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The Annals of Pharmacotherapy Mar 2019Hospitalized patients are subject to acute illness and stress which may impact appetite or weight. Loss of appetite may lead to increased morbidity or mortality....
BACKGROUND
Hospitalized patients are subject to acute illness and stress which may impact appetite or weight. Loss of appetite may lead to increased morbidity or mortality. Medications such as dronabinol, megestrol, and mirtazapine are used for weight gain in the outpatient setting; however, there is limited information about safety or effectiveness when initiated inpatient.
OBJECTIVES
To analyze the effectiveness and safety of appetite-stimulating medications in hospitalized patients.
METHODS
This was a retrospective cohort study of hospitalized patients initiated on dronabinol, megestrol, or mirtazapine for appetite. The primary outcome was change in meal intake between drug initiation and discontinuation. Secondary outcomes included documented improvement in appetite, change in weight and various laboratory parameters, and incidence of adverse effects.
RESULTS
A total of 38 patients met inclusion criteria, and mirtazapine was most commonly used (42%). There was no significant difference between groups of appetite-stimulating medications with regard to mean change in meal intake, weight, albumin, or documented improvement in diet. Within groups, each agent showed numerical improvement in percentage meal intake, with a mean change from initiation to discontinuation of 17.12%. Almost half (48%) of the patients experienced improvement in diet after the start of medications. No serious adverse effects were observed. Conclusion and Relevance: In inpatients, there was no difference in change in meal intake or weight between dronabinol, megestrol, or mirtazapine, but they may show numerical improvements in meal intake. To our knowledge, this is the first study to evaluate the use of dronabinol, megestrol, and mirtazapine initiated in the inpatient setting.
Topics: Adult; Appetite; Appetite Regulation; Appetite Stimulants; Dronabinol; Eating; Female; Humans; Inpatients; Male; Megestrol; Middle Aged; Mirtazapine; Retrospective Studies; Weight Gain
PubMed: 30229678
DOI: 10.1177/1060028018802816 -
Home Healthcare Now 2018The increasing older adult population guarantees that healthcare providers are more likely to encounter patients requiring treatment for unintended weight loss. Due to...
The increasing older adult population guarantees that healthcare providers are more likely to encounter patients requiring treatment for unintended weight loss. Due to physiologic changes that occur in the older adult, it is important to know how to assess for, and diagnose unintended weight loss, as well as understand the treatment options. In addition to the use of enteral and parenteral nutrition, appetite stimulants have been used in older adults. Understanding the dosage, side effects, and proper usage of appetite stimulants, such megestrol acetate, mirtazapine, and dronabinol, is crucial in order to provide safe and effective patient care.
Topics: Aged; Aging; Appetite Stimulants; Humans; Malnutrition; Thinness; Weight Loss
PubMed: 30192276
DOI: 10.1097/NHH.0000000000000692 -
JAMA Network Open Jan 2022Meta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associations between hormonal contraceptive use... (Review)
Review
IMPORTANCE
Meta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associations between hormonal contraceptive use and adverse health outcomes has not been quantified in aggregate.
OBJECTIVE
To grade the evidence from meta-analyses of randomized clinical trials (RCTs) and cohort studies that assessed the associations between hormonal contraceptive use and adverse health outcomes among women.
DATA SOURCES
MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to August 2020. Search terms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis.
EVIDENCE REVIEW
The methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, version 2, which rated quality as critically low, low, moderate, or high. The Grading of Recommendation, Assessment, Development and Evaluations approach was used to assess the certainty of evidence in meta-analyses of RCTs, with evidence graded as very low, low, moderate, or high. Evidence of associations from meta-analyses of cohort studies was ranked according to established criteria as nonsignificant, weak, suggestive, highly suggestive, or convincing.
RESULTS
A total of 2996 records were screened; of those, 310 full-text articles were assessed for eligibility, and 58 articles (13 meta-analyses of RCTs and 45 meta-analyses of cohort studies) were selected for evidence synthesis. Sixty associations were described in meta-analyses of RCTs, and 96 associations were described in meta-analyses of cohort studies. Among meta-analyses of RCTs, 14 of the 60 associations were nominally statistically significant (P ≤ .05); no associations between hormonal contraceptive use and adverse outcomes were supported by high-quality evidence. The association between the use of a levonorgestrel-releasing intrauterine system and reductions in endometrial polyps associated with tamoxifen use (odds ratio [OR], 0.22; 95% CI, 0.13-0.38) was graded as having high-quality evidence, and this evidence ranking was retained in the subgroup analysis. Among meta-analyses of cohort studies, 40 of the 96 associations were nominally statistically significant; however, no associations between hormonal contraceptive use and adverse outcomes were supported by convincing evidence in the primary and subgroup analyses. The risk of venous thromboembolism among those using vs not using oral contraception (OR, 2.42; 95% CI, 1.76-3.32) was initially supported by highly suggestive evidence, but this evidence was downgraded to weak in the sensitivity analysis.
CONCLUSIONS AND RELEVANCE
The results of this umbrella review supported preexisting understandings of the risks and benefits associated with hormonal contraceptive use. Overall, the associations between hormonal contraceptive use and cardiovascular risk, cancer risk, and other major adverse health outcomes were not supported by high-quality evidence.
Topics: Adult; Cohort Studies; Contraceptive Agents, Hormonal; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Long Term Adverse Effects; Meta-Analysis as Topic; Pregnancy; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Women's Health
PubMed: 35029663
DOI: 10.1001/jamanetworkopen.2021.43730 -
European Journal of Obstetrics,... Jun 2022To report the pregnancy outcomes of women with prior endometrial cancer and endometrial hyperplasia managed with fertility-sparing treatments. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To report the pregnancy outcomes of women with prior endometrial cancer and endometrial hyperplasia managed with fertility-sparing treatments.
METHODS
Medline and Embase databases were searched. Inclusion criteria were studies reporting the pregnancy outcomes of women who had undergone fertility-sparing treatments for endometrial hyperplasia or early endometrioid endometrial cancer. Outcomes explored were pregnancy, miscarriage and livebirth rates according to the type of progestin treatment used. Subgroup analyses according to the type of diagnostic follow-up were also performed. Meta-analyses of proportions using a random effects model were used to combine data.
RESULTS
Twenty-nine studies (1036 women) were included, and 82.8% [95% confidence interval (CI) 72.3-91.2] of women achieved complete remission. Pregnancy rates were 56.3% (95% CI 41.6-70.5) with megestrol (MA) or medroxyprogesterone acetate (MPA), 63.1% (95% CI 37.0-85.6) with levonorgestrel-releasing intrauterine device (LNG-IUD), 57.9% (95% CI 37.7-76.8) with MA or MPA and metformin, 59.8% (95% CI 48.3-70.7) with MPA and LNG-IUD, 15.4% (95% CI 4.3-42.2) with gonadotropin-releasing hormone analogue (GnRHa) combined with LNG-IUD or letrozole, and 40.7% (95% CI 24.5-59.3) with LNG-IUD and GnRHa. Miscarriage rates were 17.4% (95% CI 12.2-23.4), 14.3% (95% CI 6.4-24.7), 57.9% (95% CI 37.7-76.8), 26.9% (95% CI 14.6-39.3), 100% (95% CI 34.0-100) and 18.2% (95% CI 5.1-47.7), respectively, and livebirth rates were 68.8% (95% CI 56.0-80.3), 80.8% (95% CI 69.5-90.0), 69.9% (95% CI 56.1-82.0), 25.97 (95% CI 14.6-39.3), 0% (95% CI 0-66.0) and 81.8% (95% CI 52.3-94.8), respectively. Finally, stratifying the analysis considering the endometrial sampling method alone, the pregnancy rate was 68.6% (95% CI 51.2-83.6; 10 studies, I = 83.5%) in women who underwent hysteroscopy and 60.5% (95% CI 53.4-67.5; 13 studies, I = 39.8%) in women managed with dilatation and curettage biopsy; the miscarriage and livebirth rates were 13.2% (95% CI 8.0-19.5; I = 0%) and 81.2% (95% CI 67.4-91.8; I = 67.3%), respectively, for hysteroscopy, and 25.2% (95% CI 17.8-33.3; I = 15.5%) and 67.5% (95% CI 58.8-75.5; I = 0%), respectively, for dilatation and curettage biopsy.
CONCLUSION
Fertility-sparing treatment in women with endometrial cancer or hyperplasia is associated with an overall good response to therapy, good chance of achieving pregnancy and a good livebirth rate. Diagnostic follow-up with hysteroscopy was associated with a higher pregnancy rate, although this requires confirmation in adequately powered randomized trials.
Topics: Abortion, Spontaneous; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hyperplasia; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Precancerous Conditions; Pregnancy; Pregnancy Outcome
PubMed: 35526471
DOI: 10.1016/j.ejogrb.2022.04.019 -
Cancers Apr 2022Endometrial cancer (EC) rarely develops in young women. Most cases are associated with known risk factors: BMI > 30, history of Polycystic Ovary Syndrome (PCOs), and... (Review)
Review
Endometrial cancer (EC) rarely develops in young women. Most cases are associated with known risk factors: BMI > 30, history of Polycystic Ovary Syndrome (PCOs), and race differentiation. The molecular EC classification based on The Cancer Genome Atlas Research Network divides these heterogeneous cancers into four types: Polymerase Epsilon Mutation (POLE), Microsatellite Instability (MSI), Copy Number Low (CNL), and Copy Number High (CNH). This division was introduced to allow for early assessment of neoplastic changes and clinical management, including targeted therapies. The basic technique for imaging endometrium changes is transvaginal sonography. Hysteroscopy is the standard for obtaining endometrial material for histological evaluation. The MRI result permits assessment of the extent of EC cancer infiltration. In young women who want to preserve fertility, apart from surgery, conservative management is often implemented after strict selection based on clinical and pathological data. This pharmacological treatment involves the administration of progestogens MPA (medroxyprogesterone acetate) and MA (megestrol acetate). The use of metformin may increase the effectiveness of such treatment. An alternative option is to apply progestogens locally—via the levonorgestrel-releasing intrauterine device. In addition to pharmacological treatment, hysteroscopic resection may be used—part of the uterine muscle adjacent to the pathologically changed endometrium may also undergo resection. An alternative is the administration of estrogen receptor modulators (e.g., SERMs) or aromatase inhibitors, or GnRH agonists.
PubMed: 35454829
DOI: 10.3390/cancers14081922 -
The Cochrane Database of Systematic... May 2024Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets that are currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. A levonorgestrel intrauterine device may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown, in some human studies, to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. This is an update of a review first published in 2017.
OBJECTIVES
To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, PubMed, Embase, Google Scholar, OpenGrey, LILACS, and two trials registers from inception to 5 September 2022. We searched the bibliographies of all relevant studies, and contacted experts in the field for any additional trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo, no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for eligibility, extracted data from included studies, assessed the risk of bias in the included studies, and assessed the certainty of the evidence for each outcome. We resolved disagreements by discussion or by deferring to a third review author. When study details were missing, review authors contacted the study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology.
MAIN RESULTS
We included seven RCTs, in which a total of 387 women took part. In the comparison, Metformin plus megestrol versus megestrol alone, we rated the certainty of the evidence as low for the outcome, regression of endometrial hyperplasia. We rated the quality of the evidence as very low for the rest of the outcomes, in all three comparisons. Although there was a low risk of selection bias, there was a high risk of bias in the blinding of personnel and outcome assessment (performance bias and detection bias) in many studies. This update identified four new RCTs and six ongoing RCTs. Metformin versus megestrol We are uncertain whether metformin increases the regression of endometrial hyperplasia towards normal histology over megestrol (odds ratio (OR) 4.89, 95% confidence interval (CI) 1.56 to 15.32; P = 0.006; 2 RCTs, 83 participants; I² = 7%; very low-certainty evidence). This evidence suggests that if the rate of regression with megestrol is 61%, the rate of regression with metformin would be between 71% and 96%. It is unresolved whether metformin results in different rates of abnormal uterine bleeding or hysterectomy compared to megestrol. No study in this comparison reported progression of hyperplasia to endometrial cancer, recurrence of endometrial hyperplasia, health-related quality of life, or adverse effects during treatment. Metformin plus megestrol versus megestrol monotherapy The combination of metformin and megestrol may enhance the regression of endometrial hyperplasia towards normal histology more than megestrol alone (OR 3.27, 95% CI 1.65 to 6.51; P = 0.0007; 4 RCTs, 258 participants; I² = 0%, low-certainty evidence). This suggests that if the rate of regression with megestrol monotherapy is 54%, the rate of regression with the addition of metformin would be between 66% and 84%. In one study, 3/8 (37.5%) of participants who took metformin had nausea that settled without further treatment. It is unresolved whether the combination of metformin and megestrol results in different rates of recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, or hysterectomy compared to megestrol monotherapy. No study in this comparison reported abnormal uterine bleeding, or health-related quality of life. Metformin plus levonorgestrel (intrauterine system) versus levonorgestrel (intrauterine system) monotherapy We are uncertain whether there is a difference between groups in the regression of endometrial hyperplasia towards normal histology (OR 0.29, 95% CI 0.01 to 7.56; 1 RCT, 46 participants; very low-certainty evidence). This evidence suggests that if the rate of regression with levonorgestrel monotherapy is 96%, the rate of regression with the addition of metformin would be between 73% and 100%. It is unresolved whether the combination of metformin and levonorgestrel results in different rates of abnormal uterine bleeding, hysterectomy, or the development of adverse effects during treatment compared to levonorgestrel monotherapy. No study in this comparison reported recurrence of endometrial hyperplasia, progression of hyperplasia to endometrial cancer, or health-related quality of life.
AUTHORS' CONCLUSIONS
Review authors found insufficient evidence to either support or refute the use of metformin, specifically megestrol acetate, given alone or in combination with standard therapy, for the treatment of women with endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials, yielding long-term outcome data are still needed to address this clinical question.
Topics: Female; Humans; Endometrial Hyperplasia; Hypoglycemic Agents; Metformin; Randomized Controlled Trials as Topic
PubMed: 38695827
DOI: 10.1002/14651858.CD012214.pub3 -
The Cochrane Database of Systematic... Sep 2022Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review.
OBJECTIVES
To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses.
MAIN RESULTS
We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias. Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome. Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence). Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months. AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.
Topics: Adult; Anorexia; Anti-Bacterial Agents; Appetite Stimulants; Child; Cyproheptadine; Cystic Fibrosis; Humans; Megestrol Acetate; Quality of Life
PubMed: 36149378
DOI: 10.1002/14651858.CD008190.pub3 -
The Senior Care Pharmacist Jul 2022To evaluate the efficacy and safety of megestrol for off-label use in older patients with weight loss. Retrospective, nonblinded cohort study. Upstate University...
To evaluate the efficacy and safety of megestrol for off-label use in older patients with weight loss. Retrospective, nonblinded cohort study. Upstate University Hospital is a 420-bed facility and academic medical center with a level 1 trauma center. Upstate Community Hospital is a 314-bed acute care/hospital/ambulatory care center and long-term care hospital that also provides teaching services. Patients 65 years of age and older without malignancy or acquired immunodeficiency syndrome who were initiated and continued megestrol therapy at the Upstate University hospitals for at least two weeks were included. Of the 1,290 patients initially screened, 16 patients on megestrol were evaluated. An age- and gender-matched control group of 16 patients was utilized for comparison of changes in weight and other variables. Patients in the megestrol group have received daily doses of megestrol between 160 mg to 800 mg for an average duration of 19 days. Patients in the control group had no history or current use of megestrol utilization. The primary outcome was an increase in weight. Secondary outcome measures included albumin and thromboembolic events. Changes in weight and albumin were also compared with the control group. At a mean duration of 19 days, there was no significant difference in weight gain (0.95 kg, OR = 1.33 [95% CI -1.615-3.527]). Albumin decreased by (0.4 g/dL OR = 0.916 [95% CI 0.12-0.78]) and none of the patients developed a thromboembolic event. In older hospitalized patients, megestrol did not increase weight, and did not improve albumin. No thromboembolic events were observed, but this may be because of a limited duration of observation of therapy and the routine use of anticoagulation prophylaxis in the inpatient setting.
Topics: Aged; Albumins; Cohort Studies; Hospitalization; Humans; Megestrol; Retrospective Studies
PubMed: 35752918
DOI: 10.4140/TCP.n.2022.284 -
The American Journal of Geriatric... Jun 2020
Topics: Drug Therapy, Combination; Humans; Megestrol; Megestrol Acetate; Mental Disorders
PubMed: 32122805
DOI: 10.1016/j.jagp.2020.01.188