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Mar 2008 Book.Qxp Clinical Medicine & Research Volume 6, Number 1:1-2 ©2008 Marshfield Clinic clinmedres.org Letters A Potential Means of Investigating the Role either indefinite use of goserelin acetate or no treatment of Luteinizing Hormone in the Pathogenesis following radiation therapy. Thus, a cohort of patients given of Alzheimer Disease goserelin (and thus having suppressed LH levels) dating back to 1985 can be compared to a very similar cohort who did not receive such therapy. Definite conclusions, of course, will be Editor - I read with great interest the recent review article, limited due to the high percentage of patients who eventually “The Contribution of Luteinizing Hormone to Alzheimer crossed over to the goserelin arm when their disease Disease Pathogenesis” by Webber et al. 1 In this paper and in progressed, the high number of deaths since the trial began, another article, 2 the authors present some intriguing data from and the possibility that data on Alzheimer disease various lines of basic, epidemiological and clinical research development over the years was not fully documented. Of supporting their hypothesis implicating luteinizing hormone note, certain other clinical trials of goserelin or leuprolide and (LH) in the pathogenesis of Alzheimer disease. One might radiation therapy may not be as useful as cohort studies to test speculate that women who have undergone oophorectomy and the role of LH in Alzheimer disease pathogenesis. A European men who have undergone orchiectomy might be at increased study 5 had an outcome very similar to the RTOG study 4 as far risk according to this model. Conversely, one would expect as prostate cancer control goes, and many of these men never that people with lower levels of LH might be less predisposed fully recovered testicular function following withdrawal of the to Alzheimer disease. If this is true, pharmacological use of adjuvant goserelin for 3 years. Although men in both intervention to lower LH levels might potentially decrease trials had long-term reductions in testosterone levels and this risk. improved prostate cancer control compared to radiotherapy alone, at the completion of the EORTC trial, 5 LH levels The authors mention Phase II data suggesting stabilization of presumably increased, whereas in the RTOG study 4 LH levels cognitive function in men with Alzheimer disease from a trial remained suppressed. Similarly, although the effect of specifically designed to test the potential of leuprolide acetate orchiectomy may be similar to long-term goserelin or (leuprolide) (Lupron). 3 Leuprolide, along with a similar leuprolide therapy (i.e. testosterone is decreased to castration agent, goserelin acetate (goserelin) (Zoladex), are levels), the effects on LH will be drastically different with gonadotropin-releasing hormone (GnRH) agonist analogues orchiectomy leading to increased LH and “chemical that decrease circulating LH levels. GnRH is a hypothalamic castration” leading to lowered LH. In light of this intriguing hormone that stimulates LH release from the anterior hypothesis, it might be interesting and worthwhile to pituitary gonadotrophs when the pituitary is exposed to investigate the effects of LH suppression on Alzheimer GnRH in the physiologically normal pulsatile fashion. disease development in these completed, long-term cohorts. Although leuprolide and goserelin are agonists at the receptor References level, continuous stimulation of the anterior pituitary 1. Webber KM, Perry G, Smith MA, Casadesus G. The contribution gonadotrophs by these synthetic analogues paradoxically of luteinizing hormone to Alzheimer disease pathogenesis. diminishes LH release. Both agents are commonly used in the Clin Med Res 2007;5:177-183. 2. Webber KM, Casadesus G, Bowen RL, Perry G, Smith MA. treatment of endometriosis, precious puberty and metastatic Evidence for the role of luteinizing hormone in Alzheimer prostate cancer. Radiation oncologists also frequently use disease. Endocr Metab Immune Disord Drug Targets them as adjuvant therapy for locally advanced or high-risk 2007;7:300-303. 3. ClinicalTrials.gov. Antigonadotropin-Leuprolide in Alzheimer localized prostate cancer. Long-term follow-up has Disease Drug INvestigation (ALADDIN) VP 104 Study. documented improved local control, biochemical control, Available at: disease specific survival and overall survival compared to http://clinicaltrials.gov/ct/show/nct00076440?orden=6. radiotherapy alone for high-risk prostate cancer patients. Last accessed March 21, 2008. 4. Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Given that these studies were prospective, randomized Movsas B, Hug EB, Asbell SO, Grignon D. Androgen clinical trials, which began in the 1980s, they could perhaps suppression adjuvant to definitive radiotherapy in prostate provide additional evidence supporting or refuting the carcinoma—long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 2005;61:1285-1290. hypothesis. For instance, in the clinical trial RTOG 85-31, 4 patients with high-risk prostate cancer were randomized to Keywords: Alzheimer disease, Luteinizing hormone, Gonadotrophin- Received: February 1, 2008 releasing hormone Accepted: February 13, 2008 doi: 10.3121/cmr.2008.791 1 5. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff Expression of Concern – Mavoungou E. RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Interactions Between Natural Killer Cells, Pierart M. Long-term results with immediate androgen Cortisol and Prolactin in Malaria During suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III Pregnancy. Clin Med Res 2006;4:33-41. randomised trial. Lancet 2002;360:103-106. The editors of Clinical Medicine & Research were notified by a third party that the article published in 2006 by Elie James S. Welsh, MS, MD, FACRO Mavoungou 1 contains large amounts of text that appear to be Departments of Human Oncology and Medical Physics taken verbatim from, and without attribution to, an article by University of Wisconsin School of Jeffrey S. Miller 2 previously published in Experimental Medicine and Public Health and Hematology . Neither Clinical Medicine & Research nor UW Cancer Center Experimental Hematology has record of a request by 410 Dewey Street Dr. Mavoungou to reproduce the information from Wisconsin Rapids, WI 54494 Dr. Miller’s article. Tel: 715-421-7442 Fax: 715-421-7408 The editors of Clinical Medicine & Research have attempted Email: [email protected] to contact Dr. Mavoungou for an explanation, but have not received a response. At this time, we express our concern regarding the duplication of information without proper copyright permission from Experimental Hematology . We are consulting the Committee on Publication Ethics (COPE) Guidelines for Good Publication Practice 3 for advice on handling this situation. We will keep our readers informed of additional information received and decisions made regarding this article. References 1. Mavoungou E. Interactions Between Natural Killer Cells, Cortisol and Prolactin in Malaria During Pregnancy. Clin Med Res 2006;4:33-41. 2. Miller JS. The biology of natural killer cells in cancer, infection, and pregnancy. Exp Hematol 2001;29:1157-1168. 3. Committee on Publication Ethics (COPE). Guidelines on good publication practice. Available at: http://www.publicationethics.org.uk/guidelines. Accessed May 30, 2008. Kurt D. Reed, MD Editor-in-Chief Sherry A. Salzman-Scott Senior Editor 2.
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