Alvin Matsumoto

Alvin Matsumoto
University of Washington Seattle | UW · Department of Medicine

Doctor of Medicine

About

315
Publications
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27,932
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Publications

Publications (315)
Article
Background Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). Methods We evaluated...
Article
Context Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase. Objective To analyse associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men. Design, setting and partic...
Article
Objective: Serum testosterone concentrations are affected by factors unrelated to hypothalamo-pituitary-testicular axis pathology. We evaluated the impact of sociodemographic, lifestyle and medical factors, on serum testosterone and sex hormone-binding globulin (SHBG) in men aged 40-69 years. Design: Cross-sectional analysis of 208,677 community...
Article
Objective Aging in male adults is typically accompanied by adiposity accumulation and changes in circulating sex hormone concentrations. We hypothesized that an aging‐associated increase in estrogens and decrease in androgens would correlate with an increase in adiposity. Design 10‐year prospective, observational study Study Subjects 190, communi...
Article
Full-text available
The prostate-expressed sulfotransferase SULT2B1b (SULT2B) regulates intracrine androgen homeostasis by mediating 3β-sulfation of DHEA, thus reducing the precursor pool in the androgen biosynthesis pathway. We explored how loss of SULT2B might influence prostate cancer progression. Results show that SULT2B ablation in castration-resistant prostate c...
Article
Full-text available
Introduction This study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events, cancer, dementia and mortality risk, and to identify factors predicting testosterone concentrations. Data will be accrued from at...
Article
SULT2B1b (SULT2B) is a prostate-expressed hydroxysteroid sulfotransferase, which may regulate intracrine androgen homeostasis by mediating 3β-sulfation of DHEA, the precursor for DHT biosynthesis. The aldo-keto reductase AKR1C3 regulates androgen receptor (AR) activity in castration-resistant prostate cancer (CRPC) by promoting tumor-tissue androge...
Article
Objective: Recent results from the Cardiovascular (CV) Trial of the Testosterone(T) Trials showed that T treatment of older men with low T was associated with greater progression of non-calcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the T Trial. Meth...
Article
Full-text available
Background: Testosterone is a driver of prostate cancer (PC) growth via ligand-mediated activation of the androgen receptor (AR). Tumors that have escaped systemic androgen deprivation, castration-resistant prostate cancers (CRPC), have measurable intratumoral levels of testosterone, suggesting that a resistance mechanism still depends on androgen...
Article
Context Prostate specific antigen (PSA) changes during testosterone treatment of older hypogonadal men have not been rigorously evaluated. The Endocrine Society Guidelines recommendation of urological referral for a confirmed increase in PSA >1.4 ng/mL is not based on PSA changes in testosterone-treated men. Design Double-blinded, placebo-controll...
Conference Paper
Background: Anti-androgen therapies suppress castration-resistant prostate cancer (CRPC) but CRPC cells develop resistance. One of the mechanisms of resistance is through overexpression of androgen receptor (AR) and AR splice variants. In contrast to AR pathway inhibition therapies, recent clinical studies using bipolar androgen therapy demonstrate...
Article
Background: Androgen deprivation therapy improves the survival of castration-resistant prostate cancer (CRPC) patients, yet ultimately fails with debilitating side effects. Supraphysiological testosterone (SPT)-based therapy produces clinical responses with improved quality of life in a subset of patients. Currently, no information defines a durab...
Article
208 Background: The association of serum ABI and androgen levels with clinical efficacy in men with CRPC is not well understood. Methods: We measured androgens, ABI and its key metabolites (D4A and 5α) in serum at 4, 8, and 12 weeks (wks) in 29 men with CRPC treated with ABI (for associations with PSA response and time to radiographic progression (...
Article
We compared osteoporosis case-finding, evaluation and treatment in groups of Older Men and Older Women with age alone as a significant risk for fracture and Older Men with Higher Risk (older men additionally having previous hip fracture, corticosteroid use or androgen deprivation therapy). We studied 13,704 older men and women (≥70 years old) recei...
Article
Objective This study aimed to determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men. Methods A total of 41 adult men (aged 18‐50 years) from 23 twin pairs underwent fasting morning blood draw and brain magnetic resonance imaging. T2 relaxation time was used t...
Article
Background: The Physical Function Trial (PFT) was one of seven Testosterone Trials (TTrials), the aim of which was to assess the effect of testosterone on mobility, self-reported physical function, falls, and patient global impression-of-change (PGIC) in older men with low testosterone concentrations, self-reported mobility limitation, and walking...
Article
Full-text available
Purpose: Tumor androgens in castration resistant prostate cancer (CRPC) reflect de novo intra-tumoral synthesis or adrenal androgens. We used C.B.-17 SCID mice in which we observed adrenal CYP17A activity to isolate the impact of adrenal steroids on CRPC tumors in vivo Experimental Design: We evaluated tumor growth and androgens in LuCaP35CR and L...
Article
Objective The purpose of this narrative review is to summarize available data on testosterone levels in normal, healthy adult males and females, to provide a physiologic reference framework to evaluate testosterone levels reported in males and females with conditions that elevate androgens, such as disorders of sex development (DSD), and to determi...
Article
Background: Limited information is available on the performance characteristics of 2 questionnaires commonly used in clinical research, the Psychosexual Daily Questionnaire (PDQ) and the Derogatis Interview for Sexual Function (DISF)-II Assessment, especially in older men with low testosterone (T) and impaired sexual function. Aim: To determine...
Article
Full-text available
Purpose Testosterone treatment of men with low testosterone is common and, although relatively short-term, has raised concern regarding an increased risk of prostate cancer (CaP). We investigated the association between modest-duration testosterone treatment and incident aggressive CaP. Materials and methods Retrospective inception cohort study of...
Data
Association between cumulative dose and aggressive prostate cancer by formulation. (DOCX)
Data
Association between cumulative dose and any prostate cancer by formulation. (DOCX)
Data
Study cohort inclusion and exclusion. (DOCX)
Article
Objective To update the “Testosterone Therapy in Men With Androgen Deficiency Syndromes” guideline published in 2010. Participants The participants include an Endocrine Society–appointed task force of 10 medical content experts and a clinical practice guideline methodologist. Evidence This evidence-based guideline was developed using the Grading...
Article
The Testosterone Trials (TTrials) were a coordinated set of seven, placebo-controlled, double blind trials in 788 men of mean age 72 years to determine the efficacy of increasing the testosterone levels of older men with low testosterone. Testosterone treatment increased the median testosterone level from unequivocally low at baseline to midnormal...
Article
Background Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined. Hypothesis Low serum androgens are associated with an increased risk of AF. Methods We examined the prospective associations between testosterone, its...
Article
Context Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective To determine the effect of testosterone treatment on cardiovascular (CV) biomarkers in older men with low testosterone. Design Double-blind, placebo-controlled trial Setting Twelve academic medical centers in the United States Participants...
Article
KEY POINTS 1.Falls are a major health issue for older adults, leading to adverse events and even death. 2.Older persons with type 2 diabetes are at increased risk of falling compared to healthy adults of a similar age. 3.Over 400 factors are associated with falls risk, making identification and targeting of key factors to prevent falls problematic....
Article
Sarcopenia is defined as low muscle function (walking speed or grip strength) in the presence of low muscle mass. A simple screening test-the SARC-F-is available to identify persons with sarcopenia. The major endocrine causes of sarcopenia are diabetes mellitus and male hypogonadism. Other causes are decreased physical activity, loss of motor neuro...
Article
Full-text available
In circulation, testosterone and other sex hormones are bound to binding proteins which play an important role in regulating their transport, distribution, metabolism, and biologic activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Conse...
Article
In Reply Dr Martins and colleagues note that our definition of AAMI was broad with respect to the definition of subjective memory complaints and in the cutoffs used to exclude objective impairment in memory, the latter potentially resulting in inclusion of some men with mild cognitive impairment and dementia. Although our criteria may have resulted...
Article
Full-text available
Purpose: Germline variation in solute carrier organic anion (SLCO) genes influences cellular steroid uptake and is associated with prostate cancer (PCa) outcomes. We hypothesized that, due to its steroidal structure, the CYP17A inhibitor abiraterone may undergo SLCO-mediated transport and that SLCO gene variation may influence intracellular abirat...
Article
Objective: Serum sex steroid concentrations may alter body composition and glucose homeostasis in men in a dose-response manner. We evaluated these endpoints in healthy men rendered medically castrate through use of a gonadotropin-releasing hormone antagonist (acyline) with incremental doses of exogenous testosterone (T) gel. Design: Subjects (n...
Article
Importance: As men age, they experience decreased serum testosterone concentrations, decreased bone mineral density (BMD), and increased risk of fracture. Objective: To determine whether testosterone treatment of older men with low testosterone increases volumetric BMD (vBMD) and estimated bone strength. Design, setting, and participants: Plac...
Article
Importance: In one-third of older men with anemia, no recognized cause can be found. Objective: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. Design, setting, and participants: A double-blinded, placebo-controlled...
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Full-text available
Importance Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. Objective To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (...
Article
Full-text available
Importance Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants Double-blinded, placebo-co...
Article
Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating cohort-specific assays to a reference method and standard. Population: 9054 community-dwelling...
Article
Full-text available
Purpose: Prostate cancer is dependent on androgen receptor (AR) activation. Optimal AR antagonism may effectively cytoreduce local disease and suppress or eliminate micrometastases. We evaluated neoadjuvant therapy prior to prostatectomy with the potent AR antagonist enzalutamide (enza) either alone or in combination with dutasteride and leuprolid...
Article
Background: Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives: Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), D...
Article
Context: Although sex hormone binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, or older adults, whose glycemic pathophysiology differs from younger adults. Objective: To determine the associations of SHBG, T, and...
Article
Purpose: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. Experimental design: Eli...
Article
Context: Testosterone deprivation increases risk of insulin resistance in men, but whether this risk is independent of changes in body composition is unknown. Further, the metabolic roles of testosterone and its metabolite estradiol have not been clearly defined in men. Objective: To establish the effects of selective sex steroid withdrawal on i...
Article
Full-text available
Context: The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function. Objective: To assess the responsiveness of specific sexu...
Article
Context: Concern exists that testosterone replacement therapy (TRT) might increase the risk of prostate disease. There is limited data regarding the impact of TRT on prostate androgen concentrations. Objective: Determine the dose-dependent effects of exogenous testosterone (T) administration on intraprostatic androgen concentrations. Design: 1...
Article
Background Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. Methods We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone g...
Chapter
In antiquity, animal testes were prescribed to treat symptoms of androgen deficiency. In 1889, CE Brown-Séquard reported rejuvenating effects after self-administering aqueous extracts of animal testes, resulting in accelerated use of organotherapy. In 1935, E Laqueur identified the potent androgen, androsten-17α-ol-3-one, from bull testes and coine...
Article
Objective: To review the doping status of dehydroepiandrosterone (DHEA) for female athletes with adrenal insufficiency within the framework of Therapeutic Use Exemption (TUE) applications for this proandrogen, which is included on the World Anti-Doping Agency (WADA)'s Prohibited List. Data sources and main results: Current knowledge of adrenal p...
Article
Problem: The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen defi...
Article
Introduction: Clinical practice guidelines recommend that testosterone (T) levels be measured on ≥2 occasions to confirm a diagnosis of hypogonadism, gonadotropins be measured to determine whether hypogonadism is primary or secondary, and T levels be measured to monitor the adequacy of T therapy. However, it is not known whether hormone testing as...
Article
The optimal frequency for on-treatment serum testosterone (T) measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance. To determine variability of post-gel application serum T concentrations and assess whether single levels are reflective of averag...
Article
We describe the recruitment of men for The Testosterone (T) Trials, which were designed to determine the efficacy of T treatment. Men were eligible if they were ≥65 years, had an average of two morning total T values <275ng/dL with neither value >300ng/mL, and had symptoms and objective evidence of mobility limitation, sexual dysfunction, and/or lo...
Article
Total testosterone concentrations are influenced by sex hormone binding globulin (SHBG) concentrations, which are decreased by obesity and increased with aging. Therefore, we sought to understand and compare the associations of aging and obesity with SHBG. We performed a retrospective, cross-sectional analysis of the associations of obesity and age...
Article
Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) wit...
Article
Low serum testosterone (T) is common and increasingly prevalent with increased age. Recent studies report an 'epidemic' of T prescribing and concern about unnecessary T treatment. We investigated the number of men tested for T, the prevalence of low serum T levels, and initiation of T treatment among those with low T levels in men treated at Vetera...
Article
Context: The prevalence of sexual dysfunction, low vitality, and poor physical function increases with aging, as does the prevalence of low total and free testosterone (TT and FT) levels. However, the relationship between sex hormones and age-related alterations in older men is not clear. Objective: To test the hypotheses that baseline serum TT,...
Article
Introduction: This study investigated the effects of testosterone (T) treatment on cognition, mood, and quality of life in men with mild cognitive impairment (MCI) and low serum T levels. Methods: A total of 351 community-dwelling men were screened, and 37 men evidenced both MCI and low T of whom 27 agreed for further screening. Twenty-two met a...
Article
Full-text available
Background: Factors influencing differential responses of prostate tumors to androgen receptor (AR) axis-directed therapeutics are poorly understood, and predictors of treatment efficacy are needed. We hypothesized that the efficacy of inhibiting DHT ligand synthesis would associate with intra-tumoral androgen ratios indicative of relative depende...
Article
Full-text available
Purpose: Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone-releasing hormone agonist (LHRHa; leuprolide ace...
Article
The purpose of this study is to review recent studies that examined the association of endogenous and exogenous testosterone and mortality in older men. Over the past several years, there has been a steep rise in testosterone prescriptions. The increased use of testosterone occurred in the context of several studies that reported an association bet...
Article
Testosterone remains a key target in the treatment of advanced prostate cancer. The relationship of free testosterone to prostate cancer treatment and outcomes remains largely unexplored. A consensus of prostate cancer experts was convened in 2013 to review current knowledge surrounding relationship of total and free testosterone to prostate cancer...
Article
Full-text available
Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone co...
Article
Context: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this. Objective: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality. Design: In a long...
Article
Objective Ischemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine if testosterone (T) or dihydrotestosterone (DHT) were associated with incident ischemic stroke in elderly men.DesignCohort study.ParticipantsElderly men in the Cardiovascular Health Study who had no history of stroke, heart diseas...
Article
Full-text available
Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Thirt...
Article
In a carefully conducted, outstanding example of clinical research, Finkelstein et al. clearly demonstrate the physiological underpinnings for the action of testosterone and the relative roles of its androgenic and estrogenic effects on body composition and sexual function. This study has important clinical implications for testosterone replacement...
Article
The only indication for testosterone administration in older men is testosterone replacement therapy for male hypogonadism. Compared with young hypogonadal men, the diagnosis and management of male hypogonadism in older men is more challenging. Both the clinical manifestations of androgen deficiency and low testosterone levels may be caused or modi...