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International Journal of Molecular... Aug 2022Sheep ovariectomy (OVX) alone or associated to steroid therapy, deficient diet, or hypothalamic-pituitary disconnection has proven to be of critical importance for... (Review)
Review
Sheep ovariectomy (OVX) alone or associated to steroid therapy, deficient diet, or hypothalamic-pituitary disconnection has proven to be of critical importance for osteoporosis research in orthopedics. However, the impact of specific variables, such as breed, age, diet, time after OVX, and other variables, should be monitored. Thus, the design of comparative studies is mandatory to minimize the impact of these variables or to recognize the presence of unwanted variables as well as to better characterize bone remodeling in this model. Herein, we conducted a systematic review of the last 10 years on PubMed, Scopus, and Web of Knowledge considering only studies on OVX sheep where a control group was present. Of the 123 records screened, 18 studies were included and analyzed. Results showed that (i) Merino sheep are the most exploited breed; (ii) 5-6 years of age is the most used time for inducing OVX; (iii) ventral midline laparotomy is the most common approach to induce OVX; (iv) OVX associated to steroid therapy is the most widely used osteoporosis model; and (v) success of OVX was mostly verified 12 months after surgery. In detail, starting from 12 months after OVX a significant decline in bone mineral density and in microarchitectural bone parameters as well as in biochemical markers were detected in all studies in comparison to control groups. Bone alteration was also site-specific on a pattern as follows: lumbar vertebra, femoral neck, and ribs. Before 12 months from OVX and starting from 3-5 months, microarchitectural bone changes and biochemical marker alterations were present when osteoporosis was induced by OVX associated to steroid therapy. In conclusion, OVX in sheep influence bone metabolism causing pronounced systemic bone loss and structural deterioration comparable to the situation found in osteoporosis patients. Data for treating osteoporosis patients are based not only on good planning and study design but also on a correct animal use that, as suggested by 3Rs principles and by ARRIVE guidelines, includes the use of control groups to be directly contrasted with the experimental group.
Topics: Animals; Bone Density; Bone Remodeling; Disease Models, Animal; Female; Humans; Osteoporosis; Ovariectomy; Steroids
PubMed: 36012173
DOI: 10.3390/ijms23168904 -
European Journal of Surgical Oncology :... Jun 2022BRCA mutation carriers have a high lifetime risk of developing breast cancer (BC) and ovarian cancer (OC). Risk-reducing salpingo-oophorectomy (RRSO) has been shown to... (Meta-Analysis)
Meta-Analysis Review
AIM
BRCA mutation carriers have a high lifetime risk of developing breast cancer (BC) and ovarian cancer (OC). Risk-reducing salpingo-oophorectomy (RRSO) has been shown to reduce OC risk. This meta-analysis was aim to analyze the effect of RRSO on the BC risk among BRCA1/2 mutation carriers.
METHODS
Embase, PubMed, Web of Science, and Cochrane databases were searched for all studies investigating the effect of RRSO on BC risk. The pooled results were used to evaluate the association between RRSO and BC risk.
RESULTS
This meta-analysis included 13,965 BRCA1 and 7,057 BRCA2 mutation carriers from 14 observational studies. The pooled results showed that RRSO lowered BC risk among BRCA1 mutation carriers [hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.49-0.81, P < 0.01] and BRCA2 mutation carriers (HR = 0.51, 95% CI: 0.34-0.75, P < 0.01). RRSO reduced BC risk in younger women with BRCA1 mutation (HR = 0.48, 95% CI: 0.30-0.77, P < 0.01) and BRCA2 mutation (HR = 0.22, 95% CI: 0.08-0.65, P < 0.01). Analysis of the efficacy of RRSO at different time intervals after surgery showed a reduction of BC risk at <5 years after surgery in BRCA1 mutation carriers (HR = 0.60, 95% CI: 0.40-0.89, P = 0.01) and BRCA2 mutation carriers (HR = 0.42, 95% CI: 0.20-0.86, P = 0.02).
CONCLUSIONS
RRSO is an effective way to reduce BC risk among women with BRCA1/2 mutation, especially in younger women. BRCA1/2 mutation carriers could benefit from RRSO in the immediate 5 years after surgery.
Topics: BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Female; Genetic Predisposition to Disease; Humans; Mutation; Observational Studies as Topic; Ovarian Neoplasms; Ovariectomy; Risk Reduction Behavior; Salpingo-oophorectomy
PubMed: 35216860
DOI: 10.1016/j.ejso.2022.02.019 -
Journal of Minimally Invasive Gynecology May 2021Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial cancer (EC) in BRCA1 or BRCA2 germline mutation carriers and to examine the justifiability of prophylactic hysterectomy at the time of RRSO.
DATA SOURCES
PubMed, Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched. Eleven articles were selected and analyzed using the OpenMetaAnalyst 2012 software.
METHODS OF STUDY SELECTION
Randomized controlled studies, cohort studies, and case-control studies evaluating the risk of EC and specifically uterine papillary serous carcinoma (UPSC) in germline BRCA1/2 mutation carriers were included. Articles were excluded if they did not meet the inclusion criteria, or if data were not reported and the authors did not respond to inquiries. We assessed the methodological quality of the included studies on the basis of the Newcastle-Ottawa scale. Dichotomous results from each of the studies eligible for the meta-analysis were expressed as the proportion of patients with EC or UPSC per total number of BRCA mutation carriers, with 95% confidence interval (CI). The Mantel-Haenszel statistical method was used.
TABULATION, INTEGRATION, AND RESULTS
Eleven studies reported the outcome of interest and were included in the final meta-analysis. In total, 13 871 carriers of BRCA1 and BRCA2 mutations were identified. The pooled prevalence rates of EC and UPSC in BRCA1/2 mutation carriers were 82/13 827 (0.59%) and 19/11 582 (0.16%), respectively. The EC prevalence was 46/7429 (0.62%) in BRCA1 mutation carriers and 17/3546 (0.47%) in BRCA2 mutation carriers, with relative risk of 1.18 (95% CI, 0.7-2.0). For UPSC, the prevalence was 15/7429 (0.2%) and 3/3546 (0.08%) among BRCA1 and BRCA2 mutation carriers, respectively, (relative risk 1.39; 95% CI, 0.5-3.7).
CONCLUSION
Most studies in this meta-analysis suggest a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The decision regarding concurrent hysterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.
Topics: BRCA2 Protein; Breast Neoplasms; Endometrial Neoplasms; Female; Genes, BRCA2; Genetic Predisposition to Disease; Germ Cells; Germ-Line Mutation; Heterozygote; Humans; Mutation; Ovarian Neoplasms; Ovariectomy
PubMed: 33249269
DOI: 10.1016/j.jmig.2020.11.023 -
European Journal of Obstetrics,... Oct 2021In the absence of an effective screening test, women with a high genetic predisposition for ovarian cancer are recommended to undergo risk-reducing bilateral... (Meta-Analysis)
Meta-Analysis Review
The impact of risk reducing bilateral salpingo-oophorectomy on sexual function in BRCA1/2 mutation carriers and women with Lynch syndrome: A systematic review and meta-analysis.
OBJECTIVE
In the absence of an effective screening test, women with a high genetic predisposition for ovarian cancer are recommended to undergo risk-reducing bilateral salpingo-oophorectomy (RRBSO) once childbearing is complete. This reduces the risk of ovarian cancer by up to 96%, but can result in undesirable side effects, including menopausal symptoms and sexual dysfunction. We have performed a systematic review and meta-analysis to investigate the effect of RRBSO on sexual function in women at high risk of breast/and or ovarian cancer.
METHODS
A literature search of the AMED (Allied and complementary medicine), Embase and Medline databases was performed, using search terms including sexual function, risk reducing and oophorectomy. Results were filtered according to the PRISMA protocol. Quality assessment of studies was performed using the Newcastle-Ottawa scale. Data were pooled in meta-analysis.
RESULTS
There were 21 eligible studies, 10 of which reported sufficient data for meta-analysis. Most studies were retrospective cohort or observational studies. Fifteen of the 21 studies (71%) reported a negative impact of RRBSO on sexual function. Participant numbers ranged from 37 to 1522. Meta-analysis was performed with studies including 3201 patients. This demonstrated that RRBSO has a statistically significant negative impact on sexual function (SMD -0.63, [-0.82, -0.44], p = 0.03). There was a trend towards reduced sexual pleasure and increased discomfort but this did not reach statistical significance. There was minimal change in the frequency of sex. There was a significant increase in vaginal dryness post-RRBSO (SMD 9.25, [3.66, 14.83], p < 0.00001). There was no significant difference in sexual function between pre-menopausal and post-menopausal RRBSO. Hormone replacement therapy (HRT) did not abolish this negative impact.
CONCLUSION
Sexual function declines post RRBSO, independent of menopausal status. Comprehensive pre-operative counselling regarding anticipated menopausal and sexual symptoms is key to setting realistic patient expectations and minimising post-operative distress. Information and support regarding management of these side effects should be available to all patients.
Topics: BRCA1 Protein; Colorectal Neoplasms, Hereditary Nonpolyposis; Female; Humans; Mutation; Ovarian Neoplasms; Retrospective Studies; Salpingo-oophorectomy
PubMed: 34416580
DOI: 10.1016/j.ejogrb.2021.08.001 -
Osteoporosis International : a Journal... Aug 2022The present study provides evidence that women who underwent hysterectomy without oophorectomies are at a higher risk of osteoporosis and bone fractures than the general... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
The present study provides evidence that women who underwent hysterectomy without oophorectomies are at a higher risk of osteoporosis and bone fractures than the general population. Early interventions for these susceptible women may help to delay or reduce the risk of osteoporosis and bone fractures.
INTRODUCTION
Mounting studies have shown that patients with hysterectomy are at high risk of developing osteoporosis or bone fractures, but the evidence from all the relevant studies has not been previously synthesized. The present study aims to investigate whether women with hysterectomy without oophorectomies have a prominently higher prevalence of osteoporosis or fractures than healthy subjects.
METHODS
Four electronic databases were systematically searched to identify the eligible studies. The combined effect was assessed by calculating the relative risk (RR) with a 95% confidence interval (CI). More methodologies for this study were available in the PROSPERO (ID: CRD42021227255).
RESULTS
Finally, three observational studies offering osteoporosis cases and two retrospective studies reporting fracture cases were included. One eligible study has provided independent data from three groups of fractures. Synthetic results revealed that hysterectomy without oophorectomies was significantly associated with an increased risk of osteoporosis as compared to the general population (combined RR from three studies = 1.47, 95%CI 1.253 to 1.725, P < 0.001; heterogeneity, I = 76.2%, P = 0.015). Consistently, the prevalence of fractures was also significantly higher in patients with hysterectomy without oophorectomies than in healthy controls (pooled RR from four studies = 2.333, 95%CI: 1.314 to 4.144, P = 0.004; heterogeneity, I = 92.3%, P < 0.001).
CONCLUSIONS
This is the first study to quantify the association between hysterectomy without oophorectomies and osteoporosis/fracture risk through a meta-analysis and has subsequently confirmed its positive relationship. Additional large-sample rigorously prospective cohorts are still warranted to validate the present evidence.
Topics: Female; Humans; Hysterectomy; Osteoporosis; Osteoporotic Fractures; Ovariectomy; Prospective Studies; Retrospective Studies
PubMed: 35348837
DOI: 10.1007/s00198-022-06383-1 -
Experimental Brain Research Dec 2022This systematic review (SR) was aimed at answering two questions: (1) how sex and ovarian hormones alter behavior associated with cocaine use; (2) which possible... (Review)
Review
This systematic review (SR) was aimed at answering two questions: (1) how sex and ovarian hormones alter behavior associated with cocaine use; (2) which possible neurobiological mechanisms explain behavioral differences. Three different researchers conducted a search in PUBMED for all kinds of articles published between the years of 1991 to 2021 on the theme "reproductive cycle and cocaine", "estrous cycle and cocaine", "menstrual cycle and cocaine", "fluctuation of ovarian hormones and cocaine", "estrogen and cocaine" and "progesterone and cocaine". Sixty original studies were identified and subdivided into experimental rodent studies and clinical trials. Experimental studies were characterized by author/year, species/strain, sex/number, age/weight, dose/route/time of administration, hormonal assessment, or administration. Clinical trials were characterized by author/year, sex/number, age, exclusion criterion, dose/route of administration/time of cocaine, and hormonal assessment. Results gathered showed that rodent females develop increased consumption, seeking behavior, craving, relapse, locomotion, increases in stress and anxiety, among other behavioral alterations during peaks of estrogen. These observations are related to the direct effects played by ovarian hormones (in particularly estradiol), in dopamine, but also in serotonin neurons, and in brain regions such as the tegmental area, the nucleus accumbens, the hypothalamus, the amygdala and the prefrontal cortex. Increased sensitization to cocaine presented by high estradiol females was linked to the activation of a CBR1-mediated mechanism and GABA-A-dependent suppression of inhibitory synaptic activity of the prelimbic prefrontal cortex. Estradiol facilitation of cocaine-increased locomotion and self-administration was shown to require the release of glutamate and the activation of metabotropic glutamate receptors subtype 5. Clinical studies also tend to point to a stimulatory effect of estradiol on cocaine sensitization and a neuroprotective effect of progesterone. In conclusion, the results of the present review indicate a need for further preclinical and clinical trials and neurobiological studies to better understand the relationship between sex and ovarian hormones on cocaine sensitization.
Topics: Humans; Female; Cocaine; Progesterone; Ovariectomy; Estradiol; Estrogens
PubMed: 36264315
DOI: 10.1007/s00221-022-06479-4 -
Osteoarthritis and Cartilage Apr 2023Post-menopausal women are disproportionately affected by osteoarthritis (OA). As such, the purpose of this study was to (1) summarize the state-of-the-science aimed at... (Meta-Analysis)
Meta-Analysis Review
Uncovering the "riddle of femininity" in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment.
OBJECTIVE
Post-menopausal women are disproportionately affected by osteoarthritis (OA). As such, the purpose of this study was to (1) summarize the state-of-the-science aimed at understanding the effects of menopause on OA in animal models and (2) investigate how dosage and timing of initiation of estrogen treatment affect cartilage degeneration.
DESIGN
A systematic review identified articles studying menopausal effects on cartilage in preclinical models. A meta-analysis was performed using overlapping cartilage outcomes in conjunction with a rigor and reproducibility analysis. Ordinary differential equation models were used to determine if a relationship exists between cartilage degeneration and the timing of initiation or dosage of estrogen treatment.
RESULTS
Thirty-eight manuscripts were eligible for inclusion. The most common menopause model used was ovariectomy (92%), and most animals were young at the time of menopause induction (86%). Most studies did not report inclusion criteria, animal monitoring, protocol registration, or data accessibility. Cartilage outcomes were worse in post-menopausal animals compared to age-matched, non-menopausal animals, as evidenced by cartilage histological scoring [0.75, 1.72], cartilage thickness [-4.96, -0.96], type II collagen [-4.87, -0.56], and c-terminal cross-linked telopeptide of type II collagen (CTX-II) [2.43, 5.79] (95% CI of Effect Size (+greater in menopause, -greater in non-menopause)). Moreover, modeling suggests that cartilage health may be improved with early initiation and higher doses of estrogen treatment.
CONCLUSIONS
To improve translatability, animal models that consider aging and natural menopause should be utilized, and more attention to rigor and reproducibility is needed. Timing of initiation and dosage may be important factors modulating therapeutic effects of estrogen on cartilage.
Topics: Humans; Animals; Female; Collagen Type II; Reproducibility of Results; Estrogens; Osteoarthritis; Cartilage Diseases; Disease Models, Animal
PubMed: 36621591
DOI: 10.1016/j.joca.2022.12.009 -
Gynecologic Oncology Jun 2023Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating... (Review)
Review
OBJECTIVE
Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating salpingectomy with delayed oophorectomy (RRSDO) for ovarian cancer risk reduction and patients are beginning to ask their clinicians about this surgical option. This study sought to systematically review the available literature examining patient preferences regarding RRSDO and risk-reducing salpingo-oophorectomy (RRSO) to provide clinicians with an understanding of patient values, concerns, and priorities surrounding ovarian cancer risk-reducing surgery.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42023400690). We searched key electronic databases to identify studies evaluating acceptance and surgical decision-making regarding RRSO and RRSDO among patients with an increased risk of ovarian cancer.
RESULTS
The search yielded 239 results, among which six publications met the systematic review inclusion criteria. Acceptance of RRSDO was evaluated in all studies and ranged from 34% to 71%. Factors positively impacting patients' acceptance of RRSDO included: avoidance of surgical menopause, preservation of fertility, concerns about sexual dysfunction, family history of breast cancer, and avoidance of hormone replacement therapy. Factors limiting this acceptance reported by patients included concerns regarding oncologic safety, surgical timing, and surgical complications.
CONCLUSION
To date, few studies have explored patient perspectives surrounding RRSDO. Collectively, the limited data available indicate a high level of acceptance among BRCA1/2 carriers, and provides insight regarding both facilitating and limiting factors associated with patient preferences to better equip clinicians in the counseling and support of their patients.
Topics: Humans; Female; BRCA1 Protein; BRCA2 Protein; Ovariectomy; Salpingectomy; Ovarian Neoplasms; Breast Neoplasms; Risk Reduction Behavior; Mutation; Genetic Predisposition to Disease
PubMed: 37116391
DOI: 10.1016/j.ygyno.2023.04.006 -
International Urogynecology Journal Jun 2021We aimed to summarize the knowledge on the pathogenesis of pelvic organ prolapse (POP) generated in animal models.
INTRODUCTION AND HYPOTHESIS
We aimed to summarize the knowledge on the pathogenesis of pelvic organ prolapse (POP) generated in animal models.
METHODS
We searched MEDLINE, Embase, Cochrane and the Web of Science to establish what animal models are used in the study of suggested risk factors for the development of POP, including pregnancy, labor, delivery, parity, aging and menopause. Lack of methodologic uniformity precluded meta-analysis; hence, results are presented as a narrative review.
RESULTS
A total of 7426 studies were identified, of which 51 were included in the analysis. Pregnancy has a measurable and consistent effect across species. In rats, simulated vaginal delivery induces structural changes in the pelvic floor, without complete recovery of the vaginal muscular layer and its microvasculature, though it does not induce POP. In sheep, first vaginal delivery has a measurable effect on vaginal compliance; measured effects of additional deliveries are inconsistent. Squirrel monkeys can develop POP. Denervation of their levator ani muscle facilitates this process in animals that delivered vaginally. The models used do not develop spontaneous menopause, so it is induced by ovariectomy. Effects of menopause depend on the age at ovariectomy and the interval to measurement. In several species menopause is associated with an increase in collagen content in the longer term. In rodents there were no measurable effects of age apart of elastin changes. We found no usable data for other species.
CONCLUSION
In several species there are measurable effects of pregnancy, delivery and iatrogenic menopause. Squirrel monkeys can develop spontaneous prolapse.
Topics: Animals; Delivery, Obstetric; Female; Models, Animal; Parity; Pelvic Floor; Pelvic Organ Prolapse; Pregnancy; Rats; Sheep
PubMed: 33484287
DOI: 10.1007/s00192-020-04638-1 -
Obstetrics and Gynecology Jul 2024To identify the optimal hysterectomy approach for large uteri in gynecologic surgery for benign indications from a perioperative morbidity standpoint.
OBJECTIVE
To identify the optimal hysterectomy approach for large uteri in gynecologic surgery for benign indications from a perioperative morbidity standpoint.
DATA SOURCES
PubMed and Embase databases were searched from inception through September 19, 2022. Meta-analyses were conducted as feasible.
METHODS OF STUDY SELECTION
This review included studies that compared routes of hysterectomy with or without bilateral salpingo-oophorectomy for large uteri (12 weeks or more or 250 g or more) and excluded studies with any concurrent surgery for pelvic organ prolapse, incontinence, gynecologic malignancy, or any obstetric indication for hysterectomy.
TABULATION, INTEGRATION, AND RESULTS
The review included 25 studies comprising nine randomized trials, two prospective, and 14 retrospective nonrandomized comparative studies. Studies were at high risk of bias. There was lower operative time for total vaginal hysterectomy compared with laparoscopically assisted vaginal hysterectomy (LAVH) (mean difference 39 minutes, 95% CI, 18-60) and total vaginal hysterectomy compared with total laparoscopic hysterectomy (mean difference 50 minutes, 95% CI, 29-70). Total laparoscopic hysterectomy was associated with much greater risk of ureteral injury compared with total vaginal hysterectomy (odds ratio 7.54, 95% CI, 2.52-22.58). There were no significant differences in bowel injury rates between groups. There were no differences in length of stay among the laparoscopic approaches. For LAVH compared with total vaginal hysterectomy, randomized controlled trials favored total vaginal hysterectomy for length of stay. When rates of blood transfusion were compared between these abdominal hysterectomy and robotic-assisted total hysterectomy routes, abdominal hysterectomy was associated with a sixfold greater risk of transfusion than robotic-assisted total hysterectomy (6.31, 95% CI, 1.07-37.32). Similarly, single studies comparing robotic-assisted total hysterectomy with LAVH, total laparoscopic hysterectomy, or total vaginal hysterectomy all favored robotic-assisted total hysterectomy for reduced blood loss.
CONCLUSION
Minimally invasive routes are safe and effective and have few complications. Minimally invasive approach (vaginal, laparoscopic, or robotic) results in lower blood loss and shorter length of stay, whereas the abdominal route has a shorter operative time.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42021233300.
Topics: Humans; Female; Hysterectomy, Vaginal; Hysterectomy; Laparoscopy; Uterus; Operative Time; Uterine Diseases; Postoperative Complications; Robotic Surgical Procedures; Salpingo-oophorectomy; Treatment Outcome
PubMed: 38743951
DOI: 10.1097/AOG.0000000000005607