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A statistical model of death due to ovarian cancer, breast cancer, coronary heart disease, hip fracture, and stroke has suggested that women who undergo prophylactic bilateral oophorectomy are at increased risk of death for all causes. We aimed to investigate survival patterns in a population-based sample of women who had received an oophorectomy and compare these with women who had not received an oophorectomy. From an existing cohort of all women who underwent unilateral or bilateral oophorectomy while residing in Olmsted County, MN, USA, in 1950–87, we analysed those who had received an oophorectomy for a non-cancer indication before the onset of menopause. Every member of the cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. 1293 women with unilateral oophorectomy, 1097 with bilateral oophorectomy, and 2390 referent women were eligible for the study. Women were followed up until death or the end of the study (staggered over 2001–06) by use of direct or proxy interviews, medical records in a records-linkage system, and death certificates. Overall, mortality was not increased in women who underwent bilateral oophorectomy compared with referent women. However, mortality was significantly higher in women who had received prophylactic bilateral oophorectomy before the age of 45 years than in referent women (hazard ratio 1·67 [95% CI 1·16–2·40], p=0·006). This increased mortality was seen mainly in women who had not received oestrogen up to the age of 45 years. No increased mortality was recorded in women who underwent unilateral oophorectomy in either overall or stratified analyses. Although prophylactic bilateral oophorectomy undertaken before age 45 years is associated with increased mortality, whether it is causal or merely a marker of underlying risk is uncertain.

Background:Women carriers of BRCA mutations often have occult malignancy found at the time of risk-reducing bilateral salpingo-oophorectomy (RRSO). We report outcomes in 111 consecutive BRCA-positive women who had RRSO using a rigorous surgical-pathological protocol from 1996 to 2008.Method:We identified risk factors associated with finding an occult malignancy at RRSO with outcomes followed for a median of 61 months.Results:A total of 111 BRCA carriers elected RRSO, 10 patients [9.1%] had 14 sites of occult neoplasia. Two patients had invasive serous fallopian tube carcinoma (TSC) only, 1 patient had invasive serous ovarian carcinoma (OSC) only, 5 patients had tubal intraepithelial carcinoma (TIC) only, and 2 patients had multifocal lesions of the ovary (OSC) and TIC. Occult ovarian carcinomas were only detected in BRCA1 patients, and all BRCA2 carcinomas involved only the fallopian tube. The odds of finding occult carcinoma is 4 times greater (odds ratio, 4.3; 95% confidence interval, 1.06-20.7) in women older than 50 than in younger ones (P = 0.023). A history of invasive breast cancer was associated with a reduced risk of occult carcinoma (odds ratio, 0.2; 95% confidence interval, 0.05-0.85). In median follow-up of 5 years, recurrence rate after detection of an occult carcinoma was 10% and the risk for primary peritoneal carcinoma was less than 1%.Conclusion:A rigorous surgical protocol with meticulous pathologic review at RRSO yielded an overall detection rate of 9.1% for occult gynecological carcinoma in BRCA mutation carriers followed by a multidisciplinary team at a single institution. Primary peritoneal carcinoma after RRSO is rare.

The standard surgery for early-stage endometrial cancer is total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy, which is associated with substantial morbidity. Total laparoscopic hysterectomy (TLH) and bilateral salpingo-oophorectomy is less invasive and is assumed to be associated with lower morbidity, particularly in obese women. This study investigated the complication rate of TLH versus TAH in women with early-stage endometrial cancer. This randomised trial was done in 21 hospitals in the Netherlands, and 26 gynaecologists with proven sufficient skills in TLH participated. 283 patients with stage I endometrioid adenocarcinoma or complex atypical hyperplasia were randomly allocated (2:1) to the intervention group (TLH, n=187) or control group (TAH, n=96). Randomisation by sequential number generation was done centrally in alternate blocks of six and three participants, with stratification by trial centre. After assignment, the study coordinators, patients, gynaecologists, and members of the panel were not masked to intervention. The primary outcome was major complication rate, assessed by an independent panel. Data were analysed by a modified intention-to-treat analysis, since two patients in both groups were excluded from the main analysis. This trial is registered with the Dutch trial registry, number NTR821. The proportion of major complications was 14·6% (27 of 185) in the TLH group versus 14·9% (14 of 94) in the TAH group, with a difference of −0·3% (95% CI −9·1 to 8·5; p=0·95). The proportion of patients with an intraoperative major complication (nine of 279 [3·2%]) was lower than the proportion with a postoperative major complication (32 of 279 [11·5%]) and did not differ between TLH (five of 185 [2·7%]) and TAH (four of 94 [4·3%]; p=0·49). The proportion of patients with a minor complication was 13·0% (24 of 185) in the TLH group and 11·7% (11 of 94) in the TAH group (p=0·76). Conversion to laparotomy occurred in 10·8% (20 of 185) of the laparoscopic procedures. TLH was associated with significantly less blood loss (p<0·0001), less use of pain medication (p<0·0001), a shorter hospital stay (p<0·0001), and a faster recovery (p=0·002), but the procedure took longer than TAH (p<0·0001). Our results showed no evidence of a benefit for TLH over TAH in terms of major complications, but TLH (done by skilled surgeons) was beneficial in terms of a shorter hospital stay, less pain, and quicker resumption of daily activities. The Dutch Organization for Health Research and Development (ZonMw), programme efficacy.

BackgroundRisk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy.Primary ObjectiveTo evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer.Study HypothesisRisk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy.Trial DesignMulti-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause.Major Inclusion/Exclusion CriteriaInclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). Exclusion criteria: post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline.Primary EndpointSexual function measured by validated questionnaires.Sample Size1000 (333 per arm).Estimated Dates for Completing Accrual and Presenting ResultsIt is estimated recruitment will be completed by 2023 and results published by 2027.Trial Registration NumberISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360).

The present study evaluated the surgical stress response in dogs undergoing ovariectomy (OVE) using celiotomy and laparoscopy techniques. Twelve clinically healthy, intact bitches, with an average weight of 20–25 kg, were randomly and equally divided into two groups: celiotomy ovariectomy (COVE) and laparoscopy with a three‐portal midline technique (laparoscopic ovariectomy [LapOVE]). A clinical assessment was conducted, and haematological parameters and oxidative stress biomarkers were measured at baseline and 1, 24 and 168 h after extubation. Pain scoring was performed using the University of Melbourne Pain Scale at 2, 4, 8 and 12 h postoperatively. The average heart rate, respiratory rate, rectal temperature, SpO2 saturation and EtCO2 values showed no significant differences within each group or when comparing the two groups. There was no significant difference in the pain evaluation between the groups. At 168 h postoperatively, both malondialdehyde (MDA) and total antioxidant capacity (TAC) were significantly higher in the COVE group compared with LapOVE (MDA: 6.1 ± 0.844 vs. 4.1 ± 0.848; p < 0.05; TAC: 0.294 ± 0.068 vs. 0.246 ± 0.023; p < 0.05). The COVE group exhibited significantly higher white blood cell (WBC) and neutrophil counts, and lower eosinophil counts, than the LapOVE group (all p < 0.05). The findings from this research indicated that both surgical methods were safe and yielded similar pain and physiological results. The COVE group demonstrated significantly increased oxidative and inflammatory responses 1 week after surgery, suggesting a higher level of surgical stress than the LapOVE group. When available, laparoscopic OVE should be preferred as a minimally invasive option to reduce postoperative inflammation and oxidative stress. This research compares laparoscopic and open ovariectomy in bitches, focusing on surgical stress, pain, oxidative stress and immune response. Laparoscopy resulted in lower postoperative inflammation and oxidative injury. Despite similar pain scores, the minimally invasive approach demonstrated clinical benefits, endorsing its use where equipment and skills are available.

Background Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80–96 % but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. Methods A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35–40 ( BRCA1 ) or 40–45 ( BRCA2 ) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40–45 ( BRCA1 ) or 45–50 ( BRCA2 )). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed. Discussion The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL. Trial registration ClinicalTrials.gov ( NCT02321228 )

Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/β-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3β (p-GSK3β), β-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of β-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.

In premenopausal women, the rate of production of testosterone is about 300 μg (1040 nmol) per day, 1 of which about half is derived from the ovaries and half from the adrenal glands. 2 In women who undergo bilateral oophorectomy before natural menopause, serum testosterone and estradiol concentrations decrease by approximately 50 and 80 percent, respectively. 3 , 4 These women are commonly treated with estrogen to prevent or ameliorate hot flashes, vaginal atrophy, osteoporosis, and heart disease. 5 Despite estrogen therapy, many surgically postmenopausal women have decreased sexual desire (libido), activity, and pleasure 6 – 8 and a decreased general sense of well-being. 9 These symptoms are . . .

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune systems. These discoveries fuel novel approaches for the treatment of several bone pathologies including osteoporosis. Bifidobacterium longum (BL) is a preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases. Here, we evaluate the effect of BL in an ovariectomy (ovx)-induced post-menopausal osteoporotic mouse model. Our in vitro findings reveal that BL suppresses the differentiation and functional activity of RANKL-induced osteoclastogenesis in both mouse bone marrow cells and human PBMCs. Strikingly, BL-induced Bregs were found to be significantly more efficient in suppressing osteoclastogenesis and modulating Treg–Th17 cell balance with respect to control Bregs in vitro . Our in vivo µCT and bone mechanical strength data further confirm that BL supplementation significantly enhanced bone mass and bone strength, along with improving the bone microarchitecture in ovx mice. Remarkably, alterations in frequencies of CD19 + CD1d hi CD5 + IL-10 + Bregs, CD4 + Foxp3 + IL-10 + Tregs, and CD4 + Rorγt + IL-17 + Th17 cells in distinct lymphoid organs along with serum-cytokine data (enhanced anti-osteoclastogenic cytokines IFN-γ and IL-10 and reduced osteoclastogenic-cytokines IL-6, IL-17, and TNF-α) strongly support the immunomodulatory potential of BL. Altogether, our findings establish a novel osteo-protective and immunomodulatory potential of BL in augmenting bone health under osteoporotic conditions.

Spaying of female dogs is a widespread practice, performed primarily for population control. While the consequences of early spaying for health are still being debated, the consequences for behaviour are believed to be negligible. The current study focused on the reported behaviour of 8981 female dogs spayed before 520 weeks (ten years) of life for reasons other than behavioural management, and calculated their percentage lifetime exposure to gonadal hormones (PLGH) as a proportion of their age at the time of being reported to the online Canine Behavioral Assessment and Research Questionnaire (C-BARQ). We found that 23 behaviours differed between entire and spayed dogs, of which 12 were associated with PLGH and 5 with age-at-spay (AAS). Two behaviours, chewing and howling, were significantly more likely in dogs with longer PLGH. In contrast, longer PLGH was associated with significantly reduced reporting of 10 (mostly unwelcome) behaviours. Of these, one related to fearfulness and three to aggression. The current data suggest that dogs' tendency to show numerous behaviours can be influenced by the timing of spaying. They indicate how female dog behaviour matures when gonadal hormones are allowed to have their effect. The differences reported here between undesirable behaviours of spayed and entire dogs were in the range of 5.33% and 7.22%, suggesting that, for some dogs, partial or complete denial of maturation may reduce howling and chewing and improve retrieval and recall, but have other undesirable consequences. Veterinarians may take these data into account to discuss the risks and benefits of spaying with clients, and the timing of the procedure.