wartec or Aldara in Germany. But the effectiveness of these drugs in HIV-positive women has to be proven yet. In the cause of persistence of external warts or recurrence of the disease the systemical application of Intron A or Roferon A is possible. The CO2-lasertreatment is performed under colposcopic guidance, especially in cases with multicentric condylomatous lesions. The treatment of cervical intraepithelial neoplasia (CIN) by CO2-laservaporisation or Loop Electrosurgical Excision Procedure (LEEP) is based on the clear colposcopic visualisation of the upper limit of the lesion. If CIN reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal conisation by laser or cold knife has to be performed. Before performing the treatment of CIN one should exclude multicentric cervical, vaginal and vulval intraepithelial neoplasia by colposcopy, because multicentric intraepithelial neoplasia of the lower female genital tract is more frequently than in HIV-seronegative women. Multicentric disease seems to be one cause of the high recurrence of HIV-seropositive women. However, higher levels of immunosuppression (CD4+ T-lymphocyte counts < 200/microliter) are also important determinants of recurrence of the disease. Therefore, an accurate short-term follow-up with colposcopy, Pap test and HPV test should be carried out after the treatment of HIV-seropositive women with low CD4+ counts.

Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men.

OBJECTIVE: To investigate the suitability of intramuscular testosterone undecanoate (TU) injections for substitution therapy in hypogonadal men. STUDY DESIGN: Clinical, open-label, non-randomized trial of 13 hypogonadal men receiving 4 intramuscular injections of 1000 mg TU in 4-ml castor oil at 6-week intervals. General wellbeing, sexual parameters, clinical chemistry, hormone levels, prostate size and prostate-specific antigen (PSA) were evaluated over 24 weeks and compared with baseline values. RESULTS: Testosterone serum levels were never found below the lower limit of normal and only briefly after the 3rd and 4th injection above the upper limit of normal, while peak and trough values increased over the 24-week observation period. Oestradiol and dihydrotestosterone followed this pattern, not exceeding the normal limits. No serious side-effects were noted. Slight increases in body weight, haemoglobin, haematocrit, prostate volume and PSA, suppression of gonadotrophins as well as increased ejaculation frequency occurred as signs of adequate testosterone substitution. CONCLUSION: Testosterone undecanoate is well tolerated by the patients. The injection intervals can be extended even beyond the 6-week periods chosen in the present study. Altogether, intramuscular testosterone undecanoate appears to be well suited for long-term substitution therapy in hypogonadism and hormonal male contraception.

Constriction of an extremity after amnioreduction in a TRAP-like sequence.

We present an unusual case of TRAP sequence (twin reversed arterial perfusion) with persistent polyhydramnios despite spontaneous thrombosis of the vena umbilicalis of the acardius. Serial amnioreduction was performed owing to considerable maternal discomfort and preterm labor. After three procedures, spontaneous abortion occurred. Unexpectedly, the normal twin had an apparently recent constriction of the right forearm. We hypothesize that limb constriction could be a rare but specific complication of aggressive amnioreduction.

Elevated low-density lipoprotein-cholesterol in women with polycystic ovary syndrome.

Previous studies have indicated that women with the polycystic ovary syndrome (PCOS) are affected by hypertriglyceridemia and low high-density lipoprotein-cholesterol (HDL-C) level. However, most of these studies did not control for confounding factors such as body mass index (BMI) or differences in ethnicity. Therefore, we compared the lipid data for 26 women with PCOS with those for 1428 female control participants of the Prospective Cardiovascular Münster (PRO-CAM) study who did not use hormonal contraceptives and were of similar age. Data were adjusted for age, BMI and ethnicity. Women with PCOS had higher total cholesterol (5.55 +/- 1.24 vs. 4.99 +/- 0.88 mmol/l, p < 0.05) and low-density lipoprotein-cholesterol (LDL-C) levels (3.61 +/- 1.19 vs. 3.08 +/- 0.82 mmol/l, p < 0.05) than the control subjects. Compared with the women in the control population, those with PCOS more frequently had triglyceride levels exceeding 2.3 mmol/l (11.5 vs. 1.6%, p < 0.001), LDL-C levels exceeding 4.2 mmol/l (30.8 vs. 12.1, p < 0.01), and HDL-C levels below 1.2 mmol/l (46.2 vs. 15.3%, p < 0.001). We conclude that dyslipidemia is found more frequently in women with PCOS, independently of the excess weight that is often found in this patient group.

[Double umbilical cord knot in mono-amniotic twin pregnancy as the cause of intrauterine fetal death of both twins]. / Doppelter Nabelschnurknoten bei monoamniotischer Geminigravidität als Ursache des intrauterinen Fruchttods beider Zwillinge.

In cases of rare monoamniotic-monochronic geminie pregnancies there is a high risk of complications by real umbilical cord knots, including the cords of both gemini. In these cases fetal mortality is very high. Modern examination techniques (Colour doppler sonography) are able to detect such cord knots in monoamniotic twins. Therefore it is necessary in all twin pregnancies, especially following fertility treatment, to examine precisely by a routine examinator the question of mono - or diamniotic pregnancy. In monoamniotic pregnancy there should be a look for real knots of umbilical cord in regular intervals. In such a case, if a knot is present, the pregnant woman had to be supervised by CTG, to react immediately at first signs of hypoxia.