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

基本信息

批准号：
9086354
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
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9086354
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 Forteo Fracture Funding General Hospitals Grant Health 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 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 spine bone structure subcutaneous transdermal estrogen treatment response

项目摘要

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) 影响着美国 0.5-1% 的大学女性，其特征是极度的、自我诱发的饥饿，在与 AN 相关的许多医学并发症中，严重的骨质流失是其特征。重要的是，这种骨质流失与骨折风险增加有关；一项前瞻性研究表明，患有 AN 的女性骨折风险比男性高 7 倍。因此，预防与 AN 相关的严重骨质流失的治疗至关重要，但目前还没有批准的治疗方法来治疗 AN 相关的骨质流失和由此导致的低雌激素血症，这是 AN 女性的特征性表现。闭经持续时间与患有 AN 的女性骨矿物质密度 (BMD) 呈负相关，这一事实支持了这一点。尽管如此，初步研究仍调查了口服药物的影响。雌激素在患有 AN 的女性并没有表现出这种益处，这可能是因为口服雌激素抑制了 IGF-I（骨形成的重要介质）的产生，重要的是，IGF-I 是一种营养介导的激素，并且其水平已经很低。患有 AN 的女性，这些低水平是导致低骨量的重要因素，因此口服雌激素抑制 IGF-I 会加剧骨量损失，与口服雌激素不同，透皮雌激素不具有相同的 IGF-I。抑制效应和健康绝经后女性透皮雌激素会增加 IGF-I 水平透皮雌激素会增加患有 AN 的青春期女孩的 BMD，但由于患有 AN 的女性的骨转换与青少年有很大不同，所以透皮雌激素是否会改善患有 AN 的老年绝经前女性的 BMD。 Fazeli 博士是哈佛医学院的医学助理教授和马萨诸塞州总医院 (MGH) 的医学助理，她在 MGH 的神经内分泌科工作，并奉献了大部分工作。她得到了麻省总医院 (MGH) 的大力支持，并可以充分利用神经内分泌科、临床研究中心和哈佛 Catalyst CTSC 资源。她的共同导师 Anne Klibanski 和 Mary Bouxsein 博士资金充足，投资于 Fazeli 博士的研究方向在获得 K23 奖项期间，Fazeli 博士已经在哈佛大学公共卫生学院获得了生物统计学和研究设计方面的重要培训。她还发表了一篇第一作者论文，展示了特立帕肽对患有 AN 的女性 BMD 的影响（她的 K23 奖项的具体目标 1）如果获奖，这笔赠款将支持 Fazeli 博士。获取 R01 应用调查的关键初步数据特立帕肽和透皮雌激素替代疗法对患有 AN 的老年绝经前女性骨矿物质密度的影响。