Effects of bilateral salpingo-oophorectomy on menopausal symptoms and sexual functioning among women with a BRCA1 or BRCA2 mutation

Introduction

Prophylactic bilateral salpingo-oophorectomy (BSO) is recommended at an early age to BRCA mutation carriers to prevent ovarian cancer. It is critical to evaluate the impact of BSO on non-cancer outcomes, including quality of life (QOL), menopausal symptoms and sexual functioning.

Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy

BACKGROUND: Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral prophylactic oophorectomy as a risk-reducing option. CASE: We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation. CONCLUSIONS: This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.     

Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones.

OBJECTIVE: To evaluate the effect of soy isoflavones on menopausal symptoms in women who do and who do not produce equol, a daidzein metabolite. METHOD: A randomized, double-blind, placebo-controlled clinical trial was conducted over 6 months with 96 healthy menopausal women. After taking take 135 mg of isoflavones daily for 1 week, the women in the study group were assigned to the equol-producing (EP) or the non-EP group according to the presence or absence of equol in their urine. Menopausal symptoms were evaluated using a modified Kupperman Index. RESULT: Compared with the placebo group, the scores for hot flashes and excessive sweating were significantly reduced after 3 months, and the scores for weakness, palpitations, limb paresthesia, and total symptoms after 6 months, in the EP group only. CONCLUSIONS: Isoflavone supplementation improves menopausal symptoms only in women with the ability to produce equol.     

Peritoneal washing cytology in patients with BRCA1 or BRCA2 mutations undergoing risk-reducing salpingo-oophorectomies: a 10-year experience and reappraisal of its clinical utility

Objective

To evaluate the utility of peritoneal washing cytology (PWC) for detecting occult primary peritoneal carcinoma in patients with BRCA1 or BRCA2 mutations, we reviewed PWCs obtained during risk-reducing salpingo-oophorectomy (RRSO) from 117 patients at our institution and correlated the results with surgical pathology findings.

Methods

Records of 128 PWCs from 125 patients with BRCA1 or BRCA2 mutations undergoing RRSO at MD Anderson Cancer Center between 2000 and 2010 were obtained. Slides were available for review for 119 PWCs from 117 patients (2 patients had 2 PWCs each). Cytopathologists, blinded to the RRSO histopathologic diagnoses, categorized the PWCs as benign, atypical, suspicious for malignancy, or malignant. These results were correlated with the RRSO histopathologic diagnoses.

Results

PWCs from 113 patients were benign. Of the remaining 4 patients, 2 had PWCs classified as atypical, 1 as suspicious for malignancy, and 1 as malignant. The corresponding RRSO histopathologic findings of the 2 atypical PWCs showed endosalpingiosis and cystadenofibroma in one case and showed no abnormalities in the other case. Both patients with suspicious or malignant PWCs, indicating the possibility of occult peritoneal carcinoma, had RRSO histopathologic diagnoses of endometriosis and endosalpingiosis. Nine patients had abnormal tubal or ovarian histologic findings, but all 9 of these patients had benign PWCs.

Conclusion

PWC has the potential to detect occult peritoneal carcinoma in patients with BRCA1 or BRCA2 mutations. The clinical significance of a positive PWC without abnormal RRSO histology remains unclear and will require long-term follow-up for determination.     

Influence of prophylactic oophorectomy on mood and sexual function in women of menopausal transition or postmenopausal period

Aim

To evaluate the impact of prophylactic oophorectomy on mood and sexual function in women at menopausal transition or postmenopausal period.

Methods

Patients who underwent operations due to benign diseases of uterus and ovaries were included and were stratified into two groups, namely Group A with 256 patients undergoing hysterectomy and prophylactic oophorectomy and Group B with 337 patients undergoing simple hysterectomy. Follow-ups included demographic data, Self-Rating Zung Depression Scale (ZDS), Self-Rating Zung Anxiety Scale (ZAS), and Female Sexual Function of Index (FSFI).

Results

Five hundred and ninety-three patients were successfully followed. 69.27 % of patients at menopausal transition period chose ovary conservation whilst 79.22 % of postmenopausal women chose oophorectomy due to fear of potential cancer and economy issue. Ovarian cancer was not found in this cohort. Incidence of distress was higher in Group A (P = 0.001). No difference was obtained in ZAS scores between the two groups (P = 0.110). Incidence of anxiety was higher in Group A (P = 0.010). Percentage of patients scoring above 20 in FSFI was significantly higher in Group B (P = 0.003). Oophorectomy and marital status were independent factors for depression (P = 0.009 and <0.001, respectively).

Conclusion

Adverse influence on mental and sexual status was severer in women undergoing prophylactic oophorectomy at menopausal transition or postmenopausal period. Comprehensive evaluation may contribute to better ovary conservation strategy for women with benign morbidities.     

The impact of physical activity on menopausal symptoms in middle-aged women

ObjectiveTo evaluate the influence of physical activity on climacteric symptoms among middle-aged women in Brazil.MethodsA population-based sample of women aged 40–65 years was recruited from Natal, Brazil. Enrollment took place in basic health units in each health district of the city from June to September 2011. Data were collected while women waited for routine appointments at the health units. Climacteric symptoms were assessed using the Menopause Rating Scale and the Blatt–Kupperman Menopausal Index. The level of physical activity was assessed via the International Physical Activity Questionnaire. It was classified as low, moderate, or vigorous.ResultsThe mean age of the 370 participants was 49.8 ± 8.1 years. They were predominantly white (72.7%), married (61.6%), non-smokers (93.5%), and had undergone high-school education (70.5%). All domains of climacteric symptoms were significantly affected by physical activity: psychological (P < 0.001); somatovegetative (P < 0.001); and urogenital (P = 0.008). Significant differences were found between the IPAQ groups of physical activity and the Blatt–Kupperman Menopausal Index for the following symptoms: hot flashes (P < 0.001); paresthesia (P = 0.022); insomnia (P < 0.001); impatience (P < 0.001); depression (P < 0.001); vertigo (P < 0.001); fatigue (P < 0.001); arthralgia/myalgia (P < 0.001); and palpitation (P < 0.001).ConclusionPhysical activity improved climacteric symptoms among middle-aged women in Brazil.     

Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma

OBJECTIVES: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Korean women remains to be elucidated. In addition, genetic polymorphisms may affect not only cancer development but also cancer progression and, as a result, could influence cancer phenotypes. The purposes of this study were, first, to investigate the presence of BRCA1 and BRCA2 mutations in women with ovarian cancer who were unselected for family history and, second, to evaluate the relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. METHODS: We studied 37 women who were diagnosed with epithelial ovarian cancer and treated at the Yonsei University Hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using a PCR-DHPLC-sequencing method. The relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features was examined. RESULTS: Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer result in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) that led to premature termination. The patient had no family history of breast or ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. CONCLUSION: Our results were consistent with the hypothesis that BRCA1 and BRCA2 mutations have a limited role in sporadic ovarian carcinogenesis in the Korean population. Furthermore, polymorphisms of certain, selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer.     

BRCA1 and p53 protein expression in cultured ovarian surface epithelial cells derived from women with and without a BRCA1 germline mutation

Aim Mutations in the BRCA1 and TP53 genes are early genetic events leading to (hereditary) ovarian carcinoma. The human ovarian surface epithelium (OSE) is considered the tissue of origin of at least a subset of these tumours. Therefore, OSE cell cultures derived from women harbouring BRCA1 germline mutations can be a potential model to study hereditary ovarian carcinogenesis. In fact, previous in vitro studies indicate phenotypical differences between OSE from women with and without such germline mutations. Therefore, we have assessed whether differences in the expression of BRCA1 and p53 proteins in cultured OSE cells could contribute to these observations.Study design Thirty-two OSE cultures derived from women harbouring a BRCA1 mutation (Predisposed OSE [POSE]) and ten cultures from women without a cancer predisposition (Non predisposed OSE [NPOSE]) were grown under standard conditions. Immunocytochemistry was performed to assess the expression of the BRCA1- and p53 proteins. Ki67 immunocytochemical expression was assessed to determine possible differences in cell cycle status between the two groups. In addition, to study whether wild type p53 was expressed, induction of p53 by cis-platinum was assessed by Western blot.Results On the basis of Ki67 expression, three different groups were analyzed. In the group with all cultures that expressed Ki67 no significant difference was observed in BRCA1 (P = 0.19) and p53 expression (P = 0.09). In the group with moderate to high Ki67 expression no difference in BRCA1 expression (P = 0.50) was observed. However, p53 expression was significantly lower in the case group (P = 0.01). The same observation for p53 was made in the group with only high Ki67 expression (P = 0.02). Furthermore, the expression of both BRCA1 and p53 positively correlates with Ki67 expression. In POSE and NPOSE, p53 was induced by cis-platinum to a similar extent.Conclusion Our study indicates differences in the expression of p53, but not in the expression of BRCA1 between POSE and NPOSE. In addition, our findings do suggest the absence of losses of the wild type BRCA1 and p53 genes in the studied OSE cultures. This indicates that losses in these genes cannot account for observed differences in phenotypical traits between POSE and NPOSE, but that differences in levels of p53 might contribute.     

The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women

Objective. To evaluate the effect of red clover isoflavone supplementation over vasomotor and overall menopausal symptoms in postmenopausal women. Methods. One hundred and nine postmenopausal women aged 40 or more were assigned to randomly receive either two daily capsules of the active compound (80?mg red clover isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day period. After a washout period of 7 days, medication was crossed over and taken for 90 days more. Daily hot flush and night sweat frequency and overall menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97 and 187 days. Results. Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline. All indices significantly decreased after red clover phase in Group A, corresponding, respectively to a 73.5%, 72.2% and 75.4% average decrement. These decrements were significantly higher than those observed for Group B after placebo phase (8.2%, 0.9% and 6.7% respectively). In Group A, after washout and placebo phases all values significantly increased. In Group B, all indices remained similar after placebo and washout phases, however significantly dropping after red clover treatment. These values were also significantly lower than those observed in Group A after placebo phase. No side effects were encountered after treatment with the active compound or placebo. Conclusion. Red clover isoflavone supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women.     

The impact of premenstrual symptoms on activities of daily life in Korean women

Objective.?To evaluate the impact of premenstrual symptoms on activities of daily life (ADL) of Korean women, and their knowledge and treatment seeking regarding premenstrual syndromes (PMSs).

Methods.?A population-based online survey regarding premenstrual symptoms was conducted in 1000 Korean women aged 15–49 years. Symptoms were classified according to their intensity, persistence each cycle, and impairment of ADL. Women's knowledge of PMSs and physician consultations were assessed.

Results.?The approximate prevalence of PMS/premenstrual dysphoric disorder (PMDD) by the WHO's International Classification of Disease (ICD-10), American College of Obstetrics and Gynecology (ACOG), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV[4th edition]) criteria was 98.6, 32.1, and 2.8%, respectively. Among 23 documented symptoms, the most predominant symptoms were joint-muscle-back pain, abdominal pain, and irritability. Physical symptoms were more prevalent than mental symptoms. There was a high correlation between the duration and severity of symptoms. The impact of PMS on ADL and the proportion of women with impaired ADL were significantly associated with the severity of PMS. The proportion of women consulting physicians increased with severity of PMS from 2%, 2.3%, for ICD-10, ACOG PMS to 10.7% for DSM-IV PMDD, respectively. Most of the women (91.5%) had no knowledge regarding terminology pertaining to PMS and PMDD.

Conclusion.?PMSs occur frequently and have a significant impact on daily life for a proportion of Korean women. However, Korean women have little knowledge about PMSs and only infrequently consult their physicians.     

Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women

The aim of this study was to evaluate the efficacy of a food supplement combination based on isoflavones and berberine (ISB) in the treatment of menopausal symptoms and dyslipidaemia. Isoflavones are extracted from soy and absorbed in the body after being activated by lactobacillus. Berberine, extracted from the plant Berberis aristata, lowers plasma cholesterol and triglycerides (TG) by increasing low-density lipoprotein (LDL) receptors and reducing hepatic synthesis of TG. One hundred twenty women with a mean age of 54.8?±?0.6 years were enrolled and randomized to treatment with ISB (estromineral lipid [EL]?=?60 cases) or calcium and vitamin D₃ (CaD?=?60 cases). Menopausal symptoms, plasma cholesterol, and TG were evaluated at baseline, and after 4 and 12 weeks. EL treatment significantly lowered plasma total cholesterol (?13.5% ± 0.7 vs ?0.2% ± 0.5), LDL cholesterol (?12.4% ± 1.5 vs + 0.8 % ± 0.7) and TG (?18.9% ± 2.5 vs ?1.3% ± 1.2) and improved menopausal symptoms compared with CaD treatment. Safety parameters were unchanged during the study. The combination of berberine and isoflavones was effective in lowering cardiovascular (CV) risk factors in menopausal women with moderate dyslipidaemia and in improving their quality of life.     

Psychiatric evaluation of women who were assisted at a university referral center in Campinas,Brazil, following an experience of sexual violence

Objective

To present the sociodemographic characteristics and psychiatric symptoms of women who have been raped.

Methods

Between 2006 and 2010, a retrospective study was conducted of 468 women who underwent psychiatric evaluation at a university referral center in Brazil after an experience of sexual violence.

Results

The women had a mean age of 24.1 years; were predominantly white, unmarried, childless, and employed; had 9–11 years of education; and had a religion. Rape was the first sexual intercourse for 124 (26.8%) of 462 for whom data were available; 53 (13.6%) of 389 had a personal history of sexual violence and 29 (8.0%) of 361 had a family history. No psychiatric symptoms were reported in 146 (32.9%) of 444 women, mild/short-term symptoms were reported in 107 (24.1%), and a psychiatric diagnosis was made for 191 (43.0%). Psychiatric comorbidity was seen in 59 (12.6%) women, and 174 (38.0%) received pharmacologic treatment. All follow-up consultations were attended by 215 (45.9%) of 468 women; 166 (35.5%) attended some, and 87 (18.6%) attended only one during the 6-month follow-up period.

Conclusion

The frequency and severity of psychiatric symptoms and mental disorders among women who have been raped highlights the importance of mental health monitoring.     

Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma

ObjectiveUniversal genetic testing has become increasingly important in the management of epithelial tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population, given its specific genetic background (French-Canadian ancestry).MethodMainstream genetic testing was implemented in our service in May 2017 and offered to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous and borderline tumours. Data were prospectively collected in a database and retrospectively analyzed.ResultsWe tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma (HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non–BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total of 63 different variants of unknown significance (VUS) were found, of which 4 were in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only 1 was found in low-grade serous carcinoma.ConclusionIn our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%—less than half that reported in the literature. This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy. Mainstream genetic testing was successfully implemented in our service and facilitated access to genetic testing in our patient population.     

希明婷片治疗妇女围绝经期综合征的临床观察

目的:探讨希明婷片治疗妇女围绝经期综合征的有效性和安全性。方法:采用多中心、随机、开放、阳性对照研究方法,将60例围绝经期综合征患者随机分为实验组和对照组(倍美力组),应用KuppermanIndex量表,评价治疗前后潮热多汗、烦燥易怒、失眠等围绝经期症状评分值的改变及患者治疗前后血常规、尿常规、肝肾功能、激素水平、B超等变化。结果:治疗后两组患者的潮热多汗、烦燥易怒、失眠等症状总积分均低于治疗前,差异有统计学意义(P<0.05),两组间差异无统计学意义(P>0.05);治疗前后血常规、尿常规、肝肾功、血雌激素(E2)、卵泡刺激素(FSH)、子宫内膜厚度等改变两组患者均无统计学意义(P>0.05)。结论:希明婷治疗妇女围绝经期综合征有效安全。     

Gynaecologic challenging issues in the management of BRCA mutation carriers: oral contraceptives,prophylactic salpingo-oophorectomy and hormone replacement therapy

BRCA1 and BRCA2 mutation carriers have a 54–85% and 45% lifetime risk of developing breast cancer, respectively, and a 18–60% and 11–27% lifetime risk of developing ovarian cancer, respectively. Oral contraceptives (OCs) significantly reduce the risk of ovarian cancer also in BRCA1/BRCA2 mutation carriers. The association between OC use and breast cancer risk in these women is controversial. Some studies showed a modestly increased risk especially among BRCA1 mutation carriers. The risk appears to be greater for women who took OCs for at least 5 years and who took OCs before the age of 30 years. Other studies reported that duration of use before first full-term pregnancy has a positive association with breast cancer risk. Salpingo-oophorectomy reduces the risk of coelomic epithelial cancer of 80–95% and the risk of breast cancer of approximately 50%. BRCA1 and BRCA2 mutation carriers should be encouraged to undergo prophylactic bilateral salpingo-oophorectomy at the age of 35–40 years or when childbearing is complete. Short-term use of hormone replacement therapy may relieve menopausal symptoms and does not appear to affect the breast cancer risk reduction obtained with salpingo-oophorectomy.     

The founder mutation BRCA1c.2845insA identified in a fallopian tube cancer patient: a case report

Abstract.   Damayanti Z, Ali AB, Iau PTC, Ilancheran A, Sng JH. The founder mutation BRCA1 c.2845insA identified in a fallopian tube cancer patient: a case report. Int J Gynecol Cancer 2006; 16(Suppl. 1): 362–365.
Fallopian tube carcinoma is a very rare tumor, comprising less than 1% of all gynecologic cancers and found primarily in postmenopausal women. With the disease being so uncommon, little is known about its causes and/or risk factors, and treatment approaches have been taken from experiences with ovarian cancer. We describe a case of a 42-year-old woman with fallopian tube cancer in which the founder mutation BRCA1 c.2845insA was detected by mutational analysis. This same mutation was subsequently detected in four unaffected members of her family following genetic counseling. We report an association between this founder mutation and fallopian tube cancer as part of the hereditary breast cancer syndrome in an Asian population. A literature review of the association between this rare malignancy and BRCA mutation carriers and its implications to prophylactic surgery is discussed.     

Prevalence of menopausal symptoms and quality of life after menopause in women from South India

Objectives: This study was carried out to establish the age at onset of menopause and the prevalence of menopause and menopausal symptoms in South Indian women.
Materials and methods: Three hundred and fifty-two postmenopausal women attending the outpatient clinics of obstetrics and gynaecology department of Dr TMA Pai Hospital, a tertiary care Hospital in South India, were included in the study. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used in the study. Data were presented as percentages for qualitative variable.
Results: The mean age at menopause was 48.7 years. Most frequent menopausal symptoms were aching in muscle and joints, feeling tired, poor memory, lower backache and difficulty in sleeping. The vasomotor and sexual domains were less frequently complained when compared to physical and psychological domains.
Conclusion: The age at onset of menopause in southern Karnataka (India) is 48.7 years which is four years more than the mean menopause age for Indian women. This could be attributed to better socioeconomic and health-care facility in this region.