The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author. Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.
VIAGRA & SEXUAL FUNCTION IN WOMEN
In previous columns, I have reviewed research studies of female sexual function and dysfunction (please see my Archives). This is a very complex area of research, given the large number of both biological and behavioral factors at work in human sexuality. Further complicating matters is the enormous difference in sexual behavior and physiology between men and women. Male sexual dysfunction, which most commonly results from an inability to obtain a satisfactory erection (erectile dysfunction), is often treatable with Viagra and similar drugs. These medications function by dilating the arteries that supplies the erectile tissues in the penis, thus improving blood flow to these tissues. In the absence of sexual arousal, however, these medications do not have any significant effect on erectile function. Because the majority of cases of sexual dysfunction in women are related to a decreased level of sexual desire, or libido, previous research trials of Viagra, and similar drugs, in women have been disappointing, as these medications do not directly affect the sexual arousal pathways in the brain.
However, a new prospective, double-blinded clinical research trial in the Journal of the American Medical Association suggests that women who are experiencing decreased libido associated with antidepressant medications may, in fact, benefit from Viagra. This study was performed by researchers at the University of New Mexico, and an important disclaimer has been made by both the study’s authors and the Pfizer Corporation, which manufactures Viagra. Not only was this research conducted with the financial support of Pfizer, but several of the study’s authors (including the primary author) have a history of receiving funding grants from Pfizer.ÂÂÂ
Financial links between clinical researchers and for-profit pharmaceutical and medical device companies are coming under increasing scrutiny by medical ethicists due to the obvious potential for conflicts of interest (I often receive offers to speak on behalf of such companies, or to participate in research projects with their funding, and I have always politely declined such offers from for-profit companies). Unfortunately, due to the very modest pool of research funding available from governmental and non-profit sources, research scientists increasingly find themselves between the proverbial “rock and a hard place†when it comes to obtaining sufficient funds to conduct their research. In the case of this particular research trial, all authors disclosed their fiduciary relationships with Pfizer, and Pfizer published a disclaimer indicating that the company had no role in the design or conduct of this study, or in the writing of the manuscript that resulted from this research. While these disclaimers do not completely exclude the possibility of bias in favor of Viagra by the Pfizer-sponsored researchers, these public disclaimers, as well as the randomized double-blinded design of this prospective clinical trial, represent the most open and honest way of performing clinical research with a commercial sponsor which is also the manufacturer of the drug being studied. Nonetheless, all research studies that are conducted with financial support from commercial entities that have a vested interest in the outcomes of such studies should be viewed with a very critical eye.
This multi-institutional research trial enrolled 98 women with a diagnosis of major depression. All of these women gave a history of normal sexual desire and function prior to beginning treatment with antidepressant medications known as “SRIs,†or serotonin reuptake inhibitors. (These medications are known to cause decreased libido in both men and women as a side effect.) A crucial difference in this particular study, when compared to previous research looking at the treatment of sexual dysfunction in women with Viagra, is that the women in this study reported previously normal sexual function prior to starting treatment with SRI antidepressant medications. In previous Viagra studies, women volunteers reported decreased baseline sexual desire, and without any apparent medical or pharmaceutical causes.
Over the 8-week course of this study, half of the women volunteers received Viagra and the other half received a sugar pill (placebo) that was identical in appearance to Viagra. The women were instructed to take their assigned pills just prior to engaging in sexual activity. None of the women volunteers, or the research personnel conducting the study, were aware of which pills were Viagra and which were placebo pills in this double-blinded study. Throughout the study, previously validated female sexual dysfunction surveys were administered to all of the study volunteers, and all of the women maintained a personal diary of their sexual activity. Additionally, blood levels of female sex hormones were measured in all of the volunteers.
During the course of this study, 22 women (22% of the women who entered the study) dropped out of the study for various reasons. However, the researchers also, appropriately, included these 22 women in their final analysis. When the data was analyzed, the researchers noted a 60% improvement in sexual function among the women who had received Viagra pills (when compared to the patients who had received the placebo pills). In all patients, sex hormone levels in the blood were within the normal range, and did not significantly differ between the women taking Viagra versus those taking the placebo pill.
Although this study is the first ever to find a favorable effect on female sexual function with Viagra, it is important to understand that the results of this study are probably not applicable to the general population. Viagra, and related drugs, have no effect on the areas of the brain that control baseline sexual desire. These drugs work, very specifically, on the genitals (and not on the brain). Therefore, it is not at all surprising that these drugs have been shown, by multiple studies, to have no effect on women who are experiencing decreased libido that is not due to the side effects of other medications. In this study, however, women who reported previously normal levels of sexual desire and function, and who secondarily developed sexual dysfunction as a side effect of SRI antidepressants, appeared to benefit from Viagra. Because the mechanisms of sexual dysfunction are different when comparing primary sexual dysfunction versus that caused by SRI medications, Viagra may offer the latter group of women an effective therapy by improving genital function.ÂÂÂ
The most important clinical consideration arising from this study is that both men and women with major depression frequently stop taking their antidepressant medications because of the sexual dysfunction that can be induced by these drugs. If, indeed, depressed women can benefit from Viagra, as men have, then they are more likely to continue taking their antidepressant medications. Nothing in this study contradicts previous studies that have shown no benefit from Viagra in women with primary sexual dysfunction. However, for women taking SRIs for major depression, Viagra, and similar drugs, may help to reverse SRI-associated sexual dysfunction, and may therefore improve compliance with antidepressant therapy.  This would, clearly, represent a “win-win†situation for such patients.
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PATIENT-REPORTED ADVERSE HOSPITAL EVENTS
In 1999, the prestigious Institute of Medicine (IOM) estimated that nearly 100,000 Americans die every year due to medical errors (the vast majority of which involve errors in dispensing medications). Although this report subsequently set off a firestorm of debate regarding the accuracy of the IOM’s data and conclusions, there is no doubt but that numerous injuries and deaths result, every year, from negligence and errors in medical and surgical care. Today, primarily as a result of the IOM’s landmark report on medical errors, there is an enormous emphasis on improving the quality of care in the United States, using multiple approaches to drive down the incidence of preventable medical and surgical errors. Currently, the careful review of patient medical records is one of the most important methods in use to detect evidence of medical errors and patient complications.
A new research study, just published in the Annals of Internal Medicine, offers a sobering assessment of how well our current approaches to medical error discovery are functioning, as well as suggesting how we might further improve medical error detection. This study was performed by researchers at Harvard University and Brown University.
In this study, the medical records of patients who were recently discharged from the hospital were randomly selected and reviewed for evidence of medical errors. Additionally, these patients were contacted and interviewed, and additional evidence of potential medical errors was collected directly from these patients. The researchers then compared the medical records of these patients with the results of patient interviews in an effort to assess how well the medical records documented apparent medical errors.
Nearly 1,000 patients participated in this study, and 11% were found to have experienced at least 1 adverse event during their hospitalization, based upon a review of their medical records. Based upon direct patient interviews, however, the researchers determined that at least 23% of the patients had experienced some sort of adverse event (or events) during their hospital stay. Moreover, many of these adverse events were not only serious but preventable as well.
Although the authors of this study pointed out that patients may not be able to clearly recall every in-hospital adverse event when being interviewed months after discharge, the findings of this study still raise the very worrisome possibility that our current mechanisms of medical error discovery are missing many serious and potentially preventable errors. The results of this study strongly suggest that hospitals should implement routine post-discharge interviews of patients as part of the important process of identifying medical errors. This patient-centered approach may represent a very important new tool in our efforts to reduce medical and surgical errors to the lowest achievable level.
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CURCUMIN & PANCREATIC CANCER
Regular readers of this column already know that cancer of the pancreas is a particularly nasty type of cancer. More than 90% of patients diagnosed with this disease will eventually succumb to it. (Dr. Randy Pausch, the Carnegie Mellon Computer Sciences professor who touched the world with his poignant book, The Last Lecture, died yesterday of pancreatic cancer, at the age of 47.)
Currently, surgery is the mainstay of pancreatic cancer treatment, but the overwhelming majority of patients with pancreatic cancer are not candidates for surgery by the time their disease has been discovered and diagnosed. Even among the minority of patients with pancreatic cancer who are candidates for the radical surgery used to treat this dismal disease, the long term survival rates are very poor. Although chemotherapy and radiation therapy are often used, particularly in advanced cases of pancreatic cancer, their impact on this disease has not been highly effective. Therefore, a tremendous amount of research is underway to try and find more effective treatments for one of the most formidable causes of cancer-related death in the world.
Curcumin is well known to connoisseurs of Indian food, as it is a principle component of tumeric, which is used to make curry. Numerous laboratory studies have demonstrated that curcumin has both anti-cancer and anti-inflammatory activities, and so there is a great deal of interest in testing curcumin in humans as an anti-cancer medication. A new study, just published in the journal Clinical Cancer Research, examines the clinical effects of curcumin supplements in patients with advanced pancreatic cancer. This study was performed by researchers from the University of Texas M.D. Anderson Cancer Center.ÂÂÂ
In this study, 21 patients with advanced pancreatic cancer received oral curcumin supplements, and were reassessed for response every 2 months during the course of this study. In addition to radiographic imaging studies of their tumors, blood levels of proteins associated with both pancreatic cancer tumor activity and response to cancer treatment were measured every 2 months.
In one patient who received curcumin, no tumor growth or spread was noted for more than 18 months, which is remarkable for advanced pancreatic cancer. In a second patient, curcumin supplementation was associated with a 73% reduction in tumor size, which is also a remarkable response for pancreatic cancer, although this dramatic response was only temporary in this patient. Although the tumors of the remaining patients did not appear to respond as dramatically as was observed in these two patients, the blood levels of proteins associated with cancer treatment response revealed a significant biochemical response to curcumin supplements in the remaining patients as well.
Why two patients’ tumors clinically responded, however transiently, so well to curcumin and the others did not is unclear at this time. However, all patients who received curcumin showed biochemical evidence of anti-cancer activity in their blood. Although the overall clinical effects of curcumin in this early-phase clinical research study were not very dramatic in absolute terms, the fact that any of the patients with advanced pancreatic cancer in this study experienced any clinical benefit from this non-toxic dietary supplement is actually quite remarkable. In highly lethal cancers, like pancreatic cancer, which are refractory to most of our treatments, even incremental clinical signs of progress, such as were demonstrated in this study, are cause for celebration. As this was only a small early-phase clinical study, additional and larger prospective, randomized, double-blinded clinical research trials with curcumin are warranted, based upon the results of this small study.
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Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:
http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html
Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net
Copyright 2008.  Robert A. Wascher, MD, FACS. ÂÂÂ
All rights reserved.
