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By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Estrogen + Progesterone and Breast Cancer
Source: Chlebowski RT, et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med 2009;360:573-587.
The women's health initiative (WHI) provided convincing evidence that the use of estrogen plus progesterone (E+P) in postmenopausal women is associated with an increased risk of breast cancer. The outcomes of this clinical trial motivated large numbers of women and their clinicians to rethink the risk-benefit balance of hormone replacement therapy, evoking a sea-change in prescribing habits.
Despite the acknowledged association between E+P and breast cancer in WHI, a concomitant decline in use of mammography after the breaking WHI news invited the possibility that during post-WHI years, less screening for breast cancer might be influencing the observed breast cancer decline rather than simply less E+P use. To study this issue further, WHI investigators evaluated two data sets: the original WHI population (n = 16,608 women without breast cancer at baseline) and a second observational study population (n = 41,449 without breast cancer at baseline). The observational study group did not receive advice about whether to use E+P, but were informed about the results of the interventional WHI when it became available. In the observational WHI population, more than 16,000 women were taking E+P at baseline.
Long term follow-up of the observational WHI population showed an increased incidence of breast cancer in women who had used E+P. Breast cancer incidence in this population declined subsequent to hormone discontinuation. This suggests the possibility that some early breast cancers may regress or disappear if hormone therapy is stopped. The data did not, however, provide a meaningful association between less use of mammography and reduced breast cancer.
Prostate Cancer Risk with Testosterone Replacement
Source: Shabsigh R, et al. Testosterone therapy in hypogonadal men and potential prostate cancer risk: A systematic review. Int J Impot Res 2009;21:9-23.
Growth and development of the prostate is recognized to be testosterone (TST)-dependent. Clinicians have long held concerns that TST therapy might not only worsen symptoms of benign prostatic hyperplasia (BPH), but also stimulate the development, growth, proliferation, or aggressiveness of prostate cancer. Some of this concern stems logically from the observation that testosterone deprivation has salutary effects on prostate cancer growth.
This systematic review of 44 articles using FDA-approved agents (see concerns below with regard to other agents) was unable to directly provide a definitive answer to the question of whether TST replacement increases risk of prostate cancer, but provides other interesting insights.
First, trials of hypogonadal men treated with testosterone have not evidenced an increased risk for prostate cancer; if anything, a protective effect may occur. Second, TST-treated men with a history of prostate cancer did not experience more recurrences or metastases. Third, TST did not appear to influence Gleason scores when prostate cancer was detected.
The authors conclude, "There is no evidence that TST increases risk of prostate cancer in hypogonadal men." Of some concern, however, are the case reports of aggressive prostate CA in recipients of a non-FDA-approved supplement containing TST, estradiol, chrysin, and elk velvet antler.
The Suicidal Process: Time to Intervene?
Source: Deisenhammer EA, et al. The duration of the suicidal process: How much time is left for intervention between consideration and accomplishment of a suicide attempt? J Clin Psychiatry 2009;70:19-24.
Suicide has been among the most common causes of death in the United States for more than 20 years, usually ranking among the top 10. Clinicians would like to play a useful role in suicide prevention, yet data are sparse to inform about the interval between first suicidal ideation and the ultimate carrying out of a suicide attempt. Deisenhammer et al attempted to bridge this knowledge gap with a study of persons with failed suicide attempts, all of whom (n = 82) were interviewed within 72 hours of their attempted suicide.
Most (83%) subjects were alone at the time of conceptualization of suicide, and almost half reported that the time interval from first conception of suicide to attempt was 10 minutes or less. Nonetheless, during this brief interval, most (77%) had had some contact (usually via telephone) with friends or family, and the majority either indicated their wish to die, or (according to their subjective report) hinted at their death wish.
Interviews with subjects did not provide any insight as to what might have deterred the suicide attempt. Nonetheless, the fact that most suicidal subjects did make contact with others leaves open the possibility that some component of interpersonal communication has the potential to change the course of suicide attempts.