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Journal of Zoo and Wildlife Medicine :... Jun 2021The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG)...
The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin), a contraceptive used in a wide range of mammalian taxa. More recently its use has increased in birds and in some reptiles and fish. Deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, stimulates the reproductive system before downregulating receptors on pituitary cells that produce hormones that stimulate gonadal steroids in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively. Nevertheless, it has been used mostly in females. Efficacy has been high in mammals, with failures resulting in offspring in only 1.3% of treated individuals and 0.5% of treatment bouts. The failure rate has been higher in birds, with 14.7% of individuals in 7.2% of bouts producing eggs, perhaps reflecting differences in avian GnRH molecules. Too few reptiles and fish have been treated for meaningful analysis. Although deslorelin appears very safe, a possible exception exists in carnivores, because the stimulatory phase can result in ovulation and subsequent sustained progesterone secretion that may cause endometrial pathology. However, the stimulatory phase can be prevented by treatment with megestrol acetate for 7 d before and 7 d after implant insertion. The two current formulations of Suprelorin are effective for minimums of 6 (4.7 mg) or 12 mo (9.4 mg). The data indicate that Suprelorin is an effective and safe contraceptive option for female mammals, although it may not be effective in males of some mammalian species. Further research is needed to ascertain its usefulness in nonmammalian taxa.
Topics: Animals; Animals, Zoo; Birds; Contraceptive Agents; Data Collection; Drug Implants; Female; Male; Mammals; North America; Triptorelin Pamoate
PubMed: 34130384
DOI: 10.1638/2020-0217 -
Journal of Hazardous Materials Apr 2023The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and...
The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and the temporal evolution of cytostatics in wastewaters from a Portuguese hospital center was evaluated through a 9-month sampling campaign, comprising a total of one hundred and twenty-nine samples, collected from May 2019 to February 2020. Eleven cytostatics out of thirteen pharmaceuticals were studied, including flutamide, mycophenolate mofetil and mycophenolic acid, which have never been monitored before. Target analytes were extracted and quantified by solid-phase extraction coupled to liquid-chromatography-tandem mass spectrometry analysis; the method was fully validated. All pharmaceuticals were detected in at least one sample, bicalutamide being the one found with higher frequency (detected in all samples), followed by mycophenolic acid, which was also the compound detected at higher concentrations (up to 5340 ± 211 ng/L). Etoposide, classified as carcinogenic to humans, was detected in 60% of the samples at concentrations up to 142 ± 15 ng/L. The risk from exposure to cytostatics was estimated for aquatic organisms living in receiving bodies. Cyclophosphamide, doxorubicin, etoposide, flutamide, megestrol and mycophenolic acid are suspected to induce risk. Long-term and synergic effects should not be neglected, even for the cytostatics for which no risk was estimated.
Topics: Humans; Cytostatic Agents; Flutamide; Etoposide; Mycophenolic Acid; Water Pollutants, Chemical; Solid Phase Extraction; Environmental Monitoring; Pharmaceutical Preparations
PubMed: 36731320
DOI: 10.1016/j.jhazmat.2023.130883 -
The Journal of Nutrition, Health & Aging Jun 2024Anorexia of aging (AoA) is a prevalent geriatric syndrome characterized by a multifactorial decline in appetite and reduced food intake associated with the aging... (Review)
Review
BACKGROUND AND OBJECTIVES
Anorexia of aging (AoA) is a prevalent geriatric syndrome characterized by a multifactorial decline in appetite and reduced food intake associated with the aging process. This systematic review aims to investigate the use and outcomes of cannabinoids in addressing AoA, with the goal of providing a comprehensive understanding and discussing their potential integration into daily clinical practice.
METHODS
A thorough search of databases (Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science) identified 6100 studies. After eliminating duplicates and screening titles and abstracts, 25 studies underwent full appraisal. Two reviewers assessed inclusion suitability, and study methodologies were evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the modified Jadad Scoring Scale for randomized controlled trials. Ultimately, six studies published between 2002 and 2019, involving 869 participants, were included in the review.
RESULTS
Out of the 6 fin. l papers selected, 5 were randomized trials, and 1 was a prospective study. Megestrol acetate (800 mg/d) proved to be more effective than dronabinol 2.5 mg twice a day in increasing appetite. Nabilone (at a dosage of 0.5 mg per day) did not show superiority over placebo in alleviating symptoms such as pain, nausea, loss of appetite, and weight. However, with a double dosage followed by 1.0 mg/6 weeks, after eight weeks of treatment, patients recorded a significant increase in calorie intake and carbohydrate consumption compared to the placebo group, with some patients also experiencing substantial weight gain. Regarding delta-9-tetrahydrocannabinol (THC), a weight increase of ≥10% was observed in 17.6% of patients with doses of 5 mg or 10 mg capsules daily, without significant side effects. Additionally, patients treated with THC 2.5 mg reported improved chemosensory perception and increased appetite before meals compared to placebo. No significant side effects were reported in older adults taking cannabinoids.
CONCLUSIONS
Cannabinoids offer promise in enhancing the quality of life for older individuals with active neoplastic disease. However, to establish comprehensive guidelines, further research with larger sample sizes is essential. Only through this approach can we fully grasp the potential and application of cannabinoids in addressing the nutritional concerns associated with neoplastic diseases.
PubMed: 38917597
DOI: 10.1016/j.jnha.2024.100299 -
Effect-Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water.Environmental Toxicology and Chemistry Jan 2020Effect-based monitoring is increasingly applied to detect and-in conjunction with chemical analysis-to identify endocrine-disrupting compounds (EDCs) in the environment....
Effect-based monitoring is increasingly applied to detect and-in conjunction with chemical analysis-to identify endocrine-disrupting compounds (EDCs) in the environment. Although this approach of effect-directed analysis has been successfully demonstrated for estrogenicity and androgenicity, data on progestogens and glucocorticoids driving endocrine disruption are quite limited. We investigated progestogenic and glucocorticoid activities in Danube River water receiving untreated wastewater from Novi Sad, Serbia. After a 2-step fractionation, all fractions were tested with reporter gene bioassays for agonistic and antagonistic hormonal responses at progestogenic and glucocorticoid hormone receptors as well as with target and nontarget analytical screening of active fractions by liquid chromatography-high-resolution mass spectrometry. Due to masking by cytotoxic mixture components, the effects could not be detected in the raw water extract but were unraveled only after fractionation. Target chemical screening of the fraction that was active in the progesterone receptor (PR) assay revealed that progesterone and megestrol acetate were predominant drivers of PR-mediated activity along with medroxyprogesterone, dihydrotestosterone, androsterone, and epiandrosterone. Hydrocortisone was detected at sub-ng/L concentration in the active fraction in the glucocorticoid receptor (GR) assay but could not explain a significant fraction of the observed GR activity. The present study indicates that effect-based monitoring is a powerful tool to detect EDCs in the aquatic environment but that fractionation may be required to avoid masking effects of mixture components. Future effect-directed analysis studies are required to better understand the occurrence of EDCs and masking compounds in different lipophilicity windows, to finally reduce fractionation requirements for monitoring to a smart clean-up. Environ Toxicol Chem 2019;39:189-199. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Topics: Biological Assay; Cell Survival; Chromatography, Liquid; Dose-Response Relationship, Drug; Ecotoxicology; Endocrine Disruptors; Environmental Monitoring; Gas Chromatography-Mass Spectrometry; Glucocorticoids; HEK293 Cells; Humans; Progestins; Receptors, Glucocorticoid; Receptors, Progesterone; Rivers; Serbia; Wastewater; Water Pollutants, Chemical
PubMed: 31614391
DOI: 10.1002/etc.4609 -
Cancers Mar 2023Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for... (Review)
Review
Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for which other treatment types may be too toxic. Hormonal therapy is well tolerated and has response rates ranging from 9 to 33%. Hormonal treatment options take advantage of the estrogen-dependent molecular pathways in endometrial cancers. Current options for hormonal therapies include progesterone therapy (medroxyprogesterone acetate and megestrol acetate) as a single agent or in combination and agents that target the estrogen pathway. Aromatase inhibitors have had modest single-agent activity, but synergistic effects have been found when used in combination with targeted therapy including mTOR inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Molecular profiling of endometrial cancers has begun to help individualize treatments. This review will report on existing data and ongoing trials investigating novel hormonal therapy agents.
PubMed: 36980685
DOI: 10.3390/cancers15061799 -
Supportive Care in Cancer : Official... Dec 2019To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste...
PURPOSE
To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste change after cytotoxic therapies.
METHODS
Patients with acute myeloid leukemia (AML), multiple myeloma (MM), and head and neck cancer (HNC) were evaluated for taste function. Chemical gustometry was conducted assessing chemosensory qualities that included sweet, sour, salty, bitter, umami, and spicy. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and the Scale of Subjective Total Taste Acuity (STTA) were used to describe taste symptoms. Saliva flow rates were measured to determine the presence of hyposalivation. Patients were provided treatment trials for taste dysfunction, including zinc supplements, or medications that included clonazepam, megestrol acetate, and the cannabinoid dronabinol.
RESULTS
According to STTA, hematology cases reported the incidence of grades 2 and 3 taste disturbances as 60% and 40%, respectively. For HNC patients, the incidence of grades 2 and 3 was 44% each. Gustometry tests confirmed dysgeusia in all patients evaluated. In the hematology group, 80% of patients exhibited a decrease in sweet taste perception, and no patients correctly identified umami taste. In the HNC group, most patients could not identify salt taste, 66% of patients reported "no sensation" with spicy taste, bitter taste was reduced in some, and increased or altered in others, while only one patient could identify umami taste. In the hematologic and HNC patient groups, 80% and 66% reported grade 2 dry mouth, respectively, according to CTCAE 4.0. After treatment for taste dysfunction, 71% of all patients in the present study reported improvements in taste function.
CONCLUSIONS
Persisting dysgeusia in cancer survivors may be assessed by patient report and taste testing. The taste most affected in our patients was umami. Treatment trials with current interventions for dysgeusia appeared effective and should be considered in cancer survivors. Understanding taste and flavor function during and following cancer treatment is important in developing rational prospective preventive and interventional strategies.
Topics: Aged; Female; Head and Neck Neoplasms; Hematologic Neoplasms; Humans; Male; Middle Aged; Prospective Studies; Taste Disorders; Taste Perception
PubMed: 30927113
DOI: 10.1007/s00520-019-04758-5 -
Clinical Nutrition ESPEN Oct 2019Cancer cachexia (CC) syndrome and anorexia-cachexia syndrome are common terms used to describe changes in metabolism with increased inflammatory activity and can...
Ten years of Croatian national guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome - Evaluation of awareness and implementation among Croatian oncologists.
BACKGROUND & AIMS
Cancer cachexia (CC) syndrome and anorexia-cachexia syndrome are common terms used to describe changes in metabolism with increased inflammatory activity and can progressively develop through various stages such as pre-cachexia; cachexia; and refractory cachexia. Therefore in year 2007 Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome were published. Aim of this study was to assess the awareness and implementation of Croatian guidelines for use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) into clinical practice among Croatian oncologists approximately 10 years after the publication, but also to point out the importance of adequate recognition and treatment of CC.
METHODS
Survey with questions was designed to assess the awareness and implementation of Croatian guidelines for use of EPA and MA into clinical practice and was distributed among all Croatian oncologists in secondary and tertiary hospital centers. Survey was conducted in January 2011 (40 months following release of the guidelines), February 2013 and June 2018, and were formed in a way of yes/no answers. Additional multiple choice questions that focus on the implementation of guidelines were added in June 2018.
RESULTS
A total of 128 oncologists completed a questionnaire. There was no statistically significant difference in follow up period (2011-2018) of percentage of oncologists that are familiar with Croatian guidelines for use of EPA and MA in CC, percentage of oncologists in which Croatian national guidelines changed their approach in treating patients with CC syndrome and proportion of oncologists that are using MA, enteral nutrition formulas with EPA or their combination. Most of the oncologists 38% (N = 44) are using >2.2 g of EPA per day. Nutritional support is prescribed in 25-50% of patients by 42% (N = 48) of oncologists and most of the oncologists (35%, N = 41) start with nutritional support when a body mass loss is >5%. Oncologists mostly recommend patients to use nutritional support during 1 year or more (43%, N = 49) or two months to 1 year (42%, N = 48). Compliance of patients with malignant diseases for using nutritional support was mostly evaluated as medium (69%, N = 60).
CONCLUSIONS
Results have shown that majority of oncologists who filled the questionnaire believe that the Croatian national guidelines for use of EPA and MA in CC syndrome changed their approach in treating patients with CC, but also that there are several targeted issues that can be significantly improved. The awareness of and adherence to national guidelines was maintained at high level even 11 years after the guidelines were published.
Topics: Cachexia; Eicosapentaenoic Acid; Humans; Megestrol Acetate; Neoplasms; Nutritional Support; Oncologists; Surveys and Questionnaires; Syndrome
PubMed: 31451262
DOI: 10.1016/j.clnesp.2019.05.013 -
International Urology and Nephrology Sep 2019Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely used to increase appetite and weight in various clinical settings. MA has been indicated to be effective in improving quality of life in patients with cancers. The aim of the present study was to evaluate the efficacy and safety of MA in treating malnourished elderly haemodialysis patients.
METHODS
A randomized controlled study involving 46 hypoalbuminemia haemodialysis patients aged 70 years or older was conducted. The patients in MA-treated group (n = 23) took 160 mg of MA daily, while those in control group (n = 23) were enrolled without any intervention. Anthropometric parameters and laboratory results, including height, dry weight, body mass index, and modified subjective global assessment score as well as serum albumin, triglyceride, total cholesterol, hsCRP, IL-1b and IL-6 concentrations were measured in all patients before and after the intervention. Health-related quality of life was also evaluated using the KDQOL-SF 1.3.
RESULTS
In the MA-treated group, a total of 18 patients finished the therapy over a 3-month period. Appetite was reported as improved by 15 patients, and a statistically significant increase was observed in dry weight (53.36 ± 6.15 vs. 54.24 ± 6.32, P < 0.01) and serum albumin concentration (29.05 ± 3.91 vs. 37.67 ± 4.88, P < 0.01) in the MA-treated group compared to those of the control group. The quality of life in both the physical domain (46.73 ± 18.17 vs. 63.37 ± 22.35, P < 0.01) and the mental domain (50.28 ± 20.36 vs. 68.02 ± 25.48, P < 0.01) was also improved in the same group. There was no significant change in the inflammatory marker concentrations after the intervention. No serious or unexpected adverse events were observed except that one patient who withdrew due to excessive fluid gain between haemodialysis sessions.
CONCLUSION
Our data suggest that MA can be effective in improving nutritional status and quality of life by increasing appetite in elderly haemodialysis patients with acceptable side effects; however, MA might not ameliorate inflammation.
Topics: Aged; Aged, 80 and over; Appetite Stimulants; Female; Humans; Inflammation; Male; Malnutrition; Megestrol Acetate; Quality of Life; Renal Dialysis
PubMed: 31359357
DOI: 10.1007/s11255-019-02245-8 -
Clinical and Experimental Reproductive... Dec 2020Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a...
Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500-600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.
PubMed: 33181010
DOI: 10.5653/cerm.2020.03629 -
Translational Cancer Research Dec 2020Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing... (Review)
Review
Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC.
PubMed: 35117379
DOI: 10.21037/tcr-20-2092