RECENT MEDIA

Dr. Goldstein often appears in the print media, on television and on radio, talking about men’s and women’s sexual health. Please be aware that reporters put their own slant on the stories, often focusing on one particular area of interest.

Recently Dr. Goldstein was interviewed by MSNBC. To read the article, click here.

Recently Dr. Goldstein appeared on the Fox Morning Show with Mike and Juliet. To watch a clip of the show, click here.

RECENT PUBLICATIONS BY DR. IRWIN GOLDSTEIN

As a researcher, Dr. Goldstein has written more than 350 papers, chapters and books on erectile dysfunction (ED) and female sexual dysfunction (FSD). Here are a few of his recent publications:

Goldstein I. Current management strategies of the postmenopausal patient with sexual health problems. J Sex Med. 2007 Mar;4 Suppl 3:235-53.

INTRODUCTION: Sexual health concerns of menopausal women include decreases in sexual interest, arousal, lubrication, and orgasm, and increases in sexual pain, all of which may be associated with distress. AIM: To review a step-care progression of sexual healthcare management: identification of the sexual health problem; education of the patient and the partner; modification of reversible causes; first-line therapies consisting of devices and medications; and second-line therapies with more invasive treatments including surgery. METHODS: The healthcare provider is presented with a clinical diagnosis and treatment paradigm that engages mind, body, and relationship issues proceeding step-wise in a rational and cost-effective fashion. MAIN OUTCOME MEASURE: Literature review in women's sexual health. RESULTS: Women's health, including sexual health, is a fundamental human right. Supported by evidence-based data, a step-care approach to diagnosis and management of women with sexual health problems is advised. Multidisciplinary interventions should be considered as needed. Identification of sexual health concerns engages diagnostic components of psychologic consultation, history, physical examination, and laboratory testing as appropriate. Key to clinical assessment is the detailed sexual, medical, and psychosocial history. No agreement exists on necessary laboratory tests. Patient (and partner) education improves understanding of treatment options and expectations, and promotes a trusting patient-physician partnership. Modification of reversible causes includes sex therapy, lubricants, altering medications, modifying lifestyle and physical therapy for pelvic floor disorders. First-line therapies should be administered based upon diagnosis, needs, expectations, risks, benefits, and cost, and include medical devices and drugs such as hormones, vasoactive agents, dopamine agonists, topical steroids, anti-infectious agents, and analgesic agents. Second-line therapies, such as surgery, are initiated upon failure, insufficient response, or adverse side effects associated with one or more of the first-line therapies or patient preference. CONCLUSIONS: For postmenopausal women with sexual dysfunction, a rational clinical management strategy begins with treatment options that are most reversible and least invasive and costly.

Mulhall J, Althof SE, Brock GB, Goldstein I, Junemann KP, Kirby M. Erectile dysfunction: monitoring response to treatment in clinical practice--recommendations of an international study panel. J Sex Med. 2007 Mar;4(2):448-64.

INTRODUCTION: Clinical practice guidelines for management of erectile dysfunction (ED) provide limited direction in defining appropriate treatment goals with phosphodiesterase type 5 (PDE5) inhibitor therapy. AIM: To establish an evidence-based position on treatment goals in ED, including the role of erection hardness, with the potential to improve self-esteem, confidence, and overall sexual and relationship satisfaction. MAIN OUTCOME MEASURE: The target of ED therapy is optimization of a rigid erectile response, as assessed by the 4-point Erection Hardness Score (EHS). Methods. An international panel of experts in urology, psychology, and primary care convened to evaluate retrospective data from worldwide phase 2, 3, and 4 clinical trials, involving over 10,000 men with ED, as well as data from recent prospective studies, concerning the role of erection hardness in defining the response to treatment with PDE5 therapy. RESULTS: Significant positive correlations were found between EHS and the Quality of Erection Questionnaire and the International Index of Erectile Function (IIEF) erectile function domain score and other IIEF measures. Significant positive correlations were also found between erection hardness and psychosocial measures such as self-esteem, confidence, and relationship satisfaction (assessed by the Self-Esteem And Relationship questionnaire), and satisfaction with medical treatment (assessed by the Erectile Dysfunction Inventory of Treatment Satisfaction). A shift in most frequent erection from EHS 3 (hard enough for penetration but not fully hard) at baseline to EHS 4 (completely hard and fully rigid) at the end of treatment was accompanied by significant improvements in intercourse and relationship satisfaction, psychosocial benefits, and satisfaction with ED treatment. CONCLUSIONS: Support is found for monitoring and treating patients with ED to their full erectile potential. Quantitative assessment of erection hardness in clinical practice will lead to improved outcomes in overall sexual experience and optimal treatment satisfaction.

Traish AM, Goldstein I, Kim NN. Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction. Eur Urol. 2007 Feb 20; [Epub ahead of print]

OBJECTIVES: Androgens are essential for the development and growth of the penis, and they regulate erectile physiology by multiple mechanisms. Our goal is to provide a concise overview of the basic research and how this knowledge can be translated into a new clinical paradigm for patient management. In addition, this new paradigm may serve as a basis for stimulating constructive debate regarding the use of testosterone in men, and to promote new, innovative basic and clinical research to further understand the underlying mechanisms of androgen action in restoring erectile physiology. METHODS: A literature review was performed utilizing the US National Library of Medicine's PubMed database. RESULTS: On the basis of evidence derived from laboratory animal studies and clinical data, we postulate that androgen insufficiency disrupts cellular-signaling pathways and produces pathologic alterations in penile tissues, leading to erectile dysfunction. In this review, we discuss androgen-dependent cellular, molecular, and physiologic mechanisms modulating erectile function in the animal model, and the implication of this knowledge in testosterone use in the clinical setting to treat erectile dysfunction. The new clinical paradigm incorporates many of the consensed points of view discussed in traditional consensed algorithms exclusively designed for men with androgen insufficiency. There are, however, novel and innovative differences with this new clinical paradigm. This paradigm represents a fresh effort to provide mandatory and optional management strategies for men with both androgen insufficiency and erectile dysfunction. CONCLUSIONS: The new clinical paradigm is evidence-based and represents one of the first attempts to address a logical management plan for men with concomitant hormonal and sexual health concerns.

Goldstein I, Kim E, Steers W, Pryor J, Wilde D, Natanegara F, Wong D, Ahuja S. Efficacy and Safety of Tadalafil in Men with Erectile Dysfunction with a High Prevalence of Comorbid Conditions Results from MOMENTUS: Multiple Observations in Men with Erectile Dysfunction in National Tadalafil Study In the US. J Sex Med. 2007 Jan;4(1):166-75.

INTRODUCTION: Limited efficacy and safety data exist from open-label clinical trials of phosphodiesterase 5 inhibitors in men with erectile dysfunction (ED) and multiple comorbid (MCM) conditions, historically a difficult group to treat. AIM: A multicenter study (Multiple Observations in Men with Erectile Dysfunction in National Tadalafil Study in the US) assessed efficacy and safety of tadalafil in men with ED and MCM conditions. MAIN OUTCOME MEASURES: The primary end point was change from baseline in the erectile function (EF) domain of the International Index of Erectile Function. Secondary end points included the Sexual Encounter Profile, Global Assessment Questions, and Sexual Self-Confidence and Spontaneity Domains of the Psychological and Interpersonal Relationship Scales. METHODS: This was an open-label, multicenter study in men with ED. Tadalafil 20 mg was administered as needed prior to sexual activity, up to once/day, for 12 weeks following a 4-week ED-treatment-free period. The MCM group was 155 of 1,911 men enrolled in this study. Men in the MCM group met eligibility criteria but could not be included in other predefined groups: (i) Caucasian; (ii) Black American; (iii) Hispanic (groups 1-3, < or =65 years, no diabetes or depression); (iv) depression, < or =65 years, no diabetes; (v) diabetes, < or =65 years, no depression; (vi) >65 years, no diabetes or depression; and (vii) ED subsequent to traumatic spinal cord injury. RESULTS: Mean baseline EF domain score in MCM (mean age 65 +/- 9 years) was 12.2 +/- 6.5; 52% of subjects had severe ED; 72% diabetes mellitus; 67% cardiovascular disease (including hypertension); 49% hyperlipidemia; 38% depression; 84% had two or more comorbidities. At end point, there was a significant (P < 0.001) mean change of 7.6 from baseline in mean EF domain score. Among men with severe ED, 22% achieved an EF domain score > or =26. Most common adverse events were headache 5.2%; flushing 3.9% and nasal congestion 3.2%; 3% discontinued use because of an adverse event. CONCLUSIONS: In this open-label clinical trial of older men with ED and MCMs, tadalafil 20 mg significantly increased all efficacy end points and was well-tolerated.

Rubio-Aurioles E, Porst H, Eardley I, Goldstein I, Comparing, the Vardenafil–Sildenafil Comparator Study Group. Vardenafil and Sildenafil in the Treatment of Men with Erectile Dysfunction and Risk Factors for Cardiovascular Disease: A Randomized, Double-Blind, Pooled Crossover Study. J Sex Med. 2006 Nov;3(6):1037-49.

INTRODUCTION: Data from head-to-head clinical trials of phosphodiesterase type 5 (PDE5) inhibitors are scarce, making it difficult for clinicians to differentiate among these agents to select the most appropriate treatment for their patients with erectile dysfunction (ED). AIM: This randomized, double-blind, crossover head-to-head clinical trial compared patient preference, efficacy, and safety of vardenafil and sildenafil in men with ED and diabetes, hypertension, and/or hyperlipidemia. METHODS: Prospective analysis was performed on two studies in which 1,057 men were randomized to vardenafil 20 mg (N = 530) or sildenafil 100 mg (2 x 50 mg encapsulated tablets) (N = 527) for 4 weeks. Following a 1-week washout, patients switched treatment for 4 weeks. MAIN OUTCOME MEASURES: Patients were asked about overall preference: "Overall, which medication do you prefer?", plus 11 other preference questions relating to their ED treatment. Efficacy assessments after each treatment period included the erectile function (EF) domain score of the International Index of Erectile Function (IIEF); Sexual Encounter Profile (SEP) diary questions SEP2 and SEP3; Global Assessment Question (GAQ); and Treatment Satisfaction Scale (TSS). Data regarding adverse events were collected throughout the study. RESULTS: A total of 931 men (mean age 57.9 years) were included in the intent-to-treat (ITT) population. Non-inferiority of vardenafil over sildenafil was achieved for overall preference (vardenafil 38.9%; sildenafil 34.5%; and no preference 26.6%). Additionally, the change from baseline in the EF domain score of the IIEF achieved nominal significance for vardenafil over sildenafil (10.00 vs. 9.40; P = 0.0052). Patients also had a higher percentage of positive responses for vardenafil for SEP2, SEP3, GAQ, and 12 of 19 questions on the TSS. Both drugs were well tolerated. CONCLUSIONS: This randomized, double-blind, head-to-head trial in ED patients with cardiovascular risk factors demonstrated noninferiority of vardenafil for overall preference. Vardenafil achieved nominal statistical superiority over sildenafil for several frequently used efficacy measures. Both drugs were well tolerated.

Pessina MA, Hoyt RF Jr, Goldstein I, Traish AM. Differential regulation of the expression of estrogen, progesterone, and androgen receptors by sex steroid hormones in the vagina: immunohistochemical studies. J Sex Med. 2006 Sep;3(5):804-14.

OBJECTIVE: Significant structural changes occur in the rat vagina in response to sex steroid hormone deprivation and replacement. However, the mechanism by which these changes occur is not clearly understood and our current hypothesis is that these effects are mediated, at least in part, by the expression of sex steroid hormone receptors. The goal of this study was to assess changes in steroid hormone receptor expression and distribution in response to sex steroid hormone deprivation and administration. METHODS: Female rats were either kept intact (controls) or ovariectomized. Ovariectomized animals were treated with vehicle, estradiol, testosterone, progesterone, or hormone combinations. Using immunohistochemistry, hormone receptor distribution was assessed in all layers of the vaginal wall. RESULTS: After ovariectomy, estrogen receptor alpha (ERalpha) was up-regulated and progesterone receptor (PR) was down-regulated. Estradiol replacement restored these ovariectomy-induced changes, and this effect was dose-dependent. Androgen receptor (AR) expression was unaffected by ovariectomy or estradiol replacement. However, testosterone treatment resulted in increased AR density in the muscularis. Addition of either testosterone or progesterone to estradiol mitigated but did not abolish the effects of estradiol alone. CONCLUSION: Estradiol down-regulated ERalpha and up-regulated PR expression in the vagina, suggesting this may be a mechanism to prevent continued proliferation of the epithelium by surges of estradiol during the estrous cycle.

Kim NN, Stankovic M, Armagan A, Cushman TT, Goldstein I, Traish AM. Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat. BMC Womens Health. 2006 Sep 13;6:14.

ABSTRACT: BACKGROUND: Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. METHODS: Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control) or tamoxifen (150 mug/day). Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay. RESULTS: Tamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen) by the vaginal epithelium of tamoxifen-infused rats. CONCLUSION: The observations suggest that tamoxifen exerts both anti-estrogenic and pro-estrogenic effects in the vagina. These physiological alterations may eventually lead to vaginal atrophy and compromise sexual function.

Bachmann GA, Rosen R, Pinn VW, Utian WH, Ayers C, Basson R, Binik YM, Brown C, Foster DC, Gibbons JM Jr, Goldstein I, Graziottin A, Haefner HK, Harlow BL, Spadt SK, Leiblum SR, Masheb RM, Reed BD, Sobel JD, Veasley C Wesselmann U, Witkin SS. Vulvodynia: a state-of-the-art consensus on definitions, diagnosis and management. J Reprod Med. 2006 Jun;51(6):447-56.

Vulvodynia is a chronic pain syndrome affecting up to 18% of the female population. Despite its high prevalence and associated distress, the etiology, diagnosis and clinical management of the disorder have not been clearly delineated. This "white paper" describes the findings and recommendations of a consensus conference panel based on a comprehensive review of the published literature on vulvodynia in addition to expert presentations on research findings and clinical management approaches. The consensus panel also identified key topics and issues forfurther research, including the role of inflammatory mechanisms and genetic factors and psychosexual contributors.

Kim NN, Stankovic M, Cushman TT, Goldstein I, Munarriz R, Traish AM. Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers. BMC Physiol. 2006 May 30;6:4.

BACKGROUND: Diabetes is associated with declining sexual function in women. However, the effects of diabetes on genital tissue structure, innervation and function remains poorly characterized. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow, tissue morphology, and expression of arginase I, endothelial nitric oxide synthase (eNOS) and cGMP-dependent protein kinase (PKG), key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ERalpha) and androgen receptor (AR) expression. RESULTS: In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control) or 65 mg/kg of streptozotocin (diabetic), the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERalpha and AR in nuclear extracts of vaginal tissue from diabetic animals. CONCLUSION: In ovariectomized (estrogen deficient) animals, previous reports from our lab and others have documented changes in blood flow, tissue structure, ERalpha, arginase I and eNOS that parallel those observed in diabetic rats. We hypothesize that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during sexual arousal.

Armagan A, Kim NN, Goldstein I, Traish AM. Dose-response relationship between testosterone and erectile function: Evidence for the existence of a critical threshold. J Androl 2006 April 1.

Androgens play an important role in erectile function. However, the dose-response relationship between plasma testosterone levels and penile erection remains unclear. Intact (sham operated) or bilaterally orchiectomized, mature male Sprague-Dawley rats were used. Two weeks after surgery, rats were infused continuously with either vehicle (polyethyleneglycol) or varying doses of testosterone (44, 88, 220, or 440 mug/day) for 14 days using subcutaneous osmotic infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were infused with a lower range of testosterone doses (11, 22, or 44 mug/day) for 14 days (study 2). In the first study, intact rats had a mean plasma testosterone concentration of 0.56 +/- 0.12 ng/mL ( approximately 1.9 nM), as determined by standard radioimmunoassay. In the second study, a more sensitive enzyme-linked immunoassay was used to measure the lower testosterone levels. Using this assay, intact rats had a mean plasma testosterone concentration of 2.02 +/- 0.59 ng/mL. Intracavernosal pressure measurements indicated that orchiectomy resulted in a significant reduction in erectile function, when compared to intact animals, whereas testosterone infusion restored erectile function to varying degrees. Erectile function was maintained by a wide range of systemic testosterone levels as low as 10%-12% of normal physiological plasma concentrations. Below these concentrations, erectile function was significantly and positively correlated with testosterone plasma levels in a dose-dependent manner. Interestingly, prostate tissue mass was positively correlated to plasma testosterone levels across all concentrations examined. Protein expression of neural nitric oxide synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue from orchiectomized animals and increased in testosterone-infused animals, as assessed by Western blot analyses. We suggest that testosterone at levels approaching one-tenth normal physiological plasma concentration may represent a threshold value, below which erectile function declines in a dose-dependent fashion. However, different androgen-dependent tissues may exhibit varying sensitivities to circulating testosterone with regard to growth and function.

Pessina MA, Hoyt RF Jr, Goldstein I, Traish AM. Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrity. Endocrinology 2006 Jan;147(1):61-9.

Ovarian steroids are known to be important in maintaining vaginal tissue, and evidence is mounting that imbalances in the hormonal milieu contribute to vaginal pathophysiology. To date, limited data are available on the effects of hormone deprivation and replacement on vaginal tissue morphology and vaginal innervation. The goal of this study was to assess the dynamic changes in vaginal tissue structure in response to sex steroid hormone deprivation and administration. Female Sprague-Dawley rats were either kept intact (controls) or ovariectomized. Ovariectomized animals were treated with vehicle, estradiol, testosterone, progesterone, or a combination of estradiol plus testosterone or progesterone. Histological techniques, including stereological analysis and immunohistochemistry for localization of neuronal markers, were used. Ovariectomy produced a significant decrease in epithelial height that was restored with estradiol replacement. Interestingly, a subphysiological dose of estradiol resulted in hyperplasia of the vaginal epithelium and nonvascular smooth muscle. Neither testosterone nor progesterone had a significant effect on epithelial height or muscularis thickness. However, testosterone treatment resulted in a significant increase in small adrenergic nerve fibers. Addition of either testosterone or progesterone to estradiol mitigated but did not abolish the effects of estradiol alone. This study demonstrates that estradiol and testosterone have differential effects on vaginal tissue parameters and that ovarian hormones are critical for the maintenance of genital tissue structure. Present observations also suggest that combined replacement regimens may be required for an optimal physiological response.

Panzer C, Wise S, Fantini G, Kang D, Munarriz R, Guay A, Goldstein I. Impact of Oral Contraceptives on Sex Hormone Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction. J Sex Med 2006 3(1):104-113.

INTRODUCTION: Oral contraceptives (OCs) have been the preferred method of birth control because of their high rate of effectiveness. OC use, however, has been associated with women's sexual health complaints and androgen insufficiency. OC use is associated with a decrease of androgen ovarian synthesis and an increase in the production of sex hormone-binding globulin (SHBG). There have been limited studies assessing SHBG values after discontinuation of OC use. AIM: To retrospectively investigate SHBG levels before and after discontinuation of OC use. MAIN OUTCOME MEASURE: Sex hormone-binding globulin values were compared at baseline, while on the OC, and well beyond the 7-day half-life of SHBG at 49-120 (mean 80) days and >120 (mean 196) days after discontinuation of OCs. METHODS: A total of 124 premenopausal women with sexual health complaints for >6 months met inclusion/exclusion criteria. Three groups of women were defined: (i) "Continued-Users" (N = 62; mean age 32 years) had been on OCs for >6 months and continued taking them; (ii) "Discontinued-Users" (N = 39; mean age 33 years) had been on OCs for >6 months and discontinued them; and (iii) "Never-Users" (N = 23; mean age 36 years) had never taken OCs. RESULTS: Sex hormone-binding globulin values in the "Continued-Users" were four times higher than those in the "Never-User" group (mean 157 +/- 13 nmol/L vs. 41 +/- 4 nmol/L; P < 0.0001). Despite a decrease in SHBG values after discontinuation of OC use, SHBG levels in "Discontinued-Users" remained elevated in comparison with "Never-Users" (N = 26; P < 0.0001 for >120 days). CONCLUSION: In women with sexual dysfunction, SHBG changes in "Discontinued-Users" did not decrease to values consistent with "Never-Users." Long-term sexual, metabolic, and mental health consequences might result as a consequence of chronic SHBG elevation. Does prolonged exposure to the synthetic estrogens of OCs induce gene imprinting and increased gene expression of SHBG in the liver in some women? Prospective research is needed.