Low serum testosterone levels are poor predictors of sexual dysfunction

Study Type – Prognosis (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Sexual dysfunction is a common problem in elderly men, especially if they also have LUTS. Serum testosterone likewise decreases with aging, and a common conclusion from this is that low serum testosterone levels are a main cause for this. This is by far the largest population‐based study correlating sexual dysfunction with serum testosterone levels. Whereas age, body mass index and the severity of LUTS were independent risk factors for sexual dysfunction, serum testosterone levels were not. Treating sexual dysfunction only based on a low serum testosterone level therefore appears unjustified. There is a trend towards sexual dysfunction with S. testosterone levels <200 ng/dl, but only 4% of the 8231 older men studied were in this range.

OBJECTIVE

? To identify predictors of sexual dysfunction using baseline data from the reduction by dutasteride of prostate cancer events (REDUCE) study.

PATIENTS AND METHODS

? REDUCE was a 4‐year randomized, double‐blind, placebo‐controlled study evaluating the efficacy and safety of once‐daily dutasteride 0.5 mg in over 8000 men aged 50–75 years with a prostate‐specific antigen (PSA) level of 2.5–10 ng/mL (50–60 years) or 3.0–10 ng/mL (>60 years) and a negative prostate biopsy within 6 months of enrolment. ? Baseline values (mean serum testosterone, age, International Prostate Symptom Score [IPSS], total prostate volume [TPV], body mass index [BMI], and presence of diabetes/glucose intolerance) were compared in subjects with and without sexual dysfunction (sexual inactivity, impotence, decreased libido or a Problem Assessment Scale of the Sexual Function Index [PAS‐SFI] score <9).

RESULTS

? Multivariate logistic regression showed that baseline age and IPSS were significant predictors of all four sexual function criteria examined (P < 0.0001). ? BMI was a significant predictor of decreased libido, impotence and a PAS‐SFI score <9, while diabetes/glucose intolerance was a significant predictor of sexual inactivity, impotence and a PAS‐SFI score <9. ? Testosterone and TPV were not significant predictors of any sexual function criterion examined.

CONCLUSIONS

? Age, IPSS, BMI and diabetes/glucose intolerance, but not serum testosterone or TPV, were significant independent predictors of sexual dysfunction in the REDUCE study population. ? The lack of association between sexual dysfunction and serum testosterone questions the value of modestly reduced or low normal testosterone levels as criteria for choosing testosterone replacement in older men with sexual dysfunction.     

Effect of the dual 5α‐reductase inhibitor,dutasteride, on serum testosterone and body mass index in men with benign prostatic hyperplasia

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To investigate the effects of dutasteride on serum testosterone level and body mass index (BMI) in men who received medical therapy for benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

In all, 120 patients with BPH were randomized to three treatment groups: tamsulosin 0.2 mg/day (α‐blocker group), dutasteride 0.5 mg/day (dutasteride group), or tamsulosin 0.2 mg plus dutasteride 0.5 mg/day (combination group) for 1 year. For all patients the BMI and serum testosterone levels were checked at baseline and after 1 year of treatment.

RESULTS

Among the evaluable 107 patients, the dutasteride (33) and combination groups (37) had significantly greater increases in serum testosterone level (16.3% and 15%, respectively) than the α‐blocker group (37; 0.3%) after 1 year of treatment (both P < 0.001). When analysed by baseline serum testosterone tertile, the increases in serum testosterone level among the dutasteride and combination group were greatest in the lowest tertile. For BMI, the dutasteride and combination group had mean decreases of 0.17 and 0.20 kg/m², respectively, at 1 year, whereas the α‐blocker group had a mean increase of 0.04 kg/m². The decreases in BMI for the dutasteride and combination group were statistically significant only in the lowest tertile (P = 0.048 and 0.010, respectively).

CONCLUSION

Our results show that dutasteride treatment in men with BPH led to a significant increase in serum testosterone level and a significant decrease in BMI among those with relatively lower baseline serum testosterone levels.     

Serum sex hormones and the 20‐year risk of lower urinary tract symptoms in community‐dwelling older men

Study Type – Prognosis (inception cohort)
Level of Evidence 2b

OBJECTIVE

To evaluate serum sex steroid hormone concentrations and long‐term risk of subsequent lower urinary tract symptoms (LUTS) in a cohort of community‐dwelling older men.

SUBJECTS AND METHODS

Between 1984 and 1987, serum sex hormone concentrations were measured in participants in the Rancho Bernardo Study, a prospective, community‐based study. In 2006, the American Urological Association Symptom Index (AUA‐SI) was mailed to surviving male participants. Logistic regression was used to examine associations of baseline hormone concentrations with AUA‐SI.

RESULTS

Among 158 surviving men with complete data and no history of prostate cancer, the mean (sd ) age at serum sex steroid assessment was 58 (6.6) years with a mean (sd ) follow‐up of 20.3 (0.6) years. In age‐adjusted logistic regression, there was a significant inverse association of testosterone : dihydrotestosterone (DHT) with LUTS (P = 0.05). Also, men with higher concentrations of bioavailable testosterone had a 56% decreased risk of LUTS compared with those with hypogonadal concentrations, although the association was not statistically significant (odds ratios 0.44, 95% confidence interval 0.14–1.40) or distributed evenly among quartiles. There were no significant associations of total testosterone, oestradiol (E₂), testosterone : E₂, DHT, or dehydroepiandrosterone with LUTS or with any measured hormones and urinary bother.

CONCLUSIONS

In this cohort, men with higher mid‐life levels of testosterone : DHT and bioavailable testosterone had a decreased 20‐year risk of LUTS. These data support other studies reporting inverse associations of serum testosterone with LUTS. Clinical trials of testosterone therapy should include LUTS and clinical benign prostatic hyperplasia as outcomes.     

Dutasteride in men receiving testosterone therapy: a randomised,double‐blind study

We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty‐three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (?0.46 ± 0.81 ng ml^?1; P = 0.04) and in PV (?6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (?0.46 versus 0.21 ng ml^?1; P = 0.11), PV (?6.65% versus 3.4%; P = 0.08) and MSHQ scores (?10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy.     

Influence of dutasteride treatment on serum hormone levels and aging male symptoms in patients with benign prostatic enlargement

Objectives

To clarify the effects of dutasteride on serum hormone levels and aging male symptoms in patients with benign prostatic enlargement.

Methods

The present prospective study was carried out in 110 symptomatic benign prostatic enlargement patients treated with daily administration of 0.5 mg dutasteride. We analyzed serum hormonal levels and aging related symptoms using a validated Aging Male Symptom questionnaire at baseline and after 3 months of dutasteride treatment.

Results

The mean total testosterone, free testosterone and luteinizing hormone levels after dutasteride treatment were approximately 20% higher than those at baseline. The percentage increases in total and free testosterone levels were negatively correlated with these baseline levels. Baseline age, levels of total testosterone and free testosterone, and the changes in the rate of luteinizing hormone after dutasteride treatment tended to be correlated with an increase in the rate of total testosterone and free testosterone after dutasteride treatment. In a subgroup of 26 patients with moderate‐to‐severe aging male symptoms, poor morning erection and free testosterone levels <8.5 pg/mL, total aging male symptoms, and somatic symptoms scores significantly decreased after dutasteride treatment with an increase of total and free testosterone.

Conclusions

The increase of endogenous free testosterone and total testosterone by dutasteride might bring additional benefits of improvement of aging male‐related symptoms, especially in patients with lower free testosterone baseline levels and moderate‐to‐poor aging‐related symptoms.     

Benign prostatic hyperplasia

Microscopic benign prostatic hyperplasia (BPH) develops in most Western men, many of whom will develop measurable enlargement of the prostate. Lower urinary tract symptoms (LUTS), in association with prostatic enlargement, are common, especially with increasing age. About 50% of symptomatic men have measurable BPH/enlargement. A focused history and examination (with frequency/volume chart), simple tests (urine dipstick, creatinine) and assessment of voiding function (flow rate, ultrasound) help make the diagnosis, and a prostate-specific antigen (PSA) test should be considered. LUTS can be stratified according to severity by scoring systems (international prostate symptom score). Lifestyle advice can lessen mild symptoms. Medical therapy with α blockers should be offered initially to men with moderate to severe LUTS, and if the PSA is greater than 1.4 ng/ml or the prostate is estimated to be greater than 30 g, a 5-α reductase inhibitor should be offered alone or in combination with α blocker. Anticholinergics should be considered if there are concurrent storage symptoms. Severely symptomatic or obstructed men do best with a surgical technique chosen according to prostate size, that is transurethral incision of the prostate if small, transurethral resection of the prostate (TURP) or holmium laser enucleation (HoLEP) if 30-100 cm³ or open prostatectomy if large (>100 cm³). Pressure-flow studies can improve the accuracy of diagnosis and the selection of candidates for surgery, but most symptomatic men respond well to treatment. Outcomes for obstructed or moderate to severely symptomatic men are good, but the medical alternatives should always be discussed. 5-α reductase inhibitor therapy offers the opportunity to slow the development of further BPH instead of, or after, surgical treatment.     

Effects of three types of alpha‐1 adrenoceptor blocker on lower urinary tract symptoms and sexual function in males with benign prostatic hyperplasia

Objectives: The aim of the present study was to explore the effects of three different types of alpha‐1 adrenoceptor blockers (α1‐blocker) on lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and ejaculatory dysfunction (EjD) in patients with benign prostatic hyperplasia. Methods: A total of 136 male LUTS patients aged 50–80 years with International Prostate Symptom Score (IPSS) ≥8 were enrolled. They were divided into three groups. Group S received silodosin at 4 mg twice a day; group T received tamsulosin at 0.2 mg once a day; and group N received naftopidil at 50 mg once a day. Assessment included IPSS, quality of life indexes (QOL), International Index of Erectile Function (IIEF‐5), an ejaculation questionnaire, Qmax and post‐void residual urine volume (PVR). These parameters were recorded at baseline, and at 1 and 3 months after treatment had ended. Results: Mean IPSS and Qmax significantly improved after treatment in all groups without any significant difference among them. As for the IIEF‐5 score, only group N significantly improved at 1 and 3 months. After treatment, 2.6 and 2.4% of patients complained of a de novo reduced volume of ejaculation in both groups T and N, respectively. Ten out of 41 patients (24.4%) complained of a total absence of antegrade ejaculation in group S after treatment. Conclusions: All three types of α1‐blockers provided an objective and subjective improvement of LUTS in the present study population. However, erectile function only improved in patients treated with naftopidil and a higher rate of EjD was observed in those receiving silodosin. Because of their variable effects, we should consider the sexual dimension when prescribing α1‐blockers for LUTS.     

Examining the ‘gold standard’: a comparative critical analysis of three consecutive decades of monopolar transurethral resection of the prostate (TURP) outcomes

What's known on the subject? and What does the study add? Transurethral resection of the prostate (TURP) remains the dominant and definitive treatment for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS‐BPH), but the widespread use of medical therapies (particularly monotherapies) for rapid symptom improvement has meant that the most common indication for TURP has shifted to moderate–severe medical therapy refractory LUTS to, coupled with abnormal objective parameters, or when complications arise. Patients undergoing TURP as part of contemporary randomised controlled trials are not older but have a larger preoperative prostate volume and reduced major morbidity compared with large cohort studies from successive past eras. Delayed surgery because of prolonged medical monotherapy may explain a higher reported failure to void rate, possibly because of negative impact on detrusor function from unrelieved obstruction. This study examined contemporary TURP for significant changes, specifically regarding prostate size, operative parameters, and outcomes, compared with two preceding decades. Electronic databases PubMed, EMBASE & Cochrane collaboration were searched for English literature on prospective randomized controlled trials, published between 1997 and 2007 using keywords “transurethral resection” and “prostate”. Monopolar TURP (M‐TURP) cohort data of each study were selectively pooled for analysis, weighting studies according to patient numbers. Where possible, pooled post‐operative outcomes data were compared with two large cohort landmark studies of successive preceding decades. A total of 3470 patients from 67 studies were included. Mean patient age (67 years) was unchanged, while mean pre‐operative prostate volume of 47.6 g was greater than previously reported. Mean resected prostate tissue (25.8 g) with a resection time of 38.5 minutes suggested improved resection efficiency. A statistically significantly reduced transfusion rate and increased urinary tract infection (UTI) rate were reported. Hospital stay (3.6 days) and initial catheterisation duration (2.5 days) were similar, but post‐operative urinary retention rate was slightly higher (6.8%). Contemporary RCTs of M‐TURP showed larger prostate volume, and reduced major morbidity, compared with large cohort studies from successive past eras. The higher reported failure to void rate, may possibly reflect worse detrusor function at time of TURP. Delaying surgery by prolonged medical monotherapy may compound this. Trials methodology in this area requires quality improvement and standardisation in future.