Recovery of spermatogenesis after androgenic anabolic steroids abuse in men. A systematic review of the literature.

OBJECTIVE: This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies that compared different protocols for the recovery of spermatogenesis in patients after AAS use were included. RESULTS: 13 studies investigating different protocols to restore spermatogenesis in patients with AAS abuse met the inclusion criteria. The available agents that showed restoration of spermatogenesis include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their use is still poorly described in the literature. CONCLUSIONS: Clinicians need to be aware of the detrimental effects of AAS on spermatogenesis. AAS-associated infertility may be reversible, but sperm production may take over a year to normalize. Both conservative and aggressive treatment can boost spermatogenesis with positive results. Further understanding of male reproductive endocrinology and high-quality data on the field of restoration of spermatogenesis after AAS abuse are warranted.

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Scrotal ultrasound reference ranges and associations with clinical, seminal, and biochemical characteristics.

BACKGROUND: Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. OBJECTIVES: To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. METHODS: A cohort of 248 HFM (35.3 ± 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. RESULTS: The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was ~ 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. CONCLUSIONS: The present findings will help in better understanding male infertility pathophysiology, improving its management.

Association of serum testosterone levels and testicular volume in adult patients.

A retrospective observational study was undertaken to gain new insight into the relationship between total testicular volume and levels of serum testosterone, luteinising hormone, follicle-stimulating hormone, prolactin and clinical variables. A total of 312 men with sexual dysfunction or infertility were divided into groups A and B (156 each) on the basis of basal plasma testosterone ≤5 nmol/L of ≥12 nmol/L respectively. Group A was subclassified in A1 (primary hypogonadism) and A2 (secondary hypogonadism). There were significant differences in total testicular volume between group A (15.33 ± 11.94 ml) and group B (36.74 ± 6.9; p < .001) and also between subgroup A1 (11.07 ± 8.49 ml) and subgroup A2 (23.62 ± 13.04 ml; p < .001). Only 13.5% of patients in group B had a total testicular volume <30 ml. Differences in all studied parameters were found between group A and group B. There were no variations when comparing age, body mass index and testosterone in groups A1 and A2 . The use of total testicular volume and body mass index together for predicting testosterone levels yields a sensitivity and specificity of 85.3% and 86.5% respectively. Logistic regression analysis, univariate and multivariate models, using the measurement of total testicular volume resulted in a high capacity to predict testosterone levels.

[Association of nocturnal penile rigidity with testosterone, metabolic syndrome, and other variables: a prospective cross-sectional pilot study]. / Asociación de la rigidez peneana nocturna con testosterona, síndrome metabólico y otras variables: un estudio piloto prospectivo transversal.

INTRODUCTION: The aim was to study whether nocturnal penile rigidity (NPTR) correlates with metabolic syndrome (MetS) and testosterone in men consulting for erectile dysfunction (ED). MATERIAL AND METHODS: 234 men were included in a prospective, cross-sectional pilot study. Serum total and bioavailable testosterone and other biochemical constituents were measured and compared with NPTR. Patients were classified by normal or low/abnormal penile rigidity (abnormal meaning predominant organic component of ED) and presence or absence of MetS to test the hypothesized correlations. RESULTS: Application of the logistic regression model to rigidity as the dependent variable showed the risk of low penile rigidity to be significantly lower for patients with higher total (OR=0.96, 95% CI=0.92-0.99) or bioavailable testosterone (OR=0.91, 95% CI=0.84-0.99). Patients with testosterone levels between 8 and 12 mmol/L had a quadrupled risk of low penile rigidity compared with patients with higher levels (>12 mmol/L) (OR=3.96, 95% CI=1.89-8.31). Considering men without MetS, age and body mass index were associated as significant factors for low penile rigidity: age increased risk by 8% (OR=1.08, 95% CI=1.03-1.13) and BMI increased it by 18% (OR=1.18, 95% CI=1.01-1.38). CONCLUSION: Testosterone levels are weakly associated with penile rigidity and disappear when associated with MetS.

Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations.

The aetiopathogenesis of isolated cryptorchidism remains largely unknown. Mutation screenings in the most relevant candidate genes for testicular maldescent lead to controversial data in the literature. In particular, the role of the T222P genetic variant of the RXFP2 gene is still debated. Given the controversies, the aim of this study was to provide further data on this genetic variant in two Mediterranean populations. A total of 577 subjects from Spain and 550 from Italy (with and without a history of cryptorchidism) were analysed. The T222P substitution was found in both unilateral and bilateral cases and in a total of 12 controls. These data exclude a clear-cut cause-effect relationship between T222P variant and testicular maldescent. The T222P variant was found at a similar frequency in both cases and controls in the Spanish population, whereas in Italy, the frequency of T222P resulted significantly higher in the cryptorchid group (p = 0.031). The observed difference between the two countries and the highly variable phenotypic expression of the T222P variant may depend on the genetic background or on environmental conditions. The haplotype analysis of the RXFP2 gene in T222P carriers and their parents showed that this variant is linked to the previously inferred C-C-G-A-13 haplotype and consequently provides further support to the 'founder effect' hypothesis. In conclusion, our data indicate that T222P is a frequent variant in the Spanish population with no pathogenic effect. Although in Italy it seems to confer a mild risk (odds ratio = 3.17, 95% confidence interval: 1.07-9.34) to cryptorchidism, the screening for this variant for diagnostic purposes is not advised because of the relatively high frequency of control carriers (1.4% of Italian men without a history of cryptorchidism).

Sensory changes after surgical correction of penile curvature.

In 32 men (mean age 54.94 years, range 25-70 years), thresholds for penile thermal and vibratory sensation were recorded before and 3 months after surgery using a genital sensory analyser. The following significant changes were found postoperatively. The cold threshold decreased in the glans from 27.24 to 25.33 degrees C (P<0.001) in men older than 60 years, and in the ventral penile shaft from 28.54 to 25.46 degrees C (P<0.001) in men aged 35-59 years. The warm threshold increased in the glans from 38.31 to 40.61 degrees C (P=0.002) in men aged 35-59 years, and from 39.20 to 40.58 degrees C in men older than 60 years (P=0.023). The warm threshold also increased in the ventral penile shaft in men aged 35-59 years, from 36.62 to 37.82 degrees C (P=0.023). For all three age groups combined, the vibratory threshold changed in the glans from 2.33 to 2.93 mum (P<0.001). It is concluded that penile sensitivity changed significantly after surgery for penile curvature treatment, regardless of whether a ventral or dorsal surgical approach is used.

[Tadalafil vs sildenafil patient preference in Spanish men with erectile dysfunction: results from an International Multicentric Study]. / Preferencia de tadalafilo vs sildenafilo en pacientes españoles con disfunción eréctil: resultados procedentes de un estudio multicéntrico internacional.

OBJECTIVE: To compare patient preference for sildenafil citrate (sildenafil) vs. tadalafil and for their respective dosing instructions in a cohort of Spanish patients with erectile dysfunction (ED). MATERIAL AND METHODS: Sixty four Spanish patients from a multicenter, two period, cross-over, double-blind study (265 patients enrolled in total) were randomized to receive on-demand sildenafil 50 mg or tadalafil 20 mg for 12 weeks and afterwards were crossed over to the alternate regimen for another 12 weeks to assess drug preference in an extension period of the study. Similarly, to evaluate preference for their respective dosing instructions, 30 patients were randomized to one of the 2 arms treated with tadalafil: one with sildenafil (S) dosing instructions and the other with tadalafil (T) dosing instructions. RESULTS: Seventy percent of 56 patients completing the study chose to receive tadalafil treatment versus sildenafil treatment (30%) in the extension period (p<0.01). Correspondingly, 73% of 13 evaluating each drug dosing instructions preferred T dosing instructions (p>0.05). Preference did not vary with age, concomitant diseases and previous use of sildenafil. CONCLUSIONS: In this study, 7 out of 10 patients preferred tadalafil and its dosing instructions to sildenafil, for the treatment of their ED.

[Response to intracavernous administration of 3 different drugs in the same group of patients with erectile dysfunction]. / Respuesta a la administración intracavernosa de tres fármacos diferentes en el mismo grupo de pacientes con disfunción eréctil.

OBJECTIVE: To compare the subjective and objective penile rigidity in the same group of patients with erectile dysfunction after intracavernous injection of different vasoactive drugs. METHODS: 91 impotent males were randomly assigned to three groups of intracavernous injection: A: 20 micrograms PGE1 B: 30 mg papaverine hydrochloride + 1 mg phentolamine (bimix), and C: 10 micrograms PGE1 + 15 mg papaverine hydrochloride + 0.5 mg phentolamine (trimix). Each patient was scheduled to receive the three modalities of intracavernous injection randomly with an interval of 7-10 days between injections. Penile rigidity equal to or more than 60% was considered positive. Subjective and objective penile rigidity were evaluated with callipers by the same observer. RESULTS: 82 patients completed the study and 9 dropped out after prolonged erection with one of the ICI modalities. Rigidity after treatment with C (66 +/- 15%) was significantly superior to that of B (59 +/- 15%, p = 0.0001) and A (60 +/- 13%, p = 0.0115). No differences were observed between A and B (p = 0.4644). Analysis of only the positive response showed significant differences between A and C, but not between C and B (p = 0.3323). Differences were not found between the response to PGE1 (A) and bimix (B) (p = 0.1275). The order of application of the drug had no effect on response (p = 0.026). CONCLUSIONS: A higher percentage of positive response in patients with erectile dysfunction was achieved with the trimix modality. Choice of more potent ICI regimens can improve the diagnostic and/or therapeutic efficacy in males that do not respond to PGE1 alone.

Linear increase of diploidy in human sperm with age: a four-colour FISH study.

The aim of this study was to determine if donor age is associated with an increased incidence of diploidy and of disomy for the sex chromosomes and for chromosomes 6 and 21. We used simultaneous fluorescence in situ hybridisation (FISH) for chromosomes 6, 21, X and Y in sperm from 18 healthy donors, aged 24-74 years (mean 48.8 years). A total of 194 024 sperm were analysed, with a minimum of 10 000 sperm scored for each donor. Our results indicate a significant increase of the level of diploidy (P=0.002), and a marginal significance of total sex chromosome disomy (P=0.055) with age. No increase was observed for disomies XX, YY, XY, 21 or 6. The percentages of increase for disomy and for diploidy ranged from 0.3 to 17% for each 10-year period. Chromosomes 6 and 21 did not segregate preferentially with the X or Y chromosomes. Our findings show a linear trend association between age and diploidy in human males.

[Acceptability of auto-injection of vasoactive drugs in the treatment of erectile dysfunction]. / Aceptabilidad del autoinyector con fármacos vasoactivos en el tratamiento de la disfunción eréctil.

OBJECTIVES: To study the utility of the PenInject 2.25 (SHL Medical AB), an instrument for intracavernous auto-injection of vasoactive drugs. METHODS: 61 males, aged 30-70 years, with erectile dysfunction were studied. The study comprised two groups: group A consisted of 26 patients previously treated with intracavernous injections using a syringe that were started on treatment with the self-injector, and group B consisted of 35 previously untreated patients that started treatment directly with the self-injector. Different data and questions on the facility of use and acceptance of the instrument were analyzed. Data evaluation were plotted on visual analog scales of 10 cm. A score of 5 or more showed good results and less than 5 was considered unfavorable. RESULTS: The positive aspects were facility of use, comfort, design of the self-injector, which scored higher than 7. The negative aspects were pain, fear, discomfort intensity, which scored below 4. CONCLUSIONS: The use of the PenInject self-injector in this group of patients improved the acceptability of intracavernous therapy for erectile dysfunction in comparison to the classical syringe.

Melatonin concentration before and during testosterone replacement in primary hypogonadic men.

OBJECTIVE: To study circadian levels of melatonin in primary hypogonadic adult men before and after testosterone treatment. DESIGN AND METHODS: Circadian serum melatonin profiles were studied in six men with primary hypogonadism before and during testosterone substitution and compared with an age-matched control group (n = 6). RESULTS: Hypogonadal patients had higher plasma melatonin concentrations than the control group during day time (34.2 +/- 8.8 compared with 5.4 +/- 0.5 ng/l, means +/- SD; P < 0.005) and night-time (74.8 +/- 34.5 compared with 30.8 +/- 3.2 ng/l). A 3 months course of testosterone replacement treatment in the hypogonadal group was followed by a diminution of the amplified melatonin circadian rhythm, with lower mean values both during the day (34.2.8 +/- 8 compared with 12.7 +/- 2.45 ng/l, P < 0.001) and at night (74.8 +/- 34.5 compared with 41.5 +/- 13.5 ng/l, P < 0.01), and a decrease in the total area under the curve (958 +/- 318 compared with 475.5 +/- 222.9, P = 0.046). There was a significant negative correlation between melatonin (r = -0.69) and testosterone concentrations. CONCLUSIONS: These data indicate that diminished testosterone in male primary hypogonadism is associated with enhanced plasma levels of melatonin, and that testosterone substitution treatment induces a deamplification of the circadian rhythm of melatonin values in humans.

Growth hormone response to growth hormone-releasing hormone stimulation in oligozoospermic patients.

OBJECTIVE: To evaluate the GH response to growth hormone-releasing hormone (GH-RH) stimulation in oligozoospermic men. SETTING: Outpatient Clinic of Andrology at the Fundación Puigvert and the Department of Clinical Chemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. PATIENTS: Fifteen oligozoospermic patients and 15 normozoospermic fertile men matched for age and body mass index. INTERVENTION: Endocrine status was determined by assay of basal levels of gonadotropins (FSH, LH), T, E2, inhibin, and insulin-like growth factor I (IGF-I). Serum GH levels were measured before and after GH-RH administration. RESULTS: GH response to GH-RH was significantly greater in patients than in controls. There was a positive correlation between the GH response and IGF-I levels in oligozoospermic patients only. Regression analysis showed a significant negative association of GH peak with inhibin after controlling for IGF-I in oligozoospermic patients. CONCLUSION: The results indicate that there is an altered responsiveness of pituitary to GH-RH administration in oligozoospermic patients; this did not appear to be due to the influence of gonadal steroid levels but rather to inhibin or some related peptide.

[Prolonged erections after diagnostic injection of papaverine chlorhydrate]. / Erecciones prolongadas tras inyección diagnóstica de clorhidrato de papaverina.

We analyzed the incidence of prolonged erection (PE) in 495 impotent subjects following intracavernous papaverine chlorhydrate injection to evaluate sexual dysfunction. Patient course was individually assessed. The overall the incidence of PE was 5.05%. The etiology of sexual dysfunction was psychogenic in all cases. No evidence of dose- or age-related PE was observed. Fibrosis of the corpus cavernosum, although more prevalent in PEs greater than 6 hours, was also observed in PEs of a shorter duration. This suggests that a probable predisposing factor might previously be present in some patients. None of the different methods utilized to achieve penile detumescence appears to afford any significant advantage.

Sperm chromosome studies in an infertile man with partial, complete asynapsis of meiotic bivalents.

Meiotic and sperm chromosome studies were carried out in two semen samples from an infertile man with a 46,XY karyotype, oligoasthenoteratozoospermia and abundant exfoliation of spermatogenic cells. Meiotic preparations showed partial, complete asynapsis in a large proportion of metaphase I figures observed, and absence of metaphase II figures, while 24 of the 30 sperm chromosome karyotypes analysed were normal. The remaining sperm karyotypes were as follows: one with structural abnormalities, one with both structural abnormalities and hypohaploidy and four with hypohaploidy. The total frequency of chromosomal abnormalities (6.7%) is similar to that obtained by us in normal men (10.9%). The frequency of spermatozoa with structural abnormalities (6.7%) was not significantly different from that obtained by us in normal men (6.9%). These results suggest that, in some cases, asynaptic spermatogenic cells do not proceed further than metaphase I and only normal germ cells continue spermatogenesis.

Sperm recuperation and cervical insemination in retrograde ejaculation.

Seven infertile patients with retrograde ejaculation, in which spermatozoa could be recuperated from the postejaculation urine, were admitted to a sperm recuperation and cervical insemination program. A noninvasive method for sperm recuperation based on urine alcalinization and serial controls to time masturbation has been used. Insemination has been timed according to BBT charts and cervical mucus characteristics. Pregnancy has been obtained in the seven couples after one to eight treatment cycles.