Surgically-induced Menopause Research Articles

Abstract 18381: Long-Term Coronary Artery Disease Risk in Female Adults With Surgically-Induced Menopause : A Systematic Review

Introduction: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in female adults. Prior studies have suggested an association between surgically-induced menopause (SIM) and long-term CAD risk. Yet, the pathophysiology and clinical significance of this relationship remains unclear. As SIM causes a premature cessation of potentially cardioprotective hormones, this review aimed to further investigate if SIM is a risk factor for CAD. Methods: SCOPUS, Web of Science, Cochrane Library, OVID/Embase, SciELO, and LILACS were searched from inception to April 2023 for observational studies reporting the effects of hysterectomy, oophorectomy, and/or salpingectomy prior to age fifty on long-term CAD risk. Results: Among 3056 identified records, nineteen studies were included with a combination of benign and malignant surgical indications. The studies reported on coronary heart disease (n=6), CAD (n=4), ischemic heart disease (n=3), and myocardial infarction (n=7). Sixteen articles with an average of 106,433 participants per study demonstrated a significantly increased risk of CAD following SIM (Table 1). In particular, hysterectomy with or without bilateral oophorectomy, and bilateral oophorectomy alone were found to have the most profound influence. Unilateral oophorectomy or hysterectomy with salpingo-oophorectomy did not appear to increase CAD risk. Average follow-up duration after SIM ranged from six to twenty-four years. Five studies adjusted for post-menopausal hormone replacement therapy use. Conclusions: SIM may elevate long-term CAD risk following hysterectomy and/or bilateral oophorectomy. Given that the majority of SIM are performed pre- or peri-menopausal for benign indications, understanding the associated cardiovascular risks is vital for informed decision-making, early detection, and prevention.

Abstract P324: Female Reproductive Factors and Risk of Type 2 Diabetes and Cardiovascular Disease Among Women With a History of Gestational Diabetes

Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain. Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of live births, and surgically-induced menopause (uni- or bilateral oophorectomy or hysterectomy) are associated with higher risk of progression, while breastfeeding is associated with lower risk of progression from GDM to T2D/CVD. Methods: Participants in the Nurses’ Health Study II reported reproductive history at cohort baseline and over follow-up, including 5346 women with a history of GDM. Self-reported incident T2D or CVD (myocardial infarction, coronary revascularization or stroke) were confirmed via questionnaire or medical records. We estimated the hazard ratios (HR [95%]) across quintiles of each reproductive factor with incident T2D and CVD using Cox models adjusting for age, race/ethnicity, smoking, BMI at 18 years, physical activity, family history of T2D or CVD, alcohol intake, menopausal status, aspirin use, and Alternate Healthy Eating Index. Results: We documented 988 incident T2D and 149 CVD cases over 25 years of follow-up. In adjusted models, higher total lactation duration was associated with lower risk of T2D (5 categories: 0, 1-6, 7-12, 13-24, >24 months, p for trend=0.01; highest vs. lowest category: HR 0.77 [95%CI: 0.60, 0.98]) and CVD (p for trend=0.03, HR 0.39 [95%CI: 0.19, 0.80]). Early age at menarche was linearly associated with higher risk of T2D (5 categories: ≤11, 12, 13, 14, >14 y: p for trend <0.0001), lowest (≤11 y) vs. reference (13 y) category: HR 1.28 [95%CI: 1.06, 1.53], while no trend could be observed for CVD outcomes (p for trend=0.48). Higher age at 1 st birth was associated with lower CVD risk (5 categories: <23, 23-25 [reference], 26-29, 30-34, ≥35 y, p for trend=0.001; highest vs reference category: HR 0.17 [95%CI: 0.05, 0.57]), but not T2D). Compared with natural menopause, surgically induced menopause was associated with higher T2D risk: 1.32 (1.00, 1.73). Number of live births and age at menopause were not associated with T2D or CVD among women with GDM history. Conclusions: Breastfeeding was associated with lower T2D and CVD risks among women with GDM history, suggesting some shared risk factors or etiologies across reproductive lifespan and long-term cardiometabolic health. Ages at menarche and 1 st birth showed differential associations with T2D and CVD.

Modulation of vulvovaginal atrophy (VVA) by Gelam honey in bilateral oophorectomized rats.

Vulvovaginal atrophy (VVA) is a common condition in post-menopausal women. Symptoms of VVA include dyspareunia, vaginal dryness, vaginal and/or vulvar itching, burning and soreness, dysuria and vaginal bleeding accompanying sexual activity. These symptoms are physiological responses to hypoestrogenicity, inducing atrophy of the vagina epithelia and sudden reduction in mucous production. Prevailing therapy for VVA is hormone replacement therapy (HRT), notably estrogen, progesterone or a combination of the two. However, using HRT is associated with an increased incidence of breast and endometrial cancer, venous thromboembolism in the lungs and legs, stroke and cardiovascular complications. This study evaluated Malaysian Gelam honey as a nutraceutical alternative to estrogen HRT (ERT) in alleviating VVA. A total of 24 female 8-weekold Sprague Dawley rats underwent bilateral oophorectomy. A minimum of 14 days elapsed from the time of surgery and administration of the first dose of Gelam honey to allow the female hormones to subside to a stable baseline and complete recovery from surgery. Vaginal tissues were harvested following a 2-week administration of Gelam honey, the harvested vagina tissue underwent immunohistochemistry (IHC) analysis for protein localization and qPCR for mRNA expression analysis. Results indicated that Gelam honey administration had increased the localization of Aqp1, Aqp5, CFTR and Muc1 proteins in vaginal tissue compared to the menopause group. The effect of Gelam honey on the protein expressions is summarized as Aqp1>CFTR>Aqp5>Muc1. Gene expression analysis reveals Gelam honey had no effect on Aqp1 and CFTR genes. Gelam honey had up-regulated Aqp5 gene expression. However, its expression was lower than in the ERT+Ovx group. Additionally, Gelam honey up-regulated Muc1 in the vagina, with an expression level higher than those observed either in the ERT+Ovx or SC groups. Gelam honey exhibits a weak estrogenic effect on the genes and proteins responsible for regulating water in the vaginal tissue (Aqp1, Aqp5 and CFTR). In contrast, Gelam honey exhibits a strong estrogenic ability in influencing gene and protein expression for the sialic acid Muc1. Muc1 is associated with mucous production at the vaginal epithelial layer. In conclusion, the protein and gene expression changes in the vagina by Gelam honey had reduced the occurrence of vaginal atrophy in surgically-induced menopause models.

Prescription of hormone replacement therapy in women with surgically induced menopause and borderline ovarian tumors: Should we be doing more?

Borderline Ovarian Tumors (BOT) are often diagnosed in premenopausal women and the likely precursors to ovarian low-grade serous carcinoma (LGSC), a hormonally sensitive malignancy. The safety of hormone replacement therapy (HRT) after surgical treatment of BOT is unknown. We aimed to describe the HRT prescribing and preventive services practice patterns in women with surgically induced menopause (SIM) after surgery for BOT. (See Table 1.)

Psychosexual Morbidity in Women With Ovarian Cancer: Evaluation by Germline BRCA Gene Mutational Status.

IntroductionUp to 75% of women with ovarian cancer experience psychosexual morbidity and approximately 15–20% of women with ovarian cancer have a germline BRCA1/2 mutation (gBRCAm). However, psychosexual morbidity remains unexplored in women with gBRCAm ovarian cancer.AimGiven their younger age, genetic diagnosis, breast cancer risk, and increased prevalence of surgically-induced menopause, we aim to assess whether women with gBRCAm ovarian cancer experience distinct psychosexual morbidity.MethodsPsychosexual morbidity was investigated in 2 cohorts of women with ovarian cancer: women with gBRCAm ovarian cancer vs women with gBRCA wildtype (gBRCAwt) ovarian cancer. Between August 2019 and March 2020, women with high-grade serous carcinoma of the ovary, Fallopian tube or primary peritoneum were approached in clinic or telephoned and invited to take part. Exclusion criteria included: women with alternative histology; women admitted from clinic; and women who lacked capacity to independently complete the questionnaire. The Female Sexual Function Index (FSFI) and background information were collected at a single time-point per patient. Scores below 26.55 were interpreted to suggest psychosexual dysfunction.Main Outcome MeasureResponses including total and domain FSFI scores, self-reported psychosexual problems and interest in psychosexual support were compared.ResultsOf 103 women approached, 53% returned questionnaires. In this exploratory analysis, women with gBRCAm ovarian cancer were significantly younger (51–60 years vs 61–70 years, gBRCAwt, P = .010). There was a trend towards increased prevalence of surgical menopause (57% vs 27%, P = .097) and breast surgery (53% vs 22%, P = .132, gBRCAm vs gBRCAwt, respectively). Women with gBRCAm ovarian cancer scored higher in the FSFI questionnaire, particularly women under 60 years (15.1 vs 2.7, P = .070), approaching significance. Women with gBRCAm ovarian cancer expressed more interest for face-to-face services (P = .018), especially psychosexual therapy (65% vs 30%) and more often felt the service was insufficient, approaching significance (71% vs 44%, gBRCAm vs gBRCAwt, respectively, P = .076).ConclusionWomen with gBRCAm ovarian cancer are younger, express more interest for specialist psychosexual support and potentially different psychosexual problems, warranting further exploration.Logue C, Pugh J, Foden P, et al., Psychosexual Morbidity in Women With Ovarian Cancer: Evaluation by Germline BRCA Gene Mutational Status. Sex Med 2022;10:100465.

Rate of fracture among women undergoing treatment for gynecologic malignancies

Objectives: Women undergoing treatment for gynecologic malignancies have multiple risk factors for developing fractures, including surgically-induced menopause, cytotoxic chemotherapy, and radiation therapy. The incidence of fracture among women treated for gynecologic cancers is estimated to be as high as 20%, however there is limited data regarding the rate of and risk factors for fracture in this population. The objective of this study was to evaluate the incidence of fracture and characteristics of patients with fracture among women undergoing treatment for gynecologic malignancies. Methods: This was a single-institution retrospective cohort study of patients who received surgery, chemotherapy, hormonal therapy, and/or radiation for the treatment of cervical, uterine, and/or vulvar cancer between January 2012 and December 2014. Data on patient demographics, comorbidities, cancer therapies, and risk factors for fracture were manually extracted from patients’ medical records. Results: Of the 469 women included in the analysis, most (93.8%) were White or African American (3.6%), with a mean age of 58.2 (SD=13.7) years at the time of cancer diagnosis. The mean BMI was 34.8 (SD=9.8) kg/m2. Most (70.4%) patients were menopausal prior to cancer treatment and 16.4% underwent surgically-induced menopause. The majority (69.7%) of patients had a diagnosis of uterine cancer, followed by cervical cancer (16.8%) and vulvar cancer (8.5%). One third (33.7, n=158) received neoadjuvant or adjuvant chemotherapy and 28.4% (n=133) underwent adjuvant radiation. The mean pre- and post-treatment risk of major osteoporotic fracture by FRAX score was 6.9% (SD=5.7) and 8.5% (SD=6.5). Only 20 patients (4.3%) had a DXA scan performed prior to cancer treatment. The proportion of post-treatment fracture within the first two years following treatment was 3.6% (n=17). Of these, most (88.2%, n=15) were diagnosed by x-ray (n=9, 54.8%), followed by MRI (n=4, 23.5%) and CT (n=2, 11.8%). Patients with post-treatment fractures tended to be older at time of treatment (61.9 vs 57.6 years), current tobacco users (47.1% vs 14.1%), and postmenopausal prior to cancer therapy (100% vs 69.7%). Patients with post-treatment fractures also tended to have one or more comorbidity (100% vs 89.4%), have cervical cancer (41.2% vs 15.9%), and to have undergone radiation treatment (64.7% vs 27.4%) as well as chemotherapy treatment (70.6% vs 32.7%). Download : Download high-res image (274KB) Download : Download full-size image Conclusions: Our findings indicate the rate of fracture in the first two years following treatment for gynecologic malignancies is approximately 3.6%. Few women undergo bone mineral density screening prior to cancer treatment. Women with cervical cancer who are postmenopausal with multiple co-morbidities prior to treatment who receive chemotherapy and/or radiation are at higher risk. The mean post-treatment FRAX of 8.5% suggests that many patients may benefit from bone mineral density testing and risk stratification for osteoporosis following cancer therapy.

Determinants of surgically induced menopause in rural North Karnataka

Objective: The objective of the study was to quantify the effect of surgically induced menopause (SIM) on quality of life as assessed by religion, body mass index (BMI), sexual problem, menstrual history, blood spotting after intercourse, menopausal symptoms, and psychological disorder in the age group of 40–55 years of women. Materials and Methods: In this cross-sectional study, 712 rural women, comprising of 40 women (aged 40–55 years) with SIM, were surveyed, by inverse cluster sampling with proportional to population size. The aim was to study SIM and its determinants; menopause anthropometric data, menopause symptoms, and associated psychosocial symptoms. The data was analyzed using bivariate and multivariate techniques. Results: Around 6.4% of Hindu women had SIM, followed by Muslim (6.2%) and others (1.1%). SIM was significantly high in BMI group

Menopausal symptoms in epithelial ovarian cancer survivors: The GINECO VIVROVAIRE2 study.

5555 Background: We have previously shown that Epithelial Ovarian Cancer and its treatments have significant negative effects on Quality of Life (QoL) and long term fatigue. The aim of the present multicentric VIVROVAIRE2 study was to report the main menopausal, VasoMotor Symptoms (VMS) of Epithelial Ovarian Cancer survivors (EOCS). Methods: 166 patients of the 322 EOCS without relapse ≥3 years after first line of treatment accepted to participate to a gynecological consultation carried out by a gynecologist, including a questionnaire related to menopausal symptoms, a clinical examination, and an osteodensitometry. VMS (hot flashes and/or night sweats) were described according to natural menopause (NM) or surgically induced menopause (SIM). QoL and Fatigue were measured with the validated questionnaires FACT-G and FACT Fatigue. Results: Median age was 62 years [20-83], FIGO stage III/IV (48%) and < 10% BRCA1&2 mutated. Histological subtypes were: high grade serous 31%, low grade serous 23%, endometrioid G2-3 (14%) endometriod G1( 4%), clear-cell 21%, mucinous 5%. All EOCS had surgery, 97% of patients received platinum and taxane chemotherapy, median delay from treatment was 5 years [3-24] and 59 (36%) had SIM. 14% of EOCS had osteoporosis; this rate was similar to the general population. 52% of patients (85) reported either hot flashes (47%) or night sweats (32%). 72% with SIM had VMS compared to 41% with NM (p < 0.001). VMS were not associated with poor global QoL or fatigue. At the time of the survey, only 8 (5 SIM & 3 NM) EOCS received hormone replacement therapy (HRT). Among the 85 EOCS with VMS, 80 (94%) (38 SIM (93%) 42 NM (95%)) did not benefit from HRT after cancer treatment. Among 80 EOCS with VMS and no HRT, 25 (66%) with SIM and 34 (81%) of NM had high grade serous, endometriod G2-3, clear cell and mucinous histology. Conclusions: Vasomotor symptoms are frequently reported by EOCS, particularly among surgically induced menopause patients. A majority of EOCS with these symptoms might have beneficiated from hormone replacement therapy.

Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis

IntroductionExperimental and epidemiological studies suggest female sex hormones to have long-lasting neuroprotective and anti-ageing properties. Surgically-induced menopause leads to a premature cessation of exposure to female sex hormones and could thus impact late-life cognitive function. Yet, evidence remains controversial. MethodsWe systematically reviewed literature for articles investigating the association of surgical menopause (defined as bilateral oophorectomy before the onset of menopause) with risk of dementia, cognitive performance, cognitive decline, and Alzheimer’s disease neuropathological indices later in life. We evaluated study quality with the Newcastle-Ottawa scale and performed random-effects meta-analyses. ResultsWe identified 11 eligible studies (N = 18,867). Although surgical menopause at any age was not associated with risk of dementia (4 studies; HR: 1.16, 95%CI: 0.96–1.43), early surgical menopause (≤45 years of age) was associated with a statistically significantly higher risk (2 studies; HR: 1.70, 95%CI: 1.07–2.69). Surgical menopause at any age was associated with faster decline in verbal memory, semantic memory, and processing speed, whereas early surgical menopause was further associated with faster global cognitive decline. No heterogeneity was noted. Among women undergoing surgical menopause, a younger age at surgery was associated with faster decline in global cognition, semantic and episodic memory, worse performance in verbal fluency and executive function, and accumulation of Alzheimer’s neuropathology. ConclusionsCurrent evidence is limited, but suggests surgical menopause induced by bilateral oophorectomy at ≤45 years of age to be associated with higher risk of dementia and cognitive decline. Additional large-scale cohort studies are necessary to replicate these findings.

Evaluation of the CO<sub>2</sub> Laser Therapy on Vulvo-Vaginal Atrophy (VVA) in Oncological Patients: Preliminary Results

Objective: To evaluate the impact of fractionated CO2 laser therapy on vaginal atrophy and mild/moderate stress urinary incontinence (SUI) symptoms in patients with physiological or surgically-induced menopause. Materials and Methods: Post-menopausal patients (n = 33) presenting vaginal atrophy and/or SUI, underwent three vaginal CO2 laser treatment sessions, performed at 1-month intervals. Vaginal symptoms were evaluated using the Vaginal Health Index Score (VHI-S), Visual Analogue Scales (VAS) for dyspareunia and global patient satisfaction. The impact of urinary incontinence on patient quality of life was evaluated using the International Consultation on Incontinence Questionnaire (ICIQ). Symptoms were evaluated before treatment and at every subsequent treatment session, as well as 3 months following the last treatment session. RESULTS: The three-session treatment series led to a significant improvement in both subjective symptoms (dryness, burning, dyspareunia) and clinical signs (VHI-S) (P 2 laser therapy is a safe, effective and easy-to-perform treatment modality for menopause-related vaginal atrophy and SUI.

Effect of Ovarian Hormone Therapy on Cognition in the Aged Female Rhesus Macaque.

Hormone therapy after menopause is controversial. We tested the effects of hormone replacement in aged rhesus macaques, soon after surgically-induced menopause [ovariectomy (OVX)], on tests of memory and attention. Untreated ovarian-intact and OVX animals were compared with OVX animals receiving estradiol (E) alone or E with progesterone (P). E was administered in a continuous fashion via subcutaneous implant, whereas P was administered orally in a cyclic fashion. On both tests, E-treated animals performed better than the other 3 experimental groups across 1 year of treatment. Thus, in this monkey model, chronic E administered soon after the loss of ovarian hormones had long-term benefits for cognitive function.

Decisions about prophylactic gynecologic surgery: a qualitative study of the experience of female Lynch syndrome mutation carriers.

BackgroundWomen who carry a mutation for Lynch syndrome face complex decisions regarding strategies for managing their increased cancer risks. At present, there is limited understanding of the factors influencing women’s prophylactic surgery decisions.MethodsAs part of an exploratory pilot project, semi-structured interviews were conducted with 10 women who were Lynch syndrome mutation carriers and had made prophylactic surgery decisions. Nine of 10 women had chosen to undergo prophylactic hysterectomy and/or oophorectomy as a means of managing their increased gynecological cancer risks.ResultsStudy findings revealed that surgery decisions were influenced by multiple factors, including demographic variables such as age and parity, as well as psychosocial factors such as cancer worry, in addition to personal and social knowledge of gynecological cancer. While all women were satisfied with their surgery decision, some reported they were not fully informed about the negative impact on their quality of life post-surgery (e.g., complications of surgically-induced menopause), nor about the potential for, or risks and benefits of, hormone replacement therapy.ConclusionsStudy findings highlight some of the factors associated with prophylactic surgery decisions and women’s perceptions about pre-surgical information provision and needs. Suggestions are made for improving the information and support provided to female carriers of a Lynch syndrome mutation.

Effects of Hormone Replacement Therapy on Plasma and Tissue Fibrinolytic Activity in a Rat Model of Surgically Induced Menopause

The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause. Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200-250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17β-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17β-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue. HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.

Drug Utilization of Intrinsa® (Testosterone Patch) in England

Intrinsa is a transdermal testosterone patch that is indicated for use in hypoactive sexual desire disorder (HSDD) in women who have undergone bilateral oophorectomy and hysterectomy (surgically-induced menopause) receiving concomitant oestrogen therapy. To describe the utilization characteristics of the patients prescribed testosterone patch (Intrinsa) based on an interim analysis of an ongoing Prescription-Event Monitoring study in England, and to assess, where possible, if the product is being used within the licensed therapeutic indication. In this interim analysis, patients were identified from dispensed prescriptions that had been issued by general practitioners (GPs) for Intrinsa from March 2007. 'Green form' questionnaires were sent to GPs 6 months following the date of the first prescription for Intrinsa for each individual patient, requesting information including age, sex, start and stop dates of treatment (if stopped), prescribing indication and reasons for stopping. Additional questions were asked regarding the patient's menopausal status and use of concomitant oestrogen therapy. The interim cohort consisted of 756 patients. The majority of patients were reported to be female (746 [98.7%]) with a median (interquartile range) age of 50 years (44-55 years). The most commonly reported indication was the licensed indication of HSDD in 580 patients (76.7%). Just under one-half of the patients (n = 364 [48.1%]) were reported to have been hysterectomized and bilaterally oophorectomized (surgically-induced menopause) prior to starting Intrinsa; 127 patients (16.8%) were naturally menopausal. For 222 patients (29.4%) the GP specified that the patient was not using concomitant oestrogen therapy. Overall, only 219 patients (29.0%) in the cohort were being prescribed Intrinsa according to the manufacturer's recommendations. This study has highlighted that some clinicians are prescribing this product outside the recommended terms of the licence, with less than 30% of patients receiving Intrinsa according to prescribing guidelines. All events experienced by these patients will be analysed to detect any possible adverse events from using Intrinsa outside of the licensed therapeutic indication. The findings support the ongoing postmarketing risk management of the product.

Effect of an isoflavones-containing red clover preparation and alkaline supplementation on bone metabolism in ovariectomized rats

The aim of this study was to test the combined effect of a quality-controlled red clover extract (RCE) standardized to contain 40% isoflavones by weight (genistein, daidzein, biochanin A, and formononetin present as hydrolyzed aglycones) together with a modified alkaline supplementation on bone metabolic and biomechanical parameters in an experimental model of surgically-induced menopause. Sprague-Dawley female rats were maintained under controlled standard conditions of light and fed with conventional food of standard calcium content and no alfalfa or soybean components. Rats were randomized into four groups: Group A represented normal rats (sham operated) while three other groups were ovariectomized (OVX) and fed for three months as follows: standard food (group B), 6 mg/kg/day food mixed with RCE (Group C), or given 6 mg/kg/day of RCE plus a modified alkaline supplementation (BP) through a nasogastric tube at a dose of 16 mg (group D). The animals were killed 90 days after surgery. As compared to group B, RCE or RCE + BP treatments brought about significantly higher level of estradiol and mitigated the weight loss of the uterus and improved maximum load of the femoral neck. Osteocalcin level showed an over 65% increase in group B but both RCE and RCE + BP treatments prevented such abnormality with a significantly better result in RCE + BP group which virtually normalized such parameter as well as urinary excretion of DPD. Group C and D reduced the over 20% loss of bone mineral density and bone mineral content/body weight ratio observed in untreated post-ovariectomy group. Untreated ovariectomy caused about 48% decrease of cancellous bone mass in the femoral neck while this abnormality was prevented at similar extent by both RCE and RCE + BP treatments. Ovariectomy determined an over 80% increase of bone alkaline phosphatase (BALP) level but both RCE and RCE + BP treatments significantly mitigated such variable. The BALP decrease yielded by the combined RCE + BP treatment was statistically lower than RCE alone. Taken together these data show that red clover preparation in dosages amenable to clinical practice do improve OVX-induced osteoporosis while a mild metabolic alkalosis might further synergize some therapeutic aspects.

Cardiac and aortic structural alterations due to surgically‐induced menopause associated with renovascular hypertension in rats

Menopause and hypertension independently alter cardiovascular remodelling, but little is known about their effect on left ventricular and aortic wall remodelling. Eight-weeks-old Wistar rats were divided into four groups of six animals each: Sham group, OVX group (ovariectomized rats), 2K1C (two-kidneys, one-clip rats) and OVX + 2K1C group and kept until 19 weeks. Blood pressure (BP) increased 12% in OVX group, 35% in 2K1C and OVX + 2K1C groups compared with sham group. Vaginal cytology showed Sham and 2K1C rats cycling normally, whereas OVX and OVX + 2K1C rats were persistently in dioestrus or proestrus. At euthanasia, left ventricle (LV) and thoracic aorta were removed and analysed (immunohistochemistry and stereology). LV mass/tibia length ratio and cross-sectional area of cardiomyocytes increased in all groups except Sham. The intramyocardial vascularization reduced 30% in comparison with Sham group, with no difference among OVX, 2K1C and OVX + 2K1C groups. The cardiac interstitium increased more than 45% in both 2K1C and OVX + 2K1C groups compared with Sham, but there was no significant difference between Sham and OVX groups. Nuclei number of LV cardiomyocyte diminished in OVX group, followed by 2K1C group and OVX + 2K1C group, with no difference between the 2K1C and the OVX + 2K1C groups. There was positive immunostaining for angiotensin II AT1 receptor in smooth muscle cell layer of aortic tunica media in all groups. These results show that both ovariectomy and renovascular hypertension enhance BP as a single stimulus and therefore produce adverse cardiac remodelling. However, renovascular hypertension exerts a far greater influence than surgically-induced menopause in this parameter.

Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group

Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT. We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years. Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96). Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers.

Hot flashes refractory to HRT and SSRI therapy but responsive to gabapentin therapy

There is a need for alternative therapies for hot flashes, as hormone replacement therapy (HRT) is associated with increased rates of breast cancer and heart disease and some women fail to respond to HRT. A 32-year-old woman with surgically-induced menopause experienced 20-30 severe hot flashes per day and failed to respond to various formulations of HRT and selective serotonin reuptake inhibitor (SSRI) therapy for 17 years. She markedly responded to gabapentin therapy. Gabapentin, SSRIs, and estrogen may act at different cellular targets in the treatment of hot flashes.

Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis

Objectives: Following spontaneous menopause women show a greater increase in systolic and diastolic blood pressure than men of the same age. The aim of the present study was to assess the effect of acute ovarian hormone withdrawal and replacement on blood pressure and forearm blood flow. Methods: We studied 18 fertile middle-aged normotensive women (48±1.5 years, range 46–51 years) 1 week prior and 1 month subsequent to bilateral oophorectomy by means of 24-h blood pressure monitoring and strain-gauge venous occlusion plethysmography. Eighteen subjects who had undergone hysterectomy with ovarian sparing, matched for age and biophysical characteristics, were used as a control group. All women were free from cardiovascular risk factors or disease. Results: Oophorectomy increased the mean values of 24 h ( P<0.001), daytime ( P<0.05), and nighttime ( P<0.01) diastolic blood pressure and nighttime systolic blood pressure ( P<0.01). Blood pressure increase was associated with a rise in forearm vascular resistance ( P<0.01). No significant changes in either blood pressure or forearm vascular resistance values were observed in hysterectomized women. In 16 oophorectomized women a 3-month estrogen replacement therapy (ERT) (17β-estradiol, 100 mcg/day by transdermal patches) brought blood pressure and forearm vascular resistance values to a level comparable to that recorded before intervention. Conclusions: Surgically-induced menopause causes an increase in peripheral vascular resistance and blood pressure suggesting a role of ovarian hormones in the homeostatic pressure modulation. Recovery of the baseline condition after ERT suggests that the accelerated increase in blood pressure after menopause is due to ovarian and above all estrogen insufficiency.

Bone mineral density in natural and surgically-induced menopause

International Journal of Gynecology & ObstetricsVolume 66, Issue 2 p. 193-194 Brief communications Bone mineral density in natural and surgically-induced menopause A. Chittacharoen, A. Chittacharoen Department of Obstetrics and Gynaecology, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, ThailandSearch for more papers by this authorU. Theppisai, U. Theppisai Department of Obstetrics and Gynaecology, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, ThailandSearch for more papers by this authorR. Sirisriro, R. Sirisriro Division of Radiotherapy and Nuclear Medicine, Department of Radiology, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, ThailandSearch for more papers by this author A. Chittacharoen, A. Chittacharoen Department of Obstetrics and Gynaecology, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, ThailandSearch for more papers by this authorU. Theppisai, U. Theppisai Department of Obstetrics and Gynaecology, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, ThailandSearch for more papers by this authorR. Sirisriro, R. Sirisriro Division of Radiotherapy and Nuclear Medicine, Department of Radiology, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, ThailandSearch for more papers by this author First published: 23 July 1999 https://doi.org/10.1016/S0020-7292(99)00049-1Citations: 3 Corresponding author. Fax: +66-2-2011416. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume66, Issue2August 1999Pages 193-194 RelatedInformation