Transdermal Estrogen in Older Premenopausal Women with Anorexia Nervosa

经皮雌激素治疗患有神经性厌食症的老年绝经前妇女

• 批准号: 8951933
• 负责人: Pouneh Khadejeh Fazeli
• 金额: $ 8.31万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8951933
• 关键词: Adipose tissue; Adolescence; Adolescent; Adult; Affect; Age; Amenorrhea; Anorexia Nervosa; Area; Award; Biometry; Body Weight decreased; Bone Density; Bone Matrix; Bone Resorption; Characteristics; Clinical Research; Comorbidity; Complication; Data; Disease; Dual-Energy X-Ray Absorptiometry; Elements; Estrogen Replacements; Estrogen Therapy; Estrogens; Fatty acid glycerol esters; Female Adolescents; Finite Element Analysis; Fracture; Funding; General Hospitals; Grant; Hormones; Image; Insulin-Like Growth Factor I; Investigation; Magnetic Resonance Spectroscopy; Marrow; Massachusetts; Master of Public Health; Measures; Mediating; Mediator of activation protein; Medical; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolism; Minerals; Morbidity - disease rate; Neurosecretory Systems; Oral; Osteogenesis; Osteoporosis; Paper; Peripheral; Physiological; Population; Population Control; Postmenopause; Premenopause; Prevalence; Production; Property; Prospective Studies; Public Health Schools; Publishing; Randomized Controlled Trials; Recovery; Research; Research Design; Resolution; Resources; Risk; Role; Starvation; Structure; Techniques; Teriparatide; Therapeutic; Thick; Time; Training; Visceral; Weight; Woman; X-Ray Computed Tomography; aged; bone; bone loss; bone mass; bone strength; bone turnover; catalyst; college; improved; in vivo imaging; intervention effect; medical complication; medical schools; meetings; mortality; open label; prevent; professor; public health relevance; response; spine bone structure; subcutaneous; transdermal estrogen

 DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) affects 0.5-1% of college-aged women in the US and is characterized by extreme, self- induced starvation. Of the many medical co-morbidities associated with AN, severe bone loss is the most common and often persists despite weight recovery. Importantly, this bone loss is associated with an increased risk of fracture; a prospective study demonstrated that women with AN have a 7-fold increased risk of fracture compared to age-matched controls. Therefore, a treatment to prevent the severe bone loss associated with AN is critical, but there are currently no approved treatments for AN-associated bone loss. Amenorrhea and resultant hypoestrogenemia, which are characteristic findings in women with AN, are significant contributors to the loss of bone mass in this disease. This is supported by the fact that duration of amenorrhea is inversely associated with bone mineral density (BMD) in women with AN. Yet, despite this association, initial studies investigating the effects of oral estrogen in women with AN did not demonstrate a benefit. This is likely due to the fact that oral estrogen suppresses production of IGF-I - an important mediator of bone formation. Importantly, IGF-I is a nutritionally-mediated hormone and levels are already low in women with AN and these low levels are an important contributing factor to the low bone mass. Therefore further suppression of IGF-I by oral estrogen can exacerbate the loss of bone mass. Unlike oral estrogen, transdermal estrogen does not have the same IGF-I-suppressing effects and in healthy, postmenopausal women transdermal estrogen increases IGF-I levels. Transdermal estrogen increases BMD in adolescent girls with AN but because bone turnover is quite different in women with AN compared to adolescents, whether transdermal estrogen will improve BMD in older, premenopausal women with AN is currently unknown. Dr. Fazeli is an Assistant Professor of Medicine at Harvard Medical School and Assistant in Medicine at Massachusetts General Hospital (MGH). She is on staff in the Neuroendocrine Unit at MGH and devotes the majority of her time to clinical research. She is well-supported by MGH and has full access to the Neuroendocrine Unit, Clinical Research Center and Harvard Catalyst CTSC resources. Her co-mentors, Drs. Anne Klibanski and Mary Bouxsein, are well-funded and invested in the direction of Dr. Fazeli's research. During the course of her K23 award, Dr. Fazeli has already obtained critical training in biostatistics and research design at the Harvard School of Public Health, from which she earned a Master of Public Health degree. She has also published a first-author paper demonstrating the effects of teriparatide on BMD in women with AN (Specific Aim 1 of her K23 award). If awarded, this grant will support Dr. Fazeli in obtaining critical preliminary data for an R01 application investigating the effects of teriparatide and transdermal estrogen replacement on bone mineral density in older, premenopausal women with AN.

 描述(由申请人提供)：神经性厌食症(AN)影响美国0.5%-1%的大学年龄女性，其特征是极度的自我诱导饥饿。在许多与AN相关的医学合并症中，严重的骨丢失是最常见的，而且在体重恢复的情况下通常会持续存在。重要的是，这种骨丢失与骨折风险的增加有关；一项前瞻性研究表明，与年龄匹配的对照组相比，患有骨质疏松症的女性骨折风险增加了7倍。因此，预防与AN相关的严重骨丢失的治疗是至关重要的，但目前还没有批准的治疗与AN相关的骨丢失的方法。闭经和由此导致的低雌激素血症是女性AN的特征表现，是导致这种疾病骨量丢失的重要因素。这一事实得到了以下事实的支持：在患有AN的女性中，闭经时间与骨密度(BMD)呈负相关。然而，尽管存在这种联系，调查口服雌激素对患有AN的女性的影响的初步研究并未显示出益处。这可能是因为口服雌激素抑制了IGF-I的产生--IGF-I是骨形成的重要介质。重要的是，IGF-I是一种营养调节的激素，在患有AN的女性中水平已经很低，这些低水平是导致低骨量的重要因素。因此，口服雌激素进一步抑制IGF-I可能会加剧骨量的丢失。与口服雌激素不同，经皮雌激素不具有同样的IGF-I抑制作用，而在健康的绝经后妇女中，经皮雌激素会提高IGF-I水平。经皮雌激素增加了患有AN的青春期女孩的骨密度，但由于与青少年相比，患有AN的女性的骨转换非常不同，目前尚不清楚经皮雌激素是否会改善患有AN的老年、绝经前女性的BMD。Fazeli博士是哈佛医学院医学助理教授和马萨诸塞州综合医院(MGH)医学助理。她是麻省理工学院神经内分泌科的工作人员，大部分时间都致力于临床研究。她得到了MGH的良好支持，并拥有完全访问神经内分泌科、临床研究中心和哈佛大学催化剂CTSC资源的权限。她的联合导师Anne Klibanski博士和Mary Bouxsein博士资金充足，并在Fazeli博士的研究方向上进行了投资。在获得K23奖项的过程中，法泽利博士已经在哈佛大学公共卫生学院接受了生物统计学和研究设计方面的重要培训，并从中获得了公共卫生硕士学位。她还发表了一篇第一作者论文，展示了特雷帕拉特对女性骨密度的影响(她的K23奖的具体目标1)。如果获奖，这笔赠款将支持法泽利博士为R01申请调查获得关键的初步数据 特瑞帕特和经皮雌激素替代治疗对患有AN的老年绝经前妇女骨密度的影响。