Testosterone and erectile physiology

The role of testosterone deficiency in sexual dysfunction is an important aspect of aging, because it affects such a large proportion of men over 50 years old. A number of age-related factors can cause sexual dysfunction (in particular erectile dysfunction) and testosterone deficiency, such as chronic illness and multiple medications, and the causative link between hypogonadism and erectile dysfunction is still debated. However, studies in castrated animals have proven that addition of testosterone, and its conversion to dihydrotestosterone, can restore erectile function. It appears that testosterone achieves this by peripheral mechanisms (endothelial dependent and independent) and central mechanisms. Testosterone replacement therapy is therefore effective for erectile dysfunction in men with hypogonadism, with success rates of 35–40%. Testosterone supplementation is also important in men who fail on phosphodiesterase type-5 inhibitors, because a minimum plasma concentration of testosterone is required for the successful restoration of erectile function with these agents. Testosterone gels are now the preferred formulation for testosterone supplementation and they can be highly beneficial in a proportion of men with erectile dysfunction.     

Testosterone/estradiol ratio,is it useful in the diagnosis of erectile dysfunction and low sexual desire?

Erectile dysfunction and low sexual desire are multifactorial diseases. The decrease in testosterone levels is one of the causes, but the effect of estradiol is not well known. Moreover, study has shown that the testosterone/estradiol ratio has more influence over sexuality than does estradiol alone. The aim of the study was to determine whether the balance between testosterone and estradiol has any relation to some aspects of sexual function. It was an ambispective study of 230 patients with urological problems unrelated to sexuality. They underwent a detailed history and hormone study including total, free, bioavailable testosterone and estradiol. They completed the Sexual Health Inventory for Men and questions 11 and 12 of the IIEF15 were used to assess impairment in sexual desire. The T/E ratio was calculated, and the relationship between the different parameters and erectile function and sexual desire were studied by univariate and multivariate analysis. The mean age was 66.32?±?8.17 years. The percentage of patients with erectile dysfunction was 60.9% (7% severe, 14.3% moderate, 12.6% mild to moderate and 27% mild) and decreased sexual desire was 46.5%. Age, free and biodisponible testosteron were the only variables with a positive linear association with erectile dysfunction and decreased sexual desire. Age was the only independent variable for both, erectile dysfunction and sexual desire, in the multiple linear regression. There was no association between a testosterone/estradiol imbalance and an alteration in erectile function and sexual desire. Consequently, in the clinical study of these patients, it is not necessary to request estradiol in the laboratory analyses.     

Testosterone therapy in erectile dysfunction

Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel®; Schering AG, Germany/AndroGel®; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (<?400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.     

Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction

The prevalence of erectile dysfunction rises rapidly with age and is a frequent complaint presented in clinical practice. Although the etiology of erectile dysfunction is multifactorial, 10-20% of evaluations demonstrate testosterone deficiency. Testosterone deficiency due to secondary hypogonadism increases with age. Despite a higher prevalence of secondary hypogonadism in the elderly, there are no studies addressing hypothalamic-pituitary structural abnormalities in elderly impotent men with testosterone deficiency. We retrospectively reviewed the records of all elderly men who presented for general outpatient evaluation of erectile dysfunction from 1996 to 1999. To obtain a cohort control population, the records of 300 patients without erectile dysfunction were also reviewed. Amongst the erectile dysfunction patients, 225 were found to be testosterone deficient (testosterone < 300 ng/dl). Of these patients, 29 were additionally diagnosed with secondary hypogonadism based on a luteinizing hormone (LH) < 13 mIU/ml. Magnetic resonance imaging (MRI) or computed tomography (CT) imaging was available and reviewed in all patients diagnosed with secondary hypogonadism. Ten per cent of these patients had hypothalamic-pituitary imaging abnormalities. The prevalence of pituitary tumors within our population was not significantly elevated compared to the previous general population studies. Small-vessel white matter disease, hyperlipidemia and history of compression fractures were significantly increased in both univariate and multivariate analysis in the erectile dysfunction group compared with the control cohort. This study does not suggest that the use of hypothalamic-pituitary imaging in the evaluation of impotence in elderly men, in the absence of clinical characteristics of other hormonal loss or sella compression symptoms, will increase diagnosis of structural hypothalamic-pituitary abnormalities over that of the general population. However, the yield may increase with very low testosterone levels. These data suggest that there is an increase in ischemic white matter disease in elderly men with hypogonadism that may reflect microvascular injury to the hypothalamic-pituitary. Furthermore, these data confirm that low testosterone is associated with hyperlipidemia in the elderly. Future studies are required to assess the role of hypogonadism and hyperlipidemia, and to determine if treatment of the hormone deficiency improves the lipid profile.     

Measuring sexual arousal

The impact of sexual offenses and abuse is incalculable, both on the victims themselves and the society responsible for protecting them. Identifying people who sexually offend against adults and children and preventing them from engaging in abusive behavior in the future requires valid and reliable methods that accurately identify the perpetrators' characteristics and measure treatment effectiveness. This article reviews the literature on penile plethysmography (PPG), a mechanism by which erectile response to deviant sexual stimuli can be measured.     

Using Eye Tracking to Identify Faking Attempts During Penile Plethysmography Assessment

Penile plethysmography (PPG) is considered the most rigorous method for sexual interest assessment. Nevertheless, it is subject to faking attempts by participants, which compromises the internal validity of the instrument. To date, various attempts have been made to limit voluntary control of sexual response during PPG assessments, without satisfactory results. This exploratory research examined eye-tracking technologies' ability to identify the presence of cognitive strategies responsible for erectile inhibition during PPG assessment. Eye movements and penile responses for 20 subjects were recorded while exploring animated human-like computer-generated stimuli in a virtual environment under three distinct viewing conditions: (a) the free visual exploration of a preferred sexual stimulus without erectile inhibition; (b) the viewing of a preferred sexual stimulus with erectile inhibition; and (c) the free visual exploration of a non-preferred sexual stimulus. Results suggest that attempts to control erectile responses generate specific eye-movement variations, characterized by a general deceleration of the exploration process and limited exploration of the erogenous zone. Findings indicate that recording eye movements can provide significant information on the presence of competing covert processes responsible for erectile inhibition. The use of eye-tracking technologies during PPG could therefore lead to improved internal validity of the plethysmographic procedure.     

Effects of long-term testosterone replacement therapy,with a temporary intermission,on glycemic control of nine hypogonadal men with type 1 diabetes mellitus – a series of case reports

Abstract

Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone?≤?12?nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA_1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT.     

Oral Abstracts

Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality, and also affect quality of life. The ESPRIT study (Energy, Sexual desire and body PropoRtions wIth AndroGel®, Testosterone 1% gel therapy) is a 6-month, multinational, open label, observational study in hypogonadal men being treated with transdermal AndroGel® in usual daily clinical practice; 1,700–2,400 patients will be enrolled in Canada, Germany, Central and Eastern Europe, Russia and the Middle East. The main objective will be to evaluate the effect of AndroGel® on symptoms of hypogonadism and quality of life as assessed by the Aging Males' Symptoms scale. Further objectives include evaluating the effect and time to onset of improvement in erectile dysfunction and libido/sexual desire (International Index of Erectile Function), fatigue (Multi-dimensional Fatigue Index) and body composition (waist circumference, body mass index). Subgroup analyses will be performed: <50 years versus ≥ 50 years; absence versus presence of metabolic syndrome. The safety of AndroGel® will also be assessed. The study population will consist of newly diagnosed hypogonadal men (age ≥ 18 years), in whom testosterone deficiency has been confirmed by clinical features and biochemical tests according to international guidelines, who are currently being prescribed AndroGel® (testosterone 1% gel, starting dose 50 mg testosterone per day).     

The impact of physical health and socioeconomic factors on sexual activity in middle-aged and elderly Taiwanese men

Sexual activity in older people has become a topic of growing interest. The aim of this study is to investigate the effect of physical health and socioeconomic factors on the sexual activity of middle-aged and elderly Taiwanese men. From August 2007 to April 2008, 744 men older than 40 years were enrolled from a free health screening in Kaohsiung, Taiwan. All participants received detailed physical examination and answered questionnaires that collected demographic and lifestyle information, and medical history as well as answered items from the International Prostate Symptoms Score and five-item version of the International Index of Erectile Function (IIEF-5). Overall, 100 (13.4%) participants reported to be sexually inactive in previous 6 months. Older age, lower education levels, loss of a partner, erectile dysfunction, and increased number of comorbidities were found to be independent predictors for sexual inactivity. In conclusion, most middle-aged and elderly Taiwanese men remain sexually active. In addition to erectile dysfunction and loss of a partner, lower education levels and increased number of comorbidities were found to be predictors for sexual inactivity. Further research would need to elucidate whether improvement of those factors could help to preserve sexual activity.     

Endogenous hydrogen sulfide insufficiency as a predictor of sexual dysfunction in aging rats

Objective: Our earlier studies showed that endogenous hydrogen sulfide (H₂S) pathway contributed significantly to erectile function. In this study, we tested the hypothesis that age-dependent changes in the bioavailability of H₂S increased the risk of erectile dysfunction (ED). Methods: Young, adult (3-month) and older (18-month) male Sprague-Dawley rats (n?=?6?8/group) were treated daily with sodium hydrosulfide hydrate (NaHS), DL-propargylglycine, sildenafil or l-NAME for 10 weeks. Subsequent to cavernous nerve electrical stimulation, intracavernosal pressure (ICP) responses were determined, and the samples were collected and processed for hormonal (plasma) and gaseous parameters (plasma and erectile corpus cavernosum [CC]) using standard assay protocols. Results: Aging significantly reduced the ICP response (35.9?±?2.0 mmHg vs. 45.2?±?1.9 mmHg in young controls), which was countered by NaHS (53.5?±?6.0) or sildenafil (52.8?±?9.8) treatment. In these rats, marked increments to testosterone (T) or estradiol resulted from NaHS supplementation. Similar to age-dependent decline in NO, the plasma and CC level of H₂S was significantly lower in senescent rats when compared with young animals (p?<?0.05). Conclusion: Our results confirm that ED with aging may be linked to a derangement in the H₂S pathway accompanied by low T levels. It is likely that a pharmacologic intervention delivering H₂S will provide additional benefits to sexual function from an improved T milieu.     

History of herbal medicines with an insight on the pharmacological properties of Tribulus terrestris

Phytochemicals have played a vital role in the past and will continue to do so in the future. Although synthetic drugs can produce dramatic results in most cases, the side-effects associated with them are a major concern. The source of many compounds used in modern medicine today can be traced down to plant origin. Whether or not scientific justification is available for the use of most plant products, the continued use of these compounds is due to their safety profile, ease of availability and also economic reasons. Each medicinal plant that has been used in the traditional system of medicine must be scientifically tested in order to bring forth its active principle that might be effectively used as a phytomedicine. In this vast resource of phytoproducts there are various plants that are claimed to improve the sexual deficiency in man. Tribulus terrestris Linn. (TT) is one such plant that has been used for a long time in both the Indian and Chinese systems of medicine. The plant is also said to possess various other pharmacological properties. The extract obtained from the air-dried aerial parts of this plant contains mainly steroidal glycosides, the major saponin being protodioscin (PTN). In our study on this plant product it was observed that PTN produced a moderate increase in testosterone, dihydrotestosterone and dehydroepiandrosterone sulfate levels in primates following bolus intravenous administration of the TT extract at doses of 7.5, 15 and 30 mg/kg body weight. It also improved libido, sexual activity and intracavernous pressure in rats following TT extract administration orally (for 8 weeks at doses of 2.5, 5 and 10 mg/kg body weight) and had a proerectile effect on the corpus cavernosum smooth muscle of rabbits (orally for 8 weeks at doses of 2.5, 5 and 10 mg/kg body weight). In this article, the various pharmacological effects of TT have been reviewed and our studies based on TT extract in relation to male erectile dysfunction have been summarized.     

RigiScan data under long-term testosterone therapy: improving long-term blood circulation of penile arteries,penile length and girth,erectile function,and nocturnal penile tumescence and duration

Background: Late-onset hypogonadism (LOH) presents with low serum testosterone (TT) levels and sexual and nonsexual symptoms. Erectile dysfunction affects a man’s self-esteem and as a result partner relationship and quality of life.

Objectives: To investigate the andrological clinical profile outcomes of testosterone therapy (TTh) in men (n?=?88) with symptomatic LOH complaints and symptoms.

Main outcome measures: Erectile function was assessed using the International Index of Erectile Function-5 questionnaire at baseline and at 6 and 12 months of TTh. In addition, penile length was measured at baseline and 12 months. We also evaluated nocturnal penile tumescence (NPT, using RigiScan) and blood flow of cavernous arteries (penile Doppler ultrasonography) at baseline and 12 months of TT.

Materials and methods: Eighty-eight LOH men (M_age 51.1 years) with erectile dysfunction, all with serum TT?<10.4?nmol/L before TTh. Patients received intramuscular long-acting testosterone undecanoate for 12 months.

Results: Following TTh, in all patients, serum TT levels were restored within 3 months to normal levels. Compared with baseline values, erectile function significantly improved at 6 (mean score increase 1.95) and 12 months (mean score increase 2.16). No significant changes in penile length were observed. NPT significantly improved at 12 months in terms of both the frequency (mean increase 1.27 times) and duration of rigidity (mean increase 5.12?min). As regards the blood flow of the cavernous arteries, we observed a significant improvement (decrease of 1.16?cm/s) and end diastolic velocity of the penile arteries.

Conclusion: TTh in men with LOH resulted in improvement of the erectile function, NPT, and to some extent the blood flow of the cavernous arteries.     

Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone

Aims: To evaluate the cause of failure of sildenafil citrate (Viagra^®) to restore erections in patients with organic erectile dysfunction (ED) associated with type II diabetes mellitus (DM) and receiving oral antidiabetic drugs. Methods: Diabetic ED patients (n = 120), aged 43-74 years, failing to respond at least three times to 100 mg Viagra were evaluated. After at least 2 weeks' treatment with oral testosterone undecanoate (Andriol^®), 100 mg Viagra was used before coitus. ED was assessed with the International Index of Erectile Function (IIEF). Serum total testosterone, prolactin, thyroid stimulating hormone, lipid profile and prostate-specific antigen (PSA) were determined by standard methods and prostate volume by digital rectal examination. Age-matched diabetic ED patients (n = 100) served as controls for baseline values. Results: Viagra non-responders had, at baseline, significantly lower testosterone and more depressed libido than controls. Andriol restored testosterone to normal levels and increased libido. In 84/120 (70%) Viagra non-responders, combined therapy with Andriol induced satisfactory erections, a significant increase in IIEF scale (question (Q) 3 from 2.0 ± 0.2 to 3.7 ± 0.3, Q4 from 1.9 ± 0.1 to 3.4 ± 0.2, Q12 from 1.0 ± 0.1 to 4.2 ± 0.4) and increased sexual contacts from 0.5 to 3-4 per month. No adverse events were noted, and PSA levels remained below 4 ng/ml. Conclusion: Decreased testosterone levels in patients with ED and type II DM receiving oral antidiabetic agents may be responsible for failure to respond to sildenafil citrate therapy. Combination with oral testosterone undecanoate restores sexual function in these patients.     

A prospective longitudinal survey of erectile function status in symptomatic benign prostatic hyperplasia patients treated with dutasteride

We prospectively evaluated erectile function (EF) using the Sexual Health Inventory for Men (SHIM) and the erectile hardness score (EHS) as well as urinary statuses using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) before and 3, 6, and 12 months after a daily treatment with 0.5?mg dutasteride (DUT). Significant improvements were observed in IPSS and OABSS in 98 patients with the DUT treatment, and the effects were similar between 28 patients with potency with baseline SHIM of 8 or greater and 70 severe erectile dysfunction (ED) patients at baseline. In the 28 patients with potency, significant decreases were observed in SHIM and EHS after 3, 6, and 12 months of the DUT treatment, with the severity of ED according to SHIM deteriorating in half of these patients after 12 months of the DUT treatment. Eighteen out of 28 patients (64.3%) with potency at baseline had awareness of the occurrence of ED before the DUT treatment, were younger, and had higher SHIM and EHS just before the DUT treatment than their counterparts. Regular assessments of EF may be needed, especially in younger patients and those with higher levels of EF before the administration of DUT.     

How to help the aging male? Current approaches to hypogonadism in primary care

Hypogonadism is a common condition which occurs more frequently in older men. It is characterized by low testosterone (T) and is associated with symptoms which are often nonspecific. A key symptom is low libido, but it can also be associated with erectile dysfunction, reduced muscle mass and strength, increased body fat, reduced bone mineral density and osteoporosis, reduced vitality, and depressed mood. Hypogonadism is linked with a variety of comorbid conditions including erectile dysfunction, metabolic syndrome, diabetes, obesity, and osteoporosis. However, the condition is often underdiagnosed. T supplementation in hypogonadism is associated with a range of benefits including improved sexual function, increased lean body mass and/or reduced fat mass, and improved bone mineral density. A variety of T supplementation formulations are available. Although there is no evidence of increased risk of initiating prostate cancer with T supplementation, it is contraindicated in men with prostate cancer. It is important that primary care physicians are aware of both the signs and symptoms of hypogonadism, the monitoring and testing that is required and the merits and advantages of the various T preparations to ensure optimal management of the condition with a treatment approach that best suits patients’ needs.     

Diagnosing and treating testosterone deficiency in different parts of the world. Results from global market research

Aim. This study analysed variations between different regions of the world in diagnosing and treating testosterone (T) deficiency.

Methods. Physicians were interviewed in Germany, Spain and the United Kingdom, in Brazil, in Saudi Arabia and South Korea. Items in the survey: 1) reasons/motivation to use or not to use T; 2) what category of patients would not receive T on the basis of these concerns; 3) concerns about prostate pathology in the decision not to provide T treatment; 4) phosphodiesterase type 5 (PDE-5) inhibitors are efficacious, but T treatment makes a comeback.

Results. Between 5% and 10% of consulting patients suffered from T deficiency. The fear to induce prostate cancer appeared very powerful. About 68% of physicians associate the use of T more with risks than benefits, more so in Europe than elsewhere. As a result about 35% of hypogonadal men do not receive treatment. The PDE-5 inhibitors are very prominent in the treatment of erectile dysfunction. Of patients suffering from erectile dysfunction, 18% to 29% have T deficiency which is not always diagnosed and treated.

Conclusion. World-wide physicians require more education on diagnosing T deficiency, on the role of T in erectile dysfunction and the relative safety of testosterone treatment.     

Body Image and Sexuality in Indonesian Adults with a Disorder of Sex Development (DSD)

In Indonesia, disorders of sex development (DSDs) are not well recognized and medical care for affected individuals is scarce. Consequently, many patients live with ambiguous genitalia and appearance. We compared reported outcomes on body image, sexual functioning, and sexual orientation of 39 adults with DSDs (aged 18 to 41) and 39 healthy controls matched for gender, age, and residential setting (urban, suburban, rural). Differences in gender and treatment status (treated or untreated) were also explored. On body image, adults with DSDs reported dissatisfaction with sex-related body parts. Compared to the matched controls, women with DSDs reported greater sexual distress, and men with DSDs reported lower erectile and ejaculation frequencies, and more dissatisfaction with sexual life but not with sexual desire and activities. Men with DSDs who had undergone genital surgery reported higher erectile and ejaculation frequencies than untreated men. More women than men in the DSDs group reported a nonexclusive heterosexual orientation. DSDs and infertility had a great impact on sexuality. Fear of ostracism complicated DSD acceptance. Findings were compared to those of Western studies. Based on these results, education about DSDs and their psychosexual consequences may help reduce the sexual distress and problems in adults with DSDs and improve quality of life.     

Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome

Metabolic syndrome (MetS) is a diagnostic category, based on a cluster of risk factors (hyperglycemia/diabetes, abdominal obesity, hypertriglyceridaemia, low HDL cholesterol and hypertension), which identifies subjects at high risk for forthcoming type 2 diabetes mellitus and cardiovascular (CV) diseases. Recently, a close association between MetS, erectile dysfunction (ED) and male hypogonadism has been reported. In patients with MetS, hypogonadism can exacerbate sexual dysfunction and arteriogenic ED because of its typical symptoms, such as decreased sexual desire and mood disturbances. On the other hand, hypogonadism per se has been associated with an increased risk of CV and overall mortality. Obesity and in particular central obesity is nowadays considered the most important determinant of MetS-induced hypogonadism whereas hypertension and diabetes play a major role in ED associated with MetS. This review analyses the current literature regarding the relationship between ED, MetS and hypogonadism emphasising the epidemiological and psychopathological aspects and stressing the concept that ED subjects are ‘lucky’, because ED offers a unique chance to undergo medical examination and therefore to improve not only their sexual but, most importantly, their overall health.     

Testosterone, Smiling, and Facial Appearance

In a study of possible links between testosterone and dominance, 119 men and 114 women provided saliva samples for testosterone assay and posed smiling and not smiling for portrait photographs. Expert judges viewing the photographs found smaller smiles among high than low testosterone men, with less zygomatic major (raising the corners of the mouth) and orbicularis oculi (raising the cheeks and crinkling around the corners of the eyes) muscle activity. Naive judges viewing individual photographs gave higher potency ratings to smiling high testosterone men than smiling low testosterone men. Naive judges viewing photographs grouped into high and low testosterone sets gave higher potency and lower goodness ratings to high than to low testosterone men, regardless of whether they were smiling. Among women, judges found only slight relationships between testosterone and facial appearance. The pattern among men of less smiling with higher testosterone levels fits with research linking testosterone to face-to-face dominance.