Low Baseline Testosterone Levels Research Articles

Effects of Testosterone Replacement Therapy on Muscle Strength in Older Men with Low to Low-Normal Testosterone Levels: A Systematic Review and Meta‐Analysis

Background: Previous studies and meta-analyses have explored the relationship among testosterone, muscle strength, and physical function, to the best of our knowledge, no meta-analysis has investigated the effects of testosterone replacement therapy (TRT) on subgroup of relatively hypogonadal older men. Objective: The aim of this study was to evaluate the effect of TRT in older men with low testosterone levels. Methods: PubMed, Embase, and Web of Science were systematically searched for articles published between January 1990 and April 2020. We included randomized controlled studies that investigated the effect of TRT and included older men (age >60 years) with relatively low testosterone levels. Studies were extracted following the PRISMA flowchart, and the included randomized controlled trials were evaluated using RoB 2.0. Our main outcome was muscle strength changes after TRT evaluated using a metaregression of confounding factors. Secondary outcomes included changes in physical performance and the risk ratio of adverse events. Random-effects meta-analyses of TRT on muscle strength and physical function were performed. Results: Thirteen studies with 2,043 patients were included. The mean age of subjects in various studies ranged from 65.9 years to 76 years. Transdermal testosterone dosages ranged from 5 to 10 g/day, while intramuscular options were 125 mg/week or 200 mg every 2 weeks. Oral testosterone supplementation was given at 160 mg/day in one study. Pooled meta‐analyses revealed greater muscle strength improvement after TRT compared with placebo (Hedges’ g = 0.21; 95% CI: = 0.15–0.28). Intramuscular administration of TRT had greater efficacy (Hedges’ g = 0.74; 95% CI: = 0.34–1.14) than transdermal and oral TRT (p < 0.001). A metaregression revealed that baseline serum total testosterone was associated with muscle strength improvement (β = −0.004, p = 0.002). The risk ratios of adverse events, including elevated prostate-specific antigen, acute coronary syndrome, and prostate cancer, were not significantly different. Conclusion: TRT improved muscle strength in older, relatively hypogonadal men. The effect was more pronounced in populations with lower baseline testosterone levels.

Impact of gender-affirming hormone therapy on the development of COVID-19 infections and associated complications: A systematic review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can produce a wide range of clinical manifestations from asymptomatic to life-threatening. Various researchers have worked to elucidate the pathogenic mechanisms underlying these variable presentations. Differences in individual responses to systemic inflammation and coagulopathy appear to be modulated by several factors, including sex steroid hormones. Transgender men or non-binary individuals who undergo gender-affirming hormone therapy (GAHT) are a unique population of interest for exploring the androgen-mediated coronavirus disease 2019 (COVID-19) hypothesis. As the search for reliable and effective COVID-19 treatments continues, understanding the risks and benefits of GAHT may mitigate COVID-19 related morbidity and mortality in this patient population. To investigate the potential role of GAHT in the development of COVID-19 infections and complications. This systematic review implemented an algorithmic approach using PRISMA guidelines. PubMed, Scopus, Google Scholar top 100 results, and archives of Plastic and Reconstructive Surgery was on January 12, 2022 using the key words "gender" AND "hormone" AND "therapy" AND "COVID-19" as well as associated terms. Non-English articles, articles published prior to 2019 (prior to COVID-19), and manuscripts in the form of reviews, commentaries, or letters were excluded. References of the selected publications were screened as well. The database search resulted in the final inclusion of 14 studies related to GAHT COVID-19. Of the included studies, only two studies directly involved and reported on COVID-19 in transgender patients. Several clinical trials looked at the relationship between testosterone, estrogen, and progesterone in COVID-19 infected cis-gender men and women. It has been proposed that androgens may facilitate initial COVID-19 infection, however, once this occurs, testosterone may have a protective effect. Multiple clinical studies have shown that low baseline testosterone levels in men with COVID-19 are associated with worsening outcomes. The role of female sex hormones, including estrogen and progesterone have also been proposed as potential protective factors in COVID-19 infection. This was exemplified in multiple studies investigating different outcomes in pre- and post-menopausal women as well as those taking hormone replacement therapy. Two studies related specifically to transgender patients and GAHT found that estrogen and progesterone could help protect men against COVID-19, and that testosterone hormone therapy may increase the risk of contracting COVID-19. Few studies were found related to the role of GAHT in COVID-19 infections. Additional research is necessary to enhance our understanding of this relationship and provide better care for transgender patients.

Predicting hypogonadotropic hypogonadism persistence in male macroprolactinoma.

To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization. Retrospective cohort study. Male patients diagnosed with macroprolactinoma and HH that received cabergoline treatment with subsequent prolactin normalization were included: men that achieved eugonadism, and men that remained hypogonadal. Patient's demographic, clinical and biochemical parameters, sellar imaging, and visual fields tests were obtained. Univariate and multivariate models were used to identify predictors of HH persistence. Fifty-eight male patients (age 49.2 ± 12.6years) with a median baseline prolactin of 1154ng/mL (IQR 478-2763ng/mL) and adenoma (maximal) diameter of 25.9 ± 14.8mm were followed for a median of 5.6years (IQR 3.0-10.7). Twelve men (21%) suffered from HH persistence at the end of follow-up and 46 men achieved eugonadism. Forty-two out of 46 men (91%) accomplished eugonadism within the first year following prolactin normalization. In a multivariate logistic regression model, hypopituitarism (OR 10.1; 95% CI 1.10-101.94), visual field defect (OR 9.9; 95% CI 1.07-92.33), and low baseline testosterone levels (OR 0.5; 95% CI 0.29-0.93) were independent predictors of HH persistence. In our cohort of men with macroprolactinoma that reached prolactin normalization with cabergoline treatment, 21% had HH persistence. Pituitary hormone deficiency, visual field defects, and low baseline testosterone levels were independently associated with HH persistence. 91% of men achieved eugonadism within the first year following prolactin normalization. These findings may support informed clinical decision-making regarding the initiation of testosterone replacement in men with macroprolactinomas.

The Prostate Saturation Point after Testosterone Replacement Therapy in Testosterone Deficiency Patient

Background: The effect of testosterone on the prostate gland is an unresolved question. The prostate saturation model is a recent hypothesis explaining that the stimulation of prostate tissue by testosterone is limited to a certain level of testosterone due to the limited number of androgen receptors. However, data from the Thai patients related to this issue are still lacking and need to be explored. Objective: To investigate prostate changes after testosterone replacement therapy (TRT). Materials and Methods: A retrospective study including testosterone-deficient patients who had TRT between 2011 and 2017 at Ramathibodi Hospital was conducted. The change in prostate-specific antigen (PSA) levels before and after TRT, or after a 1-year observation, was measured and analyzed as the primary objective. As a secondary objective, the authors measured and evaluated normal PSA velocity (PSAV) in the patients after TRT. Results: One hundred eleven testosterone deficient patients were included for analysis. The mean age was 62 years old. The baseline testosterone level and PSA level at the beginning were 247 ng/dL and 1.16 ng/mL, respectively. After undergoing TRT for one year, the results showed that the testosterone and the PSA levels were 307 ng/dL and 1.46 ng/mL, respectively. In addition, the subgroup analysis illustrated that patients who had low baseline testosterone levels such as 247 ng/dL or less, had significant increase of PSA level after treatment. However, when the baseline testosterone level was more than 247 ng/dL, the PSA levels were steady after treatment. For the secondary-objective results, the PSAV of the testosterone deficiency patients after TRT was 0.3 ng/mL/year. Conclusion: The evidence clearly indicates that TRT significantly increased the serum testosterone level. However, it had a limited effect on PSA change. The present study results supported the hypothesis of the prostate saturation model. The authors believe that a testosterone level of 247 ng/dL can saturate all androgen receptors in the prostate gland and no longer increase prostate stimulation. Keywords: Prostate-specific antigen; Prostate cancer; Testosterone replacement Therapy; Prostate saturation

Disorders of Sex Development.

Disorders of Sex Development.

Predictive value of low testosterone concentrations regarding coronary heart disease and mortality in men and women - evidence from the FINRISK97 study.

IntroductionThe relevance of low testosterone concentrations for incident coronary heart disease (CHD) and mortality has been discussed in various studies. Here, we evaluate the predictive value of low baseline testosterone levels in a large population‐based cohort.MethodsWe measured the serum levels of testosterone in 7671 subjects (3710 male, 3961 female) of the population‐based FINRISK97 study.ResultsThe median follow‐up (FU) was 13.8 years. During the FU, a total of 779 deaths from any cause, and 395 incident CHD events were recorded. The age‐adjusted baseline testosterone levels were similar in subjects suffering incident events during FU and those without incident events during FU (men: 15.80 vs. 17.01 nmol L−1; P = 0.69, women: 1.14 vs. 1.15 nmol L−1; P = 0.92). Weak correlations of testosterone levels were found with smoking (R = 0.09; P < 0.001), HDL cholesterol levels (R = 0.22, P < 0.001), systolic blood pressure (R = −0.05; P = 0.011), BMI (R = −0.23; P < 0.001) and waist‐hip‐ratio (R = −0.21; P < 0.001) in men, and with eGFR (R = −0.05; P = 0.009) in women. Kaplan–Meier analyses did not reveal a positive association of testosterone levels with incident CHD or mortality. Accordingly, also in Cox regression analyses, testosterone levels were not predictive for incident CHD or mortality – neither in men (HR 1.02 [95%CI: 0.70–1.51]; P = 0.79 for lowest versus highest quarter regarding CHD and HR 1.06 [95%CI: 0.80–1.39]; P = 0.67 regarding mortality), nor in women (HR 1.13 [95%CI: 0.69–1.85]; P = 0.56 for lowest versus highest quarter regarding CHD and HR 0.99 [95%CI: 0.71–1.39]; P = 0.80 regarding mortality).ConclusionsLow levels of testosterone are not predictive regarding future CHD or mortality – neither in men, nor in women.

Хронобиологические особенности различных режимов терапии тестостерон-гелем у мужчин с андрогендефицитом

Androgens play a key role in the male development. All the physiological processes in the body, including the production of testosterone, have their chronobiological features. Aging is accompanied by a disruption in the regulation of chronobiological processes. With androgen deficiency, these changes occur at any age. In recent years, transdermal forms of testosterone have become very popular in the treatment of this condition. To evaluate the effectiveness and chronobiological features of various regimens of testosterone gel therapy for external use in men with androgen deficiency. The study comprised 90 men aged 45 to 60 years with testosterone deficiency. Patients were randomized into three groups of 30 people each. In group I (control) patients received basic therapy, including exercise, diet, and multivitamins. In group II, patients received basic therapy concurrently with testosterone gel for external use (Androgel) at a daily dose of 5 g (1 sachet). Patients in group III were administered basic therapy in combination with 10 g testosterone (2 sachets). The effectiveness of treatment was assessed at 3 (visit 2) and 6 (visit 3) months. Depending on the results of visit 2, a correction of therapy was carried out, if necessary. During each visit, the patients underwent evaluation, including hematocrit, levels of FSH, LH, prolactin, total testosterone, blood SHBG, waist circumference, and body weight. Patients completed the ICEF-5 questionnaire, the Hamilton scale (HDRS, HARS), and the SF-36 questionnaire. We also tested the patients for the chronobiological status and desynchronosis. During the visit I, the homogeneity of the study population was confirmed. At three months, the patients of groups II and III showed a more pronounced increase in testosterone, a decrease in body weight and waist circumference, as well as an improvement in the psycho-emotional status and quality of life according to the questionnaires. Desynchronosis persisted in 25 (83.3%), 9 (30%), and 4 (13.3%) patients in groups I, II, and III, respectively. Given the findings, the treatment was adjusted. The patients in the groups were divided into subgroups A and B. In subgroups A, patients continued to receive initial therapy, and in subgroups B, the treatment was adjusted. At six months, the level of GT increased to normal values in all subgroups except subgroup IA. The most marked reduction in body weight and waist circumference was noted in subgroups IA, IIA, and IIIB. A significant decrease in the average scores on the HDRS and HARS scales and an improvement in the SF-36 scale were observed in the subgroups IA, IIA, IIIB. Desynchronosis persisted in 3, 2, and one patient in subgroups IB, IIB, and IIIA. The testosterone gel therapy in patients with androgen deficiency can effectively reverse the manifestations of the disease and normalize the chronorhythm. Transdermal testosterone gel at a daily dose of 5 g in the morning can be recommended to alleviate clinical manifestations of the disease and eliminate desynchronosis in this category of patients. In patients with low baseline testosterone levels, it is advisable to administer the drug at a daily dose of 10 g.

Genetic Variation in the Androgen Receptor and Measures of Plasma Testosterone Levels Suggest Androgen Dysfunction in Alzheimer's Disease.

Alzheimer’s disease (AD) prevalence varies by sex, suggesting that sex chromosomes, sex hormones and/or their signaling could potentially modulate AD risk and progression. Low testosterone levels are reported in men with AD. Further, variation in the androgen receptor (AR) gene has been associated with AD risk and cognitive impairment. We assessed measures of plasma testosterone levels as a biomarker of AD in male participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Baseline testosterone levels were significantly different between clinical diagnosis groups [cognitively normal controls, mild cognitive impairment (MCI), or AD], with the lowest testosterone levels in men with AD. Lower baseline testosterone levels were associated with higher baseline clinical severity. Change in testosterone levels between baseline and 1-year follow-up varied by diagnosis; MCI had the greatest decreases in testosterone levels between baseline and 1-year follow-up. Despite differences by clinical diagnosis, there was no association between plasma testosterone and CSF biomarkers of AD pathology. We also tested single nucleotide polymorphisms (SNPs) in AR for association with AD risk in a separate cohort from ADNI and found 26 SNPs associated with risk for AD. The top associated SNP is predicted to be an expression quantitative trait locus for AR in multiple tissues, including brain, with the AD-associated risk allele predicted to confer lower AR expression. Our findings suggest a link between the androgen pathway and AD through Aβ/tau independent pathways. These effects may be most pronounced during conversion from MCI to dementia.

Demographic and Clinical Correlates of Patient-Reported Improvement in Sex Drive, Erectile Function, and Energy With Testosterone Solution 2%

IntroductionEvidence from well-designed studies documenting the benefit of testosterone replacement therapy as a function of patient demographic and clinical characteristics is lacking. AimTo determine demographic and clinical predictors of treatment outcomes in hypogonadal men with low sex drive, low energy, and/or erectile dysfunction. MethodsPost hoc analysis of a randomized, multicenter, double-blinded, placebo-controlled, 16-week study of 715 hypogonadal men (mean age = 55.3 years, age range = 19–92 years) presenting with low sex drive and/or low energy who received placebo or testosterone solution 2% for 12 weeks. Main Outcomes and MeasuresTwo levels defined patient-reported improvement (PRI) in sex drive or energy: level 1 was at least “a little better” and level 2 was at least “much better” in energy or sex drive on the Patient Global Impression of Improvement at study end point. PRI in erectile function was stratified by erectile dysfunction severity at baseline as measured by the erectile function domain of the International Index for Erectile Function: mild at baseline (change of 2), moderate at baseline (change of 5), and severe at baseline (change of 7). Associations of demographic and clinical characteristics with PRI were calculated with stepwise forward multiple logistic regression analysis. Odds ratios represented the likelihood of PRI in symptoms among variable categories. ResultsHigher levels of end-point testosterone were associated with higher rates of PRI (at levels 1 and 2) in sex drive and energy (P < .001 for the two comparisons). Lower baseline testosterone levels were associated with higher rates of level 1 PRI in sex drive (P = .028); and classic hypogonadism (vs non-classic hypogonadism) was associated with higher rates of level 2 PRI in sex drive (P = .005) and energy (P = .006). ConclusionWhen assessing the potential for improvements in men with testosterone deficiency using patient-reported outcome questionnaires, possible predictors of treatment outcomes to consider include the etiology of hypogonadism and testosterone levels (baseline and end point).

Factors Predicting the Off-treatment Duration in Patients with Prostate Cancer Receiving Degarelix as Intermittent Androgen Deprivation Therapy

BackgroundIntermittent androgen deprivation therapy (IAD) is commonly used in prostate cancer because of the benefits of the off-treatment period (OTP). The off-treatment time for patients depends on cancer progression, often measured as a rise in prostate-specific antigen (PSA). ObjectiveTo evaluate if certain factors can predict OTP duration following 7-mo degarelix therapy. Design, setting, and participantsThis multivariable analysis included 191 prostate cancer patients with baseline PSA 4–50 ng/ml or PSA doubling time <24 mo entering the first OTP with PSA ≤4 ng/ml and testosterone <0.5 ng/ml. OTP continued until disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP maximum of 24 mo, a 50% failure rate was not observed within certain strata. A Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted for the following variables: age; baseline (or end of induction period [EOI]) PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason score. According to the results and the utility of these factors in clinical practice, the model was reduced in a stepwise manner. Time to testosterone recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner. ResultsThe full five-factor model showed that baseline PSA (p<0.0001), age (p=0.004), prostate cancer stage/previous therapy (p=0.023), and baseline testosterone (p=0.039) influenced OTP. A reduced two-factor model (baseline PSA, age) showed that only baseline PSA influenced OTP (p<0.0001), and patients with baseline PSA ≤4 ng/ml had the longest OTP. In addition, EOI PSA (p<0.0001) and age (p=0.050) significantly influenced OTP. The times to testosterone >0.5 and >2.2 ng/ml were longer for older patients and those with lower baseline testosterone levels. ConclusionPatients with lower baseline and EOI PSA, and older patients can stay off therapy longer and therefore may benefit more from degarelix IAD. These factors may help in proposing an algorithm to predict the OTP and optimise visit frequency. Patient summaryWe describe extended analysis results for a trial in which patients with prostate cancer received intermittent androgen deprivation treatment. Prostate-specific antigen levels at baseline and at the end of the induction period, as well as older age, predicted the duration of the off-treatment period. Testosterone recovery was slower in older patients and in patients who had lower pretreatment testosterone levels. These factors may help in deciding whether to choose continuous or intermittent treatment as a strategy. Trial registrationClinicaltrials.gov NCT00801242

On model selections for repeated measurement data in clinical studies.

Repeated measurement designs have been widely used in various randomized controlled trials for evaluating long-term intervention efficacies. For some clinical trials, the primary research question is how to compare two treatments at a fixed time, using a t-test. Although simple, robust, and convenient, this type of analysis fails to utilize a large amount of collected information. Alternatively, the mixed-effects model is commonly used for repeated measurement data. It models all available data jointly and allows explicit assessment of the overall treatment effects across the entire time spectrum. In this paper, we propose an analytic strategy for longitudinal clinical trial data where the mixed-effects model is coupled with a model selection scheme. The proposed test statistics not only make full use of all available data but also utilize the information from the optimal model deemed for the data. The performance of the proposed method under various setups, including different data missing mechanisms, is evaluated via extensive Monte Carlo simulations. Our numerical results demonstrate that the proposed analytic procedure is more powerful than the t-test when the primary interest is to test for the treatment effect at the last time point. Simulations also reveal that the proposed method outperforms the usual mixed-effects model for testing the overall treatment effects across time. In addition, the proposed framework is more robust and flexible in dealing with missing data compared with several competing methods. The utility of the proposed method is demonstrated by analyzing a clinical trial on the cognitive effect of testosterone in geriatric men with low baseline testosterone levels.

Winning Isn't Everything: Mood and Testosterone Regulate the Cortisol Response in Competition

Dominance contests are recurrent and widespread causes of stress among mammals. Studies of activation of the stress axis in social defeat – as reflected in levels of adrenal glucocorticoid, cortisol – have generated scattered and sometimes contradictory results, suggesting that biopsychological individual differences might play an important mediating role, at least in humans. In the context of a larger study of the regulation of endocrine responses to competition, we evaluated the notion that mood states, such as self-assurance and hostility, may influence cortisol reactivity to dominance cues via an interplay with baseline testosterone, considered as a potential marker of individual differences in dominance. Seventy healthy male university students (mean age 20.02, range 18–26) provided saliva samples before and after competing for fifteen minutes on a rigged computer task. After a winner was determined, all participants were assessed on their mood states through a standardized psychometric instrument (PANAS-X). Among winners of a rigged videogame competition, we found a significant interaction between testosterone and self-assurance in relation to post-competition cortisol. Specifically, self-assurance was associated with lower post-competition cortisol in subjects with high baseline testosterone levels, but no such relationship was observed in subjects with lower baseline testosterone levels. In losers of the competition no interaction effect between basal testosterone and hostility was observed. However, in this subgroup a significant negative relationship between basal testosterone and post-competition cortisol was evident. Overall, these findings provide initial support for the novel hypothesis that biological motivational predispositions (i.e. basal testosterone) and state (i.e. mood changes) may interact in regulating the hypothalamic-pituitary-adrenal axis activation after a social contest.

Effect of Testosterone Replacement on Response to Sildenafil Citrate in Men With Erectile Dysfunction

Erectile dysfunction and low testosterone levels frequently occur together. To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels. Randomized, double-blind, parallel, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00512707) Outpatient academic research center. Men aged 40 to 70 years with scores of 25 or less for the erectile function domain (EFD) of the International Index of Erectile Function, total testosterone levels less than 11.45 nmol/L (<330 ng/dL), or free testosterone levels less than 173.35 pmol/L (<50 pg/mL). Sildenafil dose was optimized, and 140 participants were then randomly assigned to 14 weeks of daily transdermal gel that contained 10-g testosterone for 70 participants and placebo for the remaining 70 participants. All participants were included in the primary analysis, although 10 in the testosterone group and 12 in the placebo group did not complete the study. At baseline, the 2 groups had similar EFD scores. Administration of sildenafil alone was associated with a substantial increase in EFD score (mean, 7.7 [95% CI, 6.5 to 8.8]), but change in EFD score after randomization did not differ between the groups (difference, 2.2 [CI, -0.8 to 5.1]; P = 0.150). The findings were similar for other domains of sexual function in younger men, more obese men, and men with lower baseline testosterone levels or an inadequate response to sildenafil alone. Frequency of adverse events was similar for testosterone and placebo groups. Whether testosterone could improve erectile function without sildenafil was not studied. Sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with erectile dysfunction and low testosterone levels. National Institute of Child Health and Human Development.

Recovery of serum testosterone after neoadjuvant androgen deprivation therapy and radical radiotherapy in localized prostate cancer

To prospectively evaluate the time-course of recovery of serum testosterone levels after a short course of luteinizing hormone-releasing hormone analogue (LHRHa) and radical radiotherapy to the prostate. Testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were sequentially measured prospectively in 59 men who received short-course LHRHa treatment and radiotherapy for localized prostate cancer. Measurements were made before treatment (baseline), during LHRHa treatment, and at 6, 12, 18, 24 and >40 weeks after the last LHRHa injection. The median (range) time from the first to last LHRHa injection was 116 (54-194) days. The mean (95% confidence interval) testosterone levels (in nmol/L) at baseline, during treatment and at 6, 12, 18, 24 and >40 weeks afterward were 12.0 (10.8-13.1), 0.6 (0.5-0.7), 1.4 (0.6-2.2), 11.4 (9.7-13), 12.2 (10.5-14), 10.4 (8.9-12) and 11.7 (10.5-13). Four men had low baseline testosterone levels (<6.1 nmol/L). At 6 weeks after the last LHRHa injection, no men had testosterone levels in the 'normal' range; 35% were in the normal range at 12 weeks, 85% at 18 weeks, 89% at 24 weeks, and 96% at 1 year. After LHRHa treatment and radiotherapy, the testosterone levels of most men had recovered to normal by 18-24 weeks after the last LHRHa injection.

Testosterone and erectile dysfunction

The role of testosterone on sexual desire, interest and motivation is well established, but its effects on erectile function remain controversial. Animal data show that experimental or medical castration results in loss of the intracavernosal pressure, smooth muscle/connective tissue balance, and penile tissue concentration of nitric oxide synthase-containing nerves, which alter the fibroelastic properties of penile tissue compliance, leading to veno-occlusive dysfunction and therefore erectile dysfunction. Castration also induces apoptosis of penile erectile tissue, and new DNA synthesis is induced by treatment with testosterone. In an animal model of venogenic erectile dysfunction, intracavernous vascular endothelial growth factor (VEGF), in addition to testosterone, restores the smooth muscle/connective tissue balance, endothelial cell hypertrophy and hyperplasia and normalizes the diameter of the dorsal nerve fibres, thereby preventing veno-occlusive dysfunction. There is some evidence that treatment with testosterone may be beneficial to men with erectile dysfunction who have low baseline testosterone levels. Androgens may also control the expression and activity of phosphodiesterase type-5 (PDE-5) in the penile corpus cavernosum. Oral drug therapy with PDE-5 inhibitors fails in some patients with erectile dysfunction. However, when testosterone is used together with a PDE-5 inhibitor, sexual function is restored in these patients, creating the potential for pharmacological combination therapy with testosterone for the treatment of erectile dysfunction.

Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia

Objectives To examine the effect of finasteride on serum testosterone in men with benign prostatic hyperplasia (BPH). Methods The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year trial comparing the safety and efficacy of finasteride 5 mg with placebo in 3040 men with moderate to severe symptomatic BPH and enlarged prostates. PLESS included the prospective measurement of annual serum testosterone in a randomly selected subset of patients comprising approximately 10% of the randomized population (n = 301). Results Finasteride treatment led to a modest, but significant ( P <0.001), increase relative to placebo in serum testosterone, with this increase greatest in patients who had low baseline testosterone levels. The larger testosterone increases seen in finasteride-treated patients in the lower baseline testosterone tertiles were associated with significant mean reductions relative to placebo at year 4 in body mass index (BMI), ranging from 0.6 to 0.8 kg/m 2. No statistically significant between-group difference was found in BMI in the upper testosterone tertile. The sexual adverse experience profiles for finasteride and placebo were similar across the baseline testosterone cohorts examined. Conclusions Finasteride treatment led to a generally modest increase relative to placebo in serum testosterone, with the greatest increases occurring in men with low baseline testosterone levels. The physiologic significance of these changes in men with low baseline testosterone levels is unclear, but the associated reduction in BMI is intriguing and may be related, because BMI is known to be negatively correlated with serum testosterone levels in men.