Persistent gap in menopause care 20 years after the WHI: a population-based study of menopause-related symptoms and their management.

OBJECTIVES: To assess the current management of menopause in France with regard to menopause-related and genitourinary symptoms, with a focus on use of menopause hormone therapy (MHT). DESIGN, SETTING, AND PARTICIPANTS: The ELISA Study is a population-based survey of 5004 French representative women aged 50 to 65 years. From July to August 2020, the participating women answered an online computer-assisted web interview on menopause-related and genitourinary symptoms and their management, including use of MHT. MAIN OUTCOMES AND MEASURES: Prevalence of menopause-related and genitourinary symptoms in postmenopausal women. Management of these symptoms, including the reasons for not doing so, management by health care providers, and use of MHT. RESULTS: Among the 5004 selected women, 4041 whose postmenopausal status was confirmed were included in the final analyses. Of the untreated 3685 women, 87 % reported at least 1 menopausal symptom, with a significantly higher percentage of symptomatic women in the 50-54 age group (92 %, p < 0.05) than in the other two age groups (55-59 years: 89 % and 60-64 years: 82 %). 68 % of the surveyed women experienced on average 2.5 symptoms of the genitourinary syndrome of menopause (GSM). Using a visual analogue scale (VAS) from 0 (no impact) to 10 (high impact) to evaluate the impact of menopausal/GSM symptoms on their quality of life, mean VAS score was 5.9 (SD: 2.2), with 25 % of the women aged 55-59 years rating their quality of life between 8 and 10. 61 % of the surveyed women reported being regularly followed by a health care professional. 44 % of women reported never having discussed their menopausal/GSM symptoms with a health care provider. The main reasons were because menopause is "a normal part of women's lives", because it was not "necessary to do so", or their symptoms were "not serious enough". Only 242 women (6 %) were current MHT users, of whom 49 % were using estrogen-alone therapy and 71 % were using transdermal estrogens. Fear of hormones (35 %) and MHT side-effects (25 %) were the main reasons given for not using MHT. 62 % of the women reported that the decision not to take MHT was supported by their physician. CONCLUSIONS AND RELEVANCE: This large population-based survey confirmed not only the high prevalence of menopause-related and GSM symptoms in postmenopausal women within the first 10-15 years after menopause, but also the very low percentage of MHT users in France. Twenty years after the publication of the initial Women's Health Initiative (WHI) results, management of postmenopausal women is still characterized by unmet needs in menopausal care. Therefore, there is a strong need to educate the public and health care providers about menopause-related problems and possible solutions, including MHT, through dedicated educational programs.

Bone mineral density in women with deep infiltrating endometriosis who have undergone early bilateral oophorectomy.

OBJECTIVE: To study bone mineral density (BMD) in women with and without pelvic deep infiltrating endometriosis (DIE) who underwent early bilateral oophorectomy (BO). METHODS: A case-control study was performed in 83 women who underwent early BO before the age of 45 years, 31 for DIE and 52 for another clinical condition. All the women answered a standardized computer-assisted questionnaire to record their clinical and historical data and were medically examined. Lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry after early BO. Simultaneously, serum calcium, intact parathyroid, 25-hydroxyvitamin D, and cross-linked C-telopeptide were also measured. Unadjusted and adjusted odds ratios (with 95% confidence intervals [CI]) for endometriosis were calculated using logistic regression. RESULTS: The mean lumbar spine and femoral neck BMDs were significantly higher in women who underwent early BO for DIE than in those who underwent early BO for another clinical condition. After adjusting for age at BMD measurement, years since menopause, age at menarche and body mass index, odds ratio for endometriosis associated with a 1-SD increase in lumbar spine and femoral neck BMD was 2.59 (95% CI: 1.45-4.62) and 2.16 (95% CI: 1.23-3.81), respectively. CONCLUSION: Higher lumbar spine and femoral neck BMDs are associated with an increase in the likelihood of pelvic DIE in women who underwent early BO. This might be expected to the extent that endometriosis is itself associated with enhanced estrogen status, although further studies are needed to confirm such a hypothesis. These findings suggest that BMD measurement could contribute to the hormonal management of surgical menopause in women with DIE.

Osteoporosis management in patients with breast cancer: EMAS position statement.

Aromatase inhibitors (AIs) are the first-line recommended standard of care for postmenopausal estrogen receptor-positive breast cancer. Because they cause a profound suppression of estrogen levels, concerns regarding their potential to increase the risk of fracture were rapidly raised. There is currently a general consensus that a careful baseline evaluation is needed of the risk of fracture in postmenopausal women about to start treatment with AIs but also in all premenopausal women with early disease. Bisphosphonates have been shown in several phase III trials to prevent the bone loss induced by cancer treatment, although no fracture data are available. Even though they do not have regulatory approval for this indication, their use must be discussed with women at high risk of fracture. Accordingly, several guidelines recommend considering treatment in women with a T-score ≤-2 or those with two or more clinical risk factors. Moreover, recent data suggest that bisphosphonates, especially intravenous zoledronic acid, may have an anticancer effect, in that they reduce bone recurrence as well as extra-skeletal metastasis and breast cancer mortality in postmenopausal women. The anti-RANK ligand antibody denosumab is also emerging as a new adjuvant therapeutic option to prevent AI-induced bone loss. It has been shown to extend the time to first fracture in postmenopausal women treated with AIs. Several issues still need to be addressed regarding the use of these different agents in an adjuvant setting. The purpose of this position statement is to review the literature on antifracture therapy and to discuss the current guidelines for the management of osteoporosis in women with early breast cancer.

Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS position statement.

BACKGROUND: Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and non-vertebral fractures, their optimal duration of use has not been determined. The occurrence of adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), has raised the issue of bisphosphonate or denosumab discontinuation ("drug holiday") after a certain treatment period. AIM: To assess the effect of bisphosphonate and denosumab discontinuation on fracture risk, as well as its possible benefits in reducing the risk of adverse effects. METHODS: Systematic review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Discontinuation of bisphosphonates should be considered in all patients who have beentreated for more than five years with alendronate, risedronate or zoledronic acid. In view of the limited evidence, no robust recommendations can be made for ibandronate and denosumab. If the patient has not experienced fractures before or during therapy and the fracture risk is low, a "drug holiday" canbe recommended. Although there is no solid evidence, 1-2 years for risedronate, 3-5 years for alendronate and 3-6 years for zoledronic acid are suggested. After this time, the patient should be reassessed. If a new fracture is experienced, or fracture risk has increased or BMD remains low (femoral neck T-score ≤-2.5), anti-osteoporotic treatment should be resumed. In the case of denosumab discontinuation, close monitoring is suggested, due to the possibility of rebound fractures.

Association of cardiovascular risk factors with intima-media thickness of the carotid arteries in early postmenopausal women.

OBJECTIVE: The aim of this study was to examine the association between carotid intima-media thickness (IMT) and coronary heart diseases (CHD) risk factors in a large population of peri- and postmenopausal women. DESIGN: Participants in this study were 906 healthy peri- and postmenopausal women from southwestern France, 45 to 65 years old with no history of cardiovascular disease and no utilization of estrogen/hormone therapy. Women were classified either as perimenopausal (n = 240) or post-menopausal (n = 666) according both to the regularity of menses and to serum follicle-stimulating hormone and estradiol values. All women answered a questionnaire, which included 72 questions, related to the identification of familial and personal cardiovascular risk factors. Biological measurements were performed to evaluate their lipid-lipoprotein profiles and fasting glucose levels, ultrasonography was used to measure IMT and total body scanners by DXA were performed to determine the percentage of body fat. RESULTS: Multiple regression analyses were used to examine the ability of each variable to explain IMT values. Mean IMT of the right carotid artery was 0.520 (+/- 0.07) mm. Of the 906 women, 9% were currently taking lipid-lowering drugs, 12.8% and less than 2% were being treated for hypertension and diabetes, respectively. Additionally, 124 women were found to have current hypertension, 10% had a familial history of CHD, and 18% were regular smokers. In multiple regression analyses, only increasing age (P < 0.001) and systolic and diastolic blood pressure (P < 0.001) were independently and significantly associated with IMT. CONCLUSIONS: These results show that only a few risk factors were associated with IMT in this population of healthy peri- and postmenopausal women. These results might be related to the fact that this study was conducted in an area of France well known for having the lowest rates of CHD in women, which is further supported by the thinner IMT found in this population as compared with a higher-risk population. Therefore, these results might not be relevant for CHD in older or high-risk women.

Screening for osteoporosis after breast cancer: for whom, why and when.

Osteoporosis and breast cancer are common diseases in postmenopausal women. Bone and the breast are both estrogenic dependent tissues and different surrogate markers for osteoporosis are opposite of those for the risk of breast cancer. In particular, numerous studies have reported a positive relationship between high bone mineral density (BMD) and a greater risk of breast cancer. On the other hand, most treatments in early breast cancer women including ovarian suppression treatments (chemotherapy, surgery or GnRH agonists) and aromatase inhibitor (AI) therapy induce a profound and rapid suppression of estrogen levels thereby increasing the rate of bone loss. Nevertheless, their impact on the risk of fracture is still questionable, especially in postmenopausal women with no osteoporosis at baseline. The purpose of this minireview is to examine the relationship between breast cancer and the risk of fracture and to discuss a screening strategy for osteoporosis after breast cancer.

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: sensitivity of the WHO FRAX tool.

The aim of this prospective study was (1) to identify significant and independent clinical risk factors (CRFs) for major osteoporotic (OP) fracture among peri- and early postmenopausal women, (2) to assess, in this population, the discriminatory capacity of FRAX and bone mineral density (BMD) for the identification of women at high risk of fracture, and (3) to assess whether adding risk factors to either FRAX or BMD would improve discriminatory capacity. The study population included 2651 peri- and early postmenopausal women [mean age (+/- SD): 54 +/- 4 years] with a mean follow-up period of 13.4 years (+/-1.4 years). At baseline, a large set of CRFs was recorded, and vertebral BMD was measured (Lunar, DPX) in all women. Femoral neck BMD also was measured in 1399 women in addition to spine BMD. Women with current or past OP treatment for more than 3 months at baseline (n = 454) were excluded from the analyses. Over the follow-up period, 415 women sustained a first low-energy fracture, including 145 major OP fractures (108 wrist, 44 spine, 20 proximal humerus, and 13 hip). In Cox multivariate regression models, only 3 CRFs were significant predictors of a major OP fracture independent of BMD and age: a personal history of fracture, three or more pregnancies, and current postmenopausal hormone therapy. In the subsample of women who had a hip BMD measurement and who were not receiving OP therapy (including hormone-replacement therapy) at baseline, mean FRAX value was 3.8% (+/-2.4%). The overall discriminative value for fracture, as measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC), was equal to 0.63 [95% confidence interval (CI) 0.56-0.69] and 0.66 (95% CI 0.60-0.73), respectively, for FRAX and hip BMD. Sensitivity of both tools was low (ie, around 50% for 30% of the women classified as the highest risk). Adding parity to the predictive model including FRAX or using a simple risk score based on the best predictive model in our population did not significantly improve the discriminatory capacity over BMD alone. Only a limited number of clinical risk factors were found associated with the risk of major OP fracture in peri- and early postmenopausal women. In this population, the FRAX tool, like other risk scores combining CRFs to either BMD or FRAX, had a poor sensitivity for fracture prediction and did not significantly improve the discriminatory value of hip BMD alone.

Osteoporosis in otherwise healthy perimenopausal and early postmenopausal women: physical and biochemical characteristics.

Population studies have shown that about 3-5% of perimenopausal women already have osteoporosis according to the WHO definition of osteoporosis for postmenopausal women ( t -score