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（由适用提供）：神经性厌食症（AN）影响美国的0.5-1％的大学妇女，其特征是极端，自我诱发的饥饿。在与严重骨质流失相关的许多医疗合并症中，最常见的是目的地重量恢复。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，与年龄匹配的对照相比，患有骨折风险的女性增加了7倍。因此，预防与AN相关的严重骨质流失的治疗是至关重要的，但目前尚无批准的与AN相关骨质流失的治疗方法。闭经和由此产生的低雌激素血症是AN女性的特征发现，是该疾病中骨骼质量丧失的重要贡献者。这一事实支持了这一事实，即闭经的持续时间与An的女性中的骨矿物质密度（BMD）成反比。然而，尽管有这种关联，但调查口服雌激素对患有A的女性的影响的初步研究并未证明有益。这可能是由于口服雌激素抑制IGF -I的产生的事实 - 骨形成的重要介质。重要的是，IGF-I是一种营养介导的马酮，患有AN的女性的水平已经很低，而这些低水平是导致低骨量的重要因素。因此，通过口服雌激素进一步抑制IGF-I会加剧骨骼质量的损失。与口服雌激素不同，经皮雌激素没有相同的IGF-1抑制作用，并且在健康的绝经后女性妇女雌激素中，雌激素会增加IGF-I水平。与青少年相比，骨雌激素在患有骨骼更新的青少年女孩中会增加雌激素的BMD，因为透皮雌激素是否会改善年龄较大的，绝经前女性的BMD，目前尚不清楚。 Fazeli博士是哈佛医学院医学助理教授，也是马萨诸塞州综合医院（MGH）的医学助理。她是MGH神经内分泌部门的工作人员，并将大部分时间用于临床研究。她得到了MGH的良好支持，并可以完全访问神经内分泌部门，临床研究中心和哈佛催化剂CTSC资源。她的联合官员，博士。安妮·克里班斯基（Anne Klibanski）和玛丽·布克森（Mary Bouxsein）获得了充分的资金，并投入了Fazeli博士的研究方向。在获得K23奖的过程中，Fazeli博士已经在哈佛公共卫生学院获得了生物统计学和研究设计的重要培训，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Teriparatide对BMD的影响（她的K23奖的特定AIM 1）。如果获得授予，则该赠款将支持Fazeli博士获得R01申请调查的关键初步数据 teriparatide和透皮雌激素替代的影响对年龄较大，绝经前女性的骨矿物质密度的影响。