Oral Contraceptive Use and Fractures Around the Menopausal Transition

描述(申请人提供)：在美国，大约有4500万人患有骨质疏松症或骨量不足，估计每年有150万人发生骨质疏松性骨折。女性承担着不成比例的骨折费用和后果负担，部分原因是更年期前后荷尔蒙的变化会增加骨折的风险。联合口服避孕药(OCS)是美国和世界范围内领先的避孕方法，目前可能是美国女性最常见的荷尔蒙外源性暴露。由于最近建议的变化，妇女晚年生育年限的使用量可能会增加。虽然新出现的证据表明，围绝经期使用OC对骨量有好处，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的好处和风险的关键证据差距。我们建议进行一项基于人群的病例对照研究，以评估在晚育年中(年龄40岁)使用OC是否与绝经前后发生骨折的风险有关。作为评估这种联系的一部分，我们还将探索其他使用OC的模式，例如早期使用和长期使用，以及与这种骨折结果相关的其他因素。病例和对照(n=3,400)将从健康维护组织参与者的特定人群中招募。病例(n=1700)将是年龄在45-59岁的女性，她们被诊断为在选定的解剖部位被医生判定为意外骨折。控制组将是从健康计划登记数据库中随机选择的同等数量的年龄相仿的没有骨折的妇女。数据将通过标准化的电话管理访谈从病例和对照中获得。将调查参与者在晚年生殖生活中使用OC的类型和模式；其他OC使用和激素暴露；以及其他骨折风险因素。从1977年起，计算机化的药房数据可以作为OC和药物暴露的另一个来源。将对围绝经期OC使用、近期、持续时间和其他OC暴露模式的病例和对照进行比较分析，以达到研究目的。肌肉骨骼疾病是老年人残疾的主要原因。即使骨折比率的微小变化也会对公众健康产生重大影响。中年期间使用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好处很重要。公共卫生相关性：骨折发生率是公共卫生非常关注的问题，在绝经后激素变化后对妇女的影响不成比例。美国妇女广泛使用口服避孕药(OCS)，这使得了解这种荷尔蒙暴露对骨折风险的可能影响至关重要，特别是在接近更年期时使用和使用当前类型的OCS的影响。即使使用OC引起的骨折的微小增加或减少也可能对临床实践和更年期及更年期妇女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.