Tamoxifen in men: a review of adverse events.

Tamoxifen is an off-label option to treat men for breast cancer, infertility, and idiopathic gynecomastia. Lately, tamoxifen has been proposed as a treatment to prevent gynecomastia in prostate cancer patients receiving antiandrogen therapy. We reviewed the adverse events (AEs) reported in studies of men prescribed tamoxifen for these conditions to better understand its side-effect profile. We searched PubMed for randomized controlled trials (RCTs) that included safety data of tamoxifen treatment in men with prostate cancer, breast cancer, infertility, and idiopathic gynecomastia. Non-RCTs were also reviewed. The results demonstrate that the AE profile in tamoxifen-treated male populations varied. Excluding breast events, gastrointestinal, and cardiovascular problems were the most commonly reported AEs in prostate cancer patients, whereas more psychiatric disorders were reported in male breast cancer patients. Few AEs have been documented in men receiving tamoxifen for infertility and idiopathic gynecomastia. Less than 5% of men withdrew from tamoxifen therapy because of toxicity. This suggests that for most men, tamoxifen is well-tolerated. Of those who discontinued tamoxifen, the majority were male breast cancer patients, and cardiovascular events were the most common reason for stopping tamoxifen treatment. Unfortunately, in many cases, the reasons for withdrawing tamoxifen were unspecified. Based on the available evidence, tamoxifen's AE profile appears to vary depending upon which male population is treated. Also, the frequency at which AEs occur varies - less AEs in men with infertility and idiopathic gynecomastia compared to men with prostate cancer or breast cancer. Long-term studies that rigorously document the side-effect profile of tamoxifen in men are lacking.

Eroticization as a factor influencing erectile dysfunction treatment effectiveness.

We review both the medical and psychosocial literature on factors influencing male potency in order to better understand why erectile dysfunction (ED) treatments, PDE5 drugs in particular, are abandoned when otherwise effective. We incorporate anecdotal data from websites and list serves dedicated to helping patients deal with iatrogenic ED. Our goal is to distinguish between ED treatments that are medicalized versus eroticized, and how partner participation may influence their effectiveness. Recently it has been shown that ED treatment effectiveness is aided by the involvement of the patient's partner. This permits an erotic association between the partner and the ED 'aid'. We extend this idea to suggest that having the partner involved as early as possible in the discussion of treatment, and their presence at the time of prescription, should improve ED aid effectiveness. Eroticization of ED aids shifts the focus from a perceived disability of the patient toward the sexual pleasure provided by the partner. We further suggest that ED aids used without the partner's knowledge will undermine intimacy and ultimately the treatment's effectiveness. Unpartnered patients should be advised about the importance of informing potential partners about their use of such aids, as openness and honesty may increase intimacy in the long run.

Systemic bias in the medical literature on androgen deprivation therapy and its implication to clinical practice.

BACKGROUND: LHRH agonists are used for androgen deprivation therapy (ADT) to treat prostate cancer, but have many side effects that reduce of the quality of life of prostate cancer patients and their partners. Patients are poorly informed about the side effects of these drugs and how to manage them. AIM: To test the hypothesis that there is bias in the peer-reviewed literature on ADT that correlates with an association between authors and the luteinising hormone-releasing hormone (LHRH) agonists pharmaceutical industry. METHODS: We assessed 155 articles on ADT published in English-language peer-reviewed journals in terms of how comprehensive they were in acknowledging LHRH agonists' side effects. RESULTS: Although the literature regarding ADT is substantial, the vast majority of articles failed to acknowledge many of the more stressful side effects of ADT for patients and their partners. Articles most likely to acknowledge the psychosocial impact of ADT were significantly less likely to have had industrial support than those articles that did not mention those side effects. Alternative treatments to the LHRH agonists were rarely mentioned. Authors who indicated some association with a pharmaceutical company tended to minimise the side effects of LHRH agonists and not acknowledge alternatives to the LHRH agonists for ADT. CONCLUSION: Industrial support is associated with a proliferation of articles published in the peer-reviewed literature directed at practising physicians. Such flooding of the literature may, in part, limit physicians' knowledge of the side effects of these drugs and, in turn, account for the poor knowledge that patients on LHRH agonists have about the drugs they are taking and ways to manage their side effects.

The language of prostate cancer treatments and implications for informed decision making by patients.

Previous research has shown that cancer patients lack knowledge about treatments particularly for reproductive system cancers. Focusing on prostate cancer, we explored how the language used to describe treatments and their side effects is understood by both men and women. Since the language around prostate cancer is often euphemised to reduce distress and stigma, our aim was to elucidate how language (e.g. hormone therapy vs. androgen deprivation therapy) affects both patients' and partners' attitudes towards treatment decision making. We surveyed 690 male and female cancer patients and non-patients through an online questionnaire. A large proportion of participants did not understand the terminology used to describe prostate cancer treatments. Most did not know that the terms 'chemical castration', 'hormonal therapy' and 'androgen deprivation' are synonymous. Male respondents stated that they would more readily agree to hormonal therapy than to castration to treat prostate cancer and felt significantly more strongly than women about how androgen deprivation therapy, described in various terms, affected masculinity. Men and women differed substantially in their opinion about the impact of androgen deprivation. For patients and partners to make informed decisions and cope effectively with treatment side effects, it is important that healthcare practitioners provide accurate information using language that is unambiguous.

Patient preference and the impact of decision-making aids on prostate cancer treatment choices and post-intervention regret.

The number of prostate cancer survivors is rapidly growing in the Western world. As a result of better oncologic outcomes, more patients are living longer with the adverse effects of treatment, which can be both functional and psychological. Clinicians, in an era of shared decision-making, must not only cure the cancer, but also ensure that, after treatment, their patients experience the best quality of life and minimal post-treatment decisional regret. To participate in the decision-making process, men and their involved partners and family need to fully understand the relative benefits and harms of prostate cancer treatments.Patient preference studies indicate that men with prostate cancer are not well informed. Decision-making aids are a positive treatment adjunct both to convey information and to allow patients to explore their own beliefs and values during the decision-making process. The evidence suggests that decision-making aids better prepare patients for involvement in treatment decisions, but further studies are required to investigate the relationship between the use of decision-making aids and post-treatment decisional regret in prostate cancer.

Studying the visceral physiology of tadpoles through their naturally transparent abdominal walls.

We propose using anuran tadpoles with naturally transparent abdominal skin to study the visceral physiology of amphibian larvae under microgravity. The transparency of the abdominal wall in certain tadpoles enables one to evaluate the basal physiological state and temporal changes in viscera from their movements without any invasive treatment. In order to validate our experimental design, the intestinal motility and heart rate of Rhacophorus tadpoles were examined as indices of physiological responses to stepwise changes in temperature.

Plasticity and constraints on feeding kinematics in anuran larvae.

Tadpoles of the majority of anuran species have tiny, anatomically complex mouths. In most species the larval jaws are keratinized sheaths (beaks) overlying infrarostral cartilages. Surrounding the beak is a flexible oral disc and transverse rows of small, keratinized denticles. We used high-speed videography (250, 500 and 1000 frames per second) of Rana catesbeiana tadpoles to observe the kinematics of these mouthparts in feeding and breathing. Tadpoles can protract and retract their jaws as well as make them wider and narrower with each gape cycle. We demonstrate that during air-breathing, movement of the oral disc helps surfacing tadpoles to capture air quickly by preventing water from coming into the mouth. For our feeding study, we observed tadpoles as they grazed on both clean and algal covered glass surfaces. As the jaws close, the lower beak narrows to a greater degree when it encounters resistance. The denticle rows are used to both anchor the mouth and rasp surfaces during feeding. The hyperkinetic mouth parts of tadpoles permit grazing on non-planar surfaces of variable resistance. A trade-off in having such mobile jaws is loss of stability; no generalized tadpoles can generate great forces with their jaws, which would be necessary to subdue and dismember large tough prey. The feeding system of tadpoles is built out of soft tissues (such as cartilage and keratin) that can be shed (the keratinized sheaths) or remodeled (the underlying infrarostral cartilage) quickly, thus facilitating metamorphosis.

Do prostaglandins regulate external gill regression in anurans?

Although the endocrinological mechanism controlling regression of the internal, larval gills of anurans (frogs and toads) is well understood, the mechanism regulating loss of the external, embryonic gills is not known. Based on the homology of the mammalian ductus arteriosus with a portion of the amphibian branchial arches, and the regulation of blood flow in the mammalian ductus by prostaglandins of the E family (PGEs), we hypothesized that anuran external gill loss is also regulated by PGEs. To test this hypothesis, we topically applied both PGE2 and a synthetic analogue of PGE1, misoprostol, to embryos and young hatchlings of the red-eyed treefrog, Agalychnis callidryas. Both agents accelerated external gill regression. Furthermore, misoprostol overrode the inhibitory effect of hypoxia on gill regression in hatchlings and induced rapid loss of external gills in embryos, which normally maintain the gills until hatching. These observations support the hypothesis that PGEs regulate anuran external gill loss. The specific site of action for prostaglandins within the gills is not known; however, PGEs are secreted in the oral mucus of tadpoles, and this could be a natural topical source for these agents. PGEs offer a tool for manipulation of external gills and should facilitate tests of the physiological importance of these structures.

Factors influencing the susceptibility of anurans to motion sickness.

We examined the propensity for motion sickness in five anuran species, concentrating our efforts on the treefrog Rhacophorus schlegelii, because it had shown the greatest susceptibility to motion sickness in a previous study. We used parabolic flight as our provocative stimulus and fed all specimens a known volume of food 1.5-3 h before flight. The presence of vomitus in a frog's cage was our indicator of motion sickness. Significantly more emesis was observed in flight-exposed than in control R. schlegelii (P < 0.05). There was no sex difference in susceptibility to motion sickness (P > 0.5). Individuals that vomited were significantly larger (P < 0.02) than those that did not. Among microgravity-treated frogs, those that vomited spent on average 85% more time airborne and tumbling in microgravity than those that did not vomit (P=0.031). Our data support the view that postural instability and sensory conflict are elements of motion sickness in anurans. Specifically, conflicts between tactile, vestibular and visual input seem essential for producing motion-induced emesis in anurans. Since the factors that induce motion sickness in R. schlegelii are the same ones that produce motion sickness in humans, arboreal frogs may be useful alternative models to mammals in motion sickness research.

The mechanics of air-breathing in anuran larvae: implications to the development of amphibians in microgravity.

Because of their rapid development, amphibians have been important model organisms in studies of how microgravity affects vertebrate growth and differentiation. Both urodele (salamanders) and anuran (frogs and toads) embryos have been raised in orbital flight, the latter several times. The most commonly reported and striking effects of microgravity on tadpoles are not in the vestibular system, as one might suppose, but in their lungs and tails. Pathological changes in these organs disrupt behavior and retard larval growth. What causes malformed (typically lordotic) tadpoles in microgravity is not known, nor have axial pathologies been reported in every flight experiment. Lung pathology, however, has been consistently observed and is understood to result from the failure of the animals to inflate their lungs in a timely and adequate fashion. We suggest that malformities in the axial skeleton of tadpoles raised in microgravity are secondary to problems in respiratory function. We have used high speed videography to investigate how tadpoles breathe air in the 1G environment. The video images reveal alternative species-specific mechanisms, that allow tadpoles to separate air from water in less that 150 ms. We observed nothing in the biomechanics of air-breathing in 1G that would preclude these same mechanisms from working in microgravity. Thus our kinematic results suggest that the failure of tadpoles to inflate their lungs properly in microgravity is due to the tadpoles' inability to locate the air-water interface and not a problem with the inhalation mechanism per se.

Emesis and space motion sickness in amphibians.

Amphibians possess the ability to vomit in response to a variety of stimuli that provoke emesis in mammals. Pharmacological studies have establish that the ejection of gastric contents and the basic mechanism for vomiting have been phylogenetically conserved among these tetrapods. As part of on-going comparative studies on emesis in vertebrates, we previously documented that some postmetamorphic anurans and salamander larvae experience motion-induced emesis when exposed to the provocative stimulus of parabolic aircraft flight. However, more recent experiments suggest that there are strict conditions for inducing emesis in amphibians exposed to parabolic flight and that amphibians are not as sensitive to this stimulus as mammals. Further studies on emesis in lower vertebrates may help us understand the processes that cause emesis in abnormal gravitational regimes.

Survey of studies on how spaceflight affects rodent skeletal muscle.

Rodent muscles have been examined in more than 89 spaceflight studies over the last 25 years with much variation in the procedures and results. Mission duration ranged from four days to three weeks, postflight data collection ranged from a few hours to two days after landing, and there is great diversity in the number, size, and age of the rats that have flown. Several different types and sizes of animal enclosures have also been used--a significant factor because cage design affects animal activity and muscle loading. Only a small percentage (approximately 16%) of the total number of striated muscles in the rat have been examined. We have identified both substantial redundancy and inconsistencies in the results from studies to date. However, many of these appear unavoidable due to the great variation in experimental protocol of the different missions. Nevertheless these studies repeatedly confirm that exposure to spaceflight decreases the mass of limb muscles and leads to muscle atrophy. The majority of missions were flown by the former Soviet Union, but the majority of papers have been published by U.S. researchers. A relatively small number of investigators (about 50) clustered into fewer than 15 identifiable research groups worldwide account for most of the results to date. These groups have had access to rodent muscle tissue from two to seven spaceflights each. International cooperation in the post-cold war era and the publication of future work in peer-reviewed international journals should help greatly in reducing redundancy and enriching our knowledge of how gravity affects biological systems.

Allometry in vestibular responses of anurans.

Frogs and toads turn either their heads or bodies opposite to angular accelerations applied around the yaw axis. Thresholds exist for the minimum angular acceleration that induces this vestibulomotor response in individual frogs. These thresholds were recorded for several anuran species that cover a broad range of sizes and life styles. Interspecific variation in the magnitude of the thresholds, which correlated with the ecology and behavior of the species, was documented. Also an allometric relationship was observed between this threshold and body size; the larger the frog, the lower the threshold. In many species, the threshold value for reflexive vestibulomotor responses to angular acceleration was proportional to the -0.4 (+/-0.2) power of body mass. Physical dimensions of the semicircular canals determine, in part, vestibular sensitivity to angular acceleration. Hence changes with growth in the semicircular canals are believed to contribute to the slope of -0.4. The biological significance of this allometry in vestibular responses is discussed and compared to trends in vestibular sensitivity and semicircular canal morphology of other vertebrate classes.