Three-year follow-up of androgen treatment in hypogonadal men: preliminary report with testosterone gel

Transdermal testosterone gels represent an effective alternative to injectable testosterone preparations. Shortterm (6 months) data demonstrated positive effects on muscle, bone, fat, libido and mood. This report provides a preliminary analysis of longer-term treatment with a testosterone gel (AndroGel ? or Testogel®) in a group of men aged 19-67 years of age. The positive effects of testosterone treatment on all of the above parameters persisted in this 3-year follow-up. The benefits occurred independent of age (equally in the older and younger subjects). The positive effects of transdermal testosterone gel on bone mineral density previously identified at 6 months of treatment, continued with time. The positive effects on bone mineral density were greater in the spine than the hip. There were minimal effects on lipid levels. Levels of prostate-specific antigen (PSA) increased with testosterone treatment but, in general, remained in the normal range. Three subjects (1.8%) were shown to have elevated PSA and biopsy-proven prostate cancer. It was not possible to determine if this incidence is above the background rate. Monitoring for prostate disease through PSA measurements and digital rectal examination is recommended for hypogonadal men in the older age groups when treated with testosterone.     

An audit of testosterone measurement in men attending with impotence

As part of the routine assessment of 185 unselected men with undiagnosed impotence, testosterone was measured on a single serum sample to try to detect a subset of men with androgen deficiency who might benefit from testosterone replacement therapy. Those with low levels of testosterone were investigated further with repeat measurements of testosterone and luteinizing hormone (LH). In addition, prostatic specific antigen (PSA) was measured in all the men to exclude concomitant prostate cancer. Testosterone replacement therapy was offered to 20 men with consistently low levels of the hormone but few of the men continued with the therapy because of lack of benefit. It was concluded that either testosterone deficiency is rare in unselected men who actually seek help for impotence orebe our protocol of androgen assessment was not helpful for this group of men. There was correlation between PSA results and testosterone and this may have implications for the investigation of prostate cancer. The results presented here are an audit of a clinical practice and call into question the benefit of routine testosterone measurement in the investigation of all men complaining of impotence.     

The effect of testosterone treatment on prostate histology and apoptosis in men with late-onset hypogonadism

Objectives: To investigate the effect of testosterone replacement therapy (TRT) on prostate histology and apoptosis in men with late-onset hypogonadism (LOH).

Methods: The study included 25 men, having LOH with prostate-specific antigen (PSA) level of 4?ng/ml or less. All patients underwent transrectal ultrasound guided prostate biopsy at baseline, and received testosterone undecanoate treatment for 1 year. Prostate biopsy was repeated at the end of 1 year of testosterone therapy. In addition to clinical and biochemical parameters, prostate histology and apoptotic index (AI) were compared before and after the TRT.

Results: The mean serum total testosterone significantly increased from 178.04?±?51.92 to 496.28?±?103.73?ng/dl (p?=?0.001). No significant differences were observed in serum total and free PSA level, prostate volume and maximal urinary flow rate. There were also no significant differences in AI, stroma/epithelial cells ratio, Ki-67 positive cells and atrophy score of prostate tissue before and after the TRT.

Conclusions: This study demonstrated that TRT did not affect serum PSA level, prostate volume and maximal urinary flow rate. This study also suggests that TRT does not cause the risk for prostate cancer development, because of no significant differences in prostate histology after TRT.     

Testosterone,testosterone therapy and prostate cancer

Abstract

With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer. This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed. Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer. In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.     

Testosterone supplementation: what and how to give

Several epidemiological studies have demonstrated a gradual decrease of serum testosterone with aging in men. A considerable number of men will experience hypogonadal androgen levels, defined by the normal range for young men. Thus, in addition to the long-standing use of androgen replacement therapy in the classical forms of primary and secondary hypogonadism, age-associated testosterone deficiency has led to considerable developments in application modes for testosterone. Since oral preparations of testosterone are ineffective, due to the first-pass effect of the liver, or, in case of 17 α-alkylation, cause hepatotoxicity, intramuscular injection of long-acting esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. However, the large fluctuations of serum testosterone levels cause unsatisfactory shifts of mood and sexual function in some men; combined with the frequent injections, this delivery mode is thus far from being ideal. In contrast, the transdermal testosterone patches are characterized by favorable pharmacokinetic behavior and have proven to be an effective mode of delivery. Safety data over 10 years indicate no negative effect on the prostate. Nevertheless, the scrotal testosterone patch system is hampered by the application site, which is not easily accepted by many subjects; the non-scrotal patch has a high rate of skin irritations. In view of the drawbacks of the currently available preparations, the most recent developments in testosterone supplementation appear to be highly promising agents. Androgen, which has been available in the United States since mid-2000, will be introduced this year in most European markets as Testogel ® , a hydroalcoholic gel containing 1% testosterone. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and to correct the signs and symptoms of hypogonadism. The gel has shown to be very effective and successful in American patients, who have benefited from its availability for almost 3 years. Furthermore, in phase II and III clinical studies, the intramuscular injection of 1000 mg testosterone undecanoate every 12-15 weeks has led to extremely stable serum testosterone levels for a prolonged period of time and has resulted in excellent efficacy. It is very likely in the future that these products will be the mainstay of testosterone supplementation. Whereas the indication for testosterone substitution for men with classical forms of hypogonadism is unequivocal, the use of testosterone in men with ageassociated hypogonadism is less uniformly accepted. Yet, the few studies addressing this question indicate that men with testosterone serum levels below the lower normal limit for young adult men and with lack of energy, libido, depressed mood and osteoporosis may benefit from testosterone supplementation. However, it should be kept in mind that the experience documented in studies is limited. Nevertheless, serious side-effects, especially in regard to the prostate, did not occur, with the longest study extending over 3 years.     

A 1,408 km bicycle tour with prostate cancer patients—results of a pilot study

Negative psychological and physical effects of prostate cancer and its medical treatment may persist many years after diagnosis. The influence of a long cycling tour on rehabilitative or health-related effects with prostate cancer patients has not yet been studied. In practice, physicians and therapists rarely recommend cycling to prostate cancer. In May 2010, eight prostate cancer patients rode their bikes for over 1,408 km from Cologne to Marseille within 5 weeks. Endurance test, blood examinations (prostate-specific antigen (PSA), total testosterone, interleukin-6, oxidative stress, and antioxidant capacity) and quality of life questionnaires were completed before and after the tour. All eight subjects reached Marseille. Significant improvements could be observed in physical performance and certain quality of life scores (p?=?0.008), as well as a reduction of total testosterone (p?=?0.19). PSA levels did not change. This pilot study suggests that long bicycle tours with prostate cancer patients are feasible. Due to the missing control group and the small sample size, the results of this pilot study are limited.     

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.     

Preventing diseases of the prostate in the elderly using hormones and nutriceuticals

The prostate has only one function, namely to secrete fluid containing substances that are needed for reproduction. This requires an extremely high concentration of androgens in the tissues. Benign prostatic hypertrophy (BPH) seems to be related to the long-term exposure of the prostate to the strong androgen 5α-dihydrotestosterone (DHT) and, possibly, to estrogens. The relation between prostate cancer and androgens is suggested to be U-shaped, with both extremes of androgen concentrations being associated with increased risk of invasive cancer.

In the treatment of patients with BPH, the lipidic liposterolic extracts of Serenoa repens were as effective as the pharmaceutical inhibitors of the 5α-reductase enzyme or α₁-adrenergic blockers in relieving urinary symptoms. In addition to moderately inhibiting the 5α-reductase activity, Serenoa seems to exert anti-inflammatory and complementary cellular actions with beneficial effects on the prostate. Unlike the pharmaceutical 5α-reductase inhibitors, finasteride and dutasteride, Serenoa does not suppress serum PSA, facilitating the follow-up and the early detection of prostate cancer.

We suggest a strategy to prevent prostate cancer that aims at providing men with partial androgen deficiency correct testosterone substitution with a sustained release buccal bio-adhesive tablet. In addition, food supplementation with extracts of Serenoa repens and a combination of the antioxidants selenium, (cis)-lycopene and natural vitamin E, together with fish oil rich in long-chain polyunsaturated essential fatty acids of the omega-3 group seems warranted. Clearly, a holistic approach including careful clinical and biological monitoring of the aging man and his prostate remains mandatory.     

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

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

Association of DHEA-S and estradiol serum levels to symptoms of aging men

Objectives A number of interactions between agerelated changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. Methods In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. Results A total of 375 men with a mean age of 59.9 ± 9.2 years (mean ± standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 ± 90.9 μg/dl and 29.7 ± 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. Conclusion This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.     

Aging androgens and the metabolic syndrome

Objective: To assess the responses of a symptom complex related to partial androgen deficiency in the aging male (PADAM) to androgen supplementation. Subjects and methods: Eighty-six men from five hospitals in Beijing aged 50-70 years with symptoms related to PADAM received oral testosterone undecanoate for 2 months, and the effects of the therapy were evaluated. Results: After treatment, the symptom scores were significantly improved (all p < 0.001). Serum levels of luteinizing hormone and follicle stimulating hormone were suppressed, and free testosterone and albuminbound testosterone levels were elevated. However, they were not significantly different from the pretreatment values. Waist/hip ratio and blood pressure were markedly decreased, but no changes were found in serum levels of total cholesterol, triglyceride, albumin and prostate specific antigen. Conclusions: Two months of treatment with oral testosterone undecanoate clearly improved the symptoms related to PADAM. No statistical relationship was found between symptom improvement and androgen levels. Androgen therapy for 2 months was beneficial to the waist/hip ratio and blood pressure, and no harm was done to the prostate gland or lipid metabolism.     

The Philippine Male Aging Survey

The aging male is fast becoming a global concern. The problem is predicted to become a major health issue that should be addressed immediately in order to prevent disability, morbidity, and, more importantly, mortality. As part of its commitment to increase awareness and create interest in the care of Filipino aging males, The Philippine Society for the Study of the Aging Male Foundation, Inc. (PhiSSAM), a multi-specialty society established in 2000, embarked on a survey among Filipino physicians to determine their knowledge, attitudes, and practices regarding male aging. Results showed that the majority of doctors (about 87%) thought that men may experience andropause. Most would diagnose patients based on symptoms alone, while only 20–30% used testosterone levels to make a diagnosis of andropause. Decreased libido and less strong erections were the symptoms very closely associated with low testosterone. Of those doctors responding, 89% agreed that andropause can affect the quality of a man's life as much as menopause can affect a female; only 38% had already prescribed/instituted treatment for andropause. Of the 62% non-prescribers, 58% said they were either very likely or fairly likely to institute treatment in the future if there were more clinical trials, more medical information, and more information on drugs. Major concerns on testosterone replacement therapy included prostate cancer, benign prostatic hypertrophy, and heart disease. The findings in this pilot survey indicate a need among the doctors in the Philippines for education about andropause and the available treatments.     

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

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

Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency

In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol^®) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculo-skeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency.     

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.     

Speaker abstracts

Purpose: There is no consensus on possible benefits and risks of testosterone supplementation. Here we review various controlled studies of testosterone supplementation in aging males.

Methods: We performed a PubMed search using the terms “testosterone/therapeutic use” with the limits “>65 years of age”, “randomized controlled clinical trials”, and “male gender”, starting in 1999.

Results: Forty-three articles have been published since 1999. Some of these studies also included patients in middle-age or younger. Findings reported in these articles were not entirely consistent. After weighting studies by the number of patients, hints are found that testosterone supplementation increases bone mass, lean body mass, muscle mass and hematopoiesis, and improves sexual functioning and perhaps mood, but does not affect serum lipids, cardiovascular parameters, prostate-specific antigen level, or cognition. Considering studies including only men older than 65 years, and in which testosterone supplements were compared with placebo treatment, slightly different results are obtained. In these patient groups, testosterone does not improve sexual function or mood.

Conclusion: The overall benefit of testosterone supplementation for the aging male remains unclear. Any supplementation in men with age-normal testosterone levels only on grounds of subjective symptoms is not advisable.     

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.     

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

Abstract

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

No association of serum PSA with vitamin D or total oxidant-antioxidant capacity in healthy men

Background and aim: Vitamin D deficiency and oxidative stress were suggested to be related to prostate cancer risk. We aimed to investigate the association of serum PSA concentration with vitamin D and total oxidant/antioxidant levels.

Materials and methods: A total of 95 healthy men were enrolled for the cross sectional study. Serum PSA, 25(OH)D, serum total oxidant status, and total antioxidant status were measured.

Results: Serum PSA was significantly negatively correlated with serum total oxidant status (r=??0.309, p?=?.003) but there was no significant correlation between PSA and 25(OH)D (p?=?.383) or total antioxidant levels (p?=?.233). After adjustment for age BMI and smoking status with multiple regression analysis, there was no significant association between serum PSA and total oxidant status.

Conclusion: We find no evidence for an association between PSA and vitamin D levels or serum total oxidant/antioxidant levels.     

The aging male in the literature

The diagnosis of hypoandrogenism in the aging male is still difficult, since the symptomatology is aspecific and multifactorial, and it is unknown whether the androgen requirements of elderly men are the same as those of young men. Indeed, there are arguments for decreased (increased androgen feed-back sensitivity) as well as for increased (decreased concentration of androgen receptors) requirements in elderly men. In the absence of a reliable, clinically useful, parameter of androgen activity, we have to rely on plasma androgen level, an indirect parameter. In the absence of convincing arguments for altered requirements with age, we consider that the normal range of (free) testosterone levels in young adults is also valid for elderly men, the lower normal limit being 11 nmol/l for total testosterone and 0.225 nmol/l for free testosterone. There are indirect, suggestive clinical arguments for accepting these limit values. The diagnosis of hypoandrogenism in elderly males requires both the presence of clinical symptoms and decreased (free) testosterone levels. The best methods for determining free or bioavailable testosterone, are equilibrium dialysis and ammonium sulfate precipitation, respectively. They are, however, time-consuming techniques which are not easily automated. Calculation of the free androgen index (testosterone/sex hormone binding globulin (SHBG)) is not a valid method for male serum. Calculation of free testosterone from total testosterone, SHBG and albumin concentration, yields values that are in good agreement with values obtained by dialysis or ammonium sulfate precipitation. Several conditions should, however, be fulfilled: reliable methods for the determination of testosterone and SHBG, SHBG measurement in serum and not in plasma, use of fresh serum (not repeatedly frozen and thawed), absence of (exogenous) steroids competing for binding sites on SHBG and blood samples taken between 08.00 and 10.00 in the fasting state. Under these conditions an excellent correlation with dialysis and bioavailable testosterone (ammonium sulfate precipitation) is generally obtained.