Steroidogenic factor-1 inverse agonists as a treatment option for canine hypercortisolism: in vitro study.

Hypercortisolism is one of the most commonly diagnosed endocrinopathies in dogs, and new targeted medical treatment options are desirable. Steroidogenic factor-1 (SF-1), an orphan nuclear hormone receptor, is a key regulator of adrenal steroidogenesis, development, and growth. In pituitary-dependent hypercortisolism (PDH), high plasma ACTH concentrations increase the transcriptional activity of SF-1. In adrenal-dependent hypercortisolism, SF-1 expression is significantly greater in dogs with recurrence after adrenalectomy than in those without recurrence. Inhibition of SF-1 could therefore be an interesting treatment option in canine spontaneous hypercortisolism. We determined the effects of 3 SF-1 inverse agonists, compounds IsoQ A, #31, and #32, on cortisol production, on the messenger RNA (mRNA) expression of steroidogenic enzymes and SFs, and on cell viability, in primary adrenocortical cell cultures of 8 normal adrenal glands and of 3 cortisol-secreting adrenocortical tumors (ATs). To mimic PDH, the normal adrenocortical cell cultures were stimulated with ACTH. The results show that only compound #31 inhibited cortisol production and SF-1 target gene expression in non-ACTH-stimulated and ACTH-stimulated normal adrenocortical cells but did not affect cell viability. In the AT cell cultures, the effects of #31 on cortisol production and target gene expression were variable, possibly caused by a difference in the SF-1 mRNA expressions of the primary tumors. In conclusion, inhibition of SF-1 activity shows much promise as a future treatment for canine hypercortisolism.

Tadalafil (Cialis) and erectile dysfunction after radiotherapy for prostate cancer: an open-label extension of a blinded trial.

OBJECTIVES: To determine the efficacy of tadalafil (Cialis) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer in an extended open-label phase of the blinded trial. METHODS: Sixty patients entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received tadalafil 20 mg or placebo for 6 weeks and then crossed over to the alternate medication. Of these 60 patients, 51 (85%) entered a 6-week open-label extension phase. The data were collected using the International Index of Erectile Function (IIEF) questionnaire. Side effects were also recorded. RESULTS: All patients completed the double-blind cross-over study. The 9 patients who did not wish to enter the open-label phase had had significantly worse scores statistically on the erectile function domain of the IIEF with tadalafil in the blinded trial (P = 0.03). For all IIEF domains, except for sexual desire, tadalafil was equally effective in the double-blind phase as in the open-label phase. For nearly all the IIEF questions, tadalafil caused a significant increase in the mean scores from baseline in the run-in period of the blinded trial. The side effects were mild or moderate and had significantly decreased compared with tadalafil in the blinded trial. CONCLUSIONS: Tadalafil is effective in many patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer. In the open-label extension of the trial, tadalafil showed the same efficacy as in the blinded phase.

A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma.

PURPOSE: Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. METHODS AND MATERIALS: Patients (N=358) who completed radiotherapy at least 12 months before the study were approached by mail. All patients had been treated by 3DCRT; 60 patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebo for 6 weeks. Drug or placebo was taken on demand at patient's discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. At 6 weeks patients crossed over to the alternative treatment. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side effects were also recorded. RESULTS: Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil (placebo: 9%) (p<0.0001). Side effects were mild or moderate. CONCLUSIONS: Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and it is well tolerated.

Aging and sexual response in the laboratory in patients with erectile dysfunction.

Aging places men at increased risk for erectile problems, particularly beginning around their fifties and sixties. Using a psychophysiological assessment procedure that included visual erotic stimulation, vibrotactile stimulation, and intracavernosal injection, this study tested for possible age effects on erectile response and self-reported sexual arousal in a group of men clinically diagnosed with erectile dysfunction. We controlled for three factors of purported importance to erectile functioning: existing comorbidities, use of specific medications, and current tobacco and alcohol use. Results indicated effects from both age and tobacco use on erectile response, although these effects were not uniform across age groups. For example, age had inconsistent effects on erectile response in patients aged 50 to 90 years; tobacco use had its strongest effect on patients under 50 years of age. In general, such covariates were less able to account for variation in erectile response among patients with more-severe ED. Despite these effects, ED men even in the oldest group showed average penile circumference increases of 28 mm under ICI, an erectile response typically sufficient for vaginal intercourse.

[Favorable effect of sildenafil on erectile dysfunction in patients after radiotherapy for prostate cancer; randomised, double-blind, placebo-controlled crossover study]. / Gunstig effect van sildenafil op erectiele disfunctie bij patiënten na radiotherapie voor prostaatkanker; gerandomiseerd, dubbelblind, placebogecontroleerd en gekruist onderzoek.

OBJECTIVE: To determine the efficacy of sildenafil in patients with erectile dysfunction after external beam radiotherapy for prostate cancer. DESIGN: Randomised, double-blind, placebo-controlled, crossover study. METHOD: A total of 406 patients with erectile dysfunction reported in their medical records who had completed external beam radiotherapy at least 6 months prior to the study, were approached by letter. Sixty patients were included in a study which lasted 12 weeks. They received 50 mg of sildenafil citrate or placebo for two weeks; during week 2 the dose could be increased to 100 mg in the case of unsatisfactory erectile response. At week 6 patients crossed over to the alternative treatment. Data were collected using the validated 'International index of erectile function' (IIEF) questionnaire, and side-effects were recorded. Patients were given the possibility of continuing to a 6-week open-label phase. RESULTS: The mean age of those participating was 68 years. All patients completed the double-blind phase. For the majority f questions in the IIEF questionnaire, there was a significant increase in mean scores from baseline with sildenafil, but of the patients with sildenafil, versus 18% with placebo. Ninety percent of the patients required a dose adjustment to 100 mg sildenafil, and 100% of the patients in the placebo group increased the dose. Side-effects were mild or moderate. Patients who proceeded to the open-label phase reported the same results as in the double-blind phase. CONCLUSION: Sildenafil improved erectile function in about half of the patients with erectile dysfunction after external beam radiotherapy for prostate cancer, and it was well tolerated.

Efficacy of sildenafil in an open-label study as a continuation of a double-blind study in the treatment of erectile dysfunction after radiotherapy for prostate cancer.

OBJECTIVES: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer. METHODS: Sixty patients treated with radiotherapy for prostate cancer at least 6 months previously, complaining of erectile dysfunction, and not using nitrates were entered into a double-blind, placebo-controlled, crossover study lasting 12 weeks. They received 50 mg of sildenafil or placebo for 2 weeks; at week 2, the dose was increased to 100 mg in the case of an unsatisfactory erectile response. At week 6, patients crossed over to the alternative treatment. Patients were then allowed to enter a 6-week open-label phase using 50 mg of sildenafil in the first 2 weeks, increasing the dose to 100 mg in the case of an insufficient erectile response in the following 4 weeks. Data were collected before trial entry (baseline evaluation) and every 2 or 4 weeks using the International Index of Erectile Function questionnaire. Any side effects were recorded. Two years later, all patients were approached by mail to evaluate their current sexual functioning and possible use of sildenafil. RESULTS: All patients completed the double-blind, crossover study. For nearly all the International Index of Erectile Function questions, sildenafil caused a significant increase in mean scores from baseline. Placebo had no effect. Seventy-seven percent entered the open-label phase; they were the better responders in the double-blind phase. Sildenafil was as equally effective as in the double-blind phase. The side effects were mild or moderate and significantly decreased in the open-label period. Two years after trial entry, 24% still used sildenafil. CONCLUSIONS: Sildenafil is relatively effective in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer. New drugs and combination therapies are needed to improve outcome.

The plication procedure for penile curvature: surgical outcome and postoperative sexual functioning.

OBJECTIVE: This study evaluates the patients' judgement of the surgical outcome of the plication procedure, as described by Schröder and Essed, and the postoperative sexual functioning of patients with congenital curvatures and Peyronie's disease. PATIENTS AND METHODS: Of 98 patients treated for penile curvatures between 1985 and 1996, 85 patients received postoperatively a 'Questionnaire Assessing the Outcome of Surgery' and a short version of the 'Questionnaire for Screening Sexual Dysfunctions'. RESULTS: 28 patients with congenital curvatures and 31 with Peyronie's disease were evaluated. 75% of the patients with congenital curvatures and 58% of the patients with Peyronie's disease were satisfied with the result. Patients treated for Peyronie's disease reported diminished penile length and inability to have sexual intercourse more often than patients with congenital curvatures (90 vs. 64%, and 29 vs. 0%). After correction for age, patients with Peyronie's disease were less satisfied with their present sex life, had more frequent erectile problems and more trouble with considerable sexual desire than a group of 42 controls. For patients with Peyronie's disease satisfaction with the result was positively correlated with satisfaction with their present sex life and negatively correlated with the frequency of erectile problems. For patients with congenital curvatures satisfaction with the result was negatively correlated with both a postoperative curvature and a repeat operation. CONCLUSIONS: Some patients with Peyronie's disease may not benefit from surgical correction (alone). Because of the occurrence of sexual problems, future evaluation of the role of pre- and postoperative sexological counselling in achieving better results is recommended.

Treatment outcome, body image, and sexual functioning after orchiectomy and radiotherapy for Stage I-II testicular seminoma.

PURPOSE: Orchiectomy followed by infradiaphragmatic irradiation is the standard treatment for Stage I-II testicular seminoma in The Netherlands. Because body image and sexual functioning can be affected by treatment, a retrospective study was carried out to assess treatment outcome, body image, and changes in sexuality after orchiectomy and radiotherapy. METHODS AND MATERIALS: The medical charts of 166 patients with Stage I-II testicular seminoma were reviewed. A questionnaire on body image and current sexual functioning regarding the frequency and quality of erections, sexual activity, significance of sex, and changes in sexuality was sent to 157 patients (at a mean of 51 months after treatment). RESULTS: Seventy-eight percent (n = 123, mean age 42 years) completed the questionnaire. During irradiation, almost half of patients experienced nausea and 19% nausea and vomiting. Only 3 patients had disease relapse. After treatment, about 20% reported less interest and pleasure in sex and less sexual activity. Interest in sex, erectile difficulties, and satisfaction with sexual life did not differ from age-matched healthy controls. At the time of the survey, 17% of patients had erectile difficulties, a figure that was significantly higher than before treatment, but which correlated also with age. Twenty percent expressed concerns about fertility, and 52% found their body had changed after treatment. Cancer treatment had negatively influenced sexual life in 32% of the patients. CONCLUSIONS: Orchiectomy with radiotherapy is an effective and well-tolerated treatment for Stage I-II testicular seminoma. Treatment-induced changes in body image and concerns about fertility were detected, but the sexual problems encountered did not seem to differ from those of healthy controls, although baseline data are lacking.

Intracavernous injection during diagnostic screening for erectile dysfunction; five-year experience with over 600 patients.

Psychophysiological diagnostic screening (PDS) was carried out on just over 1000 consecutive patients with erectile dysfunction (ED) during 1995 through 1999. Roughly one-third did not require an intracavernous injection (ICI) because of optimal penile response during visual and tactile penile sexual stimulation. The present article deals with those other patients (n = 609) who required an ICI and completed a 24-hour-postinvestigation questionnaire (PIQ). The two ICI preparations used, prostaglandin and papaverine + fentolamine, were virtually equally effective in the doses applied, with very low and similar percentages of unwanted side effects, for example, prolonged erection. Somatic ED patients displayed the lowest penile responses to ICI, whereas psychogenic ED patients had the highest penile responses. ED patients who also suffered from premature ejaculation (PE) ejaculated significantly more readily during PDS that those without PE. An ICI following an ejaculation/orgasm could lead to an erection presumably sufficient for intromission, which indicates ICI as a therapeutic option for rapid ejaculators. Our elaborate and lengthy PDS procedure, particularly the use of penile vibration as an addition to the visual sexual stimulation, obviates the diagnostic use of the PIQ.

Sexual (dys)function after radiotherapy for prostate cancer: a review.

PURPOSE: Prostate cancer has become the most common nonskin malignant neoplasm in older men in Western countries. As treatment efficacy has improved, issues related to posttherapy quality of life and sexual functioning have become more important. METHODS AND MATERIALS: We discuss the various methods used to evaluate erectile and sexual dysfunction and the definition of potency. The etiologies of erectile dysfunction after external beam radiotherapy and brachytherapy for prostate cancer are also reviewed. The literature is summarized, and comparative studies of radiation and surgery are surveyed briefly. RESULTS: Rates of erectile dysfunction vary from 6 to 84% after external beam radiotherapy and from 0 to 51% after brachytherapy. In most of the studies, the analysis is retrospective, the definition of erectile dysfunction is not clear, only one question about sexual functioning is asked, and nonvalidated instruments are used. The etiology of erectile dysfunction after radiation for prostate cancer is not completely understood. CONCLUSIONS: Because erectile function is only one component of sexual function, it is necessary to assess sexual desire, satisfaction, frequency of intercourse, and other such factors when evaluating the effects of therapy. Patients should be offered sexual counseling and informed about the availability of effective treatments for erectile dysfunction, such as sildenafil, intracavernosal injection, and vacuum devices.

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study.

PURPOSE: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. METHODS AND MATERIALS: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. RESULTS: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. CONCLUSION: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.

Low-dose radiotherapy in 179 patients with Peyronie's disease: treatment outcome and current sexual functioning.

PURPOSE: To analyse retrospectively treatment outcome in patients irradiated for Peyronie's disease. METHODS AND MATERIALS: The records of 179 patients, median age 52 years, that received radiotherapy (RT) between 1982 and 1997 were reviewed. 78% presented with painful erections and 89% with penile deformity. The symptoms were present for a median duration of 6 months (range, 1-72 months). The RT schedule consisted of 13.5 Gy (9 x 1.5 Gy, 3 fractions per week) using orthovoltage X-rays in 123 patients or 12 Gy (6 x 2 Gy, daily fractions) using electrons in 56 patients. A questionnaire regarding current sexual functioning was mailed to 130 patients whose addresses could be traced; 106 (82%) responded. RESULTS: At mean follow-up period of 3 months, 83% reported that pain was diminished or had disappeared after RT. Twenty-three percent of patients reported a decrease in penile deformity. Following RT, surgical correction of penile curvature was performed in 29% of patients. No RT-related complications occurred except transient dysuria in 1 patient. Questionnaire data: 72% of patients were currently sexually active, 48% had erectile dysfunction, and 49% expressed dissatisfaction with their current sexual functioning. CONCLUSION: Low-dose external RT (12-13.5 Gy) results in relief of pain in the majority of patients with Peyronie's disease. Improvement in penile deformity was observed, avoiding surgery in a number of patients. No significant RT-associated morbidity was encountered. It is disappointing that almost 50% of patients complain of sexual functioning, but this is presumably not related to radiotherapy.

Current sexual functioning in 106 patients with Peyronie's disease treated with radiotherapy 9 years earlier.

OBJECTIVES: To analyze retrospectively the sexual functioning and treatment outcome in patients after radiotherapy (RT) for Peyronie's disease. METHODS: During 1982 to 1997, 179 patients with Peyronie's disease were treated at our radiation oncology department. One hundred thirty patients whose address could be traced were sent a questionnaire about their symptoms before RT, treatment outcome, and current sexual functioning (the past 4 weeks). One hundred six patients, mean age 59 years, responded. RESULTS: Before RT, 44% reported painful erections, 97% penile curvature, and 18% erectile dysfunction. Sixty-nine percent reported that after RT, penile pain was diminished and 29% that penile curvature was decreased; 13% reported improved erections. With respect to their current sex life, 51% reported sometimes or always having problems getting an erection and 61% in maintaining an erection; 36% never experienced spontaneous erections. Fifty-four percent reported not having erections rigid enough for sexual activity. Since RT (mean 9 years), there had been a moderate or severe decrease in sexual interest (17%), sexual activity (41%), and sexual pleasure (32%). Overall, 49% of patients were dissatisfied with their current sexual functioning. CONCLUSIONS: Low-dose external RT resulted in relief of pain in two thirds of patients with Peyronie's disease. An improvement in penile curvature was reported in one third of patients. One half of men reported problems in getting an erection. The rigidity of erections was satisfactory in only 54%. There was a moderate to severe decrease in sexual interest, activity, and pleasure after RT; however, this was associated with age, although comorbidity or medications cannot be excluded.

IGF-I and retinoic acid regulate the distribution pattern of IGFBPs synthesized by the canine mammary tumor cell line CMT-U335.

Stromal-epithelial interactions modulate growth and development in normal and neoplastic mammary gland. The release of IGF binding proteins (IGFBPs) by the stromal compartment of the mammary gland may play a modulating role in the IGF-mediated proliferation of mammary epithelium. Therefore, the IGFBP-expression pattern of the canine mammary tumor cell line U335 (CMT-U335), which has a mesenchymal phenotype, was determined. In addition, the effects of IGFs and all trans retinoic acid (RA) on DNA synthesis, and IGFBP secretion and distribution were examined. The IGFBPs secreted by CMT-U335 were characterized as IGFBP-2, -4, -5, and -6. Moreover, CMT-U335 appeared to be a suitable mammary mesenchymal cell line for study of the regulatory factors of IGFBP expression and the mechanism(s) involved. IGFs and RA enhanced IGFBP concentrations in cell-conditioned medium with IGF-I and RA having an additive effect. The IGF-I-stimulated DNA synthesis, however, was inhibited by RA. The difference between IGF-I and RA was an enhanced IGFBP-5 binding to the extracellular matrix (ECM) by RA, whereas IGF-I reduced binding to the ECM. Because high doses of insulin had no significant effects on IGFBP concentrations in the medium, it is concluded that IGF-I-induced changes in IGFBP concentrations are not mediated by type-IIGF receptors and may be the consequence of IGFBP redistribution.

Psychosocial functioning of children, adolescents, and adults following hypospadias surgery: a comparative study.

Used standardized questionnaires to compare psychosocial functioning of 116 children and adolescents (9 to 18 years) and 73 adults (18 to 38 years) operated on for hypospadias, a congenital penile anomaly, with that of 88 and 50 age-matched comparison males, respectively, treated for an inguinal hernia. The relationships of coping with penile appearance, subject age, severity of hypospadias, number of operations, age at final surgery, and type of surgical procedure with psychosocial functioning were also investigated. Hypospadias patients did not exhibit a poorer psychosocial functioning and no significant relationships of various medical characteristics with psychosocial functioning could be discerned. Genital/body perception of hypospadias patients ages 9 to 18 years correlated positively with psychosocial functioning, albeit with low values. These findings are important for psychologists and specialists in the counseling process of hypospadias patients and their parents.

Quantitative estimation of estrogen and androgen receptor-immunoreactive cells in the forebrain of neonatally estrogen-deprived male rats.

Using quantitative immunocytochemical procedures, the total number of estrogen and androgen receptors was estimated in a large number of hypothalamic and limbic nuclei of male rats, in which brain estrogen formation was inhibited neonatally by treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione. The highest densities of estrogen receptor immunoreactivity were observed in the periventricular preoptic area and the medial preoptic area. Neonatally estrogen-deprived males showed a higher estrogen receptor immunoreactivity than control males in the periventricular preoptic area and the ventrolateral portion of the ventromedial nucleus of the hypothalamus, i.e. those brain areas in which sex differences have been reported, with female rats showing a greater estrogen binding capacity than male rats. The highest densities of androgen receptor immunoreactivity were found in the septohypothalamic nucleus, the medial preoptic area, the posterior division of the bed nucleus of the stria terminalis and the posterodorsal division of the medial amygdaloid nucleus. No significant differences in distribution or total numbers of androgen receptors were found between neonatally estrogen-deprived males and control males. These findings suggest that neonatal estrogens, derived from the neural aromatization of testosterone, are involved in the sexual differentiation of the estrogen receptor system in the periventricular preoptic area and the ventromedial hypothalamus. The role of neonatal estrogens in the development of the forebrain androgen receptor system is less clear.

Neonatal inhibition of brain estrogen synthesis alters adult neural Fos responses to mating and pheromonal stimulation in the male rat.

Neonatal inhibition of brain estrogen formation in male rats by administration of the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), permanently changes aspects of their mating behavior and partner preference in adulthood. The medial preoptic area receives chemosensory inputs via a sexually dimorphic vomeronasal projection circuit, which responds to reproductively relevant pheromonal cues. The medial preoptic area also receives genital somatosensory inputs via the midbrain central tegmental field and the medial amygdala. We used Fos immunoreactivity as a marker of neuronal activation to determine whether there is a correspondence between the behavioral profiles of neonatally ATD-treated male rats and their neuronal responses in the medial preoptic area and other brain regions to somatosensory and chemosensory stimuli. Achieving eight intromissions with an estrous female led to a greater neuronal Fos immunoreactivity in the medial preoptic area of neonatally ATD-treated male rats compared with neonatally cholesterol-treated male rats. Exposure for 1.5 h to chemosensory cues derived from soiled bedding of estrous females induced Fos immunoreactivity throughout the vomeronasal pathway (i.e. medial amygdala, bed nucleus of the stria terminalis and medial preoptic area) in both ATD and cholesterol males (Experiment 2a). By contrast, exposure for 1.5 h to chemosensory cues derived from soiled bedding of sexually active males revealed clear differences between ATD and cholesterol males in neuronal Fos immunoreactive (Experiment 2b). At peripheral portions of the vomeronasal pathway (i.e. the accessory olfactory bulb and the medial amygdala), there were no differences in the number of Fos immunoreactivity neurons between ATD and cholesterol males. However, neurons in the more central portions of the vomeronasal pathway (i.e. the bed nucleus of the stria terminalis and the medial preoptic area) showed increased Fos immunoreactivity after exposure to odors from sexually active males in ATD males as opposed to cholesterol males. Females, like ATD males, showed neuronal Fos immunoreactivity at each level of the vomeronasal pathway after being exposed to odors from sexually active males. These results suggest that the responsiveness of neurons in the central portion of the vomeronasal projection circuit to odors from sexually active males, but not estrous females, is sexually differentiated in male rats due to the neonatal action of estrogens.

Sexual arousability and the menstrual cycle.

We have repeated a study of the objective (labium minus temperature) and subjective (semantic scales) changes in sexual arousability over the menstrual cycle to erotic video stimulation in 20 women with natural cycles. We extended the study with concomitant vibrotactile stimulation of the clitoral region. In an earlier study women tested for the first time in their follicular phase were sexually more aroused (as indicated by greater increase in labium minus temperature) than women tested for the first time during their luteal phase. When these women were retested in their alternative phase of the menstrual cycle, those who were then follicular did not score higher than those who were then luteal. We then postulated the involvement of a cognitive or conditioned phenomenon which was responsible for the women's repeating their initial phase-dependent response when tested the second time in their alternative phase of the cycle. Identical results were obtained in the present study as far as sexual arousability is concerned during the first test, i.e. follicular women generally scored higher than luteal women; this difference in response persisted during the second test. Concomitant vibrotactile stimulation had no effect on labium minus temperature change but raised subjective sexual arousal and caused a 'more pleasurable' response to the erotic video. Subjective sexual and subjective genital arousal were positively correlated, but neither was significantly correlated with labium minus temperature change. The relationship between menstrual cycle phase and sexual arousal was further substantiated by the reported greater increase in sexual desire after the first erotic video in follicular women than in luteal women. This increased desire, as well as more erotic fantasies, persisted during the next 24 h. In conclusion, studies into effects of menstrual cycle phase on sexual arousability in the laboratory should seriously consider the possible learning and conditioning effects as suggested by the present investigation.

Satisfaction with penile appearance after hypospadias surgery: the patient and surgeon view.

PURPOSE: We studied the degree of agreement between hypospadias patient and surgeon satisfaction with the cosmetic surgical result, and the relation between penile length, meatal position and patient satisfaction. MATERIALS AND METHODS: Cosmetic and functional results in 35 boys with hypospadias were assessed, and a standardized questionnaire was completed by patients and surgeon. RESULTS: There was hardly any agreement between patient and surgeon satisfaction with patient penile appearance. Patients were less satisfied than the surgeon. No significant correlation was noted between penile satisfaction and penile length. Patients with a retracted meatus were less satisfied with the meatal position than those with a glanular meatus. Of the 35 patients 4 underwent repeat surgery after our study. CONCLUSIONS: Hypospadias surgeons should explicitly asked if patients are satisfied and they should follow patients through adolescence.