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Abstract：
OBJECTIVE: What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause <40 years) and early menopause (EM; menopause 40-44years)?
CONCLUSIONS: Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective.
BACKGROUND: Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women.
METHODS: The Australian Longitudinal Study on Women\'s Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data.
METHODS: Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results.
RESULTS: Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio [OR] 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication.
CONCLUSIONS: Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007.
CONCLUSIONS: This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk.
BACKGROUND: This study was funded by The Australian NHMRC Centre of Research Excellence Women\'s Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin.
BACKGROUND: N/A.
CONCLUSIONS: Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective.
BACKGROUND: Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women.
METHODS: The Australian Longitudinal Study on Women\'s Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data.
METHODS: Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results.
RESULTS: Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio [OR] 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication.
CONCLUSIONS: Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007.
CONCLUSIONS: This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk.
BACKGROUND: This study was funded by The Australian NHMRC Centre of Research Excellence Women\'s Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin.
BACKGROUND: N/A.
摘要：
目的：和预测因子，骨质疏松,骨折,和骨质疏松症管理(调查，治疗）在卵巢早衰（POI；绝经<40年）和绝经早期（EM；绝经40-44年）的女性中？
结论：在23年的随访期间，平均年龄68岁,患有POI/EM的女性有更高的骨质疏松/骨折风险和患病率，与通常绝经年龄的女性相比,骨质疏松症筛查和抗骨质疏松药物的使用率更高;年龄增长预示着骨质疏松症/骨折的风险增加,在进入研究之前或进入研究时(年龄45~50岁),更年期激素治疗(MHT)具有保护作用.
背景：患有POI/EM的女性患骨质疏松症和骨折的风险增加，关于骨密度降低和骨折危险因素的数据有限。临床指南建议对大多数患有POI/EM的女性进行双重X线骨密度仪（DXA）筛查和MHT治疗，以减少骨质疏松症和骨折风险；然而，研究表明骨质疏松症知识的差距，指南摄取，以及临床医生和妇女的管理依从性。
方法：澳大利亚妇女健康纵向研究是对澳大利亚妇女的前瞻性纵向研究。这项研究使用了1946年至1951年之间出生的女性队列，在1996年至2019年之间进行了9次调查。来自澳大利亚行政健康记录的数据，包括住院数据(骨折，骨质疏松症)，医疗保险福利计划(DXA)，和药物福利计划(PBS；MHT，抗骨质疏松药物,仅从2002年起可用)与调查数据相关联。
方法：包括自我报告绝经年龄的调查对象。POI/EM定义为绝经<45岁。使用T检验或卡方进行基线比较(P<0.05表示显著性)。面板数据的广义估计方程探讨了骨质疏松症纵向结果的预测因素，骨折,DXA费率，MHT使用,和抗骨质疏松药物（骨质疏松/骨折妇女，仅从调查4开始)。进行单变量回归，并保留P<0.2的变量，以形成多变量模型，并在原始数据集的95%采样时进行100次重复的自举，以确保结果的鲁棒性。
结果：包括八千六百三名妇女：610（7.1％）患有POI/EM。在整个队列中，平均（SD）基线年龄为47.6（1.45）岁，在POI/EM和正常绝经年龄的女性中，绝经的平均（SD）年龄为38.2（7.95）和51.3（3.04）岁。分别(P<0.001)。23年来,有POI/EM的女性，303（49.7%）有骨质疏松/骨折，421（69.0％）进行了DXA筛查，474曾经使用过MHT（77.7％），116例(39.1%)骨质疏松/骨折患者使用抗骨质疏松药物。通常年龄更年期的女性，2929（36.6%）有骨质疏松/骨折，4920（61.6%）进行了DXA筛查，4014（50.2%）使用MHT，964（33.0％）的骨质疏松症/骨折患者使用了抗骨质疏松症药物。与年龄≥45岁和调整其他危险因素后绝经的女性相比，患有POI/EM的女性患骨质疏松症的风险增加（比值比[OR]1.37;95％CI1.07-1.77），骨折（OR1.45；1.15-1.81），DXA测试（OR1.64；1.42-1.90），MHT使用(OR6.87;5.68-8.30),和抗骨质疏松药物使用（OR1.50;1.14-1.98）。在有POI/EM女性的女性中，年龄增长与骨质疏松症/骨折的风险增加相关（OR1.09;1.08-1.11），和MHT之前或进入研究时（45-50岁），是保护性的（OR0.65，0.45-0.96）。在有POI/EM的女性中，年龄（OR1.11；1.10-1.12），骨折（OR1.80，1.38-2.34），当前吸烟（OR0.60；0.43-0.86），内部(OR0.68;0.53-0.88)或外部区域(OR0.63;0.46-0.87)居住位置与DXA筛查相关.在有POI/EM的女性中，年龄增长（OR1.02；1.01-1.02），目前饮酒（OR1.17；1.06-1.28），与使用过MHT有关。在299名患有POI/EM和骨质疏松症/骨折的女性中，只有39.1%的人曾经接受过抗骨质疏松药物治疗.年龄增加（OR1.07;1.04-1.09）和BMI降低（OR0.95;0.92-0.98）与抗骨质疏松药物治疗的可能性增加相关。
结论：包括绝经年龄在内的调查数据是参与者自我报告的；骨折问题不包括在2001年的调查中，没有询问自我报告的骨折的位置或创伤程度。其他风险/保护因素，如维生素D状态，钙摄入量，和锻炼不能被包括在内。由于样本量,将POI和EM合并进行所有分析，我们无法区分POI/EM的原因。PBS数据仅从2004年开始，入院数据是基于州的，从2007年开始，所有澳大利亚都可以使用。
结论：本研究支持以前的文献表明POI女性患骨质疏松和骨折的风险增加，并为患有POI/EM的女性增加了证据，那里的数据相对缺乏。这是第一项分析POI/EM女性骨质疏松症和骨折的各种临床和人口统计学危险因素的研究，以及分析调查和治疗率。在这些女人身上,在进入研究之前或进入研究时使用MHT，年龄45-50岁，对骨质疏松症/骨折有保护作用；然而，曾经使用过MHT不是，强调在这些女性中早期使用MHT治疗以保持骨骼强度的重要性。尽管患有POI/EM和骨质疏松症或骨折的女性比通常绝经年龄的女性更有可能使用抗骨质疏松症药物，总体治疗率低，<40%，证明了一个显著的治疗差距，应该解决，以降低未来的骨折风险。
背景：这项研究由澳大利亚NHMRC生殖健康研究卓越中心资助（CRE-WHIRL，项目编号APP1171592)。A.R.J.是国家健康与医学研究委员会研究生研究奖学金的获得者（赠款编号1169192）。P.R.E.由国家卫生和医学研究委员会资助1197958。P.R.E.报告从安进公司支付给他们机构的补助金，赛诺菲,和Alexion,安进支付给他们机构的酬金，来自Alexion和Kyowa-Kirin的酬金.
背景：不适用。
结论：在23年的随访期间，平均年龄68岁,患有POI/EM的女性有更高的骨质疏松/骨折风险和患病率，与通常绝经年龄的女性相比,骨质疏松症筛查和抗骨质疏松药物的使用率更高;年龄增长预示着骨质疏松症/骨折的风险增加,在进入研究之前或进入研究时(年龄45~50岁),更年期激素治疗(MHT)具有保护作用.
背景：患有POI/EM的女性患骨质疏松症和骨折的风险增加，关于骨密度降低和骨折危险因素的数据有限。临床指南建议对大多数患有POI/EM的女性进行双重X线骨密度仪（DXA）筛查和MHT治疗，以减少骨质疏松症和骨折风险；然而，研究表明骨质疏松症知识的差距，指南摄取，以及临床医生和妇女的管理依从性。
方法：澳大利亚妇女健康纵向研究是对澳大利亚妇女的前瞻性纵向研究。这项研究使用了1946年至1951年之间出生的女性队列，在1996年至2019年之间进行了9次调查。来自澳大利亚行政健康记录的数据，包括住院数据(骨折，骨质疏松症)，医疗保险福利计划(DXA)，和药物福利计划(PBS；MHT，抗骨质疏松药物,仅从2002年起可用)与调查数据相关联。
方法：包括自我报告绝经年龄的调查对象。POI/EM定义为绝经<45岁。使用T检验或卡方进行基线比较(P<0.05表示显著性)。面板数据的广义估计方程探讨了骨质疏松症纵向结果的预测因素，骨折,DXA费率，MHT使用,和抗骨质疏松药物（骨质疏松/骨折妇女，仅从调查4开始)。进行单变量回归，并保留P<0.2的变量，以形成多变量模型，并在原始数据集的95%采样时进行100次重复的自举，以确保结果的鲁棒性。
结果：包括八千六百三名妇女：610（7.1％）患有POI/EM。在整个队列中，平均（SD）基线年龄为47.6（1.45）岁，在POI/EM和正常绝经年龄的女性中，绝经的平均（SD）年龄为38.2（7.95）和51.3（3.04）岁。分别(P<0.001)。23年来,有POI/EM的女性，303（49.7%）有骨质疏松/骨折，421（69.0％）进行了DXA筛查，474曾经使用过MHT（77.7％），116例(39.1%)骨质疏松/骨折患者使用抗骨质疏松药物。通常年龄更年期的女性，2929（36.6%）有骨质疏松/骨折，4920（61.6%）进行了DXA筛查，4014（50.2%）使用MHT，964（33.0％）的骨质疏松症/骨折患者使用了抗骨质疏松症药物。与年龄≥45岁和调整其他危险因素后绝经的女性相比，患有POI/EM的女性患骨质疏松症的风险增加（比值比[OR]1.37;95％CI1.07-1.77），骨折（OR1.45；1.15-1.81），DXA测试（OR1.64；1.42-1.90），MHT使用(OR6.87;5.68-8.30),和抗骨质疏松药物使用（OR1.50;1.14-1.98）。在有POI/EM女性的女性中，年龄增长与骨质疏松症/骨折的风险增加相关（OR1.09;1.08-1.11），和MHT之前或进入研究时（45-50岁），是保护性的（OR0.65，0.45-0.96）。在有POI/EM的女性中，年龄（OR1.11；1.10-1.12），骨折（OR1.80，1.38-2.34），当前吸烟（OR0.60；0.43-0.86），内部(OR0.68;0.53-0.88)或外部区域(OR0.63;0.46-0.87)居住位置与DXA筛查相关.在有POI/EM的女性中，年龄增长（OR1.02；1.01-1.02），目前饮酒（OR1.17；1.06-1.28），与使用过MHT有关。在299名患有POI/EM和骨质疏松症/骨折的女性中，只有39.1%的人曾经接受过抗骨质疏松药物治疗.年龄增加（OR1.07;1.04-1.09）和BMI降低（OR0.95;0.92-0.98）与抗骨质疏松药物治疗的可能性增加相关。
结论：包括绝经年龄在内的调查数据是参与者自我报告的；骨折问题不包括在2001年的调查中，没有询问自我报告的骨折的位置或创伤程度。其他风险/保护因素，如维生素D状态，钙摄入量，和锻炼不能被包括在内。由于样本量,将POI和EM合并进行所有分析，我们无法区分POI/EM的原因。PBS数据仅从2004年开始，入院数据是基于州的，从2007年开始，所有澳大利亚都可以使用。
结论：本研究支持以前的文献表明POI女性患骨质疏松和骨折的风险增加，并为患有POI/EM的女性增加了证据，那里的数据相对缺乏。这是第一项分析POI/EM女性骨质疏松症和骨折的各种临床和人口统计学危险因素的研究，以及分析调查和治疗率。在这些女人身上,在进入研究之前或进入研究时使用MHT，年龄45-50岁，对骨质疏松症/骨折有保护作用；然而，曾经使用过MHT不是，强调在这些女性中早期使用MHT治疗以保持骨骼强度的重要性。尽管患有POI/EM和骨质疏松症或骨折的女性比通常绝经年龄的女性更有可能使用抗骨质疏松症药物，总体治疗率低，<40%，证明了一个显著的治疗差距，应该解决，以降低未来的骨折风险。
背景：这项研究由澳大利亚NHMRC生殖健康研究卓越中心资助（CRE-WHIRL，项目编号APP1171592)。A.R.J.是国家健康与医学研究委员会研究生研究奖学金的获得者（赠款编号1169192）。P.R.E.由国家卫生和医学研究委员会资助1197958。P.R.E.报告从安进公司支付给他们机构的补助金，赛诺菲,和Alexion,安进支付给他们机构的酬金，来自Alexion和Kyowa-Kirin的酬金.
背景：不适用。
