Clinical trial of treatment with saikokaryukotsuboreito for eugonadal patients with late-inset hypogonadism-related symptoms

The purpose of this study was to evaluate the efficacy and safety of saikokaryukotsuboreito (SKRBT), which is widely used for a variety of clinical conditions, neuropsychiatric disorders, for patients with LOH-related symptoms. Twenty-two eugonadal patients over 40 years of age with LOH-related symptoms were included in this study. SKRBT was given orally to these patients three times daily to a total of 7.5 g/day for more than two months. Laboratory and endocrinological profiles were reviewed, and LOH symptoms were judged by means of several health assessment instruments such as the Aging Males' Symptoms (AMS) scale, Self-rated Depression Scale (SDS), International Prostate Symptom Score (IPSS), and King's Health Questionnaire (KHQ). Total AMS scores and AMS subscores were significantly decreased after the treatment. The KHQ, general health perception and impact on life scores were also significantly decreased, although no significant improvement was observed in other KHQ factors or the SDS score or IPSS. The serum concentrations of testosterone fractions did not change with treatment. Laboratory values did not change, and no adverse effects were identified after treatment. We conclude that SKRBT may be considered for treatment of patients with LOH-related symptoms for eugonadal patients.     

Symptomatic change in Japanese hypogonadal patients several years after androgen replacement therapy

Objective.?There are few reports on the prognosis of patients receiving androgen replacement therapy (ART). In this study, we evaluated the subsequent symptoms of Japanese hypogonadal patients who had received ART, within several years previously by mail-in survey.

Methods.?Thirty-three aged men with symptoms of hypogonadism and testosterone deficiency who had received ART for 6 months responded to this survey. The survey consisted of questions associated with present physical and mental status and desire to resume ART. The Aging male’s symptoms (AMS) scale, IIEF-5 and SF-36 were also evaluated at pre-initiation, termination of ART and the time of the survey.

Results.?The mean duration from the last treatment was 55 months. Compared with the treatment period, more than half of patients (57.5%) answered that their present condition was better. Scores on the AMS scale, IIEF and SF-36 were all improved significantly in the early stages of treatment and not worsened a long period of time after ART was discontinued.

Conclusions.?For symptomatic Japanese hypogonadal patients, subjective effects of treatment were observed during the early treatment period and remained unchanged after discontinuation of ART. A short treatment period may thus be adequate in Japanese hypogonadal patients as regards symptomatic changes.     

Testofen,a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease,increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study

This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600?mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.     

Treatment with human chorionic gonadotropin for PADAM: A preliminary report

The purpose of this study was to evaluate the efficacy and safety of human chorionic gonadotropin (hCG) for patients with partial androgen deficiency of the aging male (PADAM). Twenty-one patients over 50 years of age with PADAM symptoms were included in this study. Laboratory and endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires such as the Aging Males' Symptoms (AMS) scale, short version of the International Index of Erectile Function (IIEF-5), and the Self-rating Depression Scale (SDS). Laboratory and endocrinologic values and symptom scores were evaluated and compared before and after treatment by hCG injection. The treatment period was 8.0 ± 5.0 months (3.0 – 24.0 months). Serum concentrations of testosterone, including total testosterone, calculated free testosterone, and calculated bioavailable testosterone, increased significantly. AMS total scores and subscores decreased significantly after treatment. However, IIEF-5 and SDS scores did not improve. With respect to adverse effects, laboratory tests showed that only red blood cell count, hematocrit and hemoglobin level increased significantly after treatment, however, these values remained within the normal range. No adverse effect was identified after treatment. We conclude that hCG injection may be considered as a treatment for PADAM.     

Correlation between the Japanese Aging Male Questionnaire (JAMQ) and Aging Male’s Symptom (AMS) scale in Japanese male

Abstract

Objectives: To clarify the correlation between the Japanese Aging Male Questionnaire (JAMQ) and the Aging Males’ Symptoms (AMS) scale through the factor analysis in Japanese male.

Materials and methods: In 61 male patients who visited the LOH outpatient clinic of Teikyo University Hospital, subjective symptoms featuring LOH were evaluated using the JAMQ and AMS. Factor analysis was performed on each questionnaire to clarify the LOH-related factors. Correlational analysis between the subscale scores representing such factors and the serum hormone profiles was also performed.

Results: Factor analysis of the JAMQ revealed an internal structure consisting of three subgroups: somatic, psychological and sexual factors with good categorization of the indicators to the appropriate subgroup. In contrast, the indicators of the AMS showed incomplete conformity to the subgroups of the JAMQ. Correlational analysis showed that each score on the JAMQ subgroups had the highest coefficient of correlation with the corresponding AMS subgroup (p?<?0.001). There was no significant association between total and free serum testosterone levels and the total and subscale scores on either AMS or JAMQ.

Conclusions: The results of factor analysis suggest that the sexual perceptions of Japanese populations might differ from those of Caucasian populations. JAMQ would be useful to separately assess individual aspects of somatic, psychological and sexual symptoms related to LOH among Japanese males.     

The efficacy and safety of short-acting testosterone ointment (Glowmin) for late-onset hypogonadism in accordance with testosterone circadian rhythm

Introduction: It is well known that there is a reduction of circadian rhythm in blood testosterone levels with aging. Our previous report revealed that 3?mg of short-acting testosterone ointment (Glowmin: GL) elevated serum testosterone levels to within the physiological range for 4–6?h. The aim of this study was to clarify the clinical efficacy and safety of GL used topically once every morning, to enhance the circadian rhythm of testosterone, for late-onset hypogonadism (LOH).

Methods: A total of 61 LOH patients received 3?mg of GL topically once a day in the morning on scrotal skin for 24 weeks. The clinical efficacy of GL was evaluated by the aging males symptoms (AMS) scale, and blood sampling tests were measured before and after GL treatment.

Results: Mean patients age was 55.3?±?9.2 years old. Total AMS scores at 4, 12, and 24 weeks after GL treatments significantly decreased. The results of sub-analysis of AMS, including psychological, physical, and sexual factors also significantly improved after GL treatments. No severe adverse reactions or abnormal laboratory data were reported.

Conclusions: This study shows that TRT for LOH with once daily GL treatment supports testosterone circadian rhythm and should be considered to be an effective and safe therapy for LOH.     

Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome

Abstract

Objective: We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months.

Methods: 50 males aged 50–65 years with TDS (Aging Males Symptoms Scale [AMS]?>?26 and calculated free testosterone [cFT] 250?pmol/l) were administered 50?mg testosterone gel daily for one year. During the second year, patients received 1000?mg of testosterone undecanoate every 2–3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry.

Results: There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p?<?0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months.

Conclusions: Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.     

Clinical assessment and validation of an Arabic Aging Male Symptoms questionnaire in patients with androgen deficiency

Aim.?To develop and to validate an Arabic Aging Male Symptoms (AMS) tool and to clinically assess patients with hypoganadism after hormonal treatment.

Methods.?The tool was translated into Arabic and tested on 15 Saudi men. During a period of 9 months all males presented to the andrology clinic of the main University Hospital, King Saud University, Saudi Arabia with signs and symptoms of hypogonadism, were included in the study. Arabic AMS scale was applied in the base line visit, then 12 weeks after treatment. Testosterone was monitored before treatment, 4 weeks and after 12 weeks.

Results.?Ninety-two subjects were included, Cronbach's α of 0.91 showed a very good internal consistency of the Arabic AMS questionnaire. The corresponding α for the subscales were 0.83, 0.84 and 0.73. There was a significant improvement in the mean level of TT after hormonal therapy (HT), this was reflected on the mean differences of improvement in the total Arabic AMS scores and subscales scores after HT, ranged from 31 to 35%.

Conclusion.?The present study revealed a significant association between testosterone levels and AMS tool manifested by a its good ability to measure the effect of treatment on quality of life for patients with hypogonadism.     

The effects of testosterone deficiency on male sexual function

Introduction. Patients with late onset hypogonadism (LOH) also suffered from lower urinary tract symptoms (LUTS) and LOH symptoms. The objects of this study are to evaluate the efficacy of testosterone replace therapy (TRT) by testosterone ointment (Glowmin: GL) for LUTS in LOH patients.

Methods. The Aging Male Symptom (AMS) scale, Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36), International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) were obtained from patients with LOH. A total of 41 patients with LOH have been treated with TRT using 6 mg/day of GL for 3 months. Serum free testosterone levels (FT) and these four scores were compared before and after TRT.

Results. Serum FT levels and the scores for the four parameters of AMS, six of eight domains in SF-36, IIEF-5 and total IPSS improved significantly after 3 months TRT. In addition, all IPSS domains also improved significantly, and voiding disturbance seems to have improved more than storage disturbance (P?=?0.0280 vs. 0.0483).

Conclusion. TRT by administration of GL is considered to be effective in the improvement of not only ED and LOH symptoms, but also LUTS (especially voiding disturbance) of patients with LOH.     

Comprehensive evaluation of androgen replacement therapy in aging Japanese men with late-onset hypogonadism

Abstract

Objective: This study assessed the efficacy and safety of testosterone replacement therapy (TRT) in aging Japanese men with late-onset hypogonadism (LOH).

Methods: This study included 50 (median age: 57.7 years) Japanese men with LOH, who were consecutively enrolled and treated with TRT for at least six months at our institution. We evaluated the following measurements before and after six months of treatment with TRT as follows: blood tests, prostate volume, residual urine volume, self-ratings for International Index of Erectile Function 5 (IIEF-5), International Prostate Symptom Score (IPSS), Self-Rating Depression Scale (SDS), Aging Male Symptom (AMS) and the Medical Outcomes Study 8-item Short-Form health survey (SF-8).

Results: Following six months of TRT, the levels of testosterone, red blood cells, hemoglobin and hematocrit were significantly increased from baseline, while total cholesterol level was significantly decreased from baseline. Furthermore, TRT led to a significant increase in IIEF-5 score and a significant decrease in IPSS score. Of 30 men who were diagnosed with depression at baseline, only 11 men (36.7%) were still suffering from depression after TRT, and SDS scores were significantly decreased from baseline at month six. Treatment with TRT led to a significant decrease in all scores of the AMS scale as well as a significant improvement in all scores of the SF-8 survey, with the exception of the bodily pain score.

Conclusion: These findings suggest that TRT is an effective and safe treatment for aging Japanese men with LOH. TRT improved depressive symptoms as well as health-related quality of life.     

The effect of testosterone therapy on lower urinary tract symptoms/bladder and sexual functions in men with symptomatic late-onset hypogonadism

Objective.?To prospectively investigate the effect of testosterone therapy on lower urinary tract symptoms (LUTS)/bladder and sexual functions in men with symptomatic late-onset hypogonadism (SLOH).

Methods.?The study included 25 men (age range 38 to 73 years) presented with sexual dysfunction, having SLOH, at a single university hospital. All men received testosterone replacement therapy with transdermal testosterone 50–100 mg gel per day for one year. Urodynamic studies with pressure-flow analysis, measurement of prostate volume, prostate specific antigen (PSA) and free PSA level, International Prostate Symptom Score (IPSS), Aging Male Symptom (AMS) scale and International Index of Erectile Function (IIEF-5) score were recorded in all men before and after one year of the treatment.

Results.?The mean AMS score significantly decreased from 40.4 ± 7.3 to 28.8 ± 5.31 (p = 0.001), and mean IIEF-5 score significantly increased from 8.84 ± 3.76 to 14.36 ± 3.62 (p = 0.001). The mean maximal bladder capacity and compliance significantly increased (p = 0.007 and p = 0.032, respectively), and mean detrusor pressure at Qmax significantly decreased from pre-treatment to post-treatment (p = 0.017).

Conclusion.?This study suggests that in addition to improvement in sexual functions, testosterone therapy may also improve LUTS/bladder functions by increasing bladder capacity and compliance and decreasing detrusor pressure at maximal flow in men with SLOH.     

The “Aging Males’ Symptoms” Scale (AMS): predictive value for lowered circulating androgens

Background: Symptoms of the “male climacteric” are often at least in part referred to an age-dependent decline of serum androgen levels. Therefore, we evaluated the relationship of climacteric symptoms as assessed by the “Aging Males’ Symptoms” (AMS) Questionnaire with circulating androgen levels. Methods: 146 ambulatory men (age, 27–85 years) were surveyed with the AMS Questionnaire and sampled for serum values of total testosterone (tT) and sexual hormone binding globulin (SHBG). Free testosterone (fT) was calculated from tT and SHBG. A total AMS score ≥37 was considered pathological; the lower limits for tT and fT were set to 8 nmol/l and 180 pmol/l, respectively. Results: A significant deficit in tT and fT was shown in 25 (17.1%) and 34 (24.5%) men, respectively; the AMS Questionnaire showed pathological results for 66 (45.2%) men. In predicting a tT deficit, the AMS Questionnaire rendered a sensitivity of 76% and a specificity of 61.6%, only. However, multiple regression analysis revealed a significant correlation of lowered tT with a pathological somatovegetative and psychological AMS subscore (p = 0.042 and p = 0.01) and a correlation of lowered fT with a pathological sexual subscore (p = 0.039). Conclusion: In predicting hypogonadism the AMS Questionnaire in total did not render a sufficient diagnostic efficiency.     

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

Purpose.?We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH).

Methods.?Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250?mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment.

Results.?Forty-six patients (ART group, n?=?23; control, n?=?23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7?±?8.7 vs. 12.5?±?9.5; p?<?0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p?<?0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p?<?0.05), whereas no significant changes were seen in the controls.

Conclusion.?ART improved LUTS in hypogonadal men with mild BPH.     

Sleep disturbance as a clinical sign for severe hypogonadism: efficacy of testosterone replacement therapy on sleep disturbance among hypogonadal men without obstructive sleep apnea

Objective: The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea.

Methods: Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12?months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17).

Results: We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12?months.

Conclusion: Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.     

Diagnosis,pathogenesis and treatment of erectile dysfunction

Introduction: After middle age, some men show androgen-deficiency symptoms leading to so-called PADAM (partial androgen deficiency in aging males). We tested the oral form of testosterone, testosterone undecanoate (Andriol^®, NV Organon, The Netherlands), in men with PADAM and evaluated its efficacy and safety in Korean male patients. Methods: We included those patients with the clinical symptoms of PADAM who had decreased levels of serum total testosterone (< 2.8 ng/ml) or free testosterone (< 13 pg/ml). We excluded patients with biopsy-confirmed prostrate cancer, abnormal findings in digital rectal examination or prostate specific antigen testing (until prostrate cancer was ruled out), breast cancer, severe voiding symptoms and secondary hypogonadism. At the first visit, the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) and Korean Andropause Questionnaires were administered; complete blood count, the lipid profile, and levels of total and free testosterone, prolactin, luteinizing hormone, follicle stimulating hormone and prostate specific antigen were measured and a digital rectal examination was given. Patients were administered oral testosterone undecanoate 160 mg daily for 3 weeks. The dosage was then decreased to 80 mg daily and changes in symptoms were assessed at every visit. After 3 months, serum tests, including testosterone, were repeated. Results: We evaluated 28 patients who had received testosterone undecanoate for more than 3 months. The patients' mean age was 56.1 (48-68) years. The score of the Korean Andropause Questionnaire changed from 56.2 ± 21.7 at baseline to 52.9 ± 21.3 (p = 0.03) after 3 weeks, to 49.3 ± 19.3 (p = 0.03) after 8 weeks, and to 46.5 ± 25.6 (p = 0.028) after 12 weeks. With respect to sexual function, mean IIEF scores were 37.2 ± 19.6 at baseline and 38.7 ± 19.2 and 40.2 ± 22.0 (p = 0.033) after 3 and 12 weeks, respectively. Serum total testosterone increased from 2.13 ± 1.20 ng/ml at baseline to 6.04 ± 3.08 ng/ml (p = 0.005) after 12 weeks, and free testosterone was marginally significantly changed from 8.60 ± 2.25 pg/ml to 11.40 ± 3.81 pg/ml (p = 0.13). However, there were no significant changes in liver function tests, red blood cell count or lipid profiles. There were no significant adverse reactions that led to the cessation of the administration of oral testosterone. Conclusion: Oral administration of testosterone undecanoate can improve symptoms of PADAM in Koreans. It may, therefore, be an appropriate treatment option with few adverse effects for PADAM patients.     

Voyage into our common future: from futurophobia to futurophilia

Aims.?To investigate the association between endogenous testosterone levels and psychological health symptoms in men from a general population.

Methods.?Total testosterone and sex hormone-binding globulin levels were analysed and free testosterone levels was calculated in 3413 men participating in the fifth Tromsø study in 2001. Self-administered questionnaires including information about education, marital status, smoking habits and the Hopkins Symptom Checklist-10 (SCL-10, a 10-item psychological health questionnaire) were completed. The cross-sectional data were analysed with partial association and analysis of variance and covariance.

Results.?The complete SCL-10 was not associated with total or free testosterone, but symptoms of anxiety were negatively associated with both total and free testosterone (p?p?=?0.021), before and after adjusting for age, waist circumference, marital status, education and smoking. There was an even stronger association between men presumed to be testosterone deficient and symptoms of anxiety (p?Conclusions.?Men presumed being testosterone deficient had a higher symptom score, in particularly regarding anxiety, but they did not have pathological symptoms. Thus, lower testosterone levels was only associated with subthreshold symptoms of anxiety and depression.     

Hormone profiles,body mass index and aging male symptoms: results of the Androx Vienna Municipality study

Aging in the male is accompanied by steroid hormonal decline, and men may develop symptoms associated with hypogonadism. Increased awareness of ‘andropause’ in recent years has led to greater demand for hormonal assessments, resulting in a rising burden for health economics. We conducted a cross-sectional study to define men at risk for hypogonadism, in whom further hormonal investigation should be performed.

We examined 664 blue-collar workers aged 40–60 years at their workplace and determined hormonal status and body mass index (BMI). Men with an abnormal urogenital status and those on medication that might affect endocrine status were excluded from the study. All participants completed the validated Aging Male Symptom (AMS) questionnaire and obtained scores for psychological symptoms, somatovegetative symptoms, and sexual symptoms.

Multiple logistic regression analyses revealed a significantly increased risk (represented by the odds ratio) of psychological symptoms for men with low levels of testosterone and/or bioavailable testosterone (BAT). Increased BMI as well as low testosterone levels and/or low BAT levels raised the risk of somatovegetative symptoms. Each decrease of BAT by 1?ng/ml caused an approximately 1.8-fold increase of the risk (odds ratio?=?1.832, p?=?0.005). Additional independent risk factors were increased age and low luteinizing hormone (LH) level. Men aged 55 years with BMI >?28?kg/m² and with somatovegetative symptoms and moderate or severe psychological symptoms had a 7.2-fold increase in the risk of a BAT level <?1.5?ng/ml compared to men without these risk factors (p <?0.001). Sensitivity and specificity were 75% and 71%, respectively.

The AMS score combined with age and BMI provides an easy and convenient method to identify men with probable androgen deficiency who require hormonal assessment.     

Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity,voiding function and prostate safety parameters

Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function – erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.