Early natural menopause is associated with poor lung health and increased mortality among female smokers,American Journal of Obstetrics and Gynecology

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Early natural menopause is associated with poor lung health and increased mortality among female smokers
American Journal of Obstetrics and Gynecology ( IF 9.8 ) Pub Date : 2022-08-04 , DOI: 10.1016/j.ajog.2022.07.031
Ting Zhai ₁ , Brenda Diergaarde ₂ , David O Wilson ₃ , Huining Kang ₄ , Akshay Sood ₅ , Samuel H Bayliss ₅ , Jian-Min Yuan ₆ , Maria A Picchi ₇ , Qing Lan ₈ , Steven A Belinsky ₉ , Jill M Siegfried ₁₀ , Linda S Cook ₁₁ , Shuguang Leng ₁₂

Affiliation

Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA.
University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM; Cancer Control and Population Sciences, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM.
Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM.
University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Lung Cancer Program, Lovelace Biomedical Research Institute, Albuquerque, NM.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Cancer Control and Population Sciences, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; Lung Cancer Program, Lovelace Biomedical Research Institute, Albuquerque, NM.
Department of Pharmacology, University of Minnesota, Minneapolis, MN; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA.
Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz, Arora, CO.
Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM; Cancer Control and Population Sciences, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; Lung Cancer Program, Lovelace Biomedical Research Institute, Albuquerque, NM.

Background

Early natural menopause has been regarded as a biomarker of reproductive and somatic aging. Cigarette smoking is the most harmful factor for lung health and also an established risk factor for early menopause. Understanding the effect of early menopause on health outcomes in middle-aged and older female smokers is important to develop preventive strategies.

Objective

This study aimed to examine the associations of early menopause with multiple lung health and aging biomarkers, lung cancer risk, and all-cause and cause-specific mortality in postmenopausal women who were moderate or heavy smokers.

Study Design

This study was conducted on postmenopausal women with natural (n=1038) or surgical (n=628) menopause from the Pittsburgh Lung Screening Study. The Pittsburgh Lung Screening Study is a community-based research cohort of current and former smokers, screened with low-dose computed tomography and followed up for lung cancer. Early menopause was defined as occurring before 45 years of age. The analyses were stratified by menopause types because of the different biological and medical causes of natural and surgical menopause. Statistical methods included linear model, generalized linear model, linear mixed-effects model, and time-to-event analysis.

Results

The average age of the 1666 female smokers was 59.4±6.7 years, with 1519 (91.2%) of the population as non-Hispanic Whites and 1064 (63.9%) of the population as current smokers at baseline. Overall, 646 (39%) women reported early menopause, including 198 (19.1%) women with natural menopause and 448 (71.3%) women with surgical menopause (P<.001). Demographic variables did not differ between early and nonearly menopause groups, regardless of menopause type. Significant associations were identified between early natural menopause and higher risk of wheezing (odds ratio, 1.65; P<.01), chronic bronchitis (odds ratio, 1.73; P<.01), and radiographic emphysema (odds ratio, 1.70; P<.001) and lower baseline lung spirometry in an obstructive pattern (−104.8 mL/s for forced expiratory volume in the first second with P<.01, −78.6 mL for forced vital capacity with P=.04, and −2.1% for forced expiratory volume in the first second–to–forced vital capacity ratio with P=.01). In addition, early natural menopause was associated with a more rapid decline of forced expiratory volume in the first second–to–forced vital capacity ratio (−0.16% per year; P=.01) and incident airway obstruction (odds ratio, 2.02; P=.04). Furthermore, women early natural menopause had a 40% increased risk of death (P=.023), which was mainly driven by respiratory diseases (hazard ratio, 2.32; P<.001). Mediation analyses further identified that more than 33.3% of the magnitude of the associations between early natural menopause and all-cause and respiratory mortality were explained by baseline forced expiratory volume in the first second. Additional analyses in women with natural menopause identified that the associations between continuous smoking and subsequent lung cancer risk and cancer mortality were moderated by early menopause status, and females with early natural menopause who continued smoking had the worst outcomes (hazard ratio, >4.6; P<.001). This study did not find associations reported above in female smokers with surgical menopause.

Conclusion

Early natural menopause was found to be a risk factor for malignant and nonmalignant lung diseases and mortality in middle-aged and older female smokers. These findings have strong public health relevance as preventive strategies, including smoking cessation and chest computed tomography screening, should target this population (ie, female smokers with early natural menopause) to improve their postmenopausal health and well-being.

中文翻译：

提前自然绝经与女性吸烟者的肺部健康状况不佳和死亡率增加有关

背景

提前自然绝经被认为是生殖和躯体衰老的生物标志物。吸烟是对肺部健康最有害的因素，也是提前绝经的既定危险因素。了解提前绝经对中年和老年女性吸烟者健康结果的影响对于制定预防策略很重要。

客观的

本研究旨在研究中度或重度吸烟的绝经后妇女提前绝经与多种肺部健康和衰老生物标志物、肺癌风险以及全因和特定原因死亡率之间的关系。

学习规划

本研究针对匹兹堡肺部筛查研究中自然绝经 (n=1038) 或手术绝经 (n=628) 的绝经后妇女进行。匹兹堡肺部筛查研究是一项以社区为基础的研究队列，对象是现在和曾经吸烟的人，使用低剂量计算机断层扫描进行筛查，并对肺癌进行随访。提前绝经被定义为发生在 45 岁之前。由于自然和手术绝经的不同生物学和医学原因，分析按绝经类型分层。统计方法包括线性模型、广义线性模型、线性混合效应模型和时间-事件分析。

结果

1666 名女性吸烟者的平均年龄为 59.4±6.7 岁，其中 1519 人 (91.2%) 为非西班牙裔白人，1064 人 (63.9%) 为基线时的当前吸烟者。总体而言，646 名 (39%) 女性报告提前绝经，包括 198 名 (19.1%) 自然绝经女性和 448 名 (71.3%) 手术绝经女性 ( P <.001)。无论绝经类型如何，人口统计学变量在早绝经组和非早绝经组之间没有差异。早期自然绝经与喘息（优势比 1.65；P <.01）、慢性支气管炎（优势比 1.73；P <.01）和影像学肺气肿（优势比 1.70；P<.001) 和较低的阻塞模式肺肺活量测定基线（第一秒用力呼气量 -104.8 mL/s，P <.01，用力肺活量 -78.6 mL，P =.04，以及 -2.1%第一秒用力呼气量与用力肺活量之比，P =.01）。此外，提前自然绝经与第一秒用力肺活量与用力肺活量之比（-0.16%/年；P =.01）和气道阻塞事件（比值比，2.02；P =.04）。此外，提前自然绝经的女性死亡风险增加 40% ( P =.023)，这主要是由呼吸系统疾病引起的（风险比，2.32；P <.001）。中介分析进一步确定，早期自然绝经与全因死亡率和呼吸系统死亡率之间的关联幅度超过 33.3% 可以用第一秒的基线用力呼气量来解释。对自然绝经女性的额外分析表明，持续吸烟与随后的肺癌风险和癌症死亡率之间的关联受到早期绝经状态的调节，而自然绝经早期且继续吸烟的女性结局最差（风险比 > 4.6；P <.001). 这项研究没有发现上述女性吸烟者与手术绝经的关联。