• July 12, 2011 – 10:22

    The Impact of Hypogonadism and Autonomic Dysfunction on Fatigue, Emotional Function, and Sexual Desire in Male Patients With Advanced Cancer

    A Pilot Study Strasser F, et al./Cancer 2006;107:2949–57.

    BACKGROUND. The objective of this study was to determine whether hypogonadism and autonomic dysfunction contribute substantially to cancer-related fatigue, decreased sexual desire, and depression inmale patients with advanced, incurable cancer.

    METHODS. Forty-eight patients who had received no major antineoplastic intervention for at least 2 weeks were tested for autonomic dysfunction by using Ewing tests. Total and free testosterone levels were measured. Multivariate analyses were performed to test the relation of these factors with the Functional Assessment of Cancer Therapy (FACT) (the Functional Assessment of Anorexia/Cachexia Therapy [FAACT] scale and the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] subscale), the Hospital Anxiety and Depression Scale (HADS), the Edmonton Symptom Assessment Scale, the Sexual Desire Inventory, and sexual function (Cancer Rehabilitation Evaluation System subscale). Common causes for fatigue (anemia, depression,malnutrition, symptomdistress, and medications) also were considered.

    RESULTS. Thirty-eight of 47 patients (81%) had autonomic dysfunction, although it was not associated significantly with the other variables examined. Twenty-nine of 45 patients (64%) had a low level of free testosterone (hypogonadism), which was correlated with the HADS Anxiety score (P ..002), the FACT Emotional Well-Being score (P ..02), and the HADS Depression score (P ..04). Hypogonadal men also had lower scores on the FACT Functional Well-Being scale (P ..01) and the FACIT-F subscale (P ..05). Men who reported symptoms related to weight loss (FAACTscale) had significantly lower levels of free testosterone (r . 0.34; P ..02) but did not differ from the other group in actual weight loss (P ..22). The total testosterone level was not appropriate for screening of hypogonadism unless the patients had values <100 ng/ mL. Logistic regression analysis failed to reveal a distinct multivariate model of autonomic dysfunction or hypogonadism that predicted clinical outcomes.

    CONCLUSIONS. Hypogonadism is a frequent condition in patients with advanced, incurable cancer and is associated with negative mood, fatigue, and symptoms related to anorexia/cachexia.

    COMMENT. Patients with advanced cancer frequently are hypogonadal, and also experience autonomic dysfunction. The results from this cross-sectional pilot study of men with advanced cancer indicated that hypogonadism, but not autonomic dysfunction, was associated strongly with fatigue, depression, and sexual dysfunction. Hypogonadism in men with advanced cancer appears to be mediated centrally, as demonstrated by the lack of elevated LH or FSH. Elevated inflammatory cytokines, particularly IL-6, are common in patients with advanced cancer and are associated with fatigue, depression, anorexia/cachexia, reduced free testosterone. Whether testosterone supplement does ameriolate fatigue and depression in cancer patients is not extensively studied in a large doble-blind randormized studies.Hypogonadal men with cancer who do not have hormone-sensitive tumors should be included in a clinical trial to determine the efficacy, dosage, and optimal means of administering testosterone replacement therapy.

  • July 12, 2011 – 10:20

    Low serum testosterone and frailty in older men and women

    I.-C. Wu et al. / Maturitas 67 (2010) 348–352

    BACKGROUND. Frail older persons are at high risk of morbidity and mortality, and are characterized by body composition alterations. Serum testosterone, which regulates body composition, declines with age. We investigated the relation between serum testosterone level and physiological frailty in both older menand women.

    METHODS.This was a cross-sectional study of 108 adults 65 years old or older. Frailty status was determined by hand-grip strength, weight change, walking speed, exhaustion, and activity levels, and was classified as frail (3 or more deficits), pre-frail (1 or 2 deficits), or robust (no deficit) according to the Fried criteria. Serum total testosterone (TT) and sex-hormone-binding globulin were measured while free testosterone (FT) was estimated.

    RESULTS. Median (range) TT and FT were lower in frail than in pre-frail and robust men (TT: (frail) 15.7 [2.4–26.9] vs. (pre-frail) 19.4 [7.2–39.9] and (robust) 25.9 [13.2–35.2] nmol/L, P = 0.03; FT: 230.0 [35.9–299.0] vs. 272.0 [86.7–411.0] and 303.0 [267.0–396.0] pmol/L, P = 0.02) and women (TT: 0.31 [0.10–0.51] vs. 0.47 [0.14–1.55] and 0.45 [0.36–1.25] nmol/L, P = 0.02; FT: 4.59 [0.46–6.63] vs. 4.66 [1.57–15.10] and 6.65 [3.91–21.00] pmol/L, P = 0.03). After adjusting for age, comorbidities, body mass index, and serum albumin in ordinal logistic regression model, odds ratios of being frail were significantly higher for those participants whose TT and FT levels were in the lowest tertile compared to the highest tertile in men (TT: odds ratio [OR] 3.29, 95% confidence interval [CI] 1.14–9.50; FT: OR 3.44, 95% CI 1.05–11.22) and in women (TT: OR 6.69, 95% CI 1.84–24.31; FT: OR 4.86, 95% CI 1.31–18.08).

    CONCLUSIONS. Low serum testosterone levels were independently associated with frailty in the elderly Taiwanese.

    COMMENT. Recent studies on large cohort have shown that low testosterone level is a significant risk factor for the premature death. However little has been known for the significance of testosterone elevel in post-menopausal women. This study from Taiwan showed that low testosterone level is associated with fraility in older women as well as men. Future studies focusing on women in larger cohort would be awaited to conform the significance of testosterone level as a biomarker.

  • March 29, 2011 – 10:24

    Testosterone Therapy in Men with Untreated Prostate Cancer

    Historically, testosterone has been associated with beneficial effects in aging men, but also with the concern of potential for growth of prostate cancer. This notion comes from previous research by Morgentaler and colleagues that observed regression of prostate cancer caused by androgen deprivation yielding a decreased serum PSA level, while normalization of testosterone in men who are androgen-deprived caused a rise in PSA levels. However, more recent retrospective trials of small numbers of men found no biochemical recurrence of prostate cancer with testosterone replacement after an average period of 4.5 years.

    This month in the Journal of Urology, Morgentaler and colleagues report their findings from a study of 13 men with symptomatic testosterone deficiency with prostate cancer (Gleason score 6 in 12 men; 7 in 1 man). Their results suggest that testosterone replacement in these men with localized prostate cancer did not cause tumor progression over a time frame of 1 to 8 years. While previous studies suggest that testosterone replacement causes rapid prostate cancer growth in androgen deprived men, data is still conflicting with regard to prostate cancer growth trends in hormonally intact men.

    While the major limitations of this study include its small sample size and lack control factors, it is landmark in that it is the first study to assess a group of men with untreated prostate cancer who concomitantly took testosterone replacement therapy for greater than one year. Nonetheless, its conclusions are in line with the theory that serum androgen concentrations in men with testosterone deficiency can maintain androgen-mediated growth of prostate cancer and the addition of exogenous testosterone does not yield additional tumor growth.

    Reference: Morgentaler A, Lipshultz LI, Bennett R, et al. Testosterone therapy in men with untreated prostate cancer. J Urology 2010;185:1256-61.

  • March 17, 2011 – 10:45

    Male Pattern Baldness and Prostate Cancer Risk

    A novel study conducted in France recently evaluated the potential link between androgenic alopecia and prostate cancer risk. Current estimates posit that over 50% of men will experience androgenic alopecia during their lifetime. Until now, evidence has been conflicting regarding this potential association. A case-control study of 669 subjects (388 with a history of prostate cancer and 281 without) found that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01], yet the specific pattern of hair loss was not determined to be a predictor of hair loss. Moreover, there was no association found between early-onset alopecia and an earlier diagnosis of prostate cancer, or with the development of more aggressive prostate cancer tumors.

    The authors admit the possibility of selective recall bias in this study, yet retrospective self-reporting of male balding patterns has been validated across previous studies. As androgenic alopecia can impact self-perception, it was felt that since most men remember developing baldness at an early age. Similarly, the authors did not control for increased risk factors of prostate cancer including African heritage, yet family history was stratified in both case subjects and controls.

    Data is abundant with regard to aging men and androgenic alopecia as well as the development of prostate cancer. To date, there is no statistical evidence to support a direct cause-and-effect relationship between alopecia and the development of prostate cancer at any age. As with previous studies, this is retrospective study cannot prove a direct causal relationship. Future research will focus on the identification of specific genetic markers to prove such a relationship.

    To read more go to: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62342-2/abstract

    Reference: Yassa M, Saliou M, De Rycke Y, et al. Male pattern baldness and the risk of prostate cancer. Annals of Oncology, February 2011.

  • February 17, 2011 – 10:26

    Effects of Testosterone in Frail Elderly Men

    Short-term testosterone replacement has been shown to improve muscle mass and strength in frail and elderly men, but until now these effects have not been evaluated post-treatment. The authors sought to assess the long-term effects of testosterone therapy in 274 frail men aged 65-90 with low endogenous testosterone levels and conducted a single-center, randomized, double-blind, placebo-controlled trial to investigate the effects of 6 months of testosterone therapy on muscle strength, body composition, physical function, and overall quality of life.

    After a period of 6 months, mean testosterone levels increased with statistical significance, in addition to increases in lean muscle mass and subjective improvements in somatic and sexual symptoms. After 12 months however, no significant differences in the treatment and control groups remained evident. While the authors concluded that 6 months of treatment with replacement testosterone offered improvements in lean body mass, muscle strength, and quality of life, these changes were not maintained at 6 months post-treatment. The decline in muscle mass and strength post-treatment suggests that testosterone replacement for a period of 6 months may not be sufficient to improve overall frailty in this population. Moreover, the effects of increasing serum testosterone levels to within the physiologic range in a 6-month period may have been too short to sustain significant and lasting symptomatic improvements.

    The optimal duration of treatment with testosterone replacement therapy to achieve lasting improvements in lean muscle mass and quality of life remains unknown, yet it is imperative for clinicians to offer a multi-disciplinary approach to the treatment of frail middle-aged and elderly men that includes resistance exercise, appropriate diet and pharmacologic agents.

    Reference: O'Connell MDL, Roberts SA, Srinivas-Shankar U, et al. Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment intermediate-frail and frail elderly men? J Clin Endocrinol Metab 2011; 96(2):454-458.