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Sexual Function in Men with Castrate Levels of Testosterone: Observations of a Subgroup of Sexually Active Men with Prostate Cancer Undergoing Androgen Deprivation Therapy  [PDF]
Evan Ng, Tammy Corica, Sandra Turner, Adeline Lim, Nigel Spry
Open Journal of Urology (OJU) , 2014, DOI: 10.4236/oju.2014.47017
Abstract:

Purpose: To identify possible factors that influence sexual function in men undergoing maximal androgen deprivation therapy (ADT). Patients and Methods: A descriptive exploration was performed looking at characteristics of twenty-two men reporting sexual activity after nine months of maximal ADT. This previously published Phase II study, involved 250 prostate cancer patients undergoing intermittent ADT. An analysis between this cohort and the group that did not maintain sexual function was performed to ascertain if age, testosterone level, functional status or maintenance of quadriceps strength had an impact upon sexual function. Results: There was no difference in age, testosterone level or ECOG performance status between the sexually active and non-sexually active groups. Over the course of 9 months of ADT, the sexually active group appeared to maintain quadriceps muscle strength as measured with physical stands, and maintained overall health as measured by quality of life questionaries, compared to the non-sexually active group. Conclusions: This retrospective study suggests that exercise during ADT may reduce the impact of ADT on sexual function. This warrants further testing, and could be the focus of future randomised controlled trials.

Low Testosterone Correlates with Delayed Development in Male Orangutans  [PDF]
Melissa Emery Thompson, Amy Zhou, Cheryl D. Knott
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047282
Abstract: Male orangutans (Pongo spp.) display an unusual characteristic for mammals in that some adult males advance quickly to full secondary sexual development while others can remain in an adolescent-like form for a decade or more past the age of sexual maturity. Remarkably little is understood about how and why differences in developmental timing occur. While fully-developed males are known to produce higher androgen levels than arrested males, the longer-term role of steroid hormones in male life history variation has not been examined. We examined variation in testosterone and cortisol production among 18 fully-developed (“flanged”) male orangutans in U.S. captive facilities. Our study revealed that while testosterone levels did not vary significantly according to current age, housing condition, and species origin, males that had undergone precocious development had higher testosterone levels than males that had experienced developmental arrest. While androgen variation had previously been viewed as a state-dependent characteristic of male developmental status, our study reveals that differences in the physiology of early and late developing males are detectable long past the developmental transition and may instead be trait-level characteristics associated with a male’s life history strategy. Further studies are needed to determine how early in life differences in testosterone levels emerge and what consequences this variation may have for male behavioral strategies.
The role of testosterone in type 2 diabetes and metabolic syndrome in men
Saad, Farid;
Arquivos Brasileiros de Endocrinologia & Metabologia , 2009, DOI: 10.1590/S0004-27302009000800002
Abstract: over the last three decades, it has become apparent that testosterone plays a significant role in glucose homeostasis and lipid metabolism. the metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis and cardiovascular morbidity and mortality. the main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a pro-inflammatory and thrombogenic state. cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. lower total testosterone and sex hormone-binding globulin (shbg) predict a higher incidence of the metabolic syndrome. there is evidence that hypotestosteronemia should be an element in the definition of the metabolic syndrome since low levels of testosterone are associated with or predict the development of the metabolic syndrome and of diabetes mellitus. administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis. so far, studies on the effects of normalization of testosterone in hypogonadal men on glucose homeostasis are limited, but convincing, and if diabetes mellitus is viewed in the context of the metabolic syndrome, the present results of testosterone treatment are very encouraging.
Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays
Daniel P. Venancio,Monica L. Andersen,Patricia S. L. Vilamaior,Fernanda C. Santos,Adriano Zager,Sérgio Tufik,Sebasti o R. Taboga,Marco T. De Mello
Journal of Biomedicine and Biotechnology , 2012, DOI: 10.1155/2012/285938
Abstract: We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR.
A delayed mathematical model for testosterone secretion with feedback control mechanism
Banibrata Mukhopadhyay,Rakhi Bhattacharyya
International Journal of Mathematics and Mathematical Sciences , 2004, DOI: 10.1155/s0161171204307271
Abstract: A mathematical model describing the biochemical interactions of the luteinizing hormone (LH), luteinizing hormone–releasing hormone (LHRH), and testosterone (T) is presented. The model structure consists of a negative feedback mechanism with transportation and secretion delays of different hormones. A comparison of stability and bifurcation analysis in the presence and absence of delays has been performed. Mathematical implications of castration and testosterone infusion are also studied.
Comparison of the Results of Early and Delayed Inpatient Stroke Rehabilitation
Berat Meryem ALKAN,Canan ?ULHA,Hanife ?A?LAR YA?CI
Türkiye Fiziksel Tip ve Rehabilitasyon Dergisi , 2013, DOI: 10.4274/tftr.02693
Abstract: Objective: This study was designed to investigate the best time to start rehabilitation and to identify the predictors of functional outcomes after rehabilitation in patients with stroke after their first cerebrovascular accident.Materials and Methods: A total of 138 stroke patients who had their first stroke were divided into 5 groups according to the time elapsed from the cerebrovascular accident to the onset of rehabilitation (first 20 days, 21-40, 41-60, 61-80, and 81-100 days). Motor status of the patients was evaluated with the Brunnstrom Recovery Scale (BRS) and their functional status was assessed using the Functional Independence Measure (FIM) at admission and discharge. There was no statistically significant difference among the groups in terms of age, gender, localization of the lesion, etiology, and motor and functional status at baseline as well as additional systemic diseases. According to the results of rehabilitation, efficiency (average increase in FIM per day) and effectiveness (proportion of potential improvement achieved during rehabilitation of the groups) were calculated.Results: There was no statistically significant difference among the groups in terms of efficiency and effectiveness. Correlation analysis revealed that efficiency showed negative correlations with shoulder subluxation while efficiency showed a positive correlation with BRS scores of the lower extremities and effectiveness. However, effectiveness showed positive correlations with efficiency, baseline FIM scores, and BRS scores of the hands, arms, and the lower extremities while it was inversely correlated with shoulder subluxation and bladder incontinence.Conclusion: We concluded that starting stroke rehabilitation at any time within the first 100 days following the first stroke did not affect the results of rehabilitation. Therefore, we assume that starting stroke rehabilitation even after a delayed period also seems to be as efficacious as early rehabilitation. Turk J Phys Med Rehab 2013;59:7-12.
Study protocol to investigate the effects of testosterone therapy as an adjunct to exercise rehabilitation in hypogonadal males with chronic heart failure
John M Saxton, Irena Zwierska, Atish Mathur, Kevin S Channer
BMC Cardiovascular Disorders , 2006, DOI: 10.1186/1471-2261-6-46
Abstract: Following ethical approval, 36 patients will be randomly allocated to one of two groups: testosterone or placebo therapy during exercise rehabilitation. A combined programme of moderate intensity aerobic exercise and resistance (strength) training will be used. The primary outcome measure is exercise capacity, assessed using an incremental shuttle walk test. Secondary outcome measures include measures of peak oxygen uptake, cardiac function, lower-limb skeletal muscle contractile function and oxygenation during exercise, circulating inflammatory markers, psychological health status and quality of life.Exercise rehabilitation can safely increase exercise capacity in stable CHF patients but there is a need for studies which are aimed at evaluating the long-term effects of physical training on functional status, morbidity and mortality. This pilot study will provide valuable preliminary data on the efficacy of testosterone therapy as an adjunct to exercise rehabilitation on a range of functional, physiological and health-related outcomes in this patient population. Preliminary data will be used in the design of a large-scale randomised controlled trial, aimed at informing clinical practice with respect to optimisation of exercise rehabilitation in this patient group.Chronic heart failure (CHF) is a common, debilitating condition and is a major public health burden in the Western world. It is a multi-organ disease, involving the musculoskeletal, respiratory and endocrine systems [1]. CHF most frequently results from coronary artery disease or hypertension and patients generally experience a continuing decline in their health, resulting in an increased frequency of hospitalization and premature death. As cardiac transplantation is the only option for long-term survival in patients with CHF, there is a clear requirement for new strategies aimed at altering disease progression, relieving symptoms and prolonging life.Previous studies have reported testosterone deficiency in
The Role of Testosterone in the Etiology and Treatment of Obesity, the Metabolic Syndrome, and Diabetes Mellitus Type 2
Farid Saad,Louis J. Gooren
Journal of Obesity , 2011, DOI: 10.1155/2011/471584
Abstract: Obesity has become a major health problem. Testosterone plays a significant role in obesity, glucose homeostasis, and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a proinflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis.
Metabolic Complications and Increased Cardiovascular Risks as a Result of Androgen Deprivation Therapy in Men with Prostate Cancer  [PDF]
Bhavin R. Shastri,Subhashini Yaturu
Prostate Cancer , 2011, DOI: 10.1155/2011/391576
Abstract: Prostate cancer is one of the most common malignancies in men. Charles Huggins and Clarence V. Hodges reported the androgen dependence of prostate cancer in 1941. That led to the utilization of androgen deprivation therapy as an important therapeutic modality to treat prostate cancer. Androgen deprivation therapy has additional systemic effects that include sexual dysfunction, psychological changes and more important are the metabolic changes. Metabolic changes in particular include insulin resistance, increase fat mass and low-density lipoprotein cholesterol, and induce type 2 diabetes. In this review we will focus on the cardiovascular risk associated with androgen deprivation therapy that includes the mechanisms involved. 1. Introduction Prostate cancer (PC) is one of the most common malignancies in men and the second most common cause of mortality among cancers in men after lung cancer. In recent years, incidence of PC has been rising, probably due to new and effective screening guidelines. The Centers for Disease Control (CDC) reports that in 2007 [1], (the most recent year numbers are available) 223,307 men in the United States were diagnosed with prostate cancer and 29,093 men in the United States died from prostate cancer. Per the report of the National Cancer Institute, 2,311,000 have prostate cancer and the numbers projected for 2020 will be 3,266,000 [2]. Beside watchful waiting, standard treatments for PC are surgery, radiation therapy, and hormone therapy. Androgen dependence of PC was first described by Huggins et al. in 1941 [3]. Depletion of gonadal testosterone through androgen deprivation therapy (ADT) is the frontline treatment for advanced prostate cancer and may be accomplished by medical or surgical castration. In the current era, ADT is the primary therapy for localized disease, as an adjunct to radiation therapy for high-risk localized disease and as treatment for biochemical relapse (prostate-specific antigen (PSA) rise only) after failure of localized therapy, often with uncertain benefits [4, 5]. The modalities of ADT include orchiectomy, radiation, and medical castration (antiandrogens, LHRH agonists LHRH antagonists), with latter being the most commonly used. Continuous pituitary stimulation by GnRH agonists overcomes endogenous pulsatile GnRH and suppresses LH release, resulting in low serum testosterone, rather acting as LHRH antagonists. Besides its benefit, ADT is known to cause several endocrine complications such as osteoporosis, decreased libido, changes in cognition and mood, hot flushes, and gynecomastia [6]. In
An Update on the Changing Indications for Androgen Deprivation Therapy for Prostate Cancer  [PDF]
Kristene Myklak,Shandra Wilson
Prostate Cancer , 2011, DOI: 10.1155/2011/419174
Abstract: Quality of life has become increasingly more important for men diagnosed with prostate cancer. In light of this and the recognized risks of androgen deprivation therapy (ADT), the guidelines and use of ADT have changed significantly over the last few years. This paper reviews the current recommendations and the future perspectives regarding ADT. The benefits of ADT are evident neoadjuvantly and adjuvantly in patients treated with external beam radiation therapy for intermediate- and high-risk disease, in patients who have undergone prostatectomy with lymph node involvement, in high-risk patients after definitive therapy, and in patients who have developed progression or metastasis. Finally, this paper reviews the risks and benefits of each of these scenarios and the risks of androgen deprivation in general, and it delineates the areas where ADT was previously recommended, but where evidence is lacking for its additional benefit. 1. Introduction Prostate cancer is the most frequently diagnosed cancer in males in the United States and has long been associated with hormone dependence [1]. The use of androgen deprivation therapy (ADT) for men with advanced prostate cancer continues to be the recommended therapy. Androgen deprivation is defined as a lowering of serum testosterone through the administration of a luteinizing hormone releasing hormone (LHRH) agonist. However, it has become increasingly apparent that ADT is not without its own risks. ADT-associated risks continue to become more fully elucidated through multiple recently published retrospective and prospective studies. These risks are no longer solely defined by life span and cancer progression but also by how ADT affects quality of life based on a patient’s physical, financial, and emotional well being. There is also evidence that a “middle of the road”, intermittent androgen deprivation therapy (IADT) may soon be appropriate care for some individuals with prostate cancer. This paper examines IADT and the clinical studies that are being done that suggest it as a possible alternative in the future. This paper also reviews the findings of investigations into the risks and benefits of ADT. It will delineate areas where ADT use has been deemed inappropriate/ineffective and summarizes the current clinical situations where ADT use remains recommended. 2. Androgen Deprivation and Associated Adverse Events 2.1. Cardiovascular Disease ADT utilizes the fact that malignant prostate cells require androgen stimulation for growth and division. ADT attempts to deny malignant cells a growth stimulus,
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