Non-hysterectomized Women Research Articles

A Comparison of Self-esteem, Body Image, and Depression in Hysterectomized and Non-hysterectomized Iranian Women: A Comparative Cross-sectional Study

Background: Hysterectomy is one of the factors that may affect women's body image and self-esteem and lead to serious psychological complications. Objective: The study aimed to compare self-esteem, body image, and depression in hysterectomized and non-hysterectomized Iranian women Methods: In this cross-sectional comparative study, 140 women of the reproductive age, who have undergone hysterectomy with benign causes, were compared in terms of self-esteem, body image, and depression with 140 women receiving medical treatment due to abnormal bleeding in educational and medical centers in Tabriz, Iran. Sampling was conducted by convenience method. Self-esteem was assessed with the Rosenberg self-esteem questionnaire, body image was assessed with the multidimensional body-self relations questionnaire, and depression was assessed with the Beck II depression inventory. Data were analyzed by Pearson correlation test, independent t-test, chi-square test, and general linear model. Results: The mean (standard deviation) of the body image in hysterectomized and nonhysterectomized women was 235.3 (28.5) and 250.1 (23.4) out of an achievable score of 69-395, respectively. The mean (standard deviation) self-esteem score for hysterectomized women was 20.4 (4.8) and it was 24.2 (3.4) in non-hysterectomized women (out of an achievable score of 0-30). The mean (standard deviation) depression score was 18.1 (9.7) and 5.5 (4.6) out of 0-63 in hysterectomized and non-hysterectomized women, respectively. The differences in self-esteem, body image, and depression variables were statistically significant in hysterectomized and non-hysterectomized women, respectively (P<0.001) Conclusion: According to the results of the present study, the body image and self-esteem in hysterectomized women were low compared to non-hysterectomized women, while the level of depression was high, and this difference was statistically significant.

Increased risk of stress urinary incontinence surgery after hysterectomy for benign indication—a population-based cohort study

Hysterectomy is a common procedure used to treat different gynecologic conditions. The association between hysterectomy for benign indication and stress urinary incontinence has previously been established. Stress urinary incontinence can be treated surgically, and options have improved after introduction of the midurethral sling procedure in1998. This study aimed to estimate the risk of stress urinary incontinence surgery after hysterectomy for benign indication. The study was carried out as a matched register-based cohort study including Danish women born from 1947 to 2000. Women who underwent hysterectomy for benign indication were matched to nonhysterectomized women in a 1:5 ratio on the basis of age and calendar year of hysterectomy. The risk of stress urinary incontinence surgery after hysterectomy was estimated. We adjusted for income, educational level, and parity. The risk of stress urinary incontinence surgery was further estimated in a subcohort excluding all vaginal hysterectomies. The joint effect of hysterectomy and parity was estimated in the main cohort, and the joint effect of hysterectomy and vaginal birth or cesarean delivery on stress urinary incontinence surgery was explored in a subgroup of women who only had 1 mode of delivery. All analyses were made using the Cox proportional hazards model. We included 83,370 women who underwent hysterectomy and 413,969 reference women. The overall risk of stress urinary incontinence surgery was more than doubled for women who underwent hysterectomy (adjusted hazard ratio, 2.6; 95% confidence interval, 2.4-2.8). The adjusted hazard ratio decreased slightly to 2.4 (95% confidence interval, 2.3-2.6) when excluding all vaginal hysterectomies. We found a trend of increasing risk of stress urinary incontinence surgery with increased parity among both women who underwent hysterectomy and the reference group. In the subgroup of women who only had 1 mode of delivery, we found the risk of stress urinary incontinence surgery to be particularly increased for women with a history of ≥1 vaginal births. The hazard ratio was 15.1 (95% confidence interval, 10.3-22.1) for women with a history of 1 vaginal birth who underwent hysterectomy, whereas the hazard ratio for women in the reference group with 1 vaginal birth was 5.1 (95% confidence interval, 3.8-8.1). Overall, women who underwent hysterectomy had a 3 times higher risk of stress urinary incontinence surgery than the reference group, irrespective of the number of vaginal births. This study indicates, in accordance with previous studies, that hysterectomy increases the risk of subsequent stress urinary incontinence surgery. Women should be informed and gynecologists include this knowledge in decision-making. Further precautions should be taken when treating parous women, particularly those with a history of ≥1 vaginal births.

Risk of atypical hyperplasia and endometrial carcinoma after initial diagnosis of non-atypical endometrial hyperplasia: A long-term follow-up study

ObjectivesThe strong association between atypical endometrial hyperplasia and endometrial carcinoma is well established, but data on the risk of atypical hyperplasia and carcinoma in Danish women with non-atypical endometrial hyperplasia are almost non-existent. This study aimed to investigate the prevalence of atypical hyperplasia and endometrial carcinoma diagnosed within 3 months of initial diagnosis (defined as concurrent disease) and the risk of atypical hyperplasia and carcinoma more than 3 months after initial diagnosis (classified as progressive disease) in Danish women initially diagnosed with non-atypical endometrial hyperplasia.DesignThis cohort study recruited 102 women diagnosed with non-atypical endometrial hyperplasia at Randers Regional Hospital in Randers, Denmark, between 2000 and 2015.MethodsThe endometrium was evaluated by transvaginal ultrasound examination and office mini-hysteroscopy with biopsies in all non-hysterectomized women. Data regarding subsequent hysterectomy or endometrial sampling were obtained from medical records and the Danish Pathology Registry (Patobank).ResultsA total of 15 women were diagnosed with atypical hyperplasia or carcinoma during follow-up. Concurrent atypical hyperplasia or carcinoma was seen in 2.9% (3/102), and among women who remained at risk for more than 3 months after initial diagnosis of non-atypical endometrial hyperplasia (n = 94), progression to atypical hyperplasia or carcinoma was seen in 13% (median follow-up 5.2 years, range 3.6 months to 15.1 years). Sixty-six percent of the women with progressive disease were diagnosed with atypical hyperplasia or carcinoma more than 1 year after initial diagnosis, but only two were diagnosed later than 5 years (5.2 and 9 years).ConclusionsThe risk of being diagnosed with atypical endometrial hyperplasia or endometrial carcinoma more than 5 years after an initial diagnosis of non-atypical endometrial hyperplasia seems to be low in Danish women. Specialized follow-up more than 5 years after diagnosis of non-atypical endometrial hyperplasia may not be warranted.

Pelvic organ prolapse following hysterectomy on benign indication: a nationwide, nulliparous cohort study

Hysterectomy is commonly performed and may increase the risk of pelvic organ prolapse. Previous studies in parous women have shown an increased risk of pelvic organ prolapse surgery after hysterectomy. Parity is a strong risk factor for pelvic organ prolapse and may confuse the true relation between hysterectomy and pelvic organ prolapse. This study aimed to investigate whether hysterectomy performed for benign conditions other than pelvic organ prolapse leads to an increased risk of pelvic organ prolapse surgery in a cohort of nulliparous women. We conducted a historical matched cohort study based on a nationwide population of nulliparous women born in 1947 to 2000 and living in Denmark during 1977 to 2018 (N=549,197). The data were obtained from the Danish Civil Registration System, the Danish National Patient Registry, the Fertility Register, and Statistics Denmark. Women who had a hysterectomy performed in 1977 to 2018 were included in the study (n=9535). For each of these women we randomly retrieved five nonhysterectomized women matched on age and calendar year to constitute the reference group (n=47,370). Cox proportional hazard regression analyses were performed to compare the risk of pelvic organ prolapse surgery in the 2 groups of women. The study included 56,905 women whom we observed for up to 42 years, entailing 809,435 person-years in risk. Overall, 9535 women who underwent a hysterectomy were matched individually with 47,370 reference women. Subsequently, a total of 29 women (30.4%) who underwent a hysterectomy and 85 reference women (17.9%) had a pelvic organ prolapse surgery performed, corresponding to incidence rates of 20.5 and 12.7 per 100,000 risk years, respectively. In addition, the risk of pelvic organ prolapse surgery increased by 60% in women who underwent a hysterectomy compared with women in the reference group (crude hazard ratio, 1.6; 95% confidence interval, 1.0-2.5; P=.04; adjusted hazard ratio, 1.6; 95% confidence interval, 1.0-2.5; P=.04). After the exclusion of women who underwent vaginal hysterectomy and their matches, the results were significantly the same (crude hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P=.05). Furthermore, we found higher rates of pelvic organ prolapse surgery in women who had a subtotal hysterectomy, total hysterectomy, or vaginal and laparoscopic-assisted vaginal hysterectomies than in women in the reference group. Hysterectomy increased the risk of pelvic organ prolapse surgery for nulliparous women by 60%. Previous studies of multiparous women have similarly shown an increased risk of prolapse after hysterectomy. As the most common risk factor for pelvic organ prolapse-vaginal birth-was not included and women were >72 years of age in this study, the numbers of pelvic organ prolapse surgeries were low. Despite the low absolute risk of pelvic organ prolapse surgery in nulliparous women, they were important in investigating the association between hysterectomy and pelvic organ prolapse, excluding vaginal birth, which is the most common risk factor for pelvic organ prolapse. As this cohort study of nulliparous women found an increased risk of pelvic organ prolapse surgery after hysterectomy, it is implied that the uterus per se protects against pelvic organ prolapse. As such, gynecologists should be aware of the risks associated with hysterectomy, and alternative uterus-sparing treatments should be considered when possible. Furthermore, women should be informed about the risks before being offered a hysterectomy.

Estetrol Combined to Progestogen for Menopause or Contraception Indication Is Neutral on Breast Cancer.

Simple SummaryHormonal treatments, especially those used to treat menopause symptoms are known to increase breast cancer risk. It is thus necessary to identify new formulations with a better benefit/risk profile. The aim of this translational study was to evaluate the breast cancer risk associated with a combination of a natural estrogen named estetrol, with progestogens such as natural progesterone and drospirenone. Since the assessment of breast cancer risk in patients during drug development is not possible given the requirement of long-term studies in large populations, this study provides new evidence that a therapeutic dose of estetrol for menopause treatment or contraception, combined with progesterone or drospirenone, may provide a better benefit/risk profile toward breast cancer risk compared to the hormonal treatments currently available for patients.Given the unequivocal benefits of menopause hormone therapies (MHT) and combined oral contraceptives (COC), there is a clinical need for new formulations devoid of any risk of breast cancer promotion. Accumulating data from preclinical and clinical studies support that estetrol (E4) is a promising natural estrogen for MHT and COC. Nevertheless, we report here that E4 remains active on the endometrium, even under a dose that is neutral on breast cancer growth and lung metastasis dissemination. This implies that a progestogen should be combined with E4 to protect the endometrium of non-hysterectomized women from hyperplasia and cancer. Through in vivo observations and transcriptomic analyses, our work provides evidence that combining a progestogen to E4 is neutral on breast cancer growth and dissemination, with very limited transcriptional impact. The assessment of breast cancer risk in patients during the development of new MHT or COC is not possible given the requirement of long-term studies in large populations. This translational preclinical research provides new evidence that a therapeutic dose of E4 for MHT or COC, combined with progesterone or drospirenone, may provide a better benefit/risk profile towards breast cancer risk compared to hormonal treatments currently available for patients.

Hysterectomy and ischemic heart disease: An observational study using propensity score methods in NHANES 2007–2018

Background and aimsThe association between hysterectomy and cardiovascular disease (CVD) remains controversial and research focusing on different types of CVD, especially ischemic heart disease, is scant. MethodsThis observational study was conducted with the National Health and Nutrition Examination Survey (NHANES) 2007–2018 using propensity score matching, propensity score overlap weighting, and logistic regression. ResultsAmong 15,257 women, 3476 (22.78%) had hysterectomy. Compared with non-hysterectomized women, hysterectomized women are more likely to be older, obese, with lower education level, and lower annual family income. Less favorable outcomes often occurred in unadjusted analysis. In adjusted, matched, and weighted analyses, the associations between hysterectomy and all outcomes were consistent, including ischemic heart disease (ORunadjusted = 3.18[95%CI, 2.76–3.66]; ORadjusted = 1.38[95%CI, 1.09–1.73]; ORmatched = 1.37[95%CI, 1.07–1.75]; ORweighted = 1.38[95%CI, 1.12–1.71]), coronary heart disease (ORunadjusted = 3.31[95%CI, 2.71–4.05]; ORadjusted = 1.43[95%CI, 1.04–1.98]; ORmatched = 1.46[95%CI, 1.04–2.05]; ORweighted = 1.45[95%CI, 1.06–1.99]), heart attack (ORunadjusted = 3.04[95%CI, 2.51–3.68]; ORadjusted = 1.47[95%CI, 1.09–1.99]; ORmatched = 1.42[95%CI, 1.03–1.95]; ORweighted = 1.45[95%CI, 1.10–1.91]) and angina pectoris (ORunadjusted = 3.29[95%CI, 2.66–4.08]; ORadjusted = 1.34[95%CI, 0.95–1.89]; ORmatched = 1.30[95%CI, 0.91–1.87]; ORweighted = 1.33[95%CI, 0.98–1.81]). In hysterectomized women, there were no significant associations between bilateral ovariectomy and ischemic heart disease (ORunadjusted = 1.24[95%CI, 0.99–1.54]; ORadjusted = 1.05[95%CI, 0.80–1.38]; ORmatched = 1.16[95%CI, 0.86–1.55]; ORweighted = 0.93[95%CI, 0.68–1.27]), female hormones use and ischemic heart disease (ORunadjusted = 0.94[95%CI, 0.76–1.16]; ORadjusted = 0.81[95%CI, 0.62–1.07]; ORmatched = 0.89[95%CI, 0.66–1.20]; ORweighted = 1.14[95%CI, 0.88–1.49]). ConclusionsHysterectomy may increase the risk of ischemic heart disease, especially for coronary heart disease and heart attack, but not for angina pectoris. As for the hysterectomized women, bilateral ovariectomy and female hormones use do not affect ischemic heart disease.

Genitourinary syndrome of menopause in Chinese perimenopausal and postmenopausal women

Objective The aim of this study was to investigate genitourinary syndrome of menopause (GSM) in a large cohort, analyzing the dependency on age and menopausal status and possible differences between non-hysterectomized and hysterectomized women. Methods Data were assessed by validated questionnaires, collected over 2 years for all eligible women attending our ‘Menopause Clinic’ from 31 Chinese provinces. Simple and unconditional logistic regression analysis was used with adjustments by all analyzed factors. Results A total of 4063 women (mean age 50.53 ± 6.57 years), 2107 perimenopausal and 1956 postmenopausal, were included. Almost all GSM symptoms were more frequent and severe in postmenopausal women. GSM was more frequent in hysterectomized women compared to non-hysterectomized women. Independent of menopausal status, low sexual interest (92.78%), urinary incontinence (91.65%) and vaginal dryness (91.60%) were the top three GSM symptoms. Most severe were low sexual interest (21.01%), vaginal pain (20.10%) and decreased sexual pleasure (17.13%). Prevalence and severity of GSM were not related to age, but were related to menopausal status and increased with time since menopause. Conclusions Within 2 years, more than 4000 women with GSM traveled from all over China to our specialized clinic, indicating the great importance of GSM. Hysterectomy can increase the risk of GSM, and GSM symptoms increase from perimenopause to postmenopause and with an increase of time since menopause, pointing to the dependency on the loss of ovarian function.

How often should ring pessaries be removed or changed in women with advanced POP? A prospective observational study.

Introduction and hypothesisThis study aimed to evaluate the efficacy and safety of ring pessaries under continuous use for > 2 years. Our starting hypothesis was that their use without periodic removal, cleaning or replacement for between 24 to 48 months after insertion is safe and effective.MethodsThis was a prospective observational and descriptive study. One hundred one women who successfully completed the 24 first months of continuous use of a ring pessary were included and monitored for another 24 months. The objectives were to establish the percentage of patients maintaining its use 48 months after insertion, the reasons for discontinuation and the adverse events. Another purpose of this study was to determine the timing of replacement of the vaginal pessary in long-term users.ResultsOf the women, 92.1% (93/101) had successful pessary use, and it was discontinued by three patients (2.9%, 3/101); 76.2% (77/101) of the women continued pessary use after the end of the study, and in 16 (15.8%, 16/101) patients, after pessary removal, the prolapse disappeared and did not recur. Forty-five women (48.4%, 45/93) presented some adverse events that required temporary pessary removal. The most common one was an increase in vaginal discharge (73.3%, 33/45). In four women (8.9%, 4/45), the ring pessary was detected embedded in the vaginal epithelium.ConclusionsContinuous use of a ring pessary can be recommended for 2 years in hysterectomized women and for 4 years in non-hysterectomized women if there are no complications.

The Effectiveness of Prasterone vs Placebo Therapy as the Vulvovaginal Atrophy Treatment in Menopausal Women: Meta-Analysis

Background : Vulvovaginal atrophy is a condition that often occurs in menopausal women due to Estrogen decreased. Prasterone (DHEA) is a steroid hormone that can be converted into Estrogen in the target tissue. Objective : This paper aims to evaluate the effectiveness of administering Prasterone as Vulvovaginal Atrophy therapy in menopausal women. Methods : A systematic data search was performed on a medical database (PUBMED, Google scholar, Cochrane). Inclusion criteria: (1) randomized study of Prasterone as Vulvovaginal Atrophy therapy in postmenopausal women, (2) all-inclusive papers can be accessed completely, and (3) the data obtained can be accurately analysed. Results: Three RCTs with a total of 696 patients were analysed. The average number of Superficial Cells (mean difference [MD] 7.63, and 95% [CI] 7.57 to 7.70 (P <0.00001). The average number of Parabasal Cells (mean difference [MD] -29.84, and 95% [CI] -30.25 to -29.44 (P <0.00001). The average number of vaginal pH (mean difference [MD] -0.69, and 95% [CI] -0.70 to -0.68 (P <0.00001). The average number of Dyspareunia (mean difference [MD] -0.38, and 95% [CI] -0.39 to -0.37 (P <0.00001). All diamonds do not intersect the vertical line, and have p <0.05, it proves that there are significant differences between the two groups. All non-hysterectomized women have an atrophic or inactive endometrium. Side effects that are often complained of is headache and application site discharge. Conclusion This meta-analysis concludes that Prasterone therapy has a significant therapeutic effect for Vulvovaginal Atrophy in menopausal women

A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety.

Objective:The aim of this study was to select the minimum effective dose of estetrol (E4) for the treatment of vasomotor symptoms in postmenopausal women.Methods:This was a multicenter, randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 257, of whom 32 were hysterectomized) aged 40 to 65 years, with ≥7 moderate to severe hot flushes (HFs) per day, or 50 or more moderate to severe HFs weekly, received 2.5, 5, 10, or 15 mg E4, or placebo once-daily for a period of 12 weeks. Efficacy was assessed by recording the frequency and severity of HFs. Overall safety was assessed by recording adverse events, measuring endometrial thickness, and monitoring bleeding patterns. Treatment groups were compared using analysis of covariance.Results:The frequency of moderate to severe HFs decreased with all E4 doses. The difference in the percentage change of weekly HF frequency was significant for 15 mg E4 versus placebo at both W4 (−66% vs −49%, P = 0.032) and W12 (−82% vs −65%, P = 0.022). The decrease in severity of HFs was significantly more pronounced for 15 mg E4 than for placebo at both W4 (−0.59 vs −0.33, P = 0.049) and W12 (−1.04 vs −0.66, P = 0.049); the other doses failed to achieve statistical significance. In nonhysterectomized women, endometrial thickness increased during treatment and normalized following progestin treatment at study completion. No endometrial hyperplasia was observed.Conclusions:Estetrol 15 mg is considered to be the minimum effective daily oral dose for treatment of vasomotor symptoms. Its current seemingly favorable safety profile is further to be confirmed in phase 3 clinical development.Video Summary:.

Risk of vaginal cancer among hysterectomised women with cervical intraepithelial neoplasia: a population-based national cohort study.

To study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN). Population-based national cohort study. All Swedish women, 5 million in total, aged 20 and up, 1987-2011 using national registries. The study cohort was subdivided into four exposure groups: hysterectomised with no previous history of CIN3 and without prevalent CIN at hysterectomy; hysterectomised with a history of CIN3/adenocarcinoma in situ (AIS); hysterectomised with prevalent CIN at hysterectomy; non-hysterectomised. Vaginal cancer. We identified 898 incident cases of vaginal cancer.Women with prevalent CIN at hysterectomy and those with a history of CIN3/AIS had incidence rates (IR) of vaginal cancer of 51.3 (95% CI 34.4-76.5) and 17.1 (95% CI 12.5-23.4) per 100000, respectively. Age-adjusted IR-ratios (IRRs) compared with hysterectomised women with benign cervical history were 21.0 (95% CI 13.4-32.9) and 5.81 (95% CI 4.00-8.43), respectively. IR for non-hysterectomised women was 0.87 (95% CI 0.81-0.93) and IRR was 0.37 (95% CI 0.30-0.46). In hysterectomised women with prevalent CIN, the IR remained high after 15years of follow up: 65.7 (95% CI 21.2-203.6). Our findings suggest that hysterectomised women with prevalent CIN at surgery should be offered surveillance. Hysterectomised women without the studied risk factors have a more than doubled risk of contracting vaginal cancer compared with non-hysterectomised women in the general population. Still, the incidence rate does not justify screening. High risk of contracting vaginal cancer among hysterectomised women having prevalent CIN at surgery.

Postmenopausal hormone therapy is accompanied by elevated risk for uterine prolapse.

Receptors for estrogen and progesterone are present in the pelvic floor, and therefore, postmenopausal hormone therapy may affect its function. We compared the former use of estradiol-progestogen postmenopausal hormone therapy in nonhysterectomized women with a uterine prolapse surgery (N = 12,072) and control women (N = 33,704). The women with a history of uterine prolapse operation were identified from the Finnish National Hospital Discharge Register, and the control women from the Finnish Central Population Register. The use of hormone therapy was traced from the national drug reimbursement register, and the odd ratios with 95% CIs for prolapse were calculated by using the conditional logistic regression analysis. The women with uterine prolapse had used hormone therapy more often than control women (N = 4,127; 34.2% vs N = 9,189; 27.3%; P < 0.005). The use of hormone therapy was accompanied by significant (23%-53%) elevations in the risk for prolapse, being higher with longer exposure. The risk elevations (33%-23%) were comparable between sole norethisteroneacetate-estradiol and sole medroxyprogesteroneacetate-estradiol therapy. The use of estradiol in combination with a levonorgestrel releasing intrauterine device was accompanied by a 52% elevation. The postmenopausal use of estradiol in combination with various progestogen regimens may weaken the pelvic floor, resulting in uterine prolapse. This data should be incorporated into the information given to the users of estradiol-progestogen hormone therapy.

The influence of total hysterectomy in a cervical cancer screening population: a register-based cross-sectional study

BackgroundHigh coverage of a screening program is essential to program success. Many European screening programs cover only 10–80% of their target population. A possible explanation for the low coverage may be that some women in the screening population have had a total hysterectomy, thus they are not at risk of cervical cancer. The aim of this study was to identify the prevalence of hysterectomy in the target population of the Danish National Cervical Cancer Screening Program (NCCSP) and to recalculate coverage after excluding women with total hysterectomy. Furthermore, to analyze the association between hysterectomy and sociodemographic factors within the screening population.MethodsA population-based cross-sectional study using register data on all women in the target population of the NCCSP on January 12, 2012 (women born January 12, 1947, to January 12, 1986).The total coverage included women with hysterectomy in the target population whereas the recalculated coverage was calculated excluding women with total hysterectomy. To test the differences between the total coverage and the recalculated coverage, a two-sample z-test between the proportion of covered hysterectomized women and the proportion of covered non-hysterectomised women were used. A logistic regression model adjusted for age and sociodemographic characteristics was used to analyze the association between sociodemographic factors and total hysterectomy.ResultsThe coverage among women aged 26–49 years and 55–64 years were 77.4% and 72.7%, respectively. The recalculated coverage was 78.2% (26–49 years) and 79.4% (55–64 years). Recalculating the coverage did not result in coverage higher than 82.7% at any age. The effect of excluding women with total hysterectomy increased with age, reaching its maximum of 8 % points for the oldest women. Women with higher socioeconomic status (higher education and higher disposable income) had lower odds of being hysterectomized compared to other women. Also, immigrants and descendants had lower odds of being hysterectomized compared to ethnic Danes.ConclusionsExcluding women with total hysterectomy only partly explained the low coverage of the NCCSP. Thus, initiatives must be made to improve acceptability of and accessibility to the NCCSP, especially in the youngest and the oldest women.

Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials.

Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials. Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region. There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores -1.05 and -0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001). Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss.

Clinical audit of estradiol implant therapy: Long duration of action and implications in non-hysterectomised women

We audited the files of 114 postmenopausal women who had been treated with subcutaneous Estrapel (50mg oestradiol implants). Of the 92 women who received more than one implant, the median number of days between implants was 223.5 (range 49–875), with an estimated median time to return to baseline of 311days (range 108–1228). Although oestradiol implants can provide an excellent non-oral treatment option, their prolonged action makes patient selection important, as the implants cannot easily be removed. In women with an intact uterus, the continuation of progestin therapy after cessation of implant therapy is imperative.

CE/BZA effects on bone and quality of life in European postmenopausal women: a pooled analysis

Objectives: To evaluate the efficacy of conjugated estrogens/bazedoxifene (CE/BZA) on bone mineral density (BMD), bone turnover markers (BTM), and menopause-specific quality of life (MENQOL) in European women.Methods: Data through 12 months were pooled from two double-blind, randomized, controlled trials in non-hysterectomized postmenopausal women who received CE/BZA or placebo. Women from European study sites with evaluable BMD (n = 60), BTM (n = 56), and MENQOL questionnaire (n = 236) data were included and compared with 1523 women from US study sites (n = 730 with evaluable data for bone outcomes).Results: At month 12, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg, respectively, significantly improved BMD (adjusted difference vs. placebo) in lumbar spine (2.5%, 2.9%; both p ≤ 0.011) and total hip (1.7%, 2.2%, both p ≤ 0.002), significantly improved serum BTMs (osteocalcin: –31.1%, –33.1%; C-telopeptide: –48.5%, –36.8%) vs. placebo (osteocalcin: 6.7%, C-telopeptide: 4.2%; all p < 0.001), and significantly improved MENQOL vasomotor function scores (–2.1, –2.2) vs. placebo (–0.7; both p < 0.001). No significant treatment × subpopulation interactions were observed for any of the outcomes.Conclusions: Twelve-month CE/BZA treatment prevented bone loss and improved vasomotor function in European postmenopausal women. Findings were similar to those in the subpopulation of women enrolled at US study sites.

Patient considerations in the management of menopausal symptoms: role of conjugated estrogens with bazedoxifene.

Menopausal symptoms (eg, hot flushes and vaginal symptoms) are common, often bothersome, and can adversely impact women’s sexual functioning, relationships, and quality of life. Estrogen–progestin therapy was previously considered the standard care for hormone therapy (HT) for managing these symptoms in nonhysterectomized women, but has a number of safety and tolerability concerns (eg, breast cancer, stroke, pulmonary embolism, breast pain/tenderness, and vaginal bleeding) and its use has declined dramatically in the past decade since the release of the Women’s Health Initiative trial results. Conjugated estrogens paired with bazedoxifene (CE/BZA) represent a newer progestin-free alternative to traditional HT for nonhysterectomized women. CE/BZA has demonstrated efficacy in reducing the frequency and severity of vasomotor symptoms and preventing loss of bone mineral density in postmenopausal women. CE/BZA provides an acceptable level of protection against endometrial hyperplasia and does not increase mammographic breast density. Compared with traditional estrogen–progestin therapy, it is associated with lower rates of breast pain/tenderness and vaginal bleeding. Patient-reported outcomes indicate that CE/BZA improves menopause-specific quality of life, sleep, some measures of sexual function (especially ease of lubrication), and treatment satisfaction. This review looks at the rationale for selection and combination of CE with BZA at the dose ratio in the approved product and provides a detailed look at the efficacy, safety, tolerability, and patient-reported outcomes from the five Phase III trials. Patient considerations in the choice between CE/BZA and traditional HT (eg, tolerability, individual symptoms, and preferences for route of administration) are also considered.

Evaluation of efficacy and safety of conjugated estrogens/bazedoxifene in a Latin American population

Introduction Conjugated estrogens/bazedoxifene (CE/BZA) relieves menopausal symptoms and increases bone mineral density (BMD).Objective To evaluate CE/BZA in a Latin American subpopulation from randomized, double-blind, phase-3, multinational trials.Methods Safety data were pooled from three trials from non-hysterectomized postmenopausal Latin American women assigned to CE 0.45 mg/BZA 20 mg (n = 227), CE 0.625 mg/BZA 20 mg (n = 222), or placebo (n = 193). Efficacy outcomes from one study included changes in hot flush frequency at week 12 in women with at least seven moderate/severe hot flushes/day or 50/week at baseline (n = 39), and from baseline to month 12 for BMD (n = 381) and genitourinary syndrome of menopause (GSM) (women with baseline GSM; n = 189).Results At week 12, women taking CE/BZA had four to five fewer moderate/severe hot flushes/day vs. placebo. At month 12, percentage changes in BMD with CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and placebo were 1.2%, 1.6%, and –1.1% for lumbar spine and 1.1%, 1.2%, and –0.3% for total hip. GSM improved with treatment (percentage superficial cells: 4.5, 7.4, vs. 2.0; percentage parabasal cells: –9.3, –27.8 vs. 2.8). There were no new/unexpected safety trends.Conclusion CE/BZA improved vasomotor symptoms, GSM, and BMD in Latin American women, with efficacy/safety similar to the global population.

Role of Estrogens and Estrogen-Like Compounds in Female Sexual Function and Dysfunction.

Sex steroids are important in female sexual function and dysfunction. To review the role of estrogens in the physiology and pathophysiology of female sexual functioning and the evidence for efficacy of estrogen therapy for female sexual dysfunction to update the previously published International Society of Sexual Medicine Consensus on this topic. Panel members reviewed the published literature using online databases for studies pertaining to estrogen in female sexual function and dysfunction. Attention was specifically given to clinical trials that had reported on sexual function outcomes in women treated with estrogen. Quality of data published in the literature and recommendations were based on the GRADES system. Observational studies that have considered relationship factors and physical or mental health have reported that these factors contribute more to sexual functioning than menopausal status or estrogen levels. Few clinical trials have investigated estrogen therapy with sexual function as a primary outcome. The available data do not support systemic estrogen therapy for the treatment of female sexual dysfunction. Topical vaginal estrogen therapy improves sexual function in postmenopausal women with vulvovaginal atrophy (VVA) and is considered first-line treatment of VVA. Oral ospemifene, a selective estrogen receptor modulator, is effective for the treatment of VVA and might have independent systemic effects on female sexual function. For sexual problems, the treatment of VVA remains the most pertinent indication for estrogen therapy. When systemic symptoms are absent, estrogen therapy ideally can be administered by a vaginal preparation alone. Systemic estrogen therapy with combined estrogen and progestin in non-hysterectomized women is indicated for women who require treatment for vasomotor and/or other systemic estrogen deficiency symptoms. The improvement in well-being achieved by relief of vasomotor and other symptoms might improve libido in some women and abrogate further intervention.

Long-term cancer risk after hysterectomy on benign indications: Population-based cohort study.

Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population-based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo-ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (<100 cases for the two groups combined) were excluded from analysis. A marginal risk reduction for any cancer was observed for women with previous hysterectomy and for those with hysterectomy and concurrent BSO (HR 0.93, 95% CI 0.91-0.95 and HR 0.92, 95% CI 0.87-0.96, respectively). Compared to nonhysterectomized women, significant risks were observed for thyroid cancer (HR 1.76, 95% CI 1.45-2.14). For both hysterectomy and hysterectomy with BSO, an association with brain cancer was observed (HR 1.48, 95% CI 1.32-1.65 and HR 1.45, 95% CI 1.15-1.83, respectively). Hysterectomy, with or without BSO, was not associated with breast, lung or gastrointestinal cancer. We conclude that hysterectomy on benign indications is associated with an increased risk for thyroid and brain cancer later in life. Further research efforts are needed to identify patient groups at risk of malignancy following hysterectomy.