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Prevalence of Androgen Deficiency in Men with Erectile Dysfunction
Abstract
Erectile dysfunction (ED) and androgen deficiency in aging men are two separate clinical entities that often overlap. Controversy exists regarding the most appropriate total testosterone level that defines androgen deficiency in aging men, and its prevalence in men with ED is still uncertain. We evaluated the prevalence and risk factors of low and low-normal testosterone levels in men presenting for an initial ED evaluation.
The computerized charts from 1987 to 2002 of 2794 men aged 25 to 80 years and presenting with a primary complaint of ED who also had serum total testosterone levels measured were retrospectively reviewed. Multiple testosterone level cutpoints and a linear regression model (including age, diabetes, cholesterol, anemia, creatinine, and prostate-specific antigen) were used to analyze the factors that correlated with hypogonadism.
The prevalence of androgen deficiency was 7%, 23%, 33%, and 47% for testosterone levels of less than 200, less than 300, less than 346, and less than 400 ng/dL, respectively. An abrupt increase in hypogonadism prevalence occurred in men aged 45 to 50, beyond which a plateau of prevalence was maintained until older than 80 years of age. Age, the presence of uncontrolled diabetes, high total cholesterol, and anemia all correlated with significantly decreased testosterone levels in men with ED. The prostate-specific antigen level and creatinine did not affect the testosterone levels.
Androgen deficiency was quite common in men presenting with ED and correlated significantly with age, uncontrolled diabetes, hypercholesteremia, and anemia. Although additional prospective studies evaluating the effect of testosterone supplementation in this population are needed, clinicians, including urologists, should be keenly aware of the large overlap of patients with ED who might also have the entity, androgen deficiency in the aging male.
... Male hypogonadism (MH) is defined as a clinical syndrome caused by androgen deficiency which may adversely affect multiple organ functions and quality of life [1]. Although there is limited evidence of its prevalence in patients presenting for erectile dysfunction (ED) [2][3][4], it has been shown that low total testosterone (TT) is more common in individuals with ED than in the general population [2,3]. It is estimated that between 21.3% and 33.0% of males presenting for ED also present biochemical MH [2][3][4]. ...
... Male hypogonadism (MH) is defined as a clinical syndrome caused by androgen deficiency which may adversely affect multiple organ functions and quality of life [1]. Although there is limited evidence of its prevalence in patients presenting for erectile dysfunction (ED) [2][3][4], it has been shown that low total testosterone (TT) is more common in individuals with ED than in the general population [2,3]. It is estimated that between 21.3% and 33.0% of males presenting for ED also present biochemical MH [2][3][4]. ...
... Although there is limited evidence of its prevalence in patients presenting for erectile dysfunction (ED) [2][3][4], it has been shown that low total testosterone (TT) is more common in individuals with ED than in the general population [2,3]. It is estimated that between 21.3% and 33.0% of males presenting for ED also present biochemical MH [2][3][4]. Androgens, namely testosterone and dihydrotestosterone, play an important role in the physiology of erection and ED [5,6]. ...
Although male hypogonadism (MH) is a prevalent comorbidity in patients presenting for erectile dysfunction (ED), its screening relies solely on total testosterone (TT). Ageing and other conditions can increase sex hormone-binding globulin (SHBG) and lower free testosterone (FT) causing symptomatic MH despite normal TT. The primary objective was to measure the prevalence of normal TT/low FT among patients presenting for ED. From January 2019 to December 2020, 408 patients referred for sexual dysfunction were screened; 180 men with a confirmed diagnosis of ED were included. MH was screened using TT, SHBG, albumin and LH. FT was calculated (cFT). Low TT, high SHBG and low cFT were defined as <345 ng/dL, >50 nmol/L and <6.5 ng/dL, respectively. Patients were divided into groups according to TT/cFT status and to age group. The frequency of normal TT/low cFT was 17.2%. From all 31 patients with normal TT/low cFT, only four (12.9%) had either hyperthyroidism, hepatic disease or HIV infection, while 23 (74.2%) were older than 60 years. Patients with normal TT/low cFT were older (65.57 ± 10.43 vs. 56.79 ± 10.63 yo, p = 0.001) and had higher SHBG (78.48 ± 40.14 vs. 52.35 ± 20.39 nmol/L, p = 0.014) than patients with normal TT/cFT. Patients over 60 years represented 48.9% of the sample, 52.5% had elevated SHBG and their frequency of normal TT/low cFT was 26.3%. Normal TT/low cFT is frequent and can be missed by current screening recommendations for MH in patients presenting for ED. Ageing seems to be the main culprit as elevated SHBG prevalence increases steeply after the sixth decade. TT cannot solely be relied on to exclude biochemical MH in patients presenting for ED, especially in patients over 60 years old. Current guidelines for MH screening in ED should be amended.
... Questions are scored from 1 to 5 points, with ED defined as a total score value ≤25. Severity is classified as follows: mild (22)(23)(24)(25), mild-tomoderate (17)(18)(19)(20)(21), moderate (11)(12)(13)(14)(15), and severe (6)(7)(8)(9)(10). A single point plasma TT level measurement was performed between 7 and 11 hours in subjects lacking a TT determination in the last 6 months. ...
... Low T is known to be common among men consulting for ED [21]. Our study has revealed a prevalence of low T levels among men with ED ranging from 13.7% to 33.3% when thresholds are set at 8 or 12 nmol/L, respectively. ...
... In men with ED, hypertension has shown to be independently associated with elevated pulse pressure (PP), an indicator of arterial stiffness [24]. Elevated PP has proven to be a marker of arteriogenic problems and low T and a predictor of major cardiovascular events in young men [21,25]. This is why it has been suggested that measurement of PP should become routine practice in sexual medicine [26]. ...
Introduction:
Low testosterone levels (low T) increase the cardiovascular (CV) risk of men with erectile dysfunction (ED). T levels associated with a higher CV risk are unknown.
Aim:
To determine the prevalence of CV risk factors associated with low T as defined by European Guidelines and their contribution to low T, overall and at different ages.
Methods:
Multicenter, cross-sectional, observational study conducted in Spain among men with ED aged ≥ 18 years visiting Urology/Andrology offices for sexual dysfunction. Anthropometric, clinical, and laboratory data, including total T (TT) values, were collected for 1,278 men.
Main outcome measures:
Risk factors were assessed in men with TT ≤ 8, 8-12, and ≥ 12 nmol/L, and two-group comparisons were made. Bivariate and multivariate logistic regression analyses were performed to calculate odds ratios for low T after adjusting for possible confounding factors.
Results:
Mean age (standard deviation) was 58.0 (9.2) years. Age and prevalence of CV risk factors was similar in men with TT ≤ 8 nmol/L or 8-12 nmol/L and significantly higher than in men with TT >12 nmol/L. Low T was therefore considered as TT ≤ 12 nmol/L, with a prevalence of 33.3%. Obesity, hypertension, hyperlipidemia, and severe ED were the variables most strongly associated with low T: obesity in middle-aged men; hyperlipidemia, and hypertension in older men. Severe ED was a risk factor in both groups. Hypolipidemic therapy had the greater effect in young men. Multivariate analysis showed that severe ED and obesity were the strongest predictors of low T.
Conclusion:
T levels associated with increased CV risk could go as high as 12 nmol/L in men with ED, with distribution of risk factors showing differences according to age. Obesity and severe ED are the best predictors of low T-related CV risk.
... The prevalence of low total testosterone levels (197,208,219,220), low free testosterone levels (206,214), and hyperprolactinemia (199,212,213) in men with ED varied widely across studies, with limited data from U.S. primary care settings or U.S. population representative samples. In 1 primary care clinic study, 24.1% of men with ED had total testosterone levels less than 10 nmol/L (Ͻ288 ng/dL) (205). ...
... By comparison, in a study based in 1 ED specialty clinic, 36.0% of 157 consecutively referred men with ED had hypogonadism (total testosterone level Ͻ300 ng/dL) (219). In a retrospective chart review of 2794 men presenting to a Veterans Affairs ED specialty clinic between 1987 and 2002 with a symptom of ED, 654 (23.0%) had androgen deficiency (total testosterone level Ͻ300 ng/dL) (220). ...
Background: Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain.
... In 2002, approximately 37.5% of Thai men aged 40-70 years had this condition, amounting to 3 million people across the country. 1 One study in 2006 found that 38.5% of Asian people had this condition and that the prevalence of ED was rising with increasing aging. 2 There are many contributing factors to ED. One of the most common concomitant endocrine conditions is hypogonadism or testosterone deficiency, which is found in 33% of patients with ED. 3 The causes of ED and testosterone deficiency are usually multifactorial and share the same risk factors as cardiovascular disease. 4 Signs and symptoms of testosterone deficiency are decreased libido, ED, fatigue, anemia, decreased bone density, and depression. ...
Objective
The objective of this study was to evaluate major adverse cardiovascular events in erectile dysfunction (ED) patients who received testosterone replacement therapy (TRT) compared with those who did not.
Materials and Methods
From January 2012 to October 2021, we collected the retrospective data of patients with ED at Ramathibodi Hospital. We divided the patients into two groups: those who received TRT (TRT group) and those with normal testosterone levels and therefore not requiring TRT (non-TRT group). The patients’ baseline clinicodemographic data were collected. Major adverse cardiovascular events, including cardiovascular death, ST- and non-ST-elevation myocardial infarction, hospitalization from congestive heart failure, transient ischemic attack, and ischemic stroke, were collected and analyzed within 2 years after treatment in all groups.
Results
Of the 221 patients, 111 were in the TRT group and 110 were in the non-TRT group. In the non-TRT group, one event each of the following occurred: myocardial infarction, transient ischemic attack, and stroke. In the TRT group, no major cardiovascular event occurred during the 2-year follow-up period. However, no significant difference in major cardiovascular events was noted between the two groups (p = 0.314).
Conclusion
TRT in ED patients with testosterone deficiency does not increase adverse cardiovascular events when compared with ED patients with normal testosterone level.
... First of all, ED patients are often accompanied by hypogonadism, and their natural free testosterone is often lower than that of non-ED men. [21] Androgens can not only directly stimulate bone formation, but also reduce the accumulation of reactive oxygen species (ROS) in the body and slow down the apoptosis of osteoblasts and mesenchymal cells by combating oxidative stress, thus playing an important role in male bone formation. [22,23] Multiple studies have shown a significant decrease in bone density and an increased risk of brittle fractures in patients with low testosterone levels. ...
Background:
Erectile dysfunction (ED) and osteoporosis are both common health problems and have similar risk factors. Recent studies have found that people with ED have a higher risk of osteoporosis.We aimed to systematically assess osteoporosis risk in patients with ED.
Methods:
A systematically research was carried out in Medline via PubMed, Cochrane Library, EMBASE, and Web of Science up to June 4, 2020, to identify articles related to ED and osteoporosis. The 2 researchers independently reviewed the literature, extracted the data, and evaluated the quality of the literature. All analyses were done using RevMan5.3 and Stata14.
Results:
A total of 4 studies involving 22,312 participants were included. The meta-analysis results showed that the risk of osteoporosis in the ED group was significantly higher than that in the non-ED group [odds ratio (OR) = 2.66, 95% confidence interval (95% CI) 1.42 to 4.98, P = .002, I2 = 68%]. Interestingly, compared with older participants, the increased risk of osteoporosis in ED patients seemed to be more pronounced in younger participants. Despite the lack of data for meta-analysis, more than half of the literature mentioned this tendency. We found the source of heterogeneity through sensitivity analysis, and there was no significant effect on the results before and after the removal of this literature, indicating that our results were robust. No obvious publication bias was found through Egger method (P = .672).
Conclusion:
People with ED have a higher risk of osteoporosis, especially among younger males. Because the assessment of osteoporosis is economical and noninvasive, ED patients should be evaluated by bone mineral density or men with osteoporosis should be further assessed for erectile function.
... As with women, EPO deficiency is thought to be the primary cause. In men, testosterone deficiency has been shown to contribute to the increased incidence of anemia [110], and an appreciable improvement in anemia has been observed following androgen therapy [111,112]. This suggests that hypogonadism may contribute to its pathomechanism. ...
Patient survival continues to increase with the growing quality of dialysis and management of chronic kidney disease (CKD). As such, chronic therapy must include considerations of quality of life (QOL), and this includes the disproportionate prevalence of sexual dysfunction (SD) in this patient population. This review aims to describe the pathophysiological and the psychosocial causes of SD with regard to renal replacement therapy, particularly hemo- and peritoneal dialysis. The differences in its manifestation in men and women are compared, including hormonal imbalances—and therefore fertility, libido, and sexual satisfaction—the experience of depression and anxiety, and QOL. The impact of comorbidities and the iatrogenic causes of SD are described. This review also presents validated scales for screening and diagnosis of SD in CKD patients and outlines novel therapies and strategies for the effective management of SD. Increased prevalence of CKD invariably increases the number of patients with SD, and it is crucial for health care professional teams to become familiar with the clinical tools used to manage this sensitive and under-quantified field. As a known predictor of QOL, sexual function should become a point of focus in the pursuit of patient-centered care, particularly as we seek to achieve as “normal” a life as possible for individuals who receive dialysis.
... Future directions in ED treatment include stem cell therapy as a potentially restorative treatment for ED. The goal of stem cell therapy is to replace non-functional sinusoidal endothelial cells, cavernous smooth muscle cells, and cavernous nerves, allowing for initiation and maintenance of an erection [11]. A small Korean study injected seven men with ED ages 57-87 with umbilical cord-derived stem cells. ...
Purpose of Review
Among the growing elderly population, sexual health remains an important concern for individuals and couples. An understanding of the expected changes with aging and taking care of aging men and women is important for treating sexual dysfunction. Sexual health issues related to aging can be both linked between men and women and independent. The aim of this study is to determine the most important considerations that contribute to sexual satisfaction in men and women in this population.
Recent Findings
Many factors contribute to the overall sexual health of men and women. Hypogonadism and erectile dysfunction both warrant thorough evaluation and consideration of treatment to improve sexual satisfaction. Underlying cardiovascular issues may be present in men presenting with these concerns. In addition to hormone replacement and traditional therapy for erectile dysfunction, therapeutic stem cell injection has shown some promise. Menopause, vaginal dryness, and dyspareunia play important roles in sexual satisfaction in women. Vaginal moisturizers, topical estrogen, and MonaLisa Touch laser therapy all may aid in improving these symptoms and ultimately sex lives. Studies have also demonstrated some benefit in populations with arousal disorders, which can be present in the elderly.
Summary
Male patients often describe issues related to erectile dysfunction and hypogonadism, and issues with sexual drive. The pathophysiology is linked between these conditions and treatment of one component can provide symptom relief on a larger scale. A combination of testosterone therapy, lifestyle modifications, and therapy for erectile dysfunction relates to sexual satisfaction in men. In women, an understanding of the physiological process of menopause and offering therapy when indicated can improve the quality of sexual health and provide satisfaction to both patient and partner. While aging can diminish drive and desire, proper counseling and treatment may significantly benefit some patients. A multimodal approach involving the physician, patient, and partner will optimize care and may improve the quality of life in the elderly. This review outlines some normal changes due to aging and identifies some current treatment options for a population in which sexual health can be often ignored or dismissed. By understanding the available tools, a more comprehensive approach can be taken to achieve satisfaction in couples and individuals alike.
... However, it should be seen as a proof-ofconcept study as the primary objective was to perform a direct cost analysis rather than assess the male hypogonadism prevalence. Furthermore, two independent studies with large populations have already assessed the male hypogonadism prevalence in the ED subpopulation [11,24], and their prevalence is similar to the prevalence observed in our study. Moreover, the highest of the two screening serum TT values was used to diminish physiological serum TT variation effect on the calculation of prevalence of low testosterone and on clinical decisions. ...
Hypogonadism is a prevalent comorbidity with erectile disfunction (ED) and current guidelines recommend screening for hypogonadism with total testosterone (TT). If low TT is detected, further assessment with LH and SHBG plus albumin are needed to establish an etiology and treatment. Our primary objective was to determine the cost benefit of current stepwise approach versus ad initium full hormonal assessment. Two hundred consecutive male patients referred for ED were screened after consent and 81 were included and assessed for hypogonadism according to the current stepwise approach with TT, and only if TT was less than 345 ng/mL, a full hormonal assessment with TT, LH, and SHBG plus albumin to calculate free testosterone was performed. Direct costs were calculated using the national public healthcare system reimbursement tables and were compared with a hypothetical initial full hormonal assessment. Screening TT was less than 345 ng/mL in 34.6% patients leading to a full hormonal assessment on these. Using a stepwise approach there was a direct cost increase of 5.82 € per patient. Moreover, one out of every three patients had two extra venipunctures and an additional follow-up appointment. Current stepwise recommendations may prove costly in high prevalence scenarios such as the ED subpopulation as a direct cost increase was observed.
... 4,6 Cholesterol is an essential component of the human diet and performs an important role as a raw material in the synthesis of steroid hormones and vitamin D. 7 A substantial amount of evidence indicates that hypercholesterolaemia is a crucial risk factor for mortality and morbidity, not only for cardiovascular disease 8,9 but also for non-alcoholic fatty liver disease, 10 cancer 11 and Alzheimer's disease 12,13 Our previous epidemiological study demonstrated that low testosterone was related to elevated total cholesterol (TC) in serum from 4114 middle-aged and older Chinese participants, 14 which was consistent with previous research. 15 Several animal studies have also observed that hypercholesterolaemic rats 16 and mice 17 showed low serum testosterone levels. These findings imply that hypercholesterolaemia is an important risk factor for testosterone deficiency, but the underlying mechanism is not obvious. ...
Emerging epidemiological studies indicate that hypercholesterolaemia is a risk factor for testosterone deficiency. However, the underlying mechanism is unclear. Testicular Leydig cells are the primary source of testosterone in males. To identify the effect and mechanism of cholesterol overload on Leydig cell function, rats were fed with a HC (HC) diet to induce hypercholesterolaemia. During the 16‐week feeding period, serum testosterone levels were reduced in a time‐dependent manner in rats fed the HC diet. Accordingly, these steroidogenic enzymes within the Leydig cells, including steroidogenic acute regulatory protein (StAR), cholesterol side‐chain cleavage cytochrome P450 (P450scc) and 3β‐hydroxysteroid dehydrogenase (3β‐HSD), were down‐regulated. Notably, the HC‐fed rats showed evident endoplasmic reticulum (ER) stress in the testis, including a dilated ER as an evident pathological change in the Leydig cell ultrastructure, up‐regulated ER stress biomarker (binding immunoglobulin protein) levels and activation of the activating transcription factor 6 (ATF6)‐related unfolded protein response pathway. Further analysis showed that when 4‐phenyl butyric acid (4‐PBA) was used to block ER stress in HC‐fed rats for 8 weeks, the testosterone deficiency was significantly alleviated. Our findings suggested that high dietary cholesterol intake affected serum testosterone levels by down‐regulating steroidogenic enzymes and that activated ER stress might serve as the underlying mechanism.
... It is possible that some participants in this sample may be suffering from testosterone deficiency. Testosterone deficiency may lead to erectile dysfunction 36 and sleep complications. Data on testosterone deficiency were not available to be included in the analyses of this study. ...
Introduction:
One factor that may plausibly be associated with sexual dysfunction is sleep disturbance. Like sexual problems, complaints of sleep disturbance increase with age and are commonly reported by older adults.
Aims:
To examine associations between sleep quality, duration, and a range of sexual problems in a large, representative sample of older adults.
Methods:
Data were from 2,568 men and 1,376 women (age ≥50 years) participating in Wave 6 of the English Longitudinal Study of Ageing (2012-2013). Sleep quality, duration, and problems with erectile function, sexual arousal, and orgasmic experience were self-reported; associations were examined using logistic regression models. Covariates included age, ethnicity, partner status, wealth, limiting long-standing illness, smoking, alcohol consumption, physical activity, and depressive symptoms.
Main outcome measure:
Participants self-reported problems with erectile function, sexual arousal, and orgasmic experience.
Results:
In women, moderate (odds ratio [OR] = 1.53, 95% CI 1.09-2.13, P = .013) and low sleep quality (OR = 1.70, 95% CI 1.24-2.32, P = .001) were associated with increased odds of arousal problems relative to high sleep quality. In men, moderate sleep quality was associated with increased odds of erectile difficulties (OR = 1.47, 95% CI 1.16-1.85, P = .001), the difference between low and high sleep quality did not reach statistical significance (OR = 1.24, 95% CI 0.97-1.58, P = .091). Sleep quality was not associated with difficulty achieving an orgasm in men, but in women low sleep quality was associated with increased odds of orgasmic difficulty (OR = 1.63, 95% CI 1.18-2.25, P = .003). No associations between sleep duration and problems with sexual function were observed in women, but, in men, long sleep was associated with higher odds of difficulty achieving orgasm (OR = 1.75, 95% CI 1.04-2.95, P = 0.036) relative to optimal sleep duration.
Clinical implications:
Older adults presenting sleep problems should be screened for sexual dysfunction and vice versa.
Strength & limitations:
Strengths of this study include the large representative sample of older English adults, the assessment of several aspects of sexual dysfunction and sleep, and the inclusion of potentially important confounding variables into statistical models. However, the study was cross-sectional, meaning we were unable to ascertain the direction of the observed associations.
Conclusion:
Sleep problems are associated with sexual dysfunction in older English adults, although some variation is noted between men and women. Smith L, Grabovac I, Veronese N, et al. Sleep Quality, Duration, and Associated Sexual Function at Older Age: Findings From the English Longitudinal Study of Ageing. J Sex Med 2019;16:427-433.
... While serum testosterone levels are low in opioid users (meta-analysis of 17 studies with mean difference = − 164.78 ng/mL, (P < 0.0001)), there is no significant correlation between testosterone level and ED in opioid users [22•, 23, 28, 30, 42, 43]. While numerous studies have shown an association between ED and testosterone levels in the general population, it is worth noting that others have not [44][45][46][47]. ...
Purpose of Review
Opioids are the cornerstone for pain treatment with significant recent increases in the number of prescriptions. Sexual dysfunction (SD) is a major side effect of opioid therapy. The goal of this review is to examine the current literature on the effects of opioids on male SD (erectile dysfunction [ED], hypogonadism, ejaculatory dysfunction) and infertility.
Recent Findings
High prevalence of SD exists in men with opioid use as compared to the general population, with an abundance of evidence suggesting an association between opioid use and ED and hypogonadism. There appears to be a role for testosterone replacement therapy for hypogonadism in men on opioid therapy. Screening for low testosterone levels is recommended in men on opioid therapy with signs and symptoms of androgen deficiency. Data on fertility, ejaculatory, and orgasmic dysfunction are limited.
Summary
SD is significantly affected by opioid therapy in men. Data demonstrate the benefits of screening for SD and treatment for hypogonadism.
... Hypoxia may also result in nocturnal suppression of testosterone release [29]. Several authors have found lower levels of LH and testosterone in men with OSA [10,[30][31][32][33]. ...
Objectives:
To assess the prevalence of OSA in men presenting with ED at a single centre.
Subjects and methods:
All men attending a specialised andrology outpatient department with a new diagnosis of erectile dysfunction were included in this prospective study. All patients completed 3 questionnaires: International Index of Erectile Function (IIEF) and 2 sleep questionnaires. The sleep questionnaires used were the 'OSA screening' questionnaire and the Insomnia severity index'. Their ED management was subsequently undertaken in keeping with local and European guidelines. OSA diagnosis was made based on a score of 3 or more on the OSA screening questionnaire and those patients were referred for specialist management.
Results:
Between February and September 2016, one hundred and twenty-nine men completed the study questionnaires. An OSA score ≥ 3 on the OSA screening questionnaire was found in 55% (n=71) of the patients indicating a need for specialist sleep referral. Men who scored ≥ 3 on the OSA questionnaire were significantly older (61.4yrs vs. 46.5yrs; p<0.001) with a significantly higher BMI (29.4 vs. 26.7; p<0.001) when compared to the control group (OSA <3). The sleep apnoea group (OSA ≥ 3) had significantly worse IIEF-ED scores (6.2 vs. 9.1; p=0.018) and insomnia severity scores (7.9 vs. 5.5; p=0.061).
Conclusion:
Men presenting to the andrology clinic with erectile dysfunction are at significant risk of having undiagnosed sleep disorders. This has serious adverse health consequences as well as being associated with potential dangers at work and travel. The patient compliance was high with 78% completing all 3 questionnaires. It is feasible to screen this population for sleep disturbance and this should be part of the ED assessment. This article is protected by copyright. All rights reserved.
... 6,7 Studies have reported that men with type 2 DM (T2DM) have a high prevalence of LST. 8,9,10 Another complication of diabetes is erectile dysfunction with an estimated prevalence of 20.85% (Ranging from mild to complete ED) which occurs at an earlier age than in nondiabetic men. 11 This study was conducted to determine the prevalence and level of low testosterone level and erectile dysfunction in type 2 DM patients in Indian population. ...
... 4,5 Studies have reported that men with type 2 DM (T2DM) have a high prevalence of LST. 6,7,8 Further, reduced total testosterone (TT) levels have been associated with insulin resistance and subsequent risk for developing T2DM. 9,10 Total testosterone includes both unbound and proteinbound testosterone and is measured by radioimmunoassays or immunometric assays. ...
... Een te laag testosterongehalte kan invloed hebben op ieder van de essentiële fysiologische processen die tot een erectie leiden, zoals de neuronale activiteit ten behoeve van de arteriële bloedtoevoer naar de penis, de relaxatie van de gladde spiercellen van de corpora cavernosa en de veno-occlusie [38]. Ook kan testosteron de initiatie van de erectie beïnvloeden door de secretie van de hersenneurotransmitters te veranderen, zoals dopamine, oxytocine of NO van de mediale preoptische area [39]. ...
In 2012 heeft de Sexual Medicine Society of North America (SMSNA) een commissie ingesteld, die als opdracht had het wetenschappelijk bewijs te onderzoeken voor een pathomechanistische link tussen erectiele disfunctie (ED) en cardiovasculaire metabole ziekten (CVMZ). In deze review doet de commissie verslag van haar bevindingen, na een literatuuronderzoek van vijf betrokken onderdelen van het erectiemechanisme. De commissie constateert dat er verscheidene fundamenteel wetenschappelijke bewijzen zijn, met gemeenschappelijke pathomechanismen, voor de link tussen ED en CVMZ, zoals een disbalans in de stikstofoxideproductie door de endotheelcel met oxidatieve stress, een veranderde moleculaire regulatie van de gladde spieren, autonome neuropathie en een verminderde afgifte van stikstofoxide door de neuronen, een daling van de testosteronspiegel met gevolgen voor de werking ervan, en de toegenomen glycatie met vorming van eindproducten en hyperlipidemie bij metabole ziekten. De commissie benadrukt grote leemten in kennis en doet voorstellen voor verder wetenschappelijk onderzoek naar deze relatie.
... Regarding reproductive toxicity in men, we found that the FAGs and IAGs were significantly enriched in the 'steroid hormone biosynthesis' pathway (P = 7.16×10 -9 ), 'intracellular steroid hormone receptor signaling pathway' (P = 1.24×10 -47 ) and 'androgen receptor signaling pathway' (P = 2.00×10 -44 ). These findings make very important sense, since steroid hormones, specially androgen, are well known to play an fundamental role in maintaining male sexual function [34,35]. Regarding reproductive toxicity in women, we identified two KEGG pathways that were highly enriched with FAGs and IAGs, including 'oocyte meiosis' (P = 1.43×10 -5 ) and 'progesteronemediated oocyte maturation' (P = 3.27×10 -5 ). ...
Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products.
... Hypogonadism can affect any of the critical events of erection, including neuronal activation of arterial flow into the penis, relaxation of the corporal SM, and veno-occlusion [186]. Testosterone can impact the initiation of erections by altering the release of brain neurotransmitters such as dopamine, oxytocin, or NO from the medial preoptic area [187,188]. ...
Introduction:
Although clinical evidence supports an association between cardiovascular/metabolic diseases (CVMD) and erectile dysfunction (ED), scientific evidence for this link is incompletely elucidated.
Aim:
This study aims to provide scientific evidence for the link between CVMD and ED.
Methods:
In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current literature on basic scientific support for a mechanistic link between ED and CVMD, and deficiencies in this regard with a critical assessment of current preclinical models of disease.
Results:
A link exists between ED and CVMD on several grounds: the endothelium (endothelium-derived nitric oxide and oxidative stress imbalance); smooth muscle (SM) (SM abundance and altered molecular regulation of SM contractility); autonomic innervation (autonomic neuropathy and decreased neuronal-derived nitric oxide); hormones (impaired testosterone release and actions); and metabolics (hyperlipidemia, advanced glycation end product formation).
Conclusion:
Basic science evidence supports the link between ED and CVMD. The Committee also highlighted gaps in knowledge and provided recommendations for guiding further scientific study defining this risk relationship. This endeavor serves to develop novel strategic directions for therapeutic interventions. Musicki B, Bella AJ, Bivalacqua TJ, Davies KP, DiSanto ME, Gonzalez-Cadavid NF, Hannan JL, Kim NN, Podlasek CA, Wingard CJ, and Burnett AL. Basic science evidence for the link between erectile dysfunction and cardiometabolic dysfunction. J Sex Med **;**:**-**.
... In male subjects with OSAS, testosterone [225,235] and sex hormone binding protein (SHBG) [225] were found to be reduced, negatively correlated with OSA severity [225,235], also independently from BMI and waist circumference [235], and partially responsive to active treatment of OSA [225]. Several studies [236][237][238] and one review [239] have reported a high prevalence of low serum testosterone in type 2 diabetic men, and reduced testosterone levels have been associated with insulin resistance and subsequent risk of developing type 2 diabetes [240,241]. ...
This review explores the relation between obstructive sleep apnoea syndrome (OSAS) and diabetes. It aims to address the following issues: 1. the epidemiological evidence of the association between OSAS and type 2 diabetes; 2. the independence of this association from the comorbidities shared by the two conditions; 3. the chronological and quantitative characteristics of this association (Which comes first? Is there severity interdependence? Is treatment of one condition able to modify the natural history of the other?); 4. the mechanisms that make interaction plausible; 5. the impact of the OSAS-diabetes relation on micro- and macrovascular diabetic complications. OSAS is common in type 2 diabetes. Despite the association being affected by the confounding action of type 2 diabetes comorbidities (also risk factors for OSAS), it does not seem to be fully attributable to them. There is also a relation between OSAS severity and glucose metabolism alteration. A link between OSAS and insulin resistance appears early, prior to impaired glucose tolerance and the onset of diabetes. Therefore, a debate is ongoing on the pathogenetic role of OSAS in type 2 diabetes development and any consequent relevance to diabetes treatment with no conclusive evidence to date. A multiplicity of hypothetical mechanisms may mediate this relation. Most experimental findings support sympathetic activation and changes in chemoreflex sensitivity based on the interaction between chemoreflex and baroreflex. Some studies suggest bidirectional relationship between OSAS and diabetes, additive or synergistic effects for diabetic complications and a reciprocal enhancement in their impact on hypertension and cardiovascular disease. Clarification of these items could benefit diabetes management and prevention of diabetic cardiovascular complications.
... 14 The cutoff level of testosterone for diagnosis of hypogonadism ranges from , 202 to , 404 ng/dL, and based on these numbers the prevalence of hypogonadism in men with ED varies from 7% to 47%. 15 Given that testosterone levels decrease, and vascular compromise occurs with age, elderly men are more likely to be concurrently diagnosed with ED and hypogonadism. ...
Erectile dysfunction (ED) has emerged as an important marker of cardiovascular and overall health, independent of other known conventional risk factors. ED often precedes coronary artery disease in half of affected subjects, and could indicate the presence of cardiovascular pathology. The pathophysiology and role of androgens in sexual function are described, along with the relevant literature on the effects of aging in erectile and gonadal function. The concept of testosterone supplementation (TST) in men with ED is reviewed. The authors utilize clinical vignettes to discuss the appropriate management of two clinical cases of men at different life stages who have ED in the setting of hypogonadism and propose a treatment algorithm. In patients of all ages, proper identification of the underlying pathophysiology of decreased libido and erectile function is paramount in choosing between the use of TST, phosphodiesterase type 5 inhibitors, or both, in the management of these disorders.
... The European Male Ageing Study (EMAS) found that 30 % of European men experienced ED and two-thirds of them were eugonadal [22]. The prevalence of hypogonadism ranges between 23 and 36 % of ED subjects [25] and varies according to the cut-off value adopted for the diagnosis, 7, 23, 33, or 47 % for testosterone levels of \7, 10.4, 12, or 14 nmol/L, respectively [26]. These figures, however, are simple associations that do not imply any causal association between the two conditions [27]. ...
Context
Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce.
Objective
To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia.
Design
A historical prospective cohort of males with HH.
Patients
Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease.
Results
Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41–347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3 %) men pituitary imaging was normal. Microadenoma was found in 8 (10.7 %), empty sella and thickened pituitary stalk in one patient (1.3 %) each. In other four patients (5.3 %) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies.
Conclusions
This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.
Introduction
The sexual response, including sexual desire and arousal/penile erection in men, is affected by several hormones and neurotransmitters.
Objectives
To give resources to understand the usefulness to assess different hormones when considering a man with hypoactive sexual desire or erectile dysfunction and to provide evidence-based recommendations for clinical practice. A level of evidence grading system was used to provide strong, moderate, or conditional recommendations.
Methods
An extensive revision of the scientific literature was performed by the subcommittee of the International Consultation of Sexual Medicine. The results were first extensively discussed by the sub-committee members and presented publicly for further discussion with other experts. The roles of hypothalamic (kisspeptin, α-melanocyte-stimulating hormone), pituitary (prolactin, oxytocin [OT], and growth hormone), thyroid, adrenal (dehydroepiandrosterone, glucocorticoids, and mineralocorticoids) and sex hormones were considered.
Results
Testosterone has a primary role in controlling and coordinating male sexual desire and arousal, acting at multiple levels. Accordingly, meta-analysis indicates that testosterone therapy for hypogonadal individuals can improve low desire and erectile dysfunction. Hyperprolactinemia is associated with low desire which can be successfully corrected by appropriate treatments. OT, α-melanocyte-stimulating hormone, and kisspeptin are important in eliciting sexual arousal; however, the use of these peptides or their analogs, for stimulating sexual arousal is still under investigation. Evaluation and treatment of other endocrine disorders are suggested only in selected cases.
Conclusions
Endocrine abnormalities are common in patients with sexual dysfunction. The identification of some of these is mandatory (ie, testosterone, prolactin), whereas, for others, it is known that their disorders may cause sexual dysfunction without, however, being frequently recognized in subjects consulting for sexual dysfunction (ie, thyroid and growth hormones). Others may be important, but the clinical use is limited by issues with their measurement (ie, estradiol, dihydrotestosterone), whereas for some hormones or neuropeptides, the clinical usefulness for diagnostic and/or therapeutic purposes should still be established.
The science of penile erection, including recent advances in its molecular physiology and neuroanatomic pathways, is described. The pathophysiology of erectile dysfunction is presented, acknowledging associated disease states, and accordingly follows a practical classification scheme: vasculogenic, neurogenic, endocrine, and psychogenic.
Erectile dysfunction (ED), the inability to obtain or maintain an erection, is a common condition that can have significant psychosocial consequences for patients. Since ED affects both patients and their sexual partners, difficulty with achieving or maintaining an erection can contribute to the development of depression and anxiety that causes ED to worsen. Despite the adverse impacts on quality of life for patients, patients suffering from ED often delay or avoid seeking treatment. ED is important for providers to address for several reasons. In addition to the negative psychosocial consequences of ED, ED can be one of the initial manifestations of vascular disease that increases the risk of myocardial infarction or cerebrovascular accident. Therefore addressing ED can not only improve a patient’s quality of life but also provide an opportunity to address underlying etiologies of ED.
Alcohol and other drugs have actions in limbic-hypothalamic hedonic motivational pathways that subserve basic biological functions including sexual behaviors. They may also have a range of other physiological and psychological effects on sexual function. Psychoactive drugs are often used to facilitate or enhance sexual behaviors, but they can also cause sexual dysfunction. Their use can be associated with risky or harmful sexual behaviors. Pharmacotherapies commonly used in addiction treatment, including opioid pharmacotherapies, sedative/hypnotics, antidepressants, and antipsychotics, can negatively affect sexual function, with implications for treatment adherence and effectiveness. Further, common psychological and physical comorbidities in people with substance use disorders may cause sexual dysfunction. An understanding of these issues can help clinicians working in the field of addiction better to appreciate motivations for continuing or reducing drug use, can inform motivational and harm reduction interventions, and can improve understanding of issues around treatment adherence. While there are challenges for clinicians in speaking about sexuality with their patients, this may be an important part of comprehensive assessment and treatment planning. The clinical benefits of addressing these issues, ranging from reducing sexual risk behavior to improving the quality of life of people receiving pharmacotherapies, can be substantial.
Erectile Dysfunction (ED) can affect males of all age groups and is often associated with an enormous decrease in quality of life. Furthermore, it is recognized as an early indicator of cardiovascular disease. Standard non-invasive therapy of ED encompasses mechanical options and pharmacological treatment with inhibitors of phosphodiesterase-5 (PDE5-i). More invasive options include local application of vasodilating agents and, in refractory cases, operative implantation of a penile prosthesis. Peyronie’s disease (PD) is caused by an inflammatory process of the penile tunica albuginea, resulting in the formation of fibrotic plaques, which may lead to penile deformity. While medical therapy can help to attain symptom relief and early plaque stabilization, different surgical approaches to correct penile curvature exist. A variety of novel treatment alternatives are available for both diseases. The following chapter sums up current treatment algorithms for ED and PD.
Objectives:
To assess the association of Hypoandrogenism (HA) with urethral stricture disease in a series of patients undergoing urethroplasty at two institutions. Hypoandrogenism has recently been associated with increased urethral atophy in artificial sphincter failures and decreased androgen receptors and periurethral vascularity. HA might be an etilogic factor in urethral stricture disease.
Methods:
We reviewed the charts in 202 men with anterior urethral strictures between 2011-2017. We excluded patients with radiation-induced stricture, prior prostatectomy, prior urethroplasty, pelvic fracture-related strictures, or those on testosterone replacement. We defined HA by a total testosterone of less than 300ng/dL. We used as age-matched cohort from a national database (NHANES), as a reference. Stricture characteristics, such as length, location and etiology were compared in HA and eugonadal groups.
Results:
Of 202 men with anterior urethral strictures, we excluded 45. Of the remaining 157 patients, 115 (73%) had preoperative testosterone measurements. Overall, hypoandrogenism (HA) was found in 65/115 (57 %) men in the urethral stricture group compared 28% of age matched men in the national database. Mean stricture length in HA and eugonadal men was 7.2 cm and 4.8 cm, respectively (p=0.02).
Conclusions:
HA may be more prevalent and associated with increased disease severity in men with anterior urethral strictures. The relationship between HA and stricture formation and its potential impact on therapeutic outcomes merit further prospective investigation.
The focus of this article, the fourth in the series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, is on aspects of clinical trial design and measurement that are specific to clinical trials for treatments of female sexual dysfunction. Challenges in this area include the limited extent of treatment development and clinical trial research across the spectrum of female sexual dysfunctions, changing regulatory considerations, changing diagnostic criteria for female sexual dysfunction, and the need to articulate assessment procedures to these changes. Discussion focuses on approaches to addressing these challenges in clinical trials in female sexual dysfunction.
This series of articles, Standards for Clinical Trials in Male and Female Sexual Dysfunction, began with the discussion of a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for the selection of study population and study duration in male and female sexual dysfunction. The second article in this series discussed fundamental principles in development, validation, and selection of patient- (and partner-) reported outcome assessment. The third and present article in this series discusses selected aspects of sexual dysfunction that are that are unique to male sexual dysfunctions and relevant to the conduct of clinical trials of candidate treatments for men.
Significant controversy currently exists regarding the evaluation and treatment of hypogonadism, especially in the setting of erectile dysfunction. Testosterone replacement therapy improves libido, but research supporting its role for improving erectile function is less clear. Despite the controversy and limitations in the literature, there is a role for hormonal evaluation in patients with sexual dysfunction and hormone replacement in selected patients with hypogonadism. Most recommendations support screening men with erectile dysfunction for hypogonadism, particularly among those men presenting with any additional hypogonadal symptoms. Men with very low testosterone or younger men may be initially treated with testosterone replacement therapy to improve erectile function. Eugonadal men with erectile dysfunction should not be treated with testosterone.
Despite a lack of evidence, there have been stated concerns that testosterone replacement therapy (TRT) can pose a risk to men suffering with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). TRT may improve components of the metabolic syndrome, which is associated with worsening LUTS. Furthermore, the evidence suggests that TRT may decrease prostatic inflammation, which is also associated with worsening LUTS. The data on the relationship between TRT and LUTS have never shown worsening of LUTS, often show no change in LUTS, and occasionally show improvement.
Nutraceutical is a broad term describing foods, food ingredients, and dietary supplements that provide specific health or medical benefits, in addition to the basic nutritional value found in the food. The use of nutraceuticals is increasing dramatically for reproductive disorders because there is growing evidence of clinical benefits. They are becoming more popular when traditional therapies of reproductive disorders have not been very effective due to many underlying conditions, nutritional deficiencies, and the responsiveness of traditional therapy. Many medically important nutraceuticals including nutritional supplements, vitamins, and antioxidants have been shown to improve reproductive performance and to be effective in treating reproductive senescence of aging and infertility in humans. Despite the success, most nutraceuticals have not been scientifically studied and validated for their efficacy. Many expanding spectra of nutraceuticals exist, but the mechanisms of action, indications, contraindications, adverse effects, and evidential support vary with the product and species. It is difficult to discuss the scientific behaviors of all nutraceutical products used in reproductive and developmental disorder. This chapter described the role of nutraceuticals in human infertility, endocrine disorders, pubertal development, and success of pregnancy and lactation.
Alcohol and other drugs have actions in limbic-hypothalamic hedonic motivational pathways that normally subserve basic biological functions including sexual behaviors. They may also have a range of other physiological and psychological effects on sexual function.
Psychoactive drugs are often used to facilitate or enhance sexual behaviors, but they can also cause sexual dysfunction. Their use can be associated with risky or harmful sexual behaviors.
Pharmacotherapies commonly used in addiction treatment, including opioid pharmacotherapies, sedative/hypnotics, antidepressants, and antipsychotics, can negatively affect sexual function, with implications for treatment adherence and effectiveness. Further, common psychological and physical comorbidities in people with substance use disorders may cause sexual dysfunction.
An understanding of these issues can help clinicians working in the field of addiction better to appreciate motivations for continuing or reducing drug use, can inform motivational and harm reduction interventions, and can improve understanding of issues around treatment adherence. While there are challenges for clinicians in speaking about sexuality with their patients, they are an important part of comprehensive assessment and treatment planning. The clinical benefits of addressing these issues, ranging from reducing sexual risk behavior to improving quality of life of people receiving pharmacotherapies, can be substantial.
Introduction
Several hormones and neurotransmitters orchestrate men’s sexual response, including the appetitive (sexual desire) and consummative (arousal and penile erection) phases.
Aim
To provide an overview and recommendations regarding endocrinologic control of sexual desire and arousal and erection and their disturbances.
Methods
Medical literature was reviewed by the subcommittee of the International Consultation of Sexual Medicine, followed by extensive internal discussion, and then public presentation and discussion with other experts. The role of pituitary (prolactin, oxytocin, growth hormone, and α-melanocyte-stimulating hormone), thyroid, and testicular hormones was scrutinized and discussed.
Main Outcome Measures
Recommendations were based on grading of evidence-based medical literature, followed by interactive discussion.
Results
Testosterone has a primary role in controlling and synchronizing male sexual desire and arousal, acting at multiple levels. Accordingly, meta-analysis indicates that testosterone therapy for hypogonadal individuals can improve low desire and erectile dysfunction. Hyperprolactinemia is associated with low desire that can be successfully corrected by appropriate treatments. Oxytocin and α-melanocyte-stimulating hormone are important in eliciting sexual arousal; however, use of these peptides, or their analogs, for stimulating sexual arousal is still under investigation. Evaluation and treatment of other endocrine disorders are suggested only in selected cases.
Conclusion
Endocrine abnormalities are common in patients with sexual dysfunction. Their identification and treatment is strongly encouraged in disturbances of sexual desire and arousal.
Introduction:
Erectile dysfunction (ED) has been identified as the most common sexual problem that affects mainly men older than 40 years. According to this, there is a strong evidence linking ED with a number of medical conditions and related risk factors that had been described in the literature, yet there is limited information about the specific mechanism involved in the establishment of ED among healthy older men.
Aim:
The purpose of this study is to review the literature and mainly focus on the basic physiologic and vascular alterations and morphologic changes related to aging and its related risk factors, summarizing the main and the latest findings in basic research of tissue remodeling process involved in ED pathophysiology.
Methods:
Data from the pertinent literature were examined to inform our conclusions.
Main outcome measure:
This article defines the morphologic and physiologic mechanisms involved in the process of aging, which play a key role in the development of sexual dysfunction.
Results:
ED has been considered as a nonlife-threatening condition, but the recognition of its multiple comorbid conditions, the importance of aging process over the male sexual performance among them its relation with vascular and nitric oxide content alteration, as well as penile morphologic changes, and the fact that it is a widespread under-reported disease, have established the need of an early diagnosis and treatment of this common sexual problem within the general male population.
Conclusion:
In this case, morphologic and physiologic mechanisms that are involved in the aging process play a key role in the development of sexual dysfunction in the absence of any other clinical or medical condition.
Objectives:
To identify clinical predictors of testosterone deficiency (TD) in men with erectile dysfunction (ED), thereby identifying subgroups that are most likely to benefit from targeted testosterone screening.
Methods:
Retrospective review was conducted of 498 men evaluated for ED between 1/2013 and 7/2014. Testing for TD by early morning serum measurement was offered to all eligible men. Patients with history of prostate cancer or testosterone replacement were excluded. Univariable linear regression was conducted to analyze 19 clinical variables for associations with serum TT, calculated free testosterone (cFT), and TD (T < 300 ng/dL or cFT < 6.5 ng/dL). Variables significant on univariable analysis were included in multiple regression models.
Results:
225 men met inclusion criteria. Lower TT levels were associated with greater BMI, less frequent sexual activity, and absence of clinical depression on multiple regression analysis. TT decreased by 49.5 ng/dL for each 5 point increase in BMI. BMI and age were the only independent predictors of cFT levels on multivariable analysis. Overall 62 subjects (27.6%) met criteria for TD. Older age, greater BMI, and less frequent sexual activity were the only independent predictors of TD on multiple regression. We observed a 2.2-fold increase in the odds of TD for every 5 point increase in BMI, and a 1.8-fold increase for every 10 year increase in age.
Conclusions:
Men with ED and elevated BMI, advanced age, and/or infrequent sexual activity appear to be at high risk of TD, and such patients represent excellent potential candidates for targeted testosterone screening.
Erectile dysfunction (ED) is a multifactorial disorder, and several emotional, physical and medical factors contribute to the degree of dysfunction that significantly impairs the patient and partner's quality of life, having a detrimental effect on sexual and reproductive activity. A recent analysis of all population-based studies conducted in the USA indicates that ED is indeed the most common endocrine disorder in men (Golden et al. 2009). A European survey shows that ED affects almost 30% of men in an age-dependent manner (Corona et al. 2010a). In 1993, the NIH Consensus Development Panel on Impotence defined ED as “the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance” (NIH Consensus Conference 1993). Penile erection is a neurovascular event that can be seen as an integrated feed-forward interaction within a biological dimension (with its cardiovascular, neuronal and hormonal determinants), an intrapsychic dimension (the individual's sexual identity and sense of well-being), and a marital dimension (the context for a sexual relationship). In each ED patient, biological, psychological and lifestyle factors are simultaneously present and mutually interacting (Petrone et al. 2003). In other words, ED is a frustrating symptom deriving from a continuous spectrum of clinical pictures including physical illness (organic component of ED), reaction to life stresses (intrapsychic component of ED) or an unhappy couple relationship (relational component of ED) (Petrone et al. 2003). We strongly believe that the male hormone, testosterone, plays a relevant role in determining perturbations in all three aforementioned dimensions of ED (organic, intrapsychic and relational).
IntroductionSexual dysfunction is an under-recognized problem in men and women with obstructive sleep apnea (OSA). Epidemiologic findings were inconclusive regarding the risk for sexual dysfunction associated with OSA.AimThe aim of this study was to examine the association between OSA and sexual dysfunction.Methods
The PubMed, Cochrane Library, and Embase databases were searched for observational studies on the OSA and the risk of sexual dysfunction. The methodologic quality of the case–control and cohort studies was assessed with Newcastle–Ottawa Scale (NOS). The cross-sectional study quality methodology checklist was used for cross-sectional study. Data were pooled for the random-effects model. Sensitivity analyses were conducted to assess potential bias.Main Outcome MeasureThe association between OSA and sexual dysfunction was summarized using relative risk (RR) with a 95% confidence interval (CI).ResultsThis meta-analysis included 1,275 participants from nine studies. Five studies reported the incidence of erectile dysfunction (ED); the remaining four studies reported the incidence of female sexual dysfunction (FSD). Pooled results demonstrated that OSA was associated with increased risk of ED (pooled RR = 1.82, 95% CI: 1.12–2.97) as well as FSD (pooled RR = 2.00, 95% CI: 1.29–3.08). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed.Conclusions
Evidence from the observational studies suggested that OSA individuals might have an increased incidence of sexual dysfunction despite significant heterogeneity. More researches are warranted to clarify the relationship between OSA and the increased risk of sexual dysfunction. Liu L, Kang R, Zhao S, Zhang T, Zhu W, Li E, Li F, Wan S, and Zhao Z. Sexual dysfunction in patients with obstructive sleep apnea: A systematic review and meta-analysis. J Sex Med **;**:**–**.
Sexual dysfunction is a highly prevalent, but often underdiagnosed condition affecting both men and women. It is recognized that risk factors for erectile dysfunction (ED) include diabetes mellitus, increasing age, cardiovascular disease, tobacco use, and decreased physical activity. Therefore, sexual dysfunction can be a sign and symptom of possible underlying disease and pathology-penile health reflects overall health. Beyond the obvious impact sexual dysfunction can have on an individual personally, emotionally, and socially, this dysfunction can be viewed as an opportunity to address even greater co-morbid disease. Sexual dysfunction in men includes ED, problems with ejaculation including premature ejaculation (PE) and anejaculation, anorgasmia, decreased libido, hypogonadism, and sexual pain disorders. Female sexual dysfunction (FSD) includes disorders of sexual desire, disorders of sexual arousal, and sexual pain. In comparison, the female sexual response is still not completely understood or agreed upon. Although similarities exist in the physiology and pathophysiology of male and female sexual function, the differences help explain why finding effective treatments for women pose such a challenge. Female sexuality is much less well understood, in part because of the emotional and psychological influences on the female sexual response. Pharmacotherapy, growth factor therapy, gene therapy, and regenerative medicine exist as the exciting therapeutic advances in development. It is with these novel new approaches to the treatment of sexual dysfunction under investigation that we are hopeful for improved future success and cure.
The physiology of testosterone production and action are closely related to prostatic disease. An understanding of the natural history of testosterone and prostate growth and development is needed in order to understand this complex relationship. Lower urinary tract symptoms (LUTS), benign prostatic hyperplasia (BPH), prostate cancer, and sexual function are common disorders for which testosterone is thought to play a role. Proposed in this review are some theories as to how testosterone interacts to potentially ameliorate these conditions. Further research is needed, but we feel our proposed points are valid given the review of the literature.
Description: The American College of Physicians developed this guideline to present the available evidence on hormonal testing in and pharmacologic management of erectile dysfunction. Current pharmacologic therapies include phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, vardenafil, tadalafil, mirodenafil, and udenafil, and hormonal treatment. Methods: Published literature on this topic was identified by using MEDLINE (1966 to May 2007), EMBASE (1980 to week 22 of 2007), Cochrane Central Register of Controlled Trials (second quarter of 2007), PsyclNFO (1985 to June 2007), AMED (1985 to June 2007), and SCOPUS (2006). The literature search was updated by searching for articles in MEDLINE and EMBASE published between May 2007 and April 2009. Searches were limited to English-language publications. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system. Recommendation 1: The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use (Grade: strong recommendation; high-quality evidence). Recommendation 2: The American College of Physicians recommends that clinicians base the choice of a specific PDE-5 inhibitor on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile (Grade: weak recommendation; low-quality evidence). Recommendation 3: The American College of Physicians does not recommend for or against routine use of hormonal blood tests or hormonal treatment in the management of patients with erectile dysfunction (Grade: insufficient evidence to determine net benefits and harms).
This study summarizes the literature on the prevalence, incidence, and proportion of patients receiving treatment for male hypogonadism and a systematic literature search was performed for articles published in the last 20 years. Of the 97 studies identified, 96 examined the prevalence, 2 examined the incidence, and 4 examined the proportion of males with hypogonadism patients receiving treatment. Based on studies conducted in Europe and USA, the prevalence of hypogonadism in the general population ranged from 2.1% to 12.8% of middle-aged to older men, with an estimated incidence of 12 new cases per 1,000 person-years. Prevalence was higher among patients with comorbid conditions, such as type 2 diabetes mellitus and obesity. Approximately 10-12% of men with hypogonadism were receiving testosterone treatment. This literature review suggests that there is potentially a significant burden of hypogonadism in the general population. Burden seems to increase with age and in the presence of certain disease conditions. Data suggests that many hypogonadal men who may benefit from testosterone replacement are not receiving treatment. This may be the result of underdiagnosis of the disease, lack of awareness by patients or physicians, irregularities surrounding the diagnostic criteria, and deficiency of long-term safety studies.
Description: The American College of Physicians developed this guideline to present the available evidence on hormonal testing in and pharmacologic management of erectile dysfunction. Current pharmacologic therapies include phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, vardenafil, tadalafil, mirodenafil, and udenafil, and hormonal treatment. Methods: Published literature on this topic was identified by using MEDLINE (1966 to May 2007), EMBASE (1980 to week 22 of 2007), Cochrane Central Register of Controlled Trials (second quarter of 2007), PsycINFO (1985 to June 2007), AMED (1985 to June 2007), and SCOPUS (2006). The literature search was updated by searching for articles in MEDLINE and EMBASE published between May 2007 and April 2009. Searches were limited to English-language publications. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system. Recommendation 1: The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use (Grade: strong recommendation; high-quality evidence). Recommendation 2: The American College of Physicians recommends that clinicians base the choice of a specific PDE-5 inhibitor on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile (Grade: weak recommendation; low-quality evidence). Recommendation 3: The American College of Physicians does not recommend for or against routine use of hormonal blood tests or hormonal treatment in the management of patients with erectile dysfunction (Grade: insufficient evidence to determine net benefits and harms).
To evaluate, posthoc, the relationship between serum total testosterone and response to therapy in a study of tadalafil once daily for erectile dysfunction (ED).
Men were aged ≥18 years, with ≥3-month history of ED and partial prior response to on-demand (PRN) phosphodiesterase type 5 inhibitor (PDE5I) therapy. A 4-week maximum-dose PRN PDE5I run-in was followed by a 4-week nondrug washout period, then randomization to tadalafil 2.5 mg titrated to 5 mg or tadalafil 5 mg (pooled for analyses) or placebo once daily for 12 weeks. Analyses compared endpoint efficacy results between low- (<300 ng/dL) vs normal-testosterone (≥300 ng/dL) level subgroups.
Improvements for tadalafil vs placebo were significant for the International Index of Erectile Function (IIEF) Erectile Function domain, Intercourse Satisfaction domain, Overall Satisfaction domain, and Question 15 (confidence in the ability to get and keep an erection; all P <.001), and for the Sexual Encounter Profile Questions 1-5 (all P ≤.011). Analysis of covariance modeling identified significant treatment-by-subgroup interactions for the IIEF-Overall Satisfaction domain and erection confidence question and Sexual Encounter Profile Question 3. Comparing between tadalafil-treated testosterone subgroups, the IIEF-Erectile Function domain scores improved significantly more in men with normal vs low testosterone (P = .022); no other significant differences were identified for either placebo or tadalafil. No significant differences in pre-existing conditions were observed between tadalafil and placebo within the normal- and low-testosterone subgroups.
In men with partial response to a PRN PDE5I, tadalafil 5 mg once daily significantly improved ED and sexual function vs placebo irrespective of testosterone levels.
A high prevalence of low serum testosterone (LST) in men with type 2 diabetes have been reported worldwide. The aim of this study was to determine the prevalence and associated factors of LST in men with type 2 diabetes.
This was a cross-sectional study, conducted among 1,089 men (aged 30-70 years) with type 2 diabetes who consecutively attended a major diabetes center in Amman, Jordan, between August 2008 and February 2009. The patients' demographic characteristics were collected using a prestructured questionnaire. Duration of diabetes, smoking habits, presence of retinopathy, neuropathy, and nephropathy were collected from the medical records. All participants were asked to complete the Androgen Deficiency in Ageing Male (ADAM) questionnaire. Venous blood sample was collected to test for total testosterone (TT), free testosterone (FT), sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), serum lipids, and glycosylated hemoglobin (HbA1c). LST was defined as TT <3 ng/ml.
Overall, 36.5% of patients with diabetes had TT level <3 ng/ml and 29% had symptoms of androgen deficiency. Of those with serum testosterone level <3 ng/ml, 80.2% had symptoms of androgen deficiency, 16.9% had primary hypogonadism (HG), and 83.1% had secondary HG. Univariate analysis showed a significant relationship between age, income, education, body mass index (BMI), smoking, duration of diabetes, diabetic nephropathy, diabetic neuropathy, and HbA1c. Multivariate logistic regression analysis indicated age, income, BMI, and diabetic neuropathy as the independent risk factors of LST.
The prevalence of LST among men with type 2 diabetes is high. Age, income, BMI, and diabetic neuropathy were found to be the independent risk factors for LST.
Little is known about the descriptive epidemiology of androgen deficiency. In this study, we sought to address this issue by providing estimates of the crude and age-specific prevalence and incidence rates of androgen deficiency in a randomly sampled population-based cohort of middle-aged and older men. Data on androgen deficiency (defined using both signs/symptoms plus total and calculated free testosterone) were available for n = 1691 (baseline) and n = 1087 (follow-up) men from the Massachusetts Male Aging Study. Crude and age-specific prevalence and incidence rates were calculated. Based on these estimates, projections for the number of cases of androgen deficiency in the 40- to 69-yr-old U.S. male population were computed. Estimates of the crude prevalence of androgen deficiency at baseline and follow-up were 6.0 and 12.3%, respectively. Prevalence increased significantly with age. From baseline age-specific prevalence data, it is estimated that there are approximately 2.4 million 40- to 69-yr-old U.S. males with androgen deficiency. The crude incidence rate of androgen deficiency was 12.3 per 1,000 person-years, and the rate increased significantly (P < 0.0001) with age. Based on these incidence data, we can expect approximately 481,000 new cases of androgen deficiency per year in U.S. men 40-69 yr old.
The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men.
The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer. The Task Force received no corporate funding or remuneration.
The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group.
Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications. The drafts prepared by the panelists with the help of a professional writer were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Committee, and Council. The version approved by the Council was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes.
We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and in some patients by measurement of free or bioavailable testosterone level, using accurate assays. We recommend testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 3 ng/ml without further urological evaluation, erythrocytosis (hematocrit > 50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) greater than 19, or class III or IV heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.
To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a population-based cross-sectional survey of men aged 39-70 yr conducted in 1986-89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39-70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5 alpha-dihydrotestosterone remained essentially constant between ages 39-70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2-3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10-15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2.(ABSTRACT TRUNCATED AT 400 WORDS)
The relation of the reproductive endocrine system to impotence in older men was examined by measuring the concentrations of testosterone (T), bioavailable testosterone (BT), LH, and PRL and body mass index (BMI) in 57 young controls (YC), 50 healthy potent older controls attending a health fair (HF), and 267 impotent patients (SD). The SD and HF had markedly reduced mean T and BT values compared to YC. When adjusted for age and BMI there was no difference in BT between potent and impotent older men. The percent BT was much higher in YC than in the older groups. While the percent BT rose significantly with increased T in YC, it was inversely related to T in the older subjects, suggesting that increased sex hormone-binding globulin binding was a primary event leading to a low BT. Forty-eight percent of HF and 39% of SD were hypogonadal, as defined by a mean BT of 2.5 SD or more below the mean of YC (less than or equal to 2.3 nmol/L). Ninety percent of these had LH values in the normal range, suggesting hypothalamic-pituitary dysfunction. Thirty-four SD and six each of YC and older control volunteers (OC) underwent GnRH testing. Older subjects showed impaired responsiveness to GnRH compared to YC. A low basal LH level correlated very highly with hyporesponsiveness to GnRH. Thus, secondary hypogonadism and impotence are two common, independently distributed conditions of older men.
We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities.
Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia.
Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml.
Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.
A progressive decrease in androgen production is common in males after middle age. The resulting clinical picture has been erroneously named male menopause or andropause. A more appropriate designation is androgen decline in the aging male (ADAM). The syndrome is characterized by alterations in the physical and intellectual domains that correlate with and can be corrected by manipulation of the androgen milieu. We review the epidemiological aspects of aging and endocrinological manifestations of ADAM, and provide recommendations for treatment and monitoring of these patients.
We performed MEDLINE, Pubmed, Current Contents and Pharmaceutical Abstracts searches of relevant peer reviewed publications on andropause, male climacteric, adult hypogonadism and aging. In addition, conference proceedings were researched to provide a more complete review of the literature. Information was scrutinized and collated, and contributory data were reviewed and summarized.
ADAM is a clinical entity characterized biochemically by a decrease not only in serum androgen, but also in other hormones, such as growth hormone, melatonin and dehydroepiandrosterone. Clinical manifestations include fatigue, depression, decreased libido, erectile dysfunction, and alterations in mood and cognition.
The onset of ADAM is unpredictable and its manifestations are subtle and variable, which has led to a paucity of interest in its diagnosis and treatment. Urological practice commonly includes a large proportion of men older than 50 years. Therefore, it is important for urologists to recognize the manifestations of and be familiar with evaluations necessary to document ADAM as well as its treatment and monitoring.
To our knowledge a causal relationship between altered levels of androgens and erectile dysfunction has not yet been established. We reviewed the literature to assess the usefulness of androgen replacement for erectile dysfunction.
Meta-analysis was chosen as the method of evaluating the literature. Study inclusion criteria were testosterone given as the only therapy for erectile dysfunction and a clearly stated definition of response for evaluating treatment success or failure.
We evaluated 73 articles obtained by a MEDLINE search of 1966 to 1998 and included 16 in our study. The overall response rate was 57%. In the 9 series with response rate by etiology patients with primary versus secondary testicular failure had a response rate of 64% versus 44% (p <0.001). Intramuscular and oral methods of delivery were equivalent with a response rate of 51.3% and 53.2%, respectively. However, the response to transdermal therapy was significantly different from that of intramuscular and oral treatment (80.9% versus 51.3% and 53.2%, respectively, p <0.001). The mean confidence level response for testosterone treatment was 16. 7% in the placebo and 65.4% in the treated group (p <0.0001).
Our meta-analysis of the usefulness of androgen replacement therapy for erectile dysfunction indicates that the response rate for a primary etiology was improved over that for a secondary etiology, transdermal testosterone therapy was more effective than intramuscular or oral treatment, and intramuscular and oral treatments were equivalent. In addition, there was a statistically significant difference in favor of testosterone over placebo, implying a role for supplementation in select groups.
Transdermal delivery of testosterone (T) represents an effective alternative to injectable androgens. Transdermal T patches normalize serum T levels and reverse the symptoms of androgen deficiency in hypogonadal men. However, the acceptance of the closed system T patches has been limited by skin irritation and/or lack of adherence. T gels have been proposed as delivery modes that minimize these problems. In this study we examined the pharmacokinetic profiles after 1, 30, 90, and 180 days of daily application of 2 doses of T gel (50 and 100 mg T in 5 and 10 g gel, delivering 5 and 10 mg T/day, respectively) and a permeation-enhanced T patch (2 patches delivering 5 mg T/day) in 227 hypogonadal men. This new 1% hydroalcoholic T gel formulation when applied to the upper arms, shoulders, and abdomen dried within a few minutes, and about 9-14% of the T applied was bioavailable. After 90 days of T gel treatment, the dose was titrated up (50 mg to 75 mg) or down (100 mg to 75 mg) if the preapplication serum T levels were outside the normal adult male range. Serum T rose rapidly into the normal adult male range on day 1 with the first T gel or patch application. Our previous study showed that steady state T levels were achieved 48-72 h after first application of the gel. The pharmacokinetic parameters for serum total and free T were very similar on days 30, 90, and 180 in all treatment groups. After repeated daily application of the T formulations for 180 days, the average serum T level over the 24-h sampling period (C(avg)) was highest in the 100 mg T gel group (1.4- and 1.9-fold higher than the C(avg) in the 50 mg T gel and T patch groups, respectively). Mean serum steady state T levels remained stable over the 180 days of T gel application. Upward dose adjustment from T gel 50 to 75 mg/day did not significantly increase the C(avg), whereas downward dose adjustment from 100 to 75 mg/day reduced serum T levels to the normal range for most patients. Serum free T levels paralleled those of serum total T, and the percent free T was not changed with transdermal T preparations. The serum dihydrotestosterone C(avg) rose 1.3-fold above baseline after T patch application, but was more significantly increased by 3.6- and 4.6-fold with T gel 50 and 100 mg/day, respectively, resulting in a small, but significant, increase in the serum dihydrotestosterone/T ratios in the two T gel groups. Serum estradiol rose, and serum LH and FSH levels were suppressed proportionately with serum T in all study groups; serum sex hormone-binding globulin showed small decreases that were significant only in the 100 mg T gel group. We conclude that transdermal T gel application can efficiently and rapidly increase serum T and free T levels in hypogonadal men to within the normal range. Transdermal T gel provided flexibility in dosing with little skin irritation and a low discontinuation rate.
We evaluate the prevalence of laboratory abnormalities in men presenting for initial evaluation and therapy of erectile dysfunction.
The computerized charts of men receiving treatment for erectile dysfunction from 1987 to 2002 were retrospectively reviewed. We pooled laboratory data for 3,547 men with erectile dysfunction to assess the prevalence of laboratory abnormalities. Values of the common laboratory screening tests for erectile dysfunction were recorded for testosterone, prolactin, luteinizing hormone, thyroid-stimulating hormone, hemoglobin A(Ic), prostate specific antigen, hemoglobin, cholesterol and creatinine.
Of those patients evaluated 18.7% had low testosterone, 4.6% had increased prolactin, 14.6% had abnormal luteinizing hormone, 4.0% had increased thyroid-stimulating hormone, 8.3% had increased prostate specific antigen, 26.5% had anemia and 11.9% tested had renal insufficiency. A high percentage of patients presenting with a primary complaint of erectile dysfunction had increased hemoglobin A(Ic) and total serum cholesterol levels (52.9% and 48.4%, respectively).
An evidence based approach to standardization of laboratory evaluations for men presenting with erectile dysfunction is recommended. Laboratory screening should be directed to identify those risk factors that may benefit from lifestyle modification and pharmacological intervention.
Metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia and hypertension, is highly prevalent in the United States. When left untreated, it significantly increases the risk of diabetes mellitus and cardiovascular disease. It has been suggested that hypogonadism may be an additional component of metabolic syndrome. This has potential implications for the treatment of metabolic syndrome with testosterone. We reviewed the available literature on metabolic syndrome and hypogonadism with a particular focus on testosterone therapy.
A comprehensive MEDLINE review of the world literature from 1988 to 2004 on hypogonadism, testosterone and metabolic syndrome was performed.
Observational data suggest that metabolic syndrome is strongly associated with hypogonadism in men. Multiple interventional studies have shown that exogenous testosterone has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure, which are the parameters most often disturbed in metabolic syndrome.
Hypogonadism is likely a fundamental component of metabolic syndrome. Testosterone therapy may not only treat hypogonadism, but may also have tremendous potential to slow or halt the progression from metabolic syndrome to overt diabetes or cardiovascular disease via beneficial effects on insulin regulation, lipid profile and blood pressure. Furthermore, the use of testosterone to treat metabolic syndrome may also lead to the prevention of urological complications commonly associated with these chronic disease states, such as neurogenic bladder and erectile dysfunction. Physicians must be mindful to evaluate hypogonadism in all men diagnosed with metabolic syndrome as well as metabolic syndrome in all men diagnosed with hypogonadism. Future research in the form of randomized clinical trials should focus on further defining the role of testosterone for metabolic syndrome.
Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. The demographics clearly demonstrate the increasing percentage of the population that is in the older age groups. The data also support the concept that testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adults (age 20-30 years) men. The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment on multiple target organs of hypogonadal men and recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. Long-term data on the effects of testosterone treatment in the older population are limited and specific risk data on the prostate and cardiovascular systems are needed. Answers to key questions of functional benefits that may retard frailty of the elderly are not yet available.
A review of the currently published data indicates that testosterone replacement therapy in older men may be advantageous in terms of improving bone mineral density, increasing muscle mass and strength, and, in some men, improving libido and mood. However, the long-term clinical significance of these effects is still uncertain, as larger and longer-term studies are needed. In the short term (up to 3 years), the adverse effects of testosterone replacement therapy in older men seem predictable and manageable, but the longer-term effects on target organs, such as the cardiovascular system and the prostate, are yet to be determined.
Although attention and concern about health disorders in aging men have been growing, the structure of psychological and somatic complaints of actual patients, not population-based cohorts, has not been elucidated in relation to sex hormone patterns and metabolism.
The objective of the study was investigation of factors influencing complaint structures in aging male patients.
This was a cross-sectional cohort study.
The study was conducted in an andrological outpatient department.
Subjects included 434 consecutive male patients aged 50-86 yr.
The following hypotheses were measured: 1) psychosomatic complaints and metabolic factors in aging male patients are related to sex hormone levels in a symptom-specific manner, and 2) patients form subcohorts.
A clear-cut threshold for late-onset hypogonadism was not found; rather, prevalence of psychosomatic symptoms and metabolic risk factors accumulated with decreasing androgen levels. For example, androgen-induced prevalence of loss of libido or vigor increased below testosterone concentrations of 15 nmol/liter (P < 0.001), whereas depression and diabetes mellitus type 2 (also in nonobese men) were significantly more present in men with testosterone concentrations below 10 nmol/liter (P < 0.001). Erectile dysfunction was identified as a composite pathology of metabolic risk factors, smoking, and depressivity, whereas only testosterone concentrations below 8 nmol/liter contributed to that symptom (P = 0.003). Cluster analysis revealed aging men to present within three independent groups characterized by psychosomatic complaints, metabolic disorders, and sexual health problems. These subgroups of patients exhibit distinct features in terms of androgen levels, age, and body mass index.
There is no evidence that a uniform structure of testosterone concentrations and complaints exists within the cohort of elderly male patients. Rather, in aging male patients, psychosomatic complaints and metabolic risk relate to testosterone in a symptom-specific manner.
The prevalence of erectile dysfunction increases as men age. Simultaneously, age related changes occur in male endocrine functioning. We examined the association between erectile dysfunction and total testosterone, bioavailable testosterone, sex hormone-binding globulin and luteinizing hormone.
Data were obtained from the Massachusetts Male Aging Study, a population based cohort study of 1,709 men. Self-reported erectile dysfunction was dichotomized as moderate or severe vs none or mild. Odds ratios and 95% CI were used to assess the association between sex hormone levels and erectile dysfunction. Multiple logistic regression models were used to adjust for potential confounders including age, body mass index, partner availability, phosphodiesterase type 5 inhibitor use, depression, diabetes and heart disease.
Using data from the most recent followup, analyses were conducted on 625 men with complete data. A moderate decrease in erectile dysfunction risk was observed with increasing total testosterone and bioavailable testosterone levels. However, this effect was not apparent after controlling for potential confounders. Increased luteinizing hormone levels (8 IU/l or greater) were associated with a higher risk of erectile dysfunction (adjusted OR 2.91, 95% CI 1.55-5.48) compared to luteinizing hormone levels less than 6 IU/l. A significant interaction between luteinizing hormone and total testosterone levels showed that increased testosterone levels were associated with a decrease in risk of erectile dysfunction among men with luteinizing hormone levels greater than 6 IU/l.
In this large population based cohort of older men we found no association among total testosterone, bioavailable testosterone, sex hormone-binding globulin and erectile dysfunction. Testosterone levels were associated with a decrease in risk of erectile dysfunction only in men with increased luteinizing hormone levels.
R: a language and environment for statistical computing. R Foundation for Statistical Computing Available from
- R Development
- Core Team
R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2006. Available from: http://www.R-project.org. Accessed October 3, 2007.
Diurnal serum testosterone variation in aging men: cross-sectional analysis from a large national screening program reveals only a modest decline beginning in the mid-afternoon
- O C Donnell
- A Morgentaler
Crawford ED, O'Donnell C, Morgentaler A, et al: Diurnal serum testosterone variation in aging men: cross-sectional analysis from a large national screening program reveals only a modest decline beginning in the mid-afternoon. Presented at the 2006 Annual Meeting of the American Urological Association, Atlanta, GA, May 20 –25, 2006 (poster).
Testosterone replacement therapy for male aging: ASA position statement
Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations
- Nieschlag