Raman spectroscopic analysis identifies testicular microlithiasis as intratubular hydroxyapatite.

PURPOSE: As diagnosed by ultrasonography, testicular microlithiasis is associated with various benign and malignant conditions. The molecular constitution of these microliths is largely unknown. Raman spectroscopy provides detailed in situ information about the molecular composition of tissues and to our knowledge it has not been applied to gonadal microliths. We analyzed the molecular composition of gonadal microlithiasis and its surrounding region using Raman spectroscopy in malignant and benign conditions. MATERIALS AND METHODS: Multiple microliths from 6 independent samples diagnosed with gonadal microlithiasis by ultrasound and histologically confirmed were investigated by Raman spectroscopy. The samples included 4 testicular parenchyma samples adjacent to a germ cell tumor (4 seminomas), a gonadoblastoma of a dysgenetic gonad and testicular biopsy of a subfertile male without malignancy. RESULTS: Raman spectroscopic mapping demonstrated that testicular microliths were located within the seminiferous tubule. Glycogen surrounded all microliths in the samples associated with germ cell neoplasm but not in the benign case. The molecular composition of the 26 microliths in all 6 conditions was pure hydroxyapatite. CONCLUSIONS: Microliths in the testis are located in the seminiferous tubules and composed of hydroxyapatite. In cases of germ cell neoplasm they co-localize with glycogen deposits.

Bilateral testicular microlithiasis predicts the presence of the precursor of testicular germ cell tumors in subfertile men.

PURPOSE: A high prevalence of testicular microlithiasis has been described in adolescent and adult clinical cases of invasive testicular germ cell tumor (TGCT), that is seminomas and nonseminomas. However, to our knowledge it remains to be established whether testicular microlithiasis also indicates the presence of the pre-invasive lesion of this cancer, known as carcinoma in situ (CIS). We determined the predictive value of unilateral and bilateral testicular microlithiasis for CIS in subfertile men, a known risk population for TGCTs (approximately 1%). MATERIALS AND METHODS: In a retrospective cross-sectional study the association between testicular microlithiasis and CIS was studied in a group of 263 men referred for subfertility. Testicular microlithiasis and CIS were diagnosed in all men by scrotal ultrasound and in testicular histology specimens as part of the routine evaluation of all patients. RESULTS: Of the 263 subfertile men 53 (20%) had testicular microlithiasis. No CIS or TGCT was identified in the 23 men with unilateral testicular microlithiasis. In contrast, 6 of the 30 men (20%) with bilateral testicular microlithiasis were diagnosed with CIS. Therefore, the prevalence of CIS in subfertile men with bilateral testicular microlithiasis is significantly higher than in patients without testicular microlithiasis (1 of 210, 0.5%) and with unilateral testicular microlithiasis (0 of 23, 0%) (p <0.0001). CONCLUSIONS: Bilateral testicular microlithiasis is indicative for CIS in subfertile men. Since these men are at particular risk for invasive TGCT, an assessment of testicular microlithiasis is a valuable tool for the early diagnosis of this disease.

The effect of cryptorchidism on inhibin B in a subfertile population.

OBJECTIVE: Prepubertal cryptorchidism may cause fertility problems in adulthood, due to impaired spermatogenesis. Serum inhibin B has emerged as an accurate marker of spermatogenesis. The aim of this study was to evaluate the impact of a history of cryptorchidism on serum inhibin B levels and other markers of spermatogenesis in subfertile men. PATIENTS AND MEASUREMENTS: In a retrospective study, the effect of cryptorchidism on inhibin B, FSH, LH, free testosterone, testicular volume and semen parameters was assessed in a case-control study within a population of 2613 subfertile men. Of these, 161 and 102 subjects had a history of, respectively, unilateral and bilateral cryptorchidism that was treated by orchiopexy in childhood. Hormone data were complete for 64 cryptorchid patients (32 unilateral and 32 bilateral). A group of 128 patients was randomly selected out of the remaining group of 2350 men with idiopathic subfertility. An additional control group consisted of 32 fertile men from the general population. RESULTS: In cryptorchid subfertile men, inhibin B concentrations were significantly lower than in noncryptorchid subfertile men and fertile men (103 ng/l, 143 ng/l and 148 ng/l, respectively; P < 0.01). The FSH concentration was significantly higher in cryptorchid men vs. noncryptorchid men and controls (6.1 IU/l vs. 3.3 and 2.9 IU/l, respectively; P < 0.01). Testicular volumes and sperm concentration of cryptorchid men were significantly lower than in noncryptorchid subfertile men (12 vs. 15 ml, P < 0.01 and 3.8 x 10(6) sperm/ml vs. 17.4 x 10(6) sperm/ml; P < 0.05). A significantly higher inhibin B level and sperm concentration was observed in men undergoing orchiopexy at an early age (1-4 years) compared with men treated between 5 and 9 years or later (P < 0.05). CONCLUSION: Spermatogenesis is more impaired in cryptorchid subfertile men compared to men with idiopathic subfertility, as reflected by a lower inhibin B concentration.

Effective daily treatment with clomipramine in men with premature ejaculation when 25 mg (as required) is ineffective.

OBJECTIVE: To determine whether men with premature ejaculation who fail to respond to 25 mg clomipramine as needed improve when taking 10-30 mg clomipramine daily. SUBJECTS AND METHODS: Four men with premature ejaculation whose ejaculation latencies increased minimally or not at all when taking 25 mg clomipramine as needed participated in a prospective 12-week study consisting of four treatment phases, beginning with baseline (0 mg) and progressing through increasing daily doses of 10, 20, and 30 mg clomipramine. The subjects maintained daily logs of their sexual activities and estimated their ejaculatory response, sexual arousal and penile rigidity during intercourse. The subjects were contacted 8-15 weeks after the experiment to assess their satisfaction with and continued use of clomipramine. RESULTS: There was a dose-response effect on ejaculatory latency with increasing levels of clomipramine; 30 mg increased the latency from 25 s to 220 s, a clinically significant increase. In addition, 30 mg taken daily was significantly more effective than 25 mg as required. Other variables of sexual response (sexual interest, arousal and penile rigidity) were unaffected. At follow-up all four subjects expressed satisfaction and three continued the dose. CONCLUSION: Men with premature ejaculation who do not respond to clomipramine 'as required' are probably not insensitive to pharmacological treatment, but may simply require higher doses or a different regimen. All four subjects improved when taking daily clomipramine at varying doses. These results suggest that if initial treatment is unsuccessful, 20-30 mg daily clomipramine should be considered.

Ejaculatory latency and control in men with premature ejaculation: an analysis across sexual activities using multiple sources of information.

OBJECTIVE: Men with premature ejaculation (PE) exhibit diminished control over and short latency to ejaculation. The present study attempted to delineate further characteristics of men with PE and to address a number of presumed hypotheses regarding the etiology of this disorder. METHODS: Twenty-six men with PE were compared with an age-matched group of 13 sexually functional men on multiple indices of erectile and ejaculatory response during coital and masturbatory activities. These data were collected through retrospective, prospective, and laboratory methods. RESULTS: Psychophysiological testing indicated greater ejaculatory vulnerability to penile stimulation, although not visual erotic stimulation, in PE men than functional controls. PE men also showed subtle anomalies in the way they perceived their somatic response. The correlation between measures of ejaculatory latency and control was positive and high for intercourse, but low or even negative for masturbation. Whereas functional men showed consistency in ejaculatory latency over coital and masturbatory activities, PE men exhibited much shorter latencies during coitus than masturbation. Data collected under various methodologies (retrospective, prospective, and laboratory) showed greater consistency among sexually functional subjects; and preliminary analysis of laboratory data suggests psychophysiological methodology is as effective in differentiating dysfunctional from functional men as prospective and retrospective methodologies. CONCLUSION: Although ejaculatory latency and control tend to be related, these measures are not always stable over different kinds of sexual activity or using different methods of data collection. Psychophysiological methodology is effective in differentiating group membership (PE vs. control), but does not predict individual ejaculatory responses measured prospectively.

Clomipramine in the treatment of rapid (premature) ejaculation.

Twenty-three premature ejaculators (PEs) and 11 control subjects were administered 25 mg of clomipramine in a double-blind, placebo-controlled, crossover design study. During 2-week trials, subjects took either the drug or the placebo 4 to 6 hours prior to sexual activity. Daily diary data revealed that, for both groups, orgasmic latency was significantly increased when taking the clomipramine. For the PEs, the average increase in orgasmic latency during intercourse was from less than 1 minute to more than 3.5 minutes. Subjects also participated in two laboratory sessions while on the drug and placebo. During these lab sessions they were exposed to erotic videos with and without the addition of vibrotactile stimulation to the penis. Results from the laboratory data support those from the diaries. Specifically, PEs were significantly less likely to reach orgasm during the lab sessions while on the clomipramine than while on the placebo. Further, they reported a significantly greater sense of control over their orgasm while on the drug. The results of this study, along with previous research, strongly support the value of low doses of clomipramine in the treatment of premature ejaculation, specifically when taken on an as-needed basis as little as 4 hours prior to sexual activity. It is important to note, however, that the beneficial effects of the drug were not uniform across clinical subjects. In this study, those PEs with the shortest orgasmic latencies while on the placebo were the least likely to substantially improve while on the drug. Additional research is necessary to determine whether changes in the timing and dosage of the clomipramine administration can extend the benefits of the drug to those with the shortest latencies.