Nathan Wilken

Hypogonadal symptoms in young men are associated with a serum total testosterone threshold of 400 ng/dL.

To investigate the association between hypogonadal symptoms and serum total testosterone (TT) levels in young men (aged <40 years), in an attempt to determine whether there exists a clear‐cut discriminatory threshold of TT below which hypogonadal symptoms become more prevalent.

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia

OBJECTIVE To identify gene dosage changes associated with nonobstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH). DESIGN Prospective study. SETTING Medical school. PATIENT(S) One hundred ten men with NOA and 78 fertile controls. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy number variations (CNVs); Taqman CNV assays to validate CNVs; mutation identification by Sanger sequencing; and histological analyses of testicular tissues. RESULT(S) A microduplication at 20q11.22 encompassing E2F transcription factor-1 (E2F1) was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and in an additional 102 men with NOA screened using Taqman CNV assays, for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls. CONCLUSION(S) E2F1 microduplications or microdeletions are present in men with NOA (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or overexpressing E2f1.

Hypogonadal Symptoms Are Associated With Different Serum Testosterone Thresholds in Middle-aged and Elderly Men

OBJECTIVE To determine the association between hypogonadal symptoms and total serum testosterone levels in middle-aged and elderly men (aged > 40 years), and to identify whether there exists a clear-cut discriminatory threshold of total testosterone below which the probability of hypogonadal symptoms increases. METHODS We retrospectively reviewed the charts of 360 men who presented to an outpatient mens health clinic with a chief complaint of low testosterone. Sexual, psychological, and physical symptoms were evaluated using the androgen deficiency in the aging male (ADAM) questionnaire. Serum levels of total testosterone were collected on the same day on which men completed their ADAM questionnaires. We performed the univariate (t test, chi-square, and binary logistic regression) and multivariate analyses (binary logistic regression) to evaluate the total testosterone threshold and the symptoms that predicted a low-testosterone level. RESULTS A cluster of symptoms: 1 sexual (decreased libido), 1 psychological (decreased energy), and 3 physical (decreased strength or endurance, decreased ability to play sports, and falling asleep after dinner) were most associated with total serum testosterone levels of ≤ 300 ng/dL. The threshold testosterone serum levels that were associated with an increased prevalence of these hypogonadal symptoms ranged from 320 to 375 ng/dL. On multivariate analysis, age, but not symptoms on the ADAM questionnaire, predicted a total testosterone level of < 300 ng/dL. CONCLUSION A distinct constellation of hypogonadal symptoms exists at various serum testosterone levels. Consequently, identification of the thresholds for specific symptom management will be critical in establishing patient-centered treatment algorithms.

Re: Effect of Bipolar Androgen Therapy for Asymptomatic Men with Castration-resistant Prostate Cancer: Results from a Pilot Clinical Study

assessing the association between testosterone levels and outcomes at different times during follow-up would have been helpful to determine the consistency of prognostic value of testosterone levels, specifically at the time of CRPC. Finally, investigations regarding the impact of clinical patient characteristics, type of ADT, and androgen metabolism on the testosterone response might have been helpful to identify potential confounders that contributed to castration failure. Despite these limitations, we believe that this study represents a first step toward the identification of predictors and prognosticators for the selection of patients with BCR who may benefit from early and intensive systemic therapy.

Effect of testosterone supplementation on symptoms in men with hypogonadism.

Testosterone supplementation regimens are efficacious for improving both hypogonadal symptoms and serum total testosterone levels. Younger men appear to respond better to symptom improvement following testosterone therapy.

Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men

Introduction: Both clomiphene citrate (CC) and testosterone supplementation therapy (TST) are effective treatments for men with hypogonadism. We sought to compare changes in symptoms and treatment efficacy in hypogonadal men before and after receiving CC and TST. Patients and Methods: 52 men who received TST and 23 men who received CC for symptomatic hypogonadism were prospectively followed for change in hormone levels and symptoms after treatment. These men were also compared to eugonadal men who were not on CC or TST during the same period. Comparisons were made between baseline and posttreatment hormone levels and symptoms. Symptoms were evaluated using the androgen deficiency in aging male (ADAM) and quantitative ADAM (qADAM) questionnaires. Results: Serum total testosterone increased from pretreatment levels in all men (P < 0.05), regardless of therapy type (TST: 281–541 ng/dL, CC: 235.5–438 ng/dL). Men taking TST reported fewer ADAM symptoms after treatment (5–2, P < 0.05). Similarly, men taking CC reported fewer ADAM symptoms after treatment (3.5–1.5, P < 0.05). Conversely, eugonadal men had similar T levels (352 vs. 364 ng/dL) and hypogonadal symptoms (1.5 vs. 1.4) before and after follow-up. When we evaluated individual symptoms, men treated with TST showed significant increases in qADAM scores in libido, erectile function, and sports performance. However, among the men who received CC, qADAM subscore for libido was lower following treatment (3.75–3.2, P = 0.04), indicating that CC could have an adverse effect on libido in hypogonadal men. Conclusions: Both TST and CC are effective medications in treating hypogonadism; however, our study indicates that TST is more effective in raising serum testosterone levels and improving hypogonadal symptoms. CC remains a viable treatment modality for hypogonadal men but its adverse effect on libido warrant further study.