The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses.

The prevalence of hypogonadism has been found to be increased in certain chronic illnesses, especially diabetes, hypertension and obesity. Recently, the prevalence of hypogonadism in primary care practices mirrored that in our population of men with erectile dysfunction (ED). In this study, the prevalence of hypogonadism in nearly 1000 men with ED was tabulated, using a retrospective chart review, and analyzed for association with the various contributing medical and psychological factors. The prevalence of hypogonadism was determined in men with a variety of chronic illnesses, and was further characterized by decade. We observed an association between hypertension (P=0.025), tobacco abuse (P=0.0059), sleep apnea (P=0.0001), work stress (P=0.041) and hypogonadism. These data were further analyzed for the odds ratio and confidence interval (Forest plot), which showed strong association for sleep apnea and work stress. We did not observe any significant association between diabetes, atherosclerosis, alcohol abuse, multiple medications, asthma, seizure disorder, anxiety/depression and hypogonadism (P values for Cochran-Mantel-Haenszel general association were 0.48, 0.97, 0.25, 0.69, 0.22, 0.76 and 0.98, respectively). We suggest that a host of chronic illnesses have a high prevalence of secondary hypogonadism. Men who have chronic medical or psychological illnesses should have their testosterone level checked, especially when sexual dysfunction symptoms or signs are present.

Global experiences with vardenafil in men with erectile dysfunction and underlying conditions.

OBJECTIVE: Vardenafil has demonstrated efficacy for the pharmacological management of erectile dysfunction (ED). Accumulating evidence suggests that ED is frequently associated with underlying cardiovascular and metabolic conditions which are thought to be involved in the aetiology of ED. The present review aims to summarise and discuss the available evidence for the efficacy, safety and tolerability of vardenafil in patients with underlying conditions including diabetes, hypertension and dyslipidaemia. METHODS: Relevant articles were identified through a PubMed search of clinical trials and postmarketing surveillance studies of vardenafil in patients with ED including those with diabetes, hypertension and dyslipidaemia. RESULTS: Across all trials, vardenafil showed good efficacy for the treatment of ED in patients with diabetes, hypertension and dyslipidaemia. Vardenafil also showed a favourable safety and tolerability profile. The concomitant use of medication to treat hypertension or dyslipidaemia was not associated with an increase in adverse events following vardenafil treatment. CONCLUSIONS: The prevalence of both diagnosed and undiagnosed underlying conditions is high among men with ED. The evidence presented in this review suggests that vardenafil is efficacious and well tolerated in patients with ED and diabetes, hypertension and/or dyslipidaemia and can be recommended as first-line treatment for ED in patients with these conditions.

Sexual foreplay incontinence in men with erectile dysfunction after radical prostatectomy: a clinical observation.

Incontinence is a known complication of radical prostatectomy for prostate cancer. Recently, climacturia, or orgasmic incontinence, has been reported after this procedure. Patients have occasionally reported some loss of urine during sexual foreplay, even when general daytime incontinence was not present. A review of questions on this subject was conducted in 45 men to better appreciate how often this occurred. Nine of twenty-four men (38%) with no daytime incontinence stated that they had some incontinence with sexual foreplay. These men involved have related that this causes embarrassment and frustration, with the effect of avoidance of sexual activity. This in turn causes relationship problems. The use of a rubber ring at the base of the penis during foreplay can help relieve this difficulty.

Does early morning versus late morning draw time influence apparent testosterone concentration in men aged > or =45 years? Data from the Hypogonadism In Males study.

The Hypogonadism In Males study estimated the prevalence of hypogonadism in men aged > or =45 years. A sub-analysis of patients not receiving testosterone (T) therapy was conducted. Blood draw times were 0800-1000 and 1000-1200 hours. Total T (TT) was not influenced by draw time for any age group; however, significantly greater free T (FT) and bioavailable T (BAT) values were observed in the overall population for earlier draw times. Sex hormone-binding globulin (SHBG) values were significantly lower in men aged 45-64 years at the earlier draw time. In men aged > or =75 years, no significant differences in TT, FT, BAT or SHBG were observed on the basis of draw time. Early morning draw time may not be critical for capturing TT concentrations in men > or =45 years; however, when measuring FT or BAT, an early morning draw time may be preferable for men aged <75 years.

Commentary on androgen deficiency in women and the FDA advisory board's recent decision to request more safety data.

Editor's note: The FDA's decision regarding Intrinsa has potential widespread implications for the medical treatment of female sexual dysfunction (FSD). Dr Andre Guay is a world-renowned authority on the topic of female sexuality and FSD. Accompanying Dr Spark's perspective in issue 2, this perspective will shed important light on the topic and offer insight into the past, present and future of FSD.

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part A. Serum androgen levels in women aged 20-49 years with no complaints of sexual dysfunction.

Androgen insufficiency is a recognized cause of sexual dysfunction in men and women. Age-related decrements in adrenal and gonadal androgen levels also occur naturally in both sexes. At present, it is unclear if a woman's low serum androgen level is a reflection of the expected normal age-related decline or indicative of an underlying androgen-deficient state. We studied premenopausal women with no complaints of sexual dysfunction to help define a normal female androgen profile. In all, 60 healthy, normally menstruating women, ages 20-49 y, were studied. The Abbreviated Sexual Function Questionnaire was administered along with a detailed interview. Radioimmunoassay measurements of morning serum testosterone (T), free testosterone (fT), dehydroepiandrosterone-sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were measured during days 8-15 of the menstrual cycle. In women 20-49 y old without complaints of sexual dysfunction, serum androgen levels exhibit a progressive stepwise decline. Comparing values obtained in women age 20-29 y to those obtained in women 40-49 y, specific hormone decrements were DHEAS 195.6-140.4 microg/dl, serum T 51.5-33.7 ng/dl, fT 1.51-1.03 pg/ml. SHBG did not change significantly in women in this age group. The FAI reflected the age-related decrease in female androgen levels. The framework for the development of a female androgen profile in women with no complaints of sexual dysfunction has been established, and an age-related decrease in testosterone and its adrenal precursor, DHEAS, has been demonstrated. The FAI mirrors these decreases and its usefulness in clinical practice is confirmed. A precipitous decline in all androgens occurs after the decade of the 20s, yet SHBG does not show a significant change throughout the premenopausal years.

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part B: Reduced serum androgen levels in healthy premenopausal women with complaints of sexual dysfunction.

Androgen insufficiency has been associated with decreased libido and arousal in postmenopausal women, but rarely has been evaluated in healthy premenopausal women. In all, 32 healthy premenopausal women were enrolled in this study, 18 with one or more complaints of sexual dysfunction and 14 without. Assays of ovarian and adrenal androgens were measured before and after ACTH stimulation. The women with complaints of sexual dysfunction had significantly lower adrenal androgens than did the control women. There were no differences in the basal ovarian androgens or cortisol levels. After ACTH, both groups stimulated cortisol as well as adrenal and ovarian androgens. In conclusion, premenopausal women with complaints of sexual dysfunction had lower adrenal androgen precursors and testosterone than age-matched control women without such complaints. Further study is required to determine how lower adrenal androgens contribute to female sexual dysfunction.

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results. A total of 178 men with secondary hypogonadism and ED received clomiphene citrate for 4 months. Sexual function improved in 75%, with no change in 25%, while significant increases in luteinizing hormone (P<0.001) and free testosterone (P<0.001) occurred in all patients. Multivariable analysis showed that responses decreased significantly with aging (P<0.05). Decreased responses also occurred in men with diabetes, hypertension, coronary artery disease, and multiple medication use. Since these conditions are more prevalent with aging, chronic disease may be a more important determinant of sexual dysfunction. Men with anxiety-related disorders responded better to normalization of testosterone. Assessment of androgen status should be accomplished in all men with ED. For those with lower than normal age-matched levels of testosterone treatment directed at normalizing testosterone with clomiphene citrate is a viable alternative to giving androgen supplements.

Yohimbine treatment of organic erectile dysfunction in a dose-escalation trial.

Yohimbine has had questionable effects in men with organic erectile dysfunction. We conducted this study to better define the population of men responsive to yohimbine, because tobacco was thought to affect a regimen of yohimbine more than other risk factors. We measured nocturnal penile tumescence with the RigiScan monitor, hormone profiles, answers to the Florida Sexual Health Questionnaire, and clinical responses at baseline and after two different doses of yohimbine in 18 nonsmoking men with erectile dysfunction. Of the 18 men, nine (50%) were successful in completing intercourse in more than 75% of attempts. The yohimbine responders were men with less severe erectile dysfunction as manifested by improved increased rigidity on RigiScan testing, higher Florida Sexual Health Questionnaire scores, and slightly higher levels of serum testosterone. Yohimbine is an effective therapy to treat organic erectile dysfunction in some men with erectile dysfunction.

Decreased free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) levels in women with decreased libido.

A prior study has shown that premenopausal women could have decreased testosterone levels and still have regular menstrual cycles (Guay, 2001). Since ovarian function in such women was normal, the question of a possible adrenal dysfunction causing androgen deficiency was considered. If this was true, the question then arose as to whether the same defect could be seen in postmenopausal women. We studied 105 women who presented during a 6-month period of time with the chief complaint of decreased sexual desire. On subsequent testing, 74 of the women (70%) were found to have decreased total testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEA-S). Thirty-six of these women were premenopausal (ages range 24-50 years), and 38 were postmenopausal (ages range 47-78 years). All androgen levels for the women were lower than age-matched control groups found in the literature. The decreased DHEA-S levels suggest a a defect in adrenal steroidogenesis, which was seen in both premenopausal and postmenopausal women. Possible defects in regulatory mechanisms of adrenal steroidogenesis are discussed.

Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors.

The objective of this study was to determine the efficacy and safety of sildenafil in patients with erectile dysfunction (ED) and associated organic risk factors in a multispecialty clinic. Patients (n = 521) were diagnosed with ED based on self-assessment. Associated risk factors were managed by medication or life-style modifications, or both, before treatment with sildenafil for ED. Patients received a 50-mg dose of sildenafil that could be adjusted to 100 mg or 25 mg based on tolerability and efficacy. Patients recorded the number of successful intercourse encounters for 6 to 8 weeks, and the number of adverse events. Overall, there was an 82% successful intercourse rate with sildenafil treatment. The predominant associated risk factors for ED were hypertension (39%), hypogonadism (37%), and multiple medications (34%). Common adverse events due to sildenafil treatment were mild to moderate in nature and resulted in <2% patient discontinuation. Clinicians should be particularly careful to evaluate patients presenting with ED because the condition can be accompanied by a wide spectrum of risk factors requiring monitoring and treatment. However, with adequate treatment and control of these risk factors, the use of sildenafil in a representative population of men with ED in a multispecialty clinic can achieve a higher efficacy rate than previous studies have indicated.

Decreased testosterone in regularly menstruating women with decreased libido: a clinical observation.

Much more information is available concerning decreased libido in postmenopausal than in premenopausal women. Even less is known about androgen deficiency in younger women. We measured total and free testosterone levels in 12 consecutive premenopausal women complaining of decreased libido. Of the 12 women, 8 had low or immeasurable levels of testosterone despite having regular menstrual periods. Androgen precursor hormones, DHEA-S and Androstenedione, were low-normal to high-normal. Treatment with oral DHEA, 50 to 100 mg per day, restored sexual desire in 6 of the 8 women, gave partial improvement in one, and failed in another. Possible significance and etiological mechanism are discussed.

Sexual dysfunction in the diabetic patient.

The incidence of diabetes mellitus is increasing at an alarming rate, and diabetic men already make up a quarter of the men in our own specific medically-oriented population of erectile dysfunction. The incidence of sexual dysfunction in men with diabetes approaches 50%, and this is only slightly lower in diabetic women. Hypertension is a frequent risk co-factor, being seen between 40% and 60% of diabetics in the literature. Obesity and hyperlipidemia are other frequent co-factors. Interestingly, these risk factors are the same as those for coronary artery disease. The final common pathway for most of these factors is endothelial cell dysfunction.

Assessment of the efficacy and safety of Viagra (sildenafil citrate) in men with erectile dysfunction during long-term treatment.

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.

Clinical experience with intraurethral alprostadil (MUSE) in the treatment of men with erectile dysfunction. A retrospective study. Medicated urethral system for erection.

OBJECTIVE: The Food and Drug Administration (USA) approved the transurethral administration of prostaglandin (alprostadil in January 1997), which had an efficacy of approximately 50% in clinical trials. We studied its effectiveness in clinical practice. METHODS: Patient and partner education was followed by an initial office trial of a medicated urethral system for erection (MUSE) after other medical risk factors were corrected during a 2- to 4-month period. The initial titration dose of alprostadil was usually 125 or 250 microg. Further titration, if needed, was instituted by the patient at home. Success was determined as the satisfactory completion of sexual intercourse in more than 66% of attempts, with a minimum of two being required. RESULTS: Two hundred and seventy patients entered the trials, and follow-up information was available in 229 (85%). The overall success rate was 56%. The dose required was 500 microg in 49.2% and 1,000 microg in 42.2%. Of the 44% in whom treatment failed, 61.4% did so because of lack of efficacy and 38.6% because of side effects (genital pain or urethral bleeding). Minor urogenital symptoms, which did not interfere with treatment, occurred in an additional 40% of patients. CONCLUSIONS: The efficacy of transurethral administration of alprostadil (56%) is higher than the initial published clinical trial data and higher than recent reported clinical experiences, although higher doses were required in our study. Men over 50 years of age, having an organic cause for erectile dysfunction, had better responses. Patient and partner education is important for successful treatment, and the in-office initial titration is an integral part of this success. Prior correction of medical risk factors may enhance the success rate.

Testosterone treatment in hypogonadal men: prostate-specific antigen level and risk of prostate cancer.

OBJECTIVE: To assess prostate-specific antigen (PSA) levels in hypogonadal men after testosterone replacement by three different methods and attempt to determine any possible relationship between hypogonadism and prostate cancer in this study population. METHODS: A total of 90 consecutive men who had erectile dysfunction and were found to have hypogonadism were monitored with digital rectal examination (DRE) and measurement of PSA levels before and after testosterone replacement therapy. The patients were treated with one of three options: (1) testosterone enanthate by intramuscular injections, 200 or 300 mg every 2 or 3 weeks (N = 25); (2) testosterone nonscrotal patches, 5 mg daily (N = 16); or (3) clomiphene citrate, 50 mg orally three times a week, in patients with functional secondary hypogonadism (N = 49). Treatment was continued for 2 to 3 months, after which PSA levels were reassessed. Patients with suspicious results on DRE and increased PSA levels before or after treatment with testosterone underwent prostate biopsy. For statistical analysis, patients were categorized into two age-groups--40 to 60 years old and 61 to 80 years old. RESULTS: With all methods of testosterone replacement, PSA levels increased in both age-groups. Endogenous testosterone elevation from clomiphene stimulation raised PSA levels the highest, and testosterone patches yielded the least PSA response. Ten men underwent biopsy of the prostate. In one patient, a nodule was found on DRE; the other nine men underwent biopsy because of suspicious PSA levels. Of these patients, two were found to have adenocarcinoma, and a third man who underwent rebiopsy was also found to have cancer. Therefore, 3 of the 90 patients (3.3%) had prostate cancer. CONCLUSIONS: PSA levels increased in response to all types of testosterone replacement, regardless of whether the testosterone level was raised endogenously or exogenously. PSA levels are inappropriately low in hypogonadal men and may mask an underlying cancer. Determining PSA levels before and after testosterone treatment is recommended. Elevated PSA levels before or after testosterone therapy should prompt performance of a urologic evaluation for possible prostate biopsy.

Characterization of patients in a medical endocrine-based center for male sexual dysfunction.

OBJECTIVE: To characterize the patient population in a multidisciplinary sexual dysfunction clinic whose focal person is an endocrinologist and to summarize the initial manifestations, the demographics of the study group, and their associated medical conditions. METHODS: We undertook a retrospective analysis of the medical records of all new consultations in a center for sexual function during a recent 2-year period. RESULTS: During the period from July 1995 to July 1997, 1,050 men were seen in new consultations for sexual dysfunction at our medical facility, and complete medical records could be retrieved for 990 of them. Of the overall study group of 990 men, most (93.2%) had erectile dysfunction (versus libido or ejaculatory problems), but combinations of problems were common. Most men had organic causes of their sexual dysfunction that correlated with increasing age; however, their dysfunction was more often the result of chronic medical conditions than of advancing age itself. Most men were married (72.1%) and in long-term relationships (mean duration, more than 20 years). Hypogonadism was the most common medical condition (36.3%), a finding that reflected an endocrine referral bias. Testosterone treatment alone corrected the complaints in a minority of patients. Hypertension was a more common diagnosis than diabetes (35.8% versus 23.1%), and pituitary tumors were rare. Successful outcomes were achieved in about two-thirds of men having a strong organic cause of sexual dysfunction, but treatments were less successful when pronounced psychologic factors were present. The patient dropout rate was substantial and was similar in each of the four 6-month quarters--an indication that even as newer therapies became available, dissatisfaction was still evident. CONCLUSION: Many patients have more than one manifestation of sexual dysfunction, which may have to be addressed separately. In a sexual dysfunction clinic managed by an endocrinologist, referral bias may direct more patients with hypogonadism and fewer patients who have had transurethral retropubic prostatectomy or a radical prostatectomy. Treatment of hypogonadism corrects sexual dysfunction in only a few men, and only when other medical problems are not present. Although the percentage of men with diabetes would be expected to be high in this study, the number of patients with hypertension was higher. A considerable dropout rate during evaluation and treatment persisted throughout this study.