Androgen deficit and diabetes

Low testosterone level is common in obese men and even more frequent in the presence of type 2 diabetes mellitus. Low testosterone level is probably not caused by increased aromatization of testosterone to estradiol in fat tissue. Increase of inflammation mediators, insulin and leptin resistance and low SHBG level may play more important role. Low testosterone level may manifest with low libido, erectile dysfunction, fatigue and depressive mood; it has a role in development of anaemia, osteoporosis, worsening of insulin resistance and it is probably marker of increased all-case and cardiovascular mortality. Routine investigation of testosterone level is indicated in every man with type 2 diabetes mellitus. As in non-diabetic men of middle and higher age substitution is indicated only in presence of clinical symptoms of hypogonadism. The substitution improves mainly libido, erectile dysfunction is influenced less. However, the phosphodiasterase-5 inhibitors efficiency is markedly improved. Metabolic changes during testosterone substitution are small.     

Erectile dysfunction and diabetes in Conakry (Guinea): frequency and clinical characteristics from 187 diabetic patients

Sexual dysfunction is frequent in the diabetic population. In Africa, medical care for erectile dysfunction is underprovided, profoundly altering the quality of life of the patients. We report the prevalence of erectile dysfunction in 187 diabetic patients followed in the department of Endocrinology of the Conakry teaching hospital. Prevalence was estimated from the French version of the International Index of Erectile Function (IIEF). Erectile dysfunction concerned 90 patients (48%) of whom a severe form was observed in 54%, a moderate form in 35% and a mild form in 12%. The patients who presented erectile dysfunction were significantly older, displayed longer duration of diabetes with more complications (sensorial neuropathy and macroangiopathy) and often took drugs for associated cardiovascular diseases. In 28% of the cases, erectile dysfunction was associated with a decline in libido and in 26% with ejaculation disorders. In conclusion, erectile dysfunction is frequent and severe among diabetic patients in Guinea. The medical staff plays an essential role to initiate early diagnosis, promote psychological support and provide medication, if possible.     

Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression?

Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C, but therapy-associated underlying factors for sexual dysfunction are not well defined. To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction, we prospectively investigated changes in free testosterone, total testosterone, dehydroepiandrosterone sulfate, prolactin, sex hormone-binding globulin, FSH and LH levels and psychometric self-assessment scores in 34 male patients treated with interferon alfa-2b (5 MIU three times weekly) (n=19)+ ribavirin (n=15) for 6-12 months. Depression was measured by the Hospital Anxiety and Depression Scale. Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder. Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function. Depression scores increased during therapy and were also significantly associated with sexual dysfunction. However, androgen levels displayed no significant correlation with depression. These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both androgen reduction and increased depressive symptoms. These findings may affect care for male hepatitis C patients during interferon therapy.     

Sexuality and disease

Disease is commonly associated with sexual dysfunction in both men and women. In many cases, effective treatments are available that can improve libido, erectile dysfunction, and vaginal dryness. Sexual problems in older persons with disease often lead to anxiety, marital discord, and withdrawal. It is the responsibility of all health care professionals to inquire about sexuality in all patients, no matter what the patient's age, and to be aware that frailty [79-81] is not, in itself, a barrier to sexuality. Health professionals need to give education, support, and counseling on sexuality for patients with disease.     

Androgen replacement in men with hypogonadism and erectile dysfunction

The prevalence of hypogonadism and erectile dysfunction (ED) increases with age. Hypogonadism also is frequently associated with decreased libido and ED. Testosterone replacement therapy for hypogonadal ED is effective in restoring sexual desire and erectile function, especially in younger and healthy men. It appears to be less effective in older men with comorbid diseases that may cause ED. Therapy should be individualized, considered carefully, and closely monitored because of potential risks, especially in older men. The FDA has approved several testosterone delivery systems. These include a buccal testosterone tablet, intramuscular injections, transdermal and subcutaneous forms. There also are several promising experimental androgens under investigation including non-steroidal selective androgen receptor modulators (SARMs).     

Antiretroviral therapy is associated with sexual dysfunction and with increased serum oestradiol levels in men

Our objective was to determine the relationship between highly active antiretroviral therapy (HAART), serum total oestradiol and sexual dysfunction in HIV-infected men. Sexual difficulties were recorded prospectively in a cohort of HIV-negative (or unknown status) gay/bisexual men (MSM) and a cohort of HIV-infected men. The HIV-infected men were divided into those on and not on HAART and by sexuality. Serum total oestradiol and testosterone levels were evaluated where possible. One hundred HIV-negative MSM and 73 HIV-infected men (88% MSM) were analysed. Low libido and erectile dysfunction (ED) were reported in the control group in 2% and 10% respectively. This compared to a prevalence of 26% for both problems in HIV-infected MSM not taking HAART. In those MSM on HAART reduced libido was noted in 48% and ED in 25%. In the group of men taking HAART the mean oestradiol level was 228 pmol/L and was significantly above normal limits. Low libido and ED are more commonly reported in HIV-infected men compared to gay men of negative or unknown status. HAART is associated with a higher prevalence of lack of sexual desire and raised serum oestradiol levels.     

Erectile dysfunction in cirrhosis is impacted by liver dysfunction,portal hypertension,diabetes and arterial hypertension

Background

Although several risk factors for erectile dysfunction may be present in patients with cirrhosis, data on the actual prevalence and cause of erectile dysfunction is limited. The International Index of Erectile Function‐5 (IIEF‐5) is a well‐validated survey to determine the presence and severity of erectile dysfunction in men. We assessed (i) the prevalence and severity of erectile dysfunction, and (ii) risk factors for erectile dysfunction in patients with cirrhosis.

Methods

In this prospective study, erectile dysfunction was defined as: absent (>21 IIEF‐5‐points), mild (12‐21) and severe (5‐11). Patients with overt hepatic encephalopathy, active alcohol abuse, extrahepatic malignancy, previous urologic surgery, previous liver transplantation and severe cardiac conditions were excluded.

Results

Among n = 151 screened patients, n = 41 met exclusion criteria and n = 30 were sexually inactive. Thus, a final number of n = 80 male patients with cirrhosis were included. Patient characteristics: age: 53 ± 9 years; model for end‐stage liver disease score (MELD): 12.7 ± 3.9; Child‐Pugh score (CPS) A: 30 (37.5%), B: 35 (43.8%), C: 15 (18.7%); alcohol: 38 (47.5%), viral: 25 (31.3%), alcohol/viral: 7 (8.8%) and others: 10 (12.5%). The presence of erectile dysfunction was found in 51 (63.8%) patients with 44 (55%) and 7 (8.8%) suffering from mild‐to‐moderate and moderate‐to‐severe erectile dysfunction. Mean MELD and hepatic venous pressure gradient (HVPG) were significantly higher in patients with erectile dysfunction (P = .021; P = .028). Child‐Pugh score C, MELD, creatinine, age, arterial hypertension, diabetes, low libido, low testosterone and high HVPG were associated with the presence of erectile dysfunction. Interestingly, beta‐blocker therapy was not associated with an increased risk. In multivariate models, arterial hypertension (OR: 6.36 [1.16‐34.85]; P = .033), diabetes (OR: 7.40 [1.31‐41.75]; P = .023), MELD (OR: 1.19 [1.03‐1.36]; P = .015) and increasing HVPG (n = 48; OR: 1.11 [1.002‐1.23]; P = .045) were independent risk factors for the presence of erectile dysfunction.

Conclusion

About two‐thirds of male patients with cirrhosis show erectile dysfunction. Severity of liver dysfunction, portal hypertension, arterial hypertension and diabetes were identified as risk factors for erectile dysfunction.     

Three cases of liver injury caused by Sennomotokounou, a Chinese dietary supplement for weight loss

Dietary supplements have become very popular worldwide because they are believed to be safe with few side effects. Here, we report three cases of liver injury caused by Sennomotokounou, a Chinese dietary supplement for weight reduction. All patients developed acute hepatotoxicity and recovered spontaneously after withdrawal of dietary product. This product contains fenfluramine, n-nitroso-fenfluramine, and dried thyroid tissue powder. In Japan, the regulatory agency for drug and food safety received 120 reports of hepatotoxicity associated with Sennomotokounou between 2000 and 2002. Physicians should inquire about the use of dietary supplements whenever patients present with unexplained acute liver dysfunction.     

Treatment of patients with hypothalamic-pituitary lesions as adult-onset Langerhans cell histiocytosis

We report four cases of adult-onset Langerhans cell histiocytosis (LCH) with central nervous system (CNS) lesions in the hypothalamic-pituitary region. The first clinical symptoms were diabetes insipidus (two patients), hypothyroidism (one patient), and decreased libido/erectile dysfunction (one patient). Diagnosis was delayed as the CNS lesion was not initially suspected to be secondary to LCH, with a median time from symptom onset to treatment of 3.0 (range <1–5.3) years. In three patients, the tumor mass was effectively reduced by chemotherapy; however, all patients continue to exhibit hypopituitarism. Early diagnosis and initiation of treatment are required to improve the outcome of CNS-LCH in adult patients.     

Hyperprolactinemia in men: clinical and biochemical features and response to treatment

Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treatment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.     

All Men with Vasculogenic Erectile Dysfunction Require a Cardiovascular Workup

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction.     

Depression, antidepressants, and sexual function

Recent studies have suggested that serotonin reuptake inhibitors (SSRI's), prescribed for the relief of depression, can cause sexual dysfunction in up to fifty percent of those taking them. The SSRI's--including fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)--affect mood stabilization by promoting the transmission of the neurotransmitter serotonin, although enhancing serotonergic function can decrease libido or lead to erectile difficulties. As an alternative to lowering antidepressant dosages and risking losing therapeutic gains, administering serotonin-blockers, such as cyproheptadine (Periactin) and yohimbine (Yocon), has been shown to restore sexual function. However, the serotonin antagonist, cyproheptadine, causes sedation and can reverse the antidepressant or anti-obsessive effect of the SSRI. Yohimbine enhances transmission of the neurotransmitter epinephrine, increasing the flow of blood to erectile tissue and stimulating sexual desire by activating the cerebral cortex. Its drawbacks are increased levels of panic attacks and higher required dosages. Other potential biochemical stratagems are: amantadine (Symmetrel), bromcriptine (Parlodel), and buspirone (Buspar), which enhance dopamine and serotonin transmission; and bethanecol (Urechline), which enhances choline transmission. One study indicates improved sexual response when the nonserotonergic, mildly dopamine-enhancing buproprion (Welbutrin) is substituted for fluoxetine.     

Lifespan effects of simple and complex nutraceutical combinations fed isocalorically to mice

Present data suggest that the consumption of individual dietary supplements does not enhance the health or longevity of healthy rodents or humans. It might be argued that more complex combinations of such agents might extend lifespan or health-span by more closely mimicking the complexity of micronutrients in fruits and vegetables, which appear to extend health-span and longevity. To test this hypothesis we treated long-lived, male, F1 mice with published and commercial combinations of dietary supplements and natural product extracts, and determined their effects on lifespan and health-span. Nutraceutical, vitamin or mineral combinations reported to extend the lifespan or health-span of healthy or enfeebled rodents were tested, as were combinations of botanicals and nutraceuticals implicated in enhanced longevity by a longitudinal study of human aging. A cross-section of commercial nutraceutical combinations sold as potential health enhancers also were tested, including Bone Restore®, Juvenon®, Life Extension Mix®, Ortho Core®, Ortho Mind®, Super K w k2®, and Ultra K2®. A more complex mixture of vitamins, minerals, botanical extracts and other nutraceuticals was compounded and tested. No significant increase in murine lifespan was found for any supplement mixture. Our diverse supplement mixture significantly decreased lifespan. Thus, our results do not support the hypothesis that simple or complex combinations of nutraceuticals, including antioxidants, are effective in delaying the onset or progress of the major causes of death in mice. The results are consistent with epidemiological studies suggesting that dietary supplements are not beneficial and even may be harmful for otherwise healthy individuals.     

Testosterone replacement therapy and sleep-related erections in hypogonadal men

Hypogonadal men usually have diminished libido and erectile dysfunction, and testosterone replacement therapy in these men increases sexual activity, erotic thoughts, and self-reported nocturnal erections. The polygraphic assessment of nocturnal penile tumescence (NPT) provides an objective index of erectile capability and is useful for differentiating psychogenic from organic erectile dysfunction. In this study we evaluated NPT in six hypogonadal adult men during and after termination of androgen therapy. Multinight sleep studies were conducted within 1 week and 7-8 weeks after each man received 20 mg testosterone cypionate, im. The mean serum testosterone level 4-7 days after testosterone injection was 35.9 +/- 3.4 (+/- SE) nmol/L, and it fell to 2.3 +/- 0.9 nmol/L after 7-8 weeks. Significant declines (P less than 0.05) in the number of NPT episodes (3.7 to 2.0), maximum penile circumference increase (24 to 13 mm), and total tumescence time (107 to 55 min) accompanied the fall in the serum testosterone level. No androgen-related changes in the amount or integrity of rapid eye movement sleep were found. Finally, the mean penile rigidity (buckling pressure) decreased from 770 +/- 98 to 590 +/- 81 g (P less than 0.05). Comparison of these results to those in normal men revealed that none of these men met all diagnostic criteria for organic impotence, even 7-8 weeks after discontinuation of testosterone administration. While men with androgen deficiency may have normal NPT, sleep-related erections increase in response to testosterone administration.     

Fibrinogen, lipoprotein (a) and lipids in patients with erectile dysfunction. A preliminary study.

BACKGROUND: Erectile dysfunction is associated with cardiovascular risk factors (e.g. hypertension, smoking, dyslipidemia and diabetes) and is more common in patients with cardiovascular disease. We therefore assessed the prevalence of two predictors of vascular events, fibrinogen and lipoprotein-a, in patients with and without erectile dysfunction. METHODS: Men with erectile dysfunction (48 non-smokers, 48 smokers), aged 45-70 years, were compared with controls (21 non-smokers, 21 smokers) with normal erectile function and no known pathology. RESULTS: Serum total cholesterol was significantly higher in non-smokers with erectile dysfunction compared to both control non-smokers and erectile dysfunction smokers. Men with erectile dysfunction who smoked had a significantly higher plasma fibrinogen level than control smokers. Similarly, men with erectile dysfunction, who did not smoke had higher levels of plasma fibrinogen compared to both smokers and non-smokers without erectile dysfunction. No significant difference in serum lipoprotein-a values was found. CONCLUSIONS: These findings support the concept that cardiovascular risk factors are predictors of erectile dysfunction and that this may be another manifestation of vascular disease.     

A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales,Australia

Four hundred and twenty‐one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross‐sectional study to assess sexual dysfunction and infertility post‐transplant. Survey instruments included the Sydney Post‐Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) – BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft‐versus‐Host Disease (cGVHD) Activity Assessment‐ Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post‐Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo‐HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre‐ and post‐transplant.     

Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence

This open longitudinal study investigated the prevalence of depressed sexual potency by monitoring erectile dysfunction using nocturnal penile tumescence (NPT) in 51 consecutive men with hyperprolactinemia (41 macroprolactinomas and 10 microprolactinomas) and evaluated potential reversibility of sexual failure after 6 months of treatment with cabergoline. Fifty-one healthy men served as controls. Compared with controls, the patients with either micro- or macroprolactinoma had low testosterone levels with severe alterations of erectile function. Testosterone deficiency was present in 73.2% of macro- and 50% of microprolactinomas; reduced libido and sexual potency were referred by 53.6% of macroprolactinomas, 50% of microprolactinomas, and none of controls. Fewer than three erectile events per night by NPT were found in 96.7% of patients and 13.7% of controls (P < 0.0001). After 6 months of cabergoline treatment, prolactin levels normalized in 74.5% of patients: 73.2% of macroprolactinomas and 80% of microprolactinomas. Testosterone levels normalized in 68.6% of patients, whereas NPT normalized in 60.6% of patients who had normalized prolactin levels and in 7.7% of patients who did not. In conclusion, at study entry, 50% of the patients complained of sexual disturbances, 96.7% of whom had an impairment of erectile events per night compared with 13.7% of controls. Six months of treatment with cabergoline normalized testosterone levels in most cases, thus restoring and maintaining during treatment the capability of normal sexual activity in hyperprolactinemic males.     

The erectile-endothelial dysfunction nexus: new opportunities for cardiovascular risk prevention

Erectile and endothelial dysfunction are common in individuals with multiple cardiovascular risk factors and are longitudinal predictors of cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction is intimately linked through increased expression and activation of endothelial nitric oxide synthase, and the subsequent physiological actions of nitric oxide. Endothelial production of nitric oxide by endothelial nitric oxide synthase in the corpus cavernosum is involved in the maintenance of penile erection. Erectile dysfunction can be detected clinically using systematic questioning and could potentially be employed as an independent predictor of cardiovascular risk to target treatment of cardiovascular risk factors. Both erectile and endothelial dysfunction respond to lifestyle modifications, particularly in individuals with the metabolic syndrome. Drugs that improve endothelial dysfunction can also improve erectile dysfunction, but responses are not always concordant. Phosphodiesterase type 5 inhibitors, however, are powerful agents that commonly improve erectile and endothelial dysfunction, with potential cardiac applications. The recent Princeton consensus requires more extensive implementation and evaluation in clinical practice. The judicious diagnosis of erectile dysfunction, nevertheless, provides a unique opportunity for the prevention of cardiovascular disease.     

Effect of cardiac resynchronization therapy on libido and erectile dysfunction

Background:

Chronic heart failure (HF) is a common, complex clinical syndrome characterized by dyspnea, fatigue and exercise intolerance. HF patients experience decreased libido and erectile dysfunction (ED). The effects of cardiac resynchronization therapy (CRT) on libido and erectile function have not been previously evaluated. We aimed to investigate the effects of CRT on libido and ED.

Hypothesis:

Cardiac resynchronization therapy improves libido and ED.

Methods:

Thirty‐one male patients with advanced HF, scheduled for implantation of a CRT device, were included in the study. Left ventricular systolic function, New York Heart Association (NYHA) classs, libido, and ED were assessed before and 6 months after CRT. Libido and ED were evaluated with the Aging Male Symptoms (AMS) rating scale and internationally validated Sexual Health Inventory for Men (SHIM) questionnaire, respectively.

Results:

At the 6‐month follow‐up, the mean NYHA class improved from 3.4 ± 0.5 to 2.1 ± 0.6 (P<0.001). On echocardiographic examination, an improvement in left ventricular ejection fraction (LVEF) from 18 ± 5% to 32 ± 6% was detected (P<0.001). A significant increase in mean SHIM score and a significant decrease in mean AMS were noted. Changes in SHIM and AMS scores were correlated positively with the increase in LVEF (r = 0.47, P = 0.007 and r = ? 0.36, P = 0.04, respectively). Similarly, SHIM scores were correlated negatively (r = ? 0.57, P = 0.001) and AMS scores were correlated positively (r = 0.73, P = 0.0001) with the improvement in NYHA class.

Conclusions:

CRT results in a significant improvement in libido and erectile function in patients with congestive HF. This improvement is related to the improvements in the LVEF and functional capacity. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men

The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind, placebo-controlled study on the effect of oral testosterone treatment on liver disease. At entry, 67% (95% confidence limits, 61%-74%) complained of sexual dysfunction. Sexual dysfunction was significantly (p less than 0.05) associated with lower serum concentrations of testosterone, non-protein-bound testosterone, and non-sex hormone-binding globulin-bound testosterone. The significant associations between sexual dysfunction and non-protein-bound and non-sex hormone-binding globulin-bound testosterone concentrations disappeared, however, when age, ethanol consumption, and severity of liver disease were included as covariates in the analysis. During follow-up (median 30 mo, range 1-48 mo) sexual dysfunction improved significantly (p less than 0.05) at 6, 12, and 24 mo. Furthermore, the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period (p less than 0.01). However, the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function. In conclusion, oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men. However, sexual function improved after reduction of ethanol consumption in these patients.