Search PubMed⌕ Search

Biomedical subjects

Irwin Goldstein

Publications and source records attributed to Irwin Goldstein.

72 records · Page 4Linked to original sources
PubMed2002

Biochemical and functional characterization of alpha-adrenergic receptors in the rabbit vagina.

Vascular and non-vascular smooth muscle within the vagina mediate important physiological changes during sexual arousal in women. In this study, we have characterized alpha-adrenergic receptors (AR) in rabbit vagina by assessment of radioligand binding, contractility of isolated tissue strips and genital hemodynamics. [3H]Prazosin and [3H]RX821002 (alpha-1 and alpha-2 AR selective antagonists) bound to rabbit vaginal membrane preparations with high affinity and limited capacity. Competition binding assays using both non-selective and subtype selective ligands for AR (phentolamine, prazosin, delequamine, rauwolscine and UK14304) further confirmed the presence of alpha-1 and alpha-2 AR in vaginal tissue. In organ bath preparations of vaginal tissue strips, norepinephrine-induced contraction was attenuated by alpha-1 and alpha-2 AR antagonists (prazosin, tamsulosin, delequamine and phentolamine). In anesthetized rabbits, intravaginal injection of the alpha-1 AR selective antagonist REC 15/2615 (50 and 100 microg/kg) caused a 2 to 3-fold increase in genital tissue oxyhemoglobin (OHb) concentration. Similar increases in tissue OHb were observed with intravaginal injection of phentolamine (500 microg/kg) or a tri-mixture of vasodilators (PGE1, papaverine, phentolamine). REC 15/2615, phentolamine or the tri-mixture also enhanced the amplitude and/or duration of change in genital tissue OHb after pelvic nerve stimulation. Thus, vaginal tissue expresses functional alpha-1 and alpha-2 AR, which modulate vaginal smooth muscle contractility and genital engorgement.

Administration, Intravaginal↗
PubMed2002

Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment.

OBJECTIVE: To evaluate the evidence for and against androgen insufficiency as a cause of sexual and other health-related problems in women and to make recommendations regarding definition, diagnosis, and assessment of androgen deficiency states in women. DESIGN: Evaluation of peer-review literature and consensus conference of international experts. SETTING: Multinational conference in the United States. PATIENT(S): Premenopausal and postmenopausal women with androgen deficiency. INTERVENTION(S): Evaluation of peer-review literature and development of consensus panel guidelines. RESULT(S): The term "female androgen insufficiency" was defined as consisting of a pattern of clinical symptoms in the presence of decreased bioavailable T and normal estrogen status. Currently available assays were found to be lacking in sensitivity and reliability at the lower ranges, and the need for an equilibrium dialysis measure was strongly emphasized. Causes of androgen insufficiency in women were classified as ovarian, adrenal, hypothalamic-pituitary, drug-related, and idiopathic. A simplified management algorithm and clinical guidelines were proposed to assist clinicians in diagnosis and assessment. Androgen replacement is currently available in several forms, although none has been approved for treatment of sexual dysfunction or other common symptoms of female androgen insufficiency. Potential risks associated with treatment were identified, and the need for informed consent and careful monitoring was noted. Finally, the panel identified key goals and priorities for future research. CONCLUSION(S): A new definition of androgen insufficiency in women has been proposed along with consensus-based guidelines for clinical assessment and diagnosis. A simplified management algorithm for women with low androgen in the presence of clinical symptoms and normal estrogen status has also been proposed.

Androgens↗
PubMed2002

Role of androgens in female genital sexual arousal: receptor expression, structure, and function.

OBJECTIVE: In women, androgens modulate the physiological function of many reproductive and sexual organs, including the ovaries, uterus, vagina, oviducts, clitoris, and mammary gland. In this article, we review the mechanisms of androgen action and discuss new data on the effects of androgens in vaginal and clitoral tissues. MAIN OUTCOME MEASURE(S): In this study, we characterized the androgen receptor expression in rabbit vaginal tissues from control and ovariectomized animals treated with or without androgen replacement therapy. We investigated the effects of androgen deprivation and replacement on the expression and activity of nitric oxide synthase and arginase and on vaginal smooth muscle contractility. RESULT(S): Androgens enhanced nitric oxide synthase activity and down-regulated arginase activity in proximal vagina. Estrogens down-regulated nitric oxide synthase activity and increased arginase activity in distal vagina. Androgens facilitated vaginal smooth muscle relaxation to electric field stimulation and vasoactive intestinal polypeptide, whereas estrogens attenuated vaginal tissue relaxation to electric field stimulation and to vasoactive intestinal polypeptide. CONCLUSION(S): These observations suggest that androgens may play an important role in modulating the physiology of vaginal tissue and contribute to female genital sexual arousal.

Androgens↗
PubMed2002

Biology of female sexual function.

Although the psychosocial and relationship aspects of female sexuality have been extensively investigated, studies concerning the anatomy, physiology and pathophysiology of female sexual function and dysfunction are limited. The paucity of biologic data may be attributed to a lack of reliable experimental models and tools for investigating female sexual function and to limited funding, which is critical for developing experimental approaches. Research efforts by several investigators in different laboratories have been establishing experimental models needed for investigating the physiologic mechanisms involved in the genital arousal response of sexual function. These experimental models have permitted assessment of genital hemodynamics, vaginal lubrication, regulation of genital smooth muscle contractility and signaling pathways, providing preliminary information about the role of neurotransmitters and sex steroid hormones in sexual function. Further research is needed to define the neurotransmitters responsible for vaginal smooth muscle relaxation and the role of sex steroid hormones and their receptors in modulating genital hemodynamics, smooth muscle contractility, and neurotransmitter receptor expression. Finally, a global and integral understanding of the biologic aspects of female sexual function requires investigation of the vascular, neurologic (central and peripheral), and structural components of this extremely complex physiologic process.

Animals↗
PubMed2002

Biochemical and physiological mechanisms of female genital sexual arousal.

Limited studies are available concerning physiological and biochemical mechanisms involved in female sexual function and dysfunction. The paucity of physiological and biochemical data pertaining to genital sexual arousal function is attributed, in part, to lack of reliable experimental models and tools for the investigation of female sexual arousal. This review summarizes research efforts from a number of laboratories in which several experimental models have been established. These include the development of in vivo animal models, organ bath studies, and the establishment of cell cultures. The availability of such experimental model systems have facilitated efforts aimed at defining the neurotransmitters responsible for vaginal smooth muscle relaxation, the role of sex steroid hormones and their receptors in modulating genital hemodynamics, smooth muscle contractility, and neurotransmitter receptor expression. A comprehensive and integral understanding of female sexual function requires detailed investigation of the vascular, neurological (central and peripheral), and structural components of this complex physiological process.

Animals↗
PubMed2002

Effects of ovariectomy and estrogen and androgen treatment on sildenafil-mediated changes in female genital blood flow and vaginal lubrication in the animal model.

OBJECTIVE: Our purpose was to investigate the effects of ovariectomy and estradiol and testosterone treatment on sildenafil- induced changes in genital hemodynamics and vaginal lubrication. STUDY DESIGN: Female New Zealand White rabbits were either kept intact or underwent ovariectomy. Two weeks after ovariectomy, animals were treated with vehicle, testosterone, or a combination of estradiol and testosterone for 14 days. Genital hemodynamics and vaginal lubrication were recorded at the end of the treatment period. RESULTS: Ovariectomy caused a marked decrease in vaginal lubrication but did not significantly alter genital hemodynamics. In contrast to testosterone treatment of ovariectomized animals, estradiol treatment significantly increased genital blood flow and vaginal lubrication above that observed in control animals. Sildenafil administration caused a significant increase in genital hemodynamics irrespective of the hormonal status. CONCLUSION: This study suggests that estradiol but not testosterone modulates genital hemodynamics and that sildenafil enhances genital blood flow irrespective of hormonal status.

Animals↗
PubMed2002

Androgen replacement therapy with dehydroepiandrosterone for androgen insufficiency and female sexual dysfunction: androgen and questionnaire results.

During our evaluations of women with sexual dysfunction, we have seen many with low interest, arousal, and orgasmic capabilities with associated personal distress and diminished genital sensation and blood flow following sexual stimulation. Laboratory evaluation of these women has revealed normal estrogen but androgen values that were either below or in the lower quartile of the physiologic range. Androgen insufficiency and sexual dysfunction have been the working diagnoses in these women. Although many treatment options currently are available for this syndrome, there are limited data concerning safety and efficacy. The aim of this retrospective, Institutional Review Board (IRB)--approved, single-institution study was to report on the androgen and questionnaire results from a series of patients who underwent androgen replacement therapy with dehydroepiandrosterone for treatment of androgen insufficiency and sexual dysfunction. This study revealed that there was a significant decrease in sexual distress, a significant increase in sexual function in the domains of desire, arousal, lubrication, satisfaction, and orgasm, and a normalization to values within the physiologic range in the following androgens measured: total testosterone, free or bioavAilable testosterone, DHEA, DHEA-S, and androstenedione. Side effects included increased facial hair (11%), weight gain (7%), acne (5%), temporary breast tenderness (1%), loss of head hair (1%) and skin rash (1%). Preliminary results suggest that androgen replacement therapy with dehydroepiandrosterone is a safe and effective treatment for androgen insufficiency and female sexual dysfunction. However, further research is needed, including prospective, multi-institution, placebo-controlled double-blind studies.

Adjuvants, Immunologic↗
PubMed2002

Characteristics of female patients with sexual dysfunction who also had a history of blunt perineal trauma.

Perineal trauma can occur in both genders, however, data supporting the relationship between sexual dysfunction and blunt perineal trauma in women is lacking. This study reviewed the patient characteristics of women with sexual dysfunction who also had a history of blunt perineal trauma. A neurogenic form of sexual dysfunction has been implicated, with primary complaints of orgasm disorder and abnormalities noted on genital sensory testing. Further research in this area is needed.

Adult↗
PubMed2002

The prevalence of phimosis of the clitoris in women presenting to the sexual dysfunction clinic: lack of correlation to disorders of desire, arousal and orgasm.

Physical examination of the genitalia was performed during an evaluation of women with sexual health problems. Cephalad displacement of the right and left labia minora enables full retraction of the clitoral prepuce and complete exposure of the glans clitoris, under normal circumstances. We defined clitoral examination as abnormal when the cephalad force resulted in varying degrees of incomplete foreskin retraction and limited exposure of the glans clitoris. The pathophysiology is likely to be secondary to recurrent vulvar dermal infections of blunt trauma changing prepucial elasticity. Clitoral phimosis, a previously undiagnosed physical finding, was identified in 22% of the women. Other than its link to sexual pain, the clinical significance of this finding, in particular the relation to diminished sensitivity and impaired orgasmic capability, is unclear at this time.

Adult↗
PubMed2002

Epidemiological characteristics of 250 women with sexual dysfunction who presented for initial evaluation.

There have been limited literature reports concerning the epidemiological characteristics of female patients who present for initial evaluation of sexual health problems to an outpatient sexual health clinic. This study is a single-institution, retrospective, IRB-approved, observational assessment of 250 female patients undergoing management for sexual dysfunction. In our clinic, women with sexual dysfunction were, in general, young, healthy, and free of vascular risk factors; complained of an acquired multidimensional combination of decreased desire, arousal, and orgasm; and had significantly low serum androgen levels. More research in the management of women with sexual health problems is needed.

Adult↗
PubMed2002

Androgens in female genital sexual arousal function: a biochemical perspective.

Female sexual dysfunction is a highly prevalent, multicausal, and multidimensional medical problem that has a major impact on quality of life and interpersonal relationships. It is hypothesized that genital arousal disorder is caused by diminished arterial blood flow within the hypogastric arterial bed. This hypothesis may explain the pathophysiologic mechanisms in older patients with vascular risk factors, but it does not account for either the prevalence or the mechanisms of arousal disorders seen in young women with no vascular risk factors. Hormonal imbalances may be important contributing factors to the pathophysiologic mechanisms involved in female arousal disorders. Androgens modulate the growth and function of female genital sexual organs included the labia, vagina, and clitoris. This article discusses the potential role for androgens in facilitating female genital sexual arousal.

Androgens↗
PubMed2002

Health care clinicians in sexual health medicine: focus on erectile dysfunction.

A consensus guidelines model was developed for managing erectile dysfunction (ED) by urology nurses and other health care clinicians. The model emphasizes identification of ED in all males older than 40, education and counseling as keys to intervention, and inclusion of partners whenever possible. These guidelines are intended to provide a comprehensive care model for ED patients and their partners, which would be optimally cost effective and clinically relevant. If successful, this new model will allow quality sexual health care to be provided to increasing numbers of patients and their partners.

Counseling↗
PubMedDate not supplied

Effects of medical or surgical castration on erectile function in an animal model.

The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.

Animals↗
PubMedDate not supplied

Pilot study of the endothelin-A receptor selective antagonist BMS-193884 for the treatment of erectile dysfunction.

Endothelins have been postulated to be important regulators of penile erectile function. The endothelin-A receptor antagonist BMS-193884 was evaluated as a treatment for mild-to-moderate erectile dysfunction in an animal model and in human volunteer subjects. In laboratory studies, organ bath preparations of rabbit and human penile cavernosal tissue strips were incubated with BMS-193884 and exposed to increasing concentrations of endothelins. In rabbit tissue, 1 microM BMS-193884 significantly inhibited contraction to ET-1, ET-2, and ET-3 by 34.5%, 42.9%, and 100%, respectively. In human tissue, 1 microM BMS-193884 inhibited contraction to ET-2 by 44.4%. In rabbit tissue strips contracted with 20 nM of ET-1 or ET-2, BMS-1 93884 caused dose-dependent relaxation with EC50 values of 107.2 +/- 32.3 nM and 1.7 +/- 0.5 nM, respectively. In anesthetized male rabbits, intravenous administration of BMS-193884 (systemic plasma concentration approximately 50 and 100 nM) increased the duration of pelvic nerve-stimulated penile erection. To further assess the safety and efficacy of BMS-193884, 53 men diagnosed with mild-to-moderate erectile dysfunction were administered oral placebo or 100 mg BMS-193884 in a double-blind fashion. Evaluations were based on 1) erectile function testing during 2 in-office visits and 2) diary and questionnaire data of 4 intercourse attempts over 2-4 weeks of home use. Although the drug was well tolerated, BMS-193884 did not significantly improve erectile function during office visits or home use when compared to placebo. Thus, BMS-193884 facilitated cavernosal smooth muscle relaxation ex vivo and prolonged penile tumescence in vivo. In contrast, a pilot clinical study failed to show enhancement of erectile response in men with mild-to-moderate erectile dysfunction. The disparity between the laboratory and clinical studies suggests that there may be differences between species with regard to the role of endothelin in erectile function.

Administration, Oral↗
PubMedDate not supplied

Laser oximetry: A novel noninvasive method to determine changes in penile hemodynamics in an anesthetized rabbit model.

This study was designed to determine the utility and validity of laser oximetry in measuring changes in penile hemodynamics. Anesthetized male New Zealand White Rabbits were divided into 2 groups, and penile hemodynamics were assessed by either laser oximetry (oxyhemoglobin, deoxyhemoglobin concentration, and oxygen saturation) or intracavernosal pressure (ICP) monitoring during penile erection induced by pelvic nerve stimulation (PNS) or intracavernosal administration of phentolamine, nitroprusside, papaverine, or sildenafil. PNS caused significant frequency-dependent increases in penile ICP. PNS also caused significant increases in penile tissue oxyhemoglobin concentrations and tissue oxygen saturation in a frequency-dependent manner. The changes in oxyhemoglobin concentrations and oxygen saturation correlated with frequency-dependent increases in ICP. Intracavernosal vasoactive drug administration produced significant increases in ICP, tissue oxyhemoglobin concentration, oxygen saturation, and duration of response as a function of increasing drug concentration. Laser oximetry permits reproducible and valid assessment of changes in penile hemodynamics comparable to conventional ICP measurements. Thus, we consider laser oximetry a reliable technique in evaluating penile hemodynamics. Its sensitivity in detecting small changes in oxyhemoglobin concentration and its noninvasive nature make it advantageous over invasive methods such as ICP monitoring and laser Doppler flowmetry.

Animals↗
PubMedDate not supplied

Efficacy of vardenafil and sildenafil in facilitating penile erection in an animal model.

Vardenafil and sildenafil are potent and specific phosphodiesterase type 5 (PDE 5) inhibitors. In human penile cavernosal smooth muscle cells, we have previously shown that vardenafil has a lower biochemical inhibition constant (Ki) than sildenafil. In this study, we compared the efficacy of vardenafil and sildenafil in facilitating penile erection in a rabbit model. Penile erections were elicited by submaximal (2.5 or 6 Hz) pelvic nerve stimulation (PNS) repeated every 5 minutes for 30 minutes with or without intravenous (i.v.) administration of vardenafil (1-30 microg/kg) or sildenafil (10-30 microg/kg). Erectile response was assessed by continuously recording intracavernosal pressure (ICP) and systemic arterial pressure (SAP). All data were expressed as a ratio of ICP:SAP. I.v. administration of either PDE 5 inhibitor facilitated PNS-induced erection and increased ICP:SAP in a dose-dependent manner, reaching peak response at approximately 5 minutes. However, the threshold dose at which facilitation of erection occurred was lower for vardenafil (3 microg/kg) than for sildenafil (10 microg/kg). At the 10-microg/kg dose (i.v.), the response duration was significantly greater with vardenafil (169 +/- 23 seconds) than with sildenafil (137 +/- 31 seconds). Direct intracavernosal (i.c.) injection of 1-30 microg/kg vardenafil or sildenafil also caused dose-dependent increases in ICP:SAP in the absence of PNS. Response durations increased in a dose-dependent manner and lasted more than 5 times that of i.v. drug administration coupled with PNS. Irrespective of the route of administration (i.c. or i.v.), at equivalent doses, vardenafil was significantly more efficacious than sildenafil in facilitating pelvic nerve-mediated penile erection and in eliciting erection in the absence of PNS. The increases in ICPs occurred more quickly, were of larger magnitude, and were sustained for longer durations for vardenafil than for sildenafil. On the basis of the biochemical data and physiological responses from this study, further clinical evaluation of vardenafil as treatment for erectile dysfunction is warranted.

Anesthesia↗