Lack Of Testosterone Research Articles

Endocrine Disorders in Nephrotic Syndrome-A Comprehensive Review.

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m2 per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice.

Androgen Deprivation Therapy/Androgen Receptor Signaling Inhibitor Treatments for Prostate Cancer: Pathophysiology and Review of Effects on Cardiovascular Disease.

Androgen deprivation therapy is the cornerstone of systemic management for prostate cancer but is associated with multiple adverse effects that must be considered during treatment. These effects occur because of the profound hypogonadism that is induced from lack of testosterone or due to the medications used in the treatment or in combination with androgen receptor signaling inhibitors. This article critically reviews the associations between androgen deprivation therapy, androgen receptor signaling inhibitors, and cardiovascular complications such as prolonged QT interval, atrial fibrillation, heart failure, atherosclerosis, coronary heart disease, venous thromboembolism, and peripheral arterial occlusive disease. These unfavorable outcomes reinforce the need for regular cardiovascular screening of patients undergoing androgen deprivation for the management of prostate cancer.

Orchidectomy exacerbates respiratory instability induced by intermittent hypoxia in C57BL6/J mice

IntroductionSleep apnea (SA) is characterized by obstructions of the airways or cessation of breathing during sleep leading to intermittent hypoxia (IH). In rodents, exposure to IH induces strong oxidative stress in the peripheral chemoreceptors (the main oxygen sensors inducing cardiorespiratory responses to IH), which increase their activity leading to instability of the respiratory control system, ultimately increasing the frequency of apnea during sleep. In human, patients with SA have low circulating testosterone levels and the severity of SA in overweight patients is negatively correlated with testosterone levels. However, testosterone can reduce oxidative stress in certain animal and clinical models. We therefore tested the hypothesis that testosterone modulates the respiratory instability induced by HI.MethodWe used intact (Sham) or orchidectomized (ORX) C57BL/6J male mice exposed for 14 days to IH (12h / day, 10 cycles / h, 6% nadir oxygen) or in normoxia (Nx). We used whole body plethysmography on freely behaving and non‐anesthetized mice to measure the frequency of apneas and sighs as well as the length of the apneas during sleep. The antioxidant activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were then measured in plasma.ResultsIH increases the frequency of post‐sigh apneas as well as the length of post‐sigh and spontaneous apneas in Sham and ORX mice. In ORX‐IH mice, the length of post‐sigh apneas was further increased, and there was a higher proportion of multiple apneas after a single sigh. In Nx mice, GPx activity was increased by ORX, this effect was not present in mice exposed to IH.ConclusionThe lack of testosterone in ORX mice amplifies the effects of IH on respiratory stability during sleep and alters the regulation of GPx activity in plasma. Further studies are needed to better understand the underlying mechanism

Bipolar Androgen Therapy in the management of prostate cancer

Introduction and purpose: Prostate cancer (PCa) as one of the most frequent neoplasms in men remains a challenge for oncologists. The main strategy of its treatment is the Androgen Deprivation Therapy (ADT) the principle of which is an inducement of hypogonadism. The lack of testosterone is not only a factor greatly contributing to a decrease of quality of life overall, but additionally it increases the odds of the complications, including low libido and erectile disfunction, metabolic abnormalities, high cardiovascular risk, osteoporosis, anaemia, or depression. ADT also has the potential of inducement of castration resistance (CRPC), which significantly worsen patients prognosis. The main purpose of this review is to explore the Bipolar Androgen Therapy (BAT), which has the potential to solve the aforementioned problems.
 State of knowledge: The mechanism of BAT action has been described. BAT is effective not only against CRPC, but androgen-dependant PCa as well. BAT reverses the hormone resistance in CRPC, thus allowing the rechallenging of the ADT. It has the direct cytotoxic effect on cancer cells. Additionally BTA increases the exponents of the general quality of life of the patients. There is a number of active clinical trials regarding BAT.
 Conclusions: BAT is a safe therapeutic strategy with the high efficacy in reversing hormone resistance in CRPC patients, thus significantly increasing their health prognoses and it allows to alleviate or avoid the adverse effects of ADT.

How to manage low testosterone level in men: a guide for primary care.

Male hypogonadism is a clinical syndrome characterised by testosterone deficiency and impaired spermatogenesis; due either to diseases of the hypothalamus or pituitary gland, or of the testes themselves.1 The diagnosis requires the presence of clinical features consistent with lack of testosterone plus the finding of persistent and unequivocally low serum testosterone levels. Failure to recognise and treat men with hypogonadism may predispose them to long-term health problems, such as anaemia, osteoporosis, depression, or sexual dysfunction. Over recent years, there has been a surge in testosterone prescriptions for men with sexual dysfunction or putative age-related decline in testosterone,2 possibly reflecting pharmaceutical promotion, or sharing of misleading information on the internet. With growing demands and expectations of men worried about their wellbeing, there is a real risk of overdiagnosis and unnecessary treatment with testosterone. Suboptimal sampling conditions can lead to misinterpretation of serum biochemistry, and the long-term risks of testosterone therapy for men not having verified hypogonadism may be underestimated by ‘enthusiasts’. ### Diagnosis of hypogonadism Routine screening for hypogonadism in asymptomatic men is not recommended, except in certain conditions (Supplementary Figure S1). Clinical features of hypogonadism are not limited to sexual symptoms — reduced libido, erectile dysfunction (ED), and loss of waking erections. Anaemia, osteoporosis, and vasomotor sweating or flushing are frequently present; indeed, older men may not volunteer sexual symptoms, having ascribed them to ageing. ### Sampling conditions Testosterone secretion has diurnal variation and is suppressed post-prandially, so serum testosterone and sex-hormone binding …

Disruptive effects of neonatal gonadectomy on adult sexual partner preference and brain dimorphism in male rats: partial restoration with pubertal testosterone

According to the organizational-activational hypothesis, testosterone or its metabolite estradiol, can organize the brain in a male direction (permanently or for long periods) if exposure occurs during a critical (sensitive) time of brain development like the prenatal period. Male rodents with insufficient levels of testosterone during such critical period would irreversibly fail to display sexual partner preference for receptive females in adulthood. However, exposure to testosterone during puberty is believed to function as a second critical period for organization of brain and behavior. Thus, in the present study we explored the effects of neonatal gonadectomy at postnatal day 1 (GNX) on the partner preference of adult males and the size of some sexually dimorphic regions in the brain like the SDN-MPOA, SCN, MeApd and VMH; and challenged its irreversibility by providing exogenous testosterone during puberty. Our results indicated that neonatal GNX impaired partner preference for females and reduced the size of SDN-MPOA, MeApd and VMH, but not SCN. GNX males restored with testosterone in PD30-PD59 (GNX + T) expressed partner preference for sexually receptive females and increased the size of SDN-MPOA and VMH, but not MeApd in adulthood. We conclude that neonatal castration and the lack of testosterone during the first month of life alters sexual behavior and brain dimorphism in adult male rats, but pubertal testosterone reverses the effects on behavior and brain dimorphism to some extent.

SUN-306 ESTABLISHING EQUIVALENT DIABETES IN MALE AND FEMALE NOS3 DEFICIENT MICE RESULTS IN SIMILAR ONSET OF DIABETIC KIDNEY DISEASE

Streptozotocin (STZ)-induced diabetes in male mice lacking endothelial nitric oxide synthase (Nos3-/-) is a widely used model for examining the development of diabetic kidney disease (DKD). Female mice are partially protected from developing STZ-induced diabetes due to their abundance of 17β-estradiol and lack of testosterone, and are not normally used for studies of DKD. In this study, we sought to identify whether male and female Nos3-/- mice with equivalent diabetes develop comparable renal injury, facilitating the potential to use both sexes in studies of DKD. Male and female Nos3-/- mice were made diabetic with 5 or 6 intraperitoneal injections of STZ (55mg/kg/day), respectively. Groups of male and female mice with equivalent diabetes at week 3 after STZ were assessed for diabetic kidney injury (albuminuria, podocyte loss, inflammation, renal function impairment, glomerulosclerosis, tubular injury) at week 8. STZ-treated male and female Nos3-/- mice maintained similar elevated blood glucose levels between weeks 3 and 8 and had equivalent levels of glycated hemoglobin (HbA1c) and hypertension. At week 8, Urine albumin/creatinine levels were increased 8-fold in both diabetic males and females compared to non-diabetic, and were accompanied by a similar (17-20%) loss of podocytes. In diabetic males and females, plasma cystatin-C levels were increased by 33% at week 8, demonstrating similar renal function impairment. Glomerular area of collagen IV immunostaining was also similarly increased by 30% in both genders, signifying equal development of glomerulosclerosis. In addition, kidney mRNA expression of proinflammatory markers (CD68, TNF-α, CCL2), profibrotic markers (TGF-β, Collagen I, Collagen IV, Fibronectin) and KIM-1 were equally elevated in males and females, indicating similar renal inflammation, renal fibrosis and tubular injury. Our study shows that equivalent diabetes induces a similar onset of DKD in male and female Nos3-/- mice, demonstrating it is possible to include males and females together in studies of DKD.

Hepatic actions of androgens in the regulation of metabolism.

The purpose of this review is to summarize recent findings on hepatic actions of androgens in the regulation of protein, lipid and glucose metabolism. The rationale for liver-targeted testosterone use will be provided. Liver-targeted testosterone administration, via the oral route, induces protein anabolic effect by reducing the rate of protein oxidation to a similar extent to that of systemic testosterone administration. Recent evidence indicates that testosterone exerts whole-body anabolic effect through inhibition of nitrogen loss via the hepatic urea cycle. Several hepatic effects of androgens, particularly on glucose metabolism, are direct and take place before any changes in body composition occur. This includes an increase in insulin secretion and sensitivity, and reduction in hepatic glucose output by testosterone. Furthermore, lack of testosterone in the liver exacerbates diet-induced impairment in glucose metabolism. In the liver, androgens induce the full spectrum of metabolic changes through interaction with growth hormone or aromatization to estradiol. Liver-targeted testosterone therapy may open up a new approach to achieve whole-body anabolism without systemic side-effects. Aromatizable androgens may be superior to nonaromatizable androgens in inducing a complex spectrum of direct, estrogen-mediated and other hormone-mediated effects of androgens.

Gender Differences in the Progression of Experimental Chronic Kidney Disease Induced by Chronic Nitric Oxide Inhibition.

Chronic kidney disease (CKD) is considered a public health problem, assuming epidemic proportions worldwide. In this context, the preponderance of CKD prevalence in male over age-matched female patients is of note. In the present study, we investigated the impact of the gender on the development of experimental CKD induced by chronic nitric oxide (NO) inhibition in Wistar male and female rats through the administration of L-NAME. CKD model induced by L-NAME is characterized by systemic vasoconstriction, resulting in severe hypertension, albuminuria, renal ischemia, glomerulosclerosis, interstitial expansion, and macrophage infiltration. After 30 days of CKD induction, male NAME rats exhibited remarkable albuminuria, augmented cortical histological damage, interstitial inflammation, and fibrosis. Age-matched female NAME rats showed significantly lower albuminuria, diminished glomerular ischemia, and glomerulosclerosis, as well as a significant reduction in the expression of α-smooth muscle actin renal interstitial Ang II+ cells. Thus, the present study demonstrated that female rats submitted to the NAME model developed less severe CKD than males. Female renoprotection could be promoted by both the estrogen anti-inflammatory activity and/or by the lack of testosterone, related to renin-angiotensin-aldosterone system hyperactivation and fibrogenesis. However, the influence of sex hormones on the progression of CKD needs to be further investigated.

GENDER SPECIFIC DIFFERENCES IN A NEW APOE-/-:INS2+/AKITA MOUSE MODEL OF HYPERGLYCEMIA-INDUCED ATHEROSCLEROSIS

PURPOSE: People with diabetesmellitus have a 2 to 4-fold increased risk of cardiovascular disease (CVD). Despite a vast amount of research, the underlying mechanisms that predispose individuals with diabetes to the development of CVD are unclear. Thus, to further our understanding of how diabetes promotes CVD and to begin to delineate how gender may influence pathogenesis, we have established, characterized and manipulated a new model of hyperglycemia-induced atherosclerosis: the apoE:Ins2 mouse. METHODS: Ins2 is anautosomaldominantmutation(C96Y)that induces juvenile-onset hyperglycemia in the absence of obesity. Ins2 Akita male mice were crossed to apoE female mice, which spontaneously develop atherosclerosis. At 5 weeks of age, male/female apoE:Ins2 mice were castrated/ovariectomized and fed a standard chow diet until the 25 weeks of age whenmice were euthanized and organs were harvested. Metabolic parameters and atherosclerotic developmentweremonitored and analyzed through the whole study. RESULTS: Male apoE:Ins2 developed persistent hyperglycemia. At 25 weeks of age, lesions from hyperglycemic mice were 3-4 times larger, with significantly larger necrotic cores, and presented calcifiedregions,comparedtonormoglycemicapoEmales.Castrated maleapoE:Ins2miceshowedareductioninbloodglucoselevels which correlated to a lack of testosterone, an improvement of several metabolic parameters, and a partial amelioration of atherosclerosis. Female apoE:Ins2 presented transient hyperglycemia that normalized by 15 weeks of age. Despite the transient hyperglycemia, larger atherosclerotic lesions were observed at 15 weeks of age compared to apoE females. Ovariectomized female apoE:Ins2 Akita mice presented chronic hyperglycemia and accelerated atherosclerosis relatively similar to male apoE:Ins2 mice. Estradiol levels were compensated in all ovariectomized mice suggesting a role for progesterone in the maintenance of euglycemia. CONCLUSION: We have developed gender-specific models of chronic and transient hyperglycemia-induced atherosclerosis. In both genders, sexual hormones impacted atherosclerosis through at least 3 mechanisms: i) the effect on insulin secretion and its regulation of the glucose levels, ii) the effect on lipid metabolism and the bioavailability of atherogenic lipoprotein particles, and iii) the protective effect directly exerted on the vasculature. CDA

Long-term testosterone supplementation is useful for ED with testosterone deficiency

Long-term testosterone supplementation is useful for ED with testosterone deficiency

Effect of a 60‐Day Oral Gavage of a Crude Alkaloid Extract From Chromolaena odorata Leaves on Hormonal and Spermatogenic Indices of Male Rats

The present study was aimed at investigating the effects of the crude alkaloids isolated from Chromolaena odorata leaves on the hormonal and spermatogenic indices of male rats. The alkaloids obtained from C odorata leaves using standard methods were administered to male rats for 60 days at the doses of 250, 500, and 1000 mg/kg body weight. Thin-layer chromatographic analysis of the alkaloid mixture produced 8 spots, 3 of which were alkaloids with R(f) values of 0.41, 0.49, and 0.55 as confirmed by the formation of orange color and creamy precipitates with both Dragendorff and Mayer reagents, respectively. The alkaloids were represented in the extract by a yield of 20.28 g, corresponding to a percentage yield of 90.05% of the total extract of 22.52 g. The final body weights of both the control and alkaloid-treated animals increased significantly (P < .05) compared with their respective body weights before treatment. The alkaloids significantly decreased (P < .05) the testes-body weight ratio; the concentrations of testicular total protein, glycogen, sialic acid, and cholesterol; and the activities of γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase. The serum luteinizing hormone and follicle-stimulating hormone levels, as well as testicular and serum testosterone levels, also decreased significantly (P < .05). There were decreases in the sperm count, motility, and density, as well as morphological changes in the sperm cells. The pH and whitish-gray color of the semen were not significantly affected. All of the doses of the alkaloids increased the total mean number of sperm cell abnormalities, with the secondary type predominating over the primary sperm cell abnormality. The alterations in the levels of the hormones and secretory and synthetic constituents of the testes and the spermatotoxic effects by the alkaloids from C odorata leaves may be due to nonavailability or deprivation of testosterone to the target organ. This lack of testosterone may have consequential effects on the reproductive process of the male rat.

Impact of androgen deprivation therapy on sexual function: a response

Impact of androgen deprivation therapy on sexual function: a response

Lack of Testosterone (TST) Worsens Ischemia/Reperfusion– Induced Acute Kidney Injury (I/R‐AKI) and its Deleterious Cardiac Effects

Renal I/R‐AKI results in systemic inflammation, including the heart. We recently reported that plasma TST is reduced during AKI, and its supplementation improves renal injury and inflammation by increasing cytoprotective factors. We now extended this study to test whether the lack of TST exacerbates I/R‐AKI and its cardiac abnormalities. Intact and castrated males (Cast) SD rats were treated with either vehicle or TST (20 ng/kg/min × 10min IV) given 3 hours after subjecting the rats to 40 min of bilateral renal I/R. After 48 hs, we harvested the kidney and the heart, and evaluated renal function and injury (PlCr ‐KIM‐1), cardiac stress (pro‐BNP), and cytoprotective factors (renal and cardiac heme oxygenase‐ HO‐1). PlCr mg/dl KIM‐1 pg/ml BNP ng/ug Renal HO‐1 ng/ml Cardiac HO‐1 ng/ml Sham 0.4 ±0.3 712 ±53 0.18 ±0.02 0.52±0.4 0.4 ±0.06 AKI 1.9 ±1.9* 4576 ±185* 3.8 ±0.1* 5.8±1.2* 5 ±0.1* AKI‐Cast 2.5 ±2.3&amp; 8972 ±708&amp; 4.4 ±1&amp; 3±0.1&amp; 3.7 ±0.1&amp; AKI‐Cast‐TST 1.6 ±1# 2348 ±85 # 2.4 ±0.6# 4.4±0.2# 4.6 ±0.1# Data: Mean±SEM: p&lt;0.05 vs Sham; vs AKI; vs AKI‐CT Lack of TST exacerbates I/R‐AKI and cardiac stress. Despite the increased injury, HO‐1 is decreased, suggesting that TST may be facilitating HO‐1 expression post AKI.

Ejaculatory dysfunction in streptozotocin-induced diabetic rats: the role of testosterone

Hyperglycemic and hypoinsulinemic states caused by diabetes mellitus are usually related to some type of sexual dysfunction, resulting in infertility in humans and experimental models, mostly due to their effects on ejaculatory function. This study aimed to evaluate the possible role of testosterone in the restoration of normal ejaculatory function in diabetic rats. Male Wistar rats were randomly allocated into 3 experimental groups: control, diabetic (streptozotocin), and diabetic with testosterone supplementation (streptozotocin plus testosterone). The following parameters were assessed at the end of the experiment: body weight, circulating testosterone levels, number of spermatozoa ejaculated in the uterus through natural mating, and weight and in vitro isometric contractions of the vas deferens. Diabetic rats showed reduced plasma testosterone levels and ejaculatory dysfunction as observed by a lack in the spermatozoa ejaculated into the uterus of receptive females. In these diabetic rats, no difference was observed in the sensitivity of the vas deferens to norepinephrine, with or without the presence of the cocktail (cocaine plus propranolol). In spite of this, an increased sensitivity to methoxamine through the α1-adrenoceptor was observed. Testosterone supplementation did not restore these parameters to control values. We conclude that, in this experimental model, the lack of testosterone was not directly related to the diabetes-induced ejaculatory dysfunction.

Testosterone replacement

Male hypogonadism is based on an insufficient gonadal function, especially testosterone deficiency. The decreased endogenous production of testosterone can be acquired or congenital. The lack of testosterone results in typical clinical symptoms which give initial indications for testosterone replacement therapy. Nevertheless, less than 10% of the affected patients receive an adequate treatment. Presently different preparations and application forms are available for the therapy of hypogonadism with testosterone. Intramuscular, peroral, transdermal, sublingual and subcutaneous preparations show differences in pharmacodynamics, pharmacokinetics, price and handling. Therefore these formulations should be applied individually. Regular clinical and chemical controls of effect, side effects and contraindications are essential along with long-term substitution.

LEI (Lack of tEstosterone Impact) survey in a clinical sample with surgical menopause

Objectives To assess perception of sexuality and awareness of the impact of testosterone on sexual desire in a clinical sample of Italian women with surgical menopause.Methods In the present cross-sectional study, a structured interview on sexuality-related menopausal symptoms, attitudes towards sexuality and menopausal profile was administered to 568 women (age range 35–69 years) with bilateral oophorectomy with and without hysterectomy for benign conditions.Results The majority of women (58% yes; 36% most of the time) reported they were satisfied with their sexual life before surgical menopause. After oophorectomy, 79.3% noted the appearance/worsening of vaginal dryness, whereas the reduction of sexual desire was reported by 78.7%. Women with low sexual desire (n = 436) were significantly distressed (59.7%) and reported an impairment (24.8% yes/yes, very much) in the relationship with their partner. Sexual reactions of the partner reported by women included reduced sexual desire (17.8%), sexual dysfunction (5.1%) and fears of giving pain/lack of pleasure (28.3%). A high number of women (88.2%) would be willing to discuss sexual matters with their doctors and would consider therapeutic options. Only 36.8% were aware that a lack of testosterone might impact on sexual desire but 71% would like to know more about the role of testosterone. Hormone replacement therapy was used by 38.4% of the women.Conclusions These data suggest that women experience significant vaginal dryness and low sexual desire and report a significant distress in the relationship with their partner after surgical menopause. Sexual counseling is mandatory in order to discuss potential therapeutic strategies, including testosterone use.

Andrologische Testosteronersatztherapie

Male hypogonadism is characterised by decreased testicular function, especially testosterone deficiency. Its prevalence increases with age but may be acquired in all stages of life if it is not inborn. The lack of testosterone results in typical clinical symptoms. However, only about 10% of the affected men currently receive adequate treatment. A variety of testosterone preparations are available to meet the main needs of treatment, including intramuscular, transcutaneous, sublingual, and oral forms. In patients with prostate cancer, breast cancer, polycythemia, severe heart failure, obstruction of the lower urinary tract, or untreated sleep apnoea, testosterone treatment must be avoided. Therefore, clinical and laboratory screening are essential along with a long-term substitution.

On sexual dimorphism in immune function

Sexual dimorphism in immune function is a common pattern in vertebrates and also in a number of invertebrates. Most often, females are more 'immunocompetent' than males. The underlying causes are explained by either the role of immunosuppressive substances, such as testosterone, or by fundamental differences in male and female life histories. Here, we investigate some of the main predictions of the immunocompetence handicap hypothesis (ICHH) in a comparative framework using mammals. We focus specifically on the prediction that measures of sexual competition across species explain the observed patterns of variation in sex-specific immunocompetence within species. Our results are not consistent with the ICHH, but we do find that female mammals tend to have higher white blood cell counts (WBC), with some further associations between cell counts and longevity in females. We also document positive covariance between sexual dimorphism in immunity, as measured by a subset of WBC, and dimorphism in the duration of effective breeding. This is consistent with the application of 'Bateman's principle' to immunity, with females maximizing fitness by lengthening lifespan through greater investment in immune defences. Moreover, we present a meta-analysis of insect immunity, as the lack of testosterone in insects provides a means to investigate Bateman's principle for immunity independently of the ICHH. Here, we also find a systematic female bias in the expression of one of the two components of insect immune function that we investigated (phenoloxidase). From these analyses, we conclude that the mechanistic explanations of the ICHH lack empirical support. Instead, fitness-related differences between the sexes are potentially sufficient to explain many natural patterns in immunocompetence.

Effect of Sex Hormones on Non-Esterified Fatty Acids, Intra-Abdominal Fat Accumulation, and Hypertension Induced by Sucrose Diet in Male Rats

Sucrose-fed rats () had higher intra-abdominal fat mass and plasma non-esterified fatty acids and lower testosterone levels, () were hypertensive, and () had lower plasma NO metabolites than controls. The lack of testosterone by castration of sucrose-fed rats decreased high blood pressure and circulating non-esterified fatty acids and increased NO metabolites. The administration of testosterone to castrated sucrose-fed rats restored hypertension, fat accumulation, and high-circulating non-esterified fatty acids, and lowered NO metabolite levels whereas estradiol treatment did not significantly affect these variables in castrated animals. This study proposes that the low levels of testosterone found in sucrose-fed rats are sufficient to maintain central obesity and increased circulating non-esterified fatty acids, which contribute to the development of hypertension in sucrose-fed rats by modulating the biosynthesis of NO.