Oral Contraceptive Use and Fractures Around the Menopausal Transition

描述（由申请人提供）：在美国，大约4500万人患有骨质疏松症或低骨量，估计每年发生150万例骨质疏松性骨折。女性在骨折的成本和后果方面承担了不成比例的负担，部分原因是更年期荷尔蒙的变化增加了骨折的风险。复方口服避孕药（OC）是美国和全球领先的避孕方法，目前可能是美国女性最常见的激素外源性暴露。由于最近建议的变化，育龄妇女中的使用可能会增加。虽然新出现的证据表明使用围绝经期OC对骨量有益，但目前OC制剂对骨折的影响尚不清楚。世界卫生组织最近的一份报告指出，这是关于使用OC的益处和风险的关键证据差距。我们提出了一项基于人群的病例对照研究，以评估在生育后期（年龄>40岁）使用OC是否与绝经前后发生骨折的风险相关。作为评估这种相关性的一部分，我们还将探讨OC使用的其他模式，如早期使用和长期使用，以及与这种骨折结局相关的其他因素。病例组和对照组（n= 3，400）将从健康维护组织登记的特定人群中招募。病例（n= 1，700）为45-59岁的女性，诊断为在选定解剖部位发生医生裁定的偶发骨折。对照组是从健康计划登记数据库中随机选择的相同数量的年龄相似的无骨折妇女。数据将通过标准化的电话访谈从病例组和对照组中获得。参与者将被调查的类型和模式的OC使用在以后的生殖生活;其他OC使用和激素暴露;和其他风险因素骨折。从1977年起，计算机化药房数据可作为OC和药物暴露的额外来源。将进行比较病例和对照组在围绝经期OC使用、近期、持续时间和其他OC暴露模式方面的分析，以解决研究目的。肌肉骨骼疾病是老年人残疾的主要原因。即使骨折率的微小变化也会对公共卫生产生重要影响。在中年使用OC是一个可改变的因素，这项研究对确定这些药物的风险或益处很重要。公共卫生相关性：骨折率是一个重大的公共卫生问题，对绝经后荷尔蒙变化的妇女的影响尤为严重。美国妇女广泛使用口服避孕药（OC），这使得了解这种激素暴露对骨折风险的可能影响至关重要，特别是接近绝经期使用和使用当前类型的OC的影响。即使是OC使用导致的骨折的小幅增加或减少，也可能对临床实践和绝经期及以后女性骨折的公共卫生负担产生重要影响。

DESCRIPTION (provided by applicant): In the U.S., approximately 45 million individuals have osteoporosis or low bone mass, and an estimated 1.5 million osteoporotic fractures occur annually. Women bear a disproportionate burden of the costs and consequences of fracture, in part because the hormonal changes around menopause heighten fracture risk. Combined oral contraceptives (OCs), the leading method of contraception in the U.S. and worldwide, may currently represent the most common hormonal exogenous exposure for U.S. women. Use among women in their later reproductive years may be increasing due to recent changes in recommendations. While emerging evidence suggests benefits to bone mass from perimenopausal OC use, the effects on fracture of present-day OC formulations are unknown. A recent report from the World Health Organization notes this as a key evidence gap regarding the benefits and risks of OC use. We propose a population-based case-control study to evaluate whether OC use during later reproductive years (age >40 years ) is associated with the risk of fractures occurring around the time of menopause. As part of evaluating this association, we will also explore other patterns of OC use, such as early use and long-term use, and other factors associated with this fracture outcome. Cases and controls (n=3,400) will be recruited from a defined population of health maintenance organization enrollees. Cases (n=1,700) will be women 45-59 years of age who are diagnosed with incident physician adjudicated fractures at selected anatomic sites. Controls will be an equal number of age-similar women without fracture, selected randomly from the health plan enrollment databases. Data will be obtained from cases and controls via a standardized telephone-administered interview. Participants will be surveyed regarding types and patterns of OC use during later reproductive life; other OC use and hormonal exposures; and other risk factors for fracture. Computerized pharmacy data are available from 1977 forward as an additional source of OC and medication exposure. Analyses comparing cases and controls with respect to perimenopausal OC use, recency, duration, and other patterns of OC exposure will be conducted to address the study aim. Musculoskeletal disease is the major cause of disability in older persons. Even small changes in the rate of fractures have important public health implications. OC use during middle age is a modifiable factor and this research is important to defining the risks or benefits of these medications. PUBLIC HEALTH RELEVANCE: Fracture rates are of great public health concern and disproportionately affect women after the hormonal changes accompanying menopause. The widespread use of oral contraceptives (OCs) by U.S. women makes understanding the possible effects of this hormonal exposure on fracture risk critical, particularly effects of use close to menopause and use of current types of OCs. Even a small increase or decrease in fracture resulting from OC use could have important implications for clinical practice and for the public health burden of fracture in women transitioning through menopause and beyond.