Oral Contraceptive Use and Fractures Around the Menopausal Transition

描述（由申请人提供）：在美国，大约有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上承担着不成比例的负担，部分原因是更年期前后荷尔蒙的变化增加了骨折的风险。联合口服避孕药（OCs）是美国和世界范围内的主要避孕方法，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，生育年龄较晚的妇女的使用可能会增加。虽然新出现的证据表明围绝经期使用骨量有好处，但目前的骨量制剂对骨折的影响尚不清楚。世界卫生组织（World Health Organization）最近的一份报告指出，这是关于使用大麻的好处和风险的一个关键证据缺口。我们提出了一项基于人群的病例对照研究，以评估在生育年龄后期（50 - 40岁）使用卵巢囊肿是否与绝经前后发生骨折的风险相关。作为评估这种关联的一部分，我们还将探讨其他骨臼使用模式，如早期使用和长期使用，以及与骨折结果相关的其他因素。病例和对照（n= 3400）将从健康维护组织注册的确定人群中招募。病例（n=1,700）为45-59岁的女性，在选定的解剖部位被诊断为偶发性骨折。对照组将从健康计划登记数据库中随机选择相同数量的年龄相近但没有骨折的女性。将通过标准化的电话访谈从病例和对照中获得数据。参与者将接受调查，了解在生育后期使用雌激素的类型和模式；其他使用酒精饮料和激素暴露；以及其他导致骨折的危险因素。计算机化的药房数据从1977年开始作为OC和药物暴露的额外来源。将对病例和对照进行分析，比较围绝经期OC的使用、近期、持续时间和其他OC暴露模式，以实现研究目标。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众健康产生重要影响。在中年使用OC是一个可改变的因素，这项研究对于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，对绝经后激素变化的妇女影响尤为严重。口服避孕药（OCs）在美国妇女中的广泛使用，使得了解这种激素暴露对骨折风险的可能影响至关重要，特别是接近绝经期和使用当前类型的口服避孕药的影响。使用骨臼导致骨折的增加或减少即使很小，也可能对临床实践和绝经后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.