Evaluation of a patient decision aid for BRCA1/2 pathogenic variant carriers choosing an ovarian cancer prevention strategy.

OBJECTIVE: Risk-reducing surgery is advised to BRCA1/2 pathogenic variant (PV) carriers around the age of 40 years to reduce ovarian cancer risk. In the TUBA-study, a multicenter preference study (NCT02321228), BRCA1/2-PV carriers are offered a choice: the standard strategy of risk-reducing salpingo-oophorectomy or the novel strategy of risk-reducing salpingectomy with delayed oophorectomy. We evaluated feasibility and effectiveness of a patient decision aid for this choice. METHODS: Premenopausal BRCA1/2-PV carriers were counselled for risk-reducing surgical options in the TUBA-study; the first cohort was counselled without and the second cohort with decision aid. Evaluation was performed using digital questionnaires for participating women and their healthcare professionals. Outcome measures included actual choice, feasibility (usage and experiences) and effectiveness (knowledge, cancer worry, decisional conflict, decisional regret and self-estimated influence on decision). RESULTS: 283 women were counselled without and 282 women with decision aid. The novel strategy was chosen less frequently in women without compared with women with decision aid (67% vs 78%, p = 0.004). The decision aid was graded with an 8 out of 10 by both women and professionals, and 78% of the women would recommend this decision aid to others. Users of the decision aid reported increased knowledge about the options and increased insight in personal values. Knowledge on cancer risk, decisional conflict, decisional regret and cancer worry were similar in both cohorts. CONCLUSIONS: The use of the patient decision aid for risk-reducing surgery is feasible, effective and highly appreciated among BRCA1/2-PV carriers facing the decision between salpingo-oophorectomy or salpingectomy with delayed oophorectomy.

Ginkgo biloba extract (GbE) attenuates obesity and anxious/depressive-like behaviours induced by ovariectomy.

While several pieces of evidence link obesity and mood disorders in menopause, the mechanisms involved are not yet fully understood. We have previously demonstrated that Ginkgo biloba extract (GbE) both attenuated diet-induced obesity of male rats and restored serotonin-induced hypophagia in ovariectomized female rats. The present study aimed at exploring whether GbE treatment ameliorates ovariectomy-related obesity and anxious/depressive-like behaviours. Wistar female rats were either ovariectomized (OVX) or sham-operated (Sham). After 2 months, either 500 mg/kg of GbE or vehicle were administered daily by gavage for 14 days. Anxious/depressive-like behaviours were assessed by the Elevated Plus Maze and the Forced Swim Tests, respectively. Ovariectomy caused high visceral adiposity, hyperleptinemia, and hypercholesterolemia, and increased the anxiety index (p = 0.048 vs. Sham + GbE) while it decreased the latency to immobility (p = 0.004 vs. Sham). GbE treatment in OVX rats improved body composition, adiponectin levels and blood lipid profile. It also reduced the anxiety index (p = 0.004) and increased the latency to immobility (p = 0.003) of OVX rats. Linear regression analysis demonstrated that leptin (p = 0.047) and total cholesterol levels (p = 0.022) were associated with anxious-like behaviours while body adiposity (p = 0.00005) was strongly associated with depressive-like behaviours. The results showed that GbE therapy was effective in attenuating the deleterious effects of ovariectomy on body composition, lipid profile, and anxious/depressive-like behaviours. Further studies are warranted to better understand the therapeutic potential of GbE in menopause.

Estrogen receptors-ß and serotonin mediate the antidepressant-like effect of an aqueous extract of pomegranate in ovariectomized rats.

Pomegranate (Punica granatum) fruit is of particular interest because of its high nutritional value and therapeutic actions. Recently, we showed that an aqueous extract of pomegranate (AE-PG) given by oral route induced antidepressant-like actions mediated by estrogen receptors (ERs) suggesting its potential to function as an alternative to estrogen therapy replacement in menopause-related depression treatment. Orally administered AE-PG allows the biotransformation of ellagitannins into active estrogenic compounds through the intestinal microbiota. However, it is necessary to know if compounds that do not need to be biotransformed by the intestinal microbiota are involved in the antidepressant-like effects. Therefore, the first aim of this study was to determine if AE-PG produces an antidepressant-like effect when administered intraperitoneally. Also, to determine the participation of specific ER-subtypes (α or ß) and to analyze the role of the serotonergic system. Young female Wistar rats were ovariectomized as a surgical model of menopause. The intraperitoneal administration of AE-PG (1 mg/kg; i. p.) was evaluated in the forced swimming test and open field tests. Also, the ERα antagonist (TPBM; 50 µg/rat; s. c.) or the ERß antagonist (PHTPP; 25 µg/rat; s. c.) were administered with AE-PG to analyze the participation of the specific ERs. Finally, the effect of the serotonin neurotoxin 5,7-DHT (200 µg/rat; i. c.v.) on the antidepressant-like effect of the AE-PG was studied in independent experimental groups. RESULTS: showed that AE-PG administered by intraperitoneal route induced antidepressant-like effects. This result suggests that gut microbiota biotransformation is not necessary to exert its actions. The mechanism of action involves the activation of the ERß and the serotonergic system. Altogether, this information contributes to the elucidation of the antidepressant action of the pomegranate fruit, which could be further considered as an alternative treatment for depression during menopause.

Association between oophorectomy and depression in patients with comorbidities: A nationwide cohort study in Taiwan.

OBJECTIVE: This study investigated the long-term rates of depression after oophorectomy for benign gynecological conditions with or without comorbidities. MATERIALS AND METHODS: This retrospective cohort study examined data from the National Health Insurance Research Database (NHIRD) involving 8199 women aged ≥20 years who underwent unilateral or bilateral oophorectomy for benign gynecological conditions (cases) between 2000 and 2013 (index date). A second cohort consisted of 32,796 women who did not undergo oophorectomy (controls) who were matched 4:1 to cases by age and index year. The follow-up time was more than 10 years. For all participants, the analysis accounted for comorbidities including hypertension, diabetes mellitus, hyperlipidemia, stroke, chronic obstructive pulmonary disease (COPD), chronic liver disease and cirrhosis, chronic kidney disease, and anxiety. Crude hazard ratios, adjusted hazard ratios, and 95% confidence intervals (CIs) were calculated according to multivariable Cox proportional hazard regression models adjusting for age, comorbidity, and the combination of oophorectomy with one comorbidity. RESULTS: Our results show that unilateral or bilateral oophorectomy, whether performed by laparotomy or laparoscopy, increases the overall risk of depression (aHR: 1.36, 95%CI: 1.19-1.55). Compared with controls, women aged <50 years had a significantly higher incidence of depression. Having diabetes (aHR: 1.66, 95%CI: 1.09-2.51), hypertension (aHR:1.56, 95%CI:1.14-2.14), hyperlipidemia (aHR: 1.46, 95%CI: 1.04-2.05), stroke (aHR: 1.91, 95%CI: 1.01-3.60), COPD (aHR: 2.06, 95%CI: 1.3-3.26), chronic liver cirrhosis (aHR: 1.99, 95%CI:1.52-2.61), or anxiety (aHR: 5.01, 95%CI: 3.74-6.70) increased higher risk of depression compared with not having these comorbidities after oophorectomy. The likelihood of depression was highest within the first 6 years following oophorectomy (3-5years:aHR:1.26, 95%CI:1.00-1.58). CONCLUSIONS: Oopherectomy increases the overall risk of depression. We offer useful information for surgical decision-making and preoperative assessments of women undergoing oophorectomy. It is concluded that a synergistic effect exists between oophorectomy and the comorbidities. Post-surgery, physicians should carefully evaluate the risk of depression developing amongst women with comorbidities. A postoperative follow-up time of at least 6 years is recommended, as this period was associated with a significantly higher rate of depression during our over 10-year follow-up.

Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma: A Multicenter Retrospective Study.

With delayed childbearing in women, preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma (EOC). Fertility-sparing surgery (FSS) can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life. In order to evaluate oncological safety, attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS, this multicenter retrospective study was conducted. Between January 2005 and December 2014, total of 87 young women with FIGO stage I EOC were included, with their clinicopathologic parameters in relation to disease-free survival (DFS) and overall survival (OS) assessed. Attitudes toward childbearing, ovarian function and fertility were studied in women undergoing FSS (n=36). As a result, in contrast to radical surgery, FSS did not affect prognosis by Kaplan-Meier curves (log-rank test; DFS: P=0.484; OS: P=0.125). However, two of the three recurrence cases and both death cases were in FSS group stage IC. All women undergoing FSS resumed regular menstrual periods after chemotherapy. Only 16 (44.44%) had tried to conceive, and 17 pregnancies occurred in 15 (93.75%) women. Among 20 women who did not attempt conception, the most common reason was not being married (70%), followed by already having children (15%). In summary, FSS is considered safe in young women with stage IA EOC. Regular menstruation and good obstetric outcomes can be achieved. This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

17ß-Estradiol augments the neuroprotective effect of agomelatine in depressive- and anxiety-like behaviors in ovariectomized rats.

RATIONALE AND OBJECTIVE: Estradiol decline has been associated with depression and anxiety in post-menopausal women. Agomelatine (Ago) is an agonist of the melatonergic MT1/MT2 receptors and an antagonist of the serotonergic 5-HT2c receptors. The present study aimed to evaluate the effects of combining Ago with 17ß-estradiol (E2) on ovariectomy (OVX)-induced depressive- and anxiety-like behaviors in young adult female rats. METHODS: OVX rats were treated with Ago (40 mg/kg/day, p.o.) for 10 days starting 1 week after surgery alone or combined with two doses of E2 (40 µg/kg/day, s.c.) given before behavioral testing. RESULTS: Co-administration of E2 enhanced the anti-depressant and anxiolytics effects of Ago as evidenced by decreased immobility time in the forced swimming test, as well as increased time spent in the open arms and number of entries to open arms in the elevated plus-maze. In parallel, Ago increased hippocampal norepinephrine, dopamine, melatonin, and brain-derived neurotrophic factor (BDNF). Meanwhile, Ago-treated rats exhibited reduced hippocampal nuclear factor kappa beta (NF-kB) P65 expression and pro-inflammatory cytokine level. Ago upregulated estrogen receptor (ER α and ß) mRNA expression in the hippocampus of OVX rats and elevated serum estradiol levels. Co-administration of E2 with Ago synergistically decreased NF-kB P65 expression and pro-inflammatory cytokines, and increased BDNF levels. CONCLUSION: E2 augmented the neuroprotective effect of Ago in OVX rats via its anti-inflammatory and neurotrophic effects. The combined treatment of E2 and Ago should be further investigated as a treatment of choice for depression, anxiety, and sleep disturbances associated with menopause.

Optimized integration of fluoxetine and 7, 8-dihydroxyflavone as an efficient therapy for reversing depressive-like behavior in mice during the perimenopausal period.

Fluoxetine (FLX) has been considered as an effective anti-depressant drug. Besides, previous studies reported reasonable anti-depressant effects for 7, 8-dihydroxyflavone (7, 8 DHF). However, the combination of FLX and 7, 8 DHF in a well-established depression model has not been explored. In this study, we demonstrate that the 7, 8 DHF can improve the anti-depressant efficacy of FLX in a chronic unpredictable mild stress (CUMS)-induced depression during the perimenopausal period. The corresponding mechanism of FLX+7, 8 DHF therapy and the effect of ANA-12 are also investigated. Moreover, the influences of 7, 8 DHF (5 mg/kg/day), FLX (18 mg/kg/day), and ANA-12 (0.5 mg/kg/day) on a depressive-like behavior are displayed. Inflammatory, autophagic and apoptotic changes of hippocampus and cortex are examined by using western blot, immunofluorescence, and Real-Time Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) techniques. The protein levels of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/phosphorylated extracellular signal-regulated kinase1/2 (p-ErK 1/2)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) of hippocampus and cortex are assessed by western blot. The combined FLX and 7, 8 DHF treatment can significantly improve depressive-like behavior in sucrose preference and forced swimming tests accompanied by a noticeable upregulation of autophagy, neuronal nuclei (NeuN), ionized calcium-binding adaptor molecule 1 (Iba1) expressions, and PI3K/Akt/ mTOR/ p-ErK 1/2 signaling pathways. Besides, an obvious increase of the brain-derived neurotrophic factor (BDNF) and TrkB levels are observed with down-regulated inflammation and apoptosis. These findings suggest that the integrated FLX and 7, 8 DHF holds a potential as an efficient treatment to ameliorate depressive-like behavior in perimenopausal patients.

A retrospective internet-based survey of French cat breeders about early-age neutering.

OBJECTIVES: The aim of this study was to analyse cat breeders' application of and opinions concerning early-age (ie, <16 weeks old) neutering in cats in France. METHODS: This study analysed a retrospective cohort. A web survey was designed for French cat breeders and was published in June 2017 on the Facebook page of Livre Officiel des Origines Félines, the official feline studbook for purebred cats born in France. The early-age cat neutering habits, opinions and expectations of breeders were collected. RESULTS: A total of 999 breeders returned the questionnaire. Almost half of the breeders (49%) reported consistently requesting neutering of kittens before selling them, 32% claimed that they never requested it and the remaining 19% reported that they inconsistently requested it. When performed, 83% of breeders had kittens neutered at 12 weeks of age; for a large majority of these breeders (94%), the neutering was undertaken on their own initiative. Various reasons for neutering were provided, including the prevention of uncontrolled breeding, short- and long-term welfare benefits for neutered cats, and practical and economic reasons. Reported incidents related to early-age neutering were scarce. Nearly half of breeders who did not apply early-age neutering to their kittens cited a veterinarian's unwillingness to perform the surgery as a cause. CONCLUSIONS AND RELEVANCE: A large majority of surveyed French cat breeders supported early-age neutering that would occur before kittens were sold, most of the time at the age of 3 months. These breeders reported high satisfaction with early-age neutered cats, with a low number of incidents and accidents reported.

Increased suicide risk among patients oophorectomized following benign conditions and its association with comorbidities.

Objective: To evaluate the suicide rate among patients oophorectomized for benign conditions and its association with confounding comorbidities.Method: We conducted a population-based, retrospective cohort study of women aged ≥20 years that underwent oophorectomy including unilateral or bilateral in laparotomy or laparoscopy for benign conditions during 2000-2013. A total of 145,588 oophorectomized and 582,352 non-oophorectomized women were included with an average follow-up time of 7 years. The comorbidities assessed were hypertension (HTN), diabetes mellitus, hyperlipidemia, stroke, chronic obstructive pulmonary disease (COPD), chronic liver disease and cirrhosis, chronic kidney disease and anxiety disorder.Result: The overall suicide rate was significantly higher in the oophorectomized group. The rate among oophorectomized patients of 20-49 years was significantly greater than in non-oophorectomized patients of the same age group. Hypertension, COPD, anxiety disorder and chronic liver disease and cirrhosis were associated with a significantly higher suicide rate in oophorectomized women. A significant increase in suicide incidence was observed in patients with <6 years' follow-up.Conclusion: A significant increase in suicide rate among oophorectomized women aged 20-49 years was found. The decision to perform oophorectomy should be made cautiously, especially in patients with hypertension, COPD, chronic liver disease and cirrhosis or anxiety disorder. Patients should be followed for at least 6 years postoperatively since the suicide rate is significantly higher in this period.

Ovariectomy Influences Cognition and Markers of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most devastating and costly diseases, and prevalence of AD increases with age. Furthermore, females are twice as likely to suffer from AD compared to males. The cessation of reproductive steroid hormone production during menopause is hypothesized to cause this difference. Two rodent AD models, APP21 and APP+PS1, and wild type (WT) rats underwent an ovariectomy or sham surgery. Changes in learning and memory, brain histology, amyloid-ß (Aß) deposition, levels of mRNAs involved in Aß production and clearance, and synaptic and cognitive function were determined. Barnes maze results showed that regardless of ovariectomy status, APP+PS1 rats learned slower and had poor memory retention. Ovariectomy caused learning impairment only in the APP21 rats. High levels of Aß42 and very low levels of Aß40 were observed in the brain cortices of APP+PS1 rats indicating limited endogenous PS1. The APP+PS1 rats had 43-fold greater formic acid soluble Aß42 than Aß40 at 17 months. Furthermore, levels of formic acid soluble Aß42 increased 57-fold in ovariectomized APP+PS1 rats between 12 and 17 months of age. The mRNA encoding Grin1 significantly decreased due to ovariectomy whereas levels of Bace1, Chat, and Prkcb all decreased with age. The expression levels of mRNAs involved in Aß degradation and AßPP cleavage (Neprilysin, Ide, Adam9, and Psenen) were found to be highly correlated with each other as well as hippocampal Aß deposition. Taken together, these results indicate that both ovariectomy and genotype influence AD markers in a complex manner.

Sexual function, menopausal symptoms, depression and cancer worry in women with BRCA mutations.

OBJECTIVES: Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status. METHODS: Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre- or post-menopausal risk-reducing salpingo-oophorectomy (RRSO). RESULTS: Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ-8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms. CONCLUSIONS: Risk-reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.

Behavioural risks in female dogs with minimal lifetime exposure to gonadal hormones.

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.

Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study.

OBJECTIVE: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications. METHODS: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression. RESULTS: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001). CONCLUSIONS: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. VIDEO SUMMARY:: http://links.lww.com/MENO/A458.

G protein-coupled oestrogen receptor stimulation ameliorates iron- and ovariectomy-induced memory impairments through the cAMP/PKA/CREB signalling pathway.

Iron accumulation in the brain has been associated with neurodegenerative disorders, and imaging studies in humans indicate that iron content in brain regions correlates with poor performance in cognitive tasks. In rats, iron overload impairs memory retention in a variety of memory tasks. Although the effects of iron on cognition in rodents are extensively reported, no previous study has been conducted in female rats. The incidence of certain dementias, such as Alzheimer's disease, is higher in women after menopause compared to aged-matched men. The role of oestrogen depletion in memory deficits in menopausal women is still a matter of debate. The present study aimed to characterise the effects of iron overload on memory in female rats by investigating the effects of ovariectomy (OVX, an experimental model of oestrogen depletion) in rats submitted to iron overload, as well as examining the effects of G protein-coupled oestrogen receptor (GPER) agonism on memory impairments induced by iron and OVX. Female rats received iron (30 mg kg-1 , orally) or vehicle at postnatal days 12-14 and were submitted to OVX in adulthood. Results showed that either iron or OVX impaired memory for object placement and inhibitory avoidance. The selective GPER agonist G1, administered immediately after training, reversed both iron- and OVX-induced memory impairments. G1 effects were abolished by protein kinase A (PKA) inhibition, suggesting the involvement of the cAMP/PKA/CREB signalling pathway. The search for novel oestrogen agonists with positive effects on cognition may be promising for the development of treatments for memory disorders.

Sexual Function Under Adequate Estrogen Therapy in Women After Oophorectomy Versus Natural Menopause.

Background: There is scarce evidence regarding endogenous postmenopausal ovarian testosterone (T) production and estrogen replacement roles in different sexual domains. This study aimed to determine whether lower endogenous T in oophorectomized women that were estradiol (E2)-treated influenced global or specific domains of sexual function. Depressive and cognitive symptoms were evaluated to exclude potential confounders. Materials and Methods: Eighty-one recently postmenopausal women treated with transdermal E2, 36 with bilateral oophorectomy (O), and 45 controls (C) were investigated through hormonal profile, Female Sexual Function Index, Mini Mental, and Beck Depression Inventory. Results: T levels, as expected, were lower in O than in C (p = 0.001); nonetheless, O presented a lower risk of sexual dysfunction (55.6% vs. 85.7%, p = 0.037), due to less pain (p = 0.005), increased lubrication (p = 0.012), and satisfaction (p = 0.042). O, however, required 50% higher E2 gel doses to control vasomotor symptoms (VMS) than did C. In O, all T measurements were positively, although weakly, correlated with desire (r = 0.374-0.381, p = 0.016-0.024). E2 levels were positively correlated with arousal in all women (r = 0.338, p = 0.038) and in O (r = 0.521, p = 0.032). Depression and cognition scores did not differ between the groups. Conclusions: Despite lower T levels, O women receiving E2 therapy had better global sexual function. Earlier onset and longer E2 treatment could have prevented vulvovaginal atrophy in O. Oophorectomized patients may require higher doses of E2 replacement. E2 levels, achieved by appropriate hormone therapy for VMS control, and very low T levels correlated with distinct sexual domains and may act in complementary areas of sexuality in postmenopausal women.

The effect of the anti-diabetic drug metformin on behavioral manifestations associated with ovariectomy in mice.

The aim of this study was to evaluate the anti-diabetic drug metformin (Met) effects on the anxiety and cognitive impairment in ovariectomized mice. Thirty-two female adult mice were distributed into four groups: control, sham ovariectomy, ovariectomy + Met 7 mg/kg and ovariectomy + Met 15 mg/kg. The vaginal cytology was used to confirm the ovariectomy surgery. Anxiety was monitored using elevated plus maze test and cognitive function was assessed by novel object recognition task. Animal's brains were analyzed for the brain-derived neurotrophic factor (BDNF). Our results demonstrated that ovariectomy caused cognitive impairments and anxiety, as well as decreased BDNF levels. Moreover, administration of Met improves ovariectomy-related disorders such as cognitive impairments and anxiety, as well as increased BDNF levels. The results of the present study suggest that Met could be used as a novel therapeutic strategy for the treatment of ovariectomy-related conditions.

Estrogen Modulates Ethanol-Induced Memory Deficit in Postpubertal Adolescent Rats.

BACKGROUND: Our laboratory and others have reported that ethanol (EtOH) impairs hippocampus-associated memory formation in prepubertal adolescent rats. Acute alcohol exposure in humans produces a syndrome of memory loss ("blackouts") that is similar to impairments caused by hippocampal damage. The ability to form new long-term explicit memories is affected, but not short-term memory storage or recall of information from long-term storage. Alcohol-induced memory impairment, similar to teenage alcohol blackouts, has been shown in prepubertal adolescent rodents. In the present study, EtOH's effect on contextual fear memory was examined in postpubertal rats. METHODS: In Experiment 1, intact male and female postpubertal rats were treated with an acute intraperitoneal injection of EtOH or vehicle. Thirty minutes later, rats were trained in the fear conditioning paradigm, and 24 hours after training, all rats were tested for contextual fear conditioning. In Experiment 2, groups of intact postpubertal female rats were treated with a single injection of EtOH, or vehicle, during different phases of the estrus cycle and tested for fear conditioning. In Experiment 3, groups of postpubertal female rats were ovariectomized (OVX) and were given hormonal supplementation (estrogen with or without progesterone) and tested for EtOH-induced memory formation. Additional controls included sham-operated, oil-treated postpubertal female rats. In Experiment 4, intact postpubertal male rats were administered exogenous estrogen alone or together with progesterone and tested for EtOH-induced contextual memory formation. RESULTS: Following an acute EtOH exposure, intact postpubertal female rats exhibited significant impairments in contextual fear conditioning. But acute EtOH had little effect on contextual fear conditioning in intact postpubertal males. EtOH impaired memory formation during all phases of the estrus cycle except during estrus phase when blood levels of estrogen are low. Ovariectomized rats did not show any EtOH-induced impairment in contextual freezing compared to vehicle-treated ovariectomized rats. In female rats, bilateral ovariectomy eliminated EtOH-induced memory deficit and estrogen replacement reintroduced EtOH-induced memory impairment. Although postpubertal male rats were insensitive to EtOH's effect on contextual fear conditioning, but when treated with exogenous estrogen, they performed poorly in the contextual memory task. CONCLUSIONS: Together, these data suggest that the female gonadal hormone estrogen is an important modulator of EtOH-induced cognitive behavior in postpubertal female and male rats, and that it may play an important role in teenage alcohol blackout.

Chrysin (5,7-dihydroxyflavone) exerts anxiolytic-like effects through GABAA receptors in a surgical menopause model in rats.

The present study investigated the effects of the flavonoid chrysin (5,7-dihydroxyflavone) on anxiety-like behavior in rats in a model of surgical menopause and evaluated the participation of γ-aminobutyric acid-A (GABAA) receptors in these actions. At 12 weeks post-ovariectomy, the effects of different doses of chrysin (0.5, 1, 2, and 4 mg/kg) were evaluated in the elevated plus maze, light/dark test, and locomotor activity test, and comparisons were made with the clinically effective anxiolytic diazepam. The participation of GABAA receptors in the actions of chrysin was explored by pretreating the rats with the noncompetitive GABAA chloride ion channel antagonist picrotoxin (1 mg/kg). The results showed that chrysin (2 and 4 mg/kg) reduced anxiety-like behavior in both the elevated plus maze and light/dark test, and these effects were similar to diazepam. Pretreatment with picrotoxin had no effects on its own but prevented the anxiolytic-like effects of chrysin in both tests. Chrysin also increased rearing and grooming, without significantly altering the number of crossings in the locomotor activity test; these effects were also similar to diazepam. In conclusion, the flavonoid chrysin produced anxiolytic-like effects through actions on GABAA receptors in a model of surgical menopause in rats. These findings support the hypothesis that this flavonoid could be a future natural alternative for ameliorating symptoms of anxiety after surgical menopause in women.

Using the Health Belief Model to explore why women decide for or against the removal of their ovaries to reduce their risk of developing cancer.

BACKGROUND: Women at an increased risk of ovarian cancer often have to decide for or against the surgical removal of their healthy ovaries to reduce their cancer risk. This decision can be extremely difficult. Despite this, there is a lack of guidance on how to best support women in making this decision. Research that is guided by theoretical frameworks is needed to help inform clinical practice. We explored the decision-making process of women who are at an increased risk of developing ovarian cancer and had to decide for or against the removal of their ovaries. METHODS: A qualitative study of 18 semi-structured interviews with women who have attended a cancer treatment centre or cancer counselling and information service in New South Wales, Australia. Data collection and analysis were informed by the Health Belief Model (HBM). Data was analysed using qualitative content analysis. RESULTS: The paper describes women's decision making with the help of the four constructs of the HBM: perceived susceptibility, perceived severity, perceived benefits, and perceived barriers. The more anxious and susceptible women felt about getting ovarian cancer, the more likely they were to have an oophorectomy. Women's anxiety was often fuelled by witnessing family members suffer or die from cancer. Women considered a number of barriers and potential benefits to having the surgery but based their decision on "gut feeling" and experiential factors, rather than statistical risk assessment. Age, menopausal status and family commitments seemed to influence but not determine women's decisions on oophorectomy. Women reported a lack of decision support and appreciated if their doctor explained their treatment choice, provided personalised information, involved their general practitioner in the decision-making process and offered a second consultation to follow-up on any questions women might have. CONCLUSIONS: These findings suggest that deciding on whether to have an oophorectomy is a highly personal decision which can be described with the help of the HBM. The results also highlight the need for tailored decision support which could help improve doctor-patient-communication and patient-centred care related to risk reducing surgery in women at an increased risk of ovarian cancer.

Effects of Ficus umbellata (Moraceae) Aqueous Extract and 7-Methoxycoumarin on Scopolamine-Induced Spatial Memory Impairment in Ovariectomized Wistar Rats.

The present work was undertaken to evaluate the ability of F. umbellata aqueous extract and its major component 7-methoxycoumarin (MC) to improve scopolamine-induced spatial memory impairment in ovariectomized Wistar rats. For this to be done, 10 sham-operated and 30 postmenopausal-like rats were randomly distributed in eight groups (n = 5) and treated with distilled water (2 mL/250 g), estradiol valerate (1 mg/kg BW), piracetam (1.5 mg/kg BW), F. umbellata aqueous extract (50 and 200 mg/kg BW), or MC (1 mg/kg BW) for 21 consecutive days. Before and after the memory impairment with scopolamine (2 mg/kg BW), animals underwent behavioral evaluations on Y- and radial mazes. As results, age and ovariectomy did not induce significant changes in the reference memory errors. While age decreased working memory errors, ovariectomy increased it. The MC as well as F. umbellata extract significantly increased (p < 0.01) the percentage of spontaneous alternation and decreased (p < 0.001) working and spatial reference memory errors and anxiety parameters (rearing and grooming) in ovariectomized rats. MC significantly reduced (p < 0.05) the MDA level, but resulted in an increase in GSH level in brain homogenates. These results suggest that MC is endowed with neuroprotective effects and could account for the neuroprotective effects of F. umbellata in rats.