Milena Braga-Basaria

Metabolic Syndrome in Men With Prostate Cancer Undergoing Long-Term Androgen-Deprivation Therapy

PURPOSE Prostate cancer (PCa) is one of the most common cancers in men. Men with recurrent or metastatic PCa are treated with androgen-deprivation therapy (ADT), resulting in profound hypogonadism. Because male hypogonadism is a risk factor for metabolic syndrome and men with PCa have high cardiovascular mortality, we evaluated the prevalence of metabolic syndrome in men undergoing long-term ADT. PATIENTS AND METHODS This was a cross-sectional study. We evaluated 58 men, including 20 with PCa undergoing ADT for at least 12 months (ADT group), 18 age-matched men with nonmetastatic PCa who had received local treatment and were recently found to have an increasing prostate-specific antigen (non-ADT group), and 20 age-matched controls (control group). Men in the non-ADT and control groups were eugonadal. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. RESULTS Mean age was similar among the groups. Men on ADT had significantly higher body mass index and lower total and free testosterone levels. The prevalence of metabolic syndrome was higher in the ADT group compared with the non-ADT (P < .01) and control (P = .03) groups. Among the components of metabolic syndrome, men on ADT had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated triglycerides compared with controls (P = .02). The prevalence of hypertension and low high-density lipoprotein levels were similar. CONCLUSION These data suggest that metabolic syndrome was present in more than 50% of the men undergoing long-term ADT, predisposing them to higher cardiovascular risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence. We recommend prospective studies to further delineate this association.

Androgen Deprivation Therapy in Prostate Cancer and Metabolic Risk for Atherosclerosis

CONTEXT Prostate cancer (PCa) is the most common cancer in men. Androgen-deprivation therapy (ADT) is generally employed in the treatment of locally advanced and metastatic PCa. Although its use as an adjuvant therapy has resulted in improved survival in some patients, ADT has negative consequences. Complications like osteoporosis, sexual dysfunction, gynecomastia, and adverse body composition are well known. Recently, metabolic complications like insulin resistance, diabetes, dyslipidemia, and metabolic syndrome have emerged, which may be responsible for the increased cardiovascular mortality in this population. EVIDENCE ACQUISITION A MEDLINE search was conducted for articles published over the last 20 yr based on the key words androgen deprivation therapy AND insulin resistance, hyperglycemia, diabetes, dyslipidemia, metabolic syndrome, and cardiovascular disease. Relevant studies in non-PCa populations evaluating the association between testosterone and metabolism were also reviewed and briefly mentioned where relevant. EVIDENCE SYNTHESIS Prospective studies evaluating early (3-6 months) metabolic changes of ADT show development of hyperinsulinemia; however, glucose levels remain normal. Cross-sectional studies of men undergoing long-term (> or =12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. Furthermore, men undergoing ADT also experience higher cardiovascular mortality. CONCLUSION Long-term prospective studies of ADT are needed to determine the timing of onset of these metabolic complications and to investigate the mechanism behind them. In the meantime, we recommend baseline and serial screening for fasting glucose, lipids, and other cardiovascular risk factors in men receiving ADT. Glucose tolerance tests and cardiac evaluation may be required in selected cases.

Androgens and erythropoiesis: Past and present

Association between androgens and erythropoiesis has been known for more than seven decades. Androgens stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells. Before the discovery of recombinant erythropoietin (rhEpo), androgens were used in the treatment of anemia associated with renal disease, bone marrow suppression, and hypopituitarism. Anabolism is an additional advantage of androgen therapy. Furthermore, in light of recent reports regarding adverse effects of rhEpo, the role of androgen therapy in various types of anemias should be readdressed. Polycythemia remains a known side effect of androgen therapy. In this review, we will briefly discuss the initial animal and human studies which demonstrated the role of androgens in the treatment of anemia, their mechanism of action, a detailed account of the efficacy of androgens in the treatment of various anemias, the erythropoietic side effects of androgens and finally, the relationship between hematocrit levels and cardiovascular disease.

Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy

Sex steroids are known to modulate serum lipoproteins. Studies have suggested that serum testosterone levels are associated with a beneficial lipid profile. Androgen deprivation therapy (ADT) is employed in the treatment of recurrent and metastatic prostate cancer (PCa), resulting in profound hypogonadism. As male hypogonadism unfavorably influences lipid profile and men with PCa have high cardiovascular mortality, we evaluated the effects of long-term ADT on fasting lipids. This Cross-sectional study was conducted in a university-based research institution. We evaluated 44 men, 16 undergoing ADT for at least 12 months before the study (ADT group), 14 age-matched eugonadal men with non-metastatic PCa who were status post prostatectomy and/or radiotherapy and not on ADT (non-ADT group) and 14 age-matched eugonadal controls (Control group). None of the men had known history of diabetes or dyslipidemia. Mean age was similar in the three groups (P=0.37). Serum total (P<0.01) and free (P<0.01) testosterone levels were lower in the ADT group compared to the other groups. Men on ADT had higher body mass index (BMI) compared to the other groups (P<0.01). Men in the ADT group had significantly higher levels of total cholesterol compared to the other two groups (P=0.03). After adjustment for BMI, men on ADT continued to have significantly higher fasting levels of total cholesterol (P=0.02), LDL cholesterol (P=0.04) and non-HDL cholesterol (P=0.03) compared to the control group. No significant differences were seen in the levels of other lipoproteins between the three groups. These data show that men undergoing long-term ADT have higher total and LDL cholesterol than age-matched controls. Long-term prospective studies are needed to determine the time of onset of changes in these lipoproteins while on ADT and the influence of these changes on cardiovascular mortality.

Lack of an Effect of High Dose Isoflavones in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy

PURPOSE The profound hypogonadism due to androgen deprivation therapy for prostate cancer results in complications such as sexual dysfunction, poor quality of life, vasomotor symptoms and altered cognition. Since estrogen is associated with cardiovascular risks, phytoestrogens are being increasingly evaluated as a potential treatment for these adverse effects. We evaluated the effects of high dose isoflavones, equivalent to that consumed by Asian populations, on the aforementioned consequences of androgen deprivation therapy. MATERIALS AND METHODS A total of 33 men undergoing androgen deprivation therapy for prostate cancer were enrolled in this randomized, double-blind, placebo controlled, 12-week pilot trial. Participants were randomly assigned to receive 20 gm soy protein containing 160 mg total isoflavones (17) vs taste matched placebo, that is 20 gm whole milk protein (16). The study was performed at a tertiary care center in the United States. RESULTS At baseline the groups were well matched in demographic parameters, sleep quality, cognition and overall quality of life. However, men in the isoflavone group had a higher baseline prevalence of hot flashes and poor intercourse satisfaction compared to those on placebo. At 12 weeks there were no significant differences between the 2 groups in any outcome measure. CONCLUSIONS This pilot study of high dose isoflavones in androgen deprived men showed no significant improvement in cognition, vasomotor symptoms or any other aspect of quality of life measures compared to placebo. Future studies should use variable doses of isoflavones for a longer period before ruling out beneficial isoflavone effects in this population.

Necrobiosis lipoidica diabeticorum: response to pentoxiphylline.

Necrobiosis lipoidica diabeticorum (NLD) is a condition that can be physically and psychologically distressing. Angiopathy leading to thrombosis and occlusion of the cutaneous vessels has been implicated in its etiology. Pentoxiphylline is a hemorrheological agent that improves blood flow and decreases red cell and platelet aggregation. Based on these data, aim of our study was to report clinical course of a 20-yr-old diabetic woman with NLD during therapy with Pentoxiphylline 400 mg 3 times daily. After 1 month of therapy, the lesions stopped enlarging. After 3 months, the lesions showed initial signs of healing. At 6-month follow-up, there was near resolution of the lesions. The patient continued therapy and remained in remission at 2-yr follow-up. This improvement relieved psychological stress on the patient. No side effects of treatment were reported.In conclusion, patients with NLD may benefit from treatment with pentoxiphylline. We recommend therapy with 400 mg 3 times daily. The drug should be continued for at least 6 months.

Tratamento de nódulos autônomos e císticos da tireóide com injeção intranodular de etanol

O tratamento com injecao intranodular de etanol vem sendo utilizado ha uma decada como modalidade terapeutica eficaz no manejo de pacientes com nodulos da tireoide. Diversos estudos validaram o papel desta forma de tratamento em nodulos autonomos, cisticos e, mais recentemente, nodulos frios benignos. OBJETIVO: Avaliar a efetividade da injecao intranodular de etanol no tratamento de nodulos cisticos e autonomos da tireoide. METODOS: 42 pacientes (26 pacientes com nodulos cisticos e 16 com nodulos autonomos da tireoide) foram submetidos a tratamento com aplicacao intranodular de etanol a 99%, guiada por ultra-sonografia e acompanhados por um periodo minimo de seis meses. RESULTADOS: Nao observamos a ocorrencia de complicacoes maiores durante ou apos o tratamento, porem, na maioria dos casos, houve queixa de dor de leve a moderada intensidade e/ou desconforto apos a aplicacao do etanol. A maioria dos nodulos apresentou reducao volumetrica significativa. A media de reducao obtida para os nodulos autonomos foi de 50,3% e para os nodulos cisticos, 69,3%. Nao houve diferenca significativa entre os valores basais de T3 total, T4 total e TSH em comparacao aos valores obtidos seis meses apos o tratamento para o grupo de pacientes com nodulos cisticos. O grupo de pacientes com nodulos autonomos apresentou reducao nos valores sericos de T3 total e T4 total, assim como elevacao dos niveis de TSH, confirmando a efetividade do tratamento. CONCLUSAO: A injecao intranodular de etanol e uma alternativa segura e eficaz no tratamento de nodulos autonomos e cisticos da tireoide.

Interferon-alpha-induced transient severe hypothyroidism in a patient with Graves' disease

Interferons (IFNs) are proteins with anti-viral activity and are widely used in the treatment of patients with chronic hepatitis C virus (HCV) infection. The use of IFNs has resulted in thyroid dysfunction in a variety of ways. We report a case of a woman with hyperthyroidism due to Graves’ disease who developed significant hypothyroidism during treatment with IFN-α 2a for HCV infection. However, after discontinuation of IFN-α 2a, hyperthyroidism recurred. Potential mechanisms by which IFNs influence thyroid function are discussed.

Pseudo-central hypothyroidism

Central hypothyroidism is an exceedingly rare form of hypothyroidism that results from a variety of conditions affecting the hypothalamus and the pituitary gland. The classic biochemical abnormality seen in these patients includes a low serum level of circulating thyroxine (T4) concomitant with an inappropriately low level of thyrotropin. Because patients with isolated triiodothyronine (T3) toxicosis also present with this biochemical pattern, it is important to measure T3 levels in such patients before making a diagnosis of central hypothyroidism.