Reproductive Health of Young Adult Women Who Have Sickle Cell Disease

患有镰状细胞病的年轻成年女性的生殖健康

基本信息

批准号：
10216318
负责人：
Penelope P. Howards
金额：
$ 23.4万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216318
关键词：
Address Adolescent Adult Affect African American Age Amenorrhea Anovulation Anterior Pituitary Gland Birth Blood Blood Transfusion Bone Density Cancer Survivor Cardiovascular Diseases Caring Child Childhood Chronic Chronic Disease Clinic Clinical Counseling Country Data Disease Disease Outcome Failure Feeling Ferritin Fertility Fertility Study Fetal Hemoglobin Goals Gonadal Hormones Hemoglobin Hemoglobin concentration result Hospitals Hypothalamic structure Impairment Individual Infertility Interview Iron Iron Overload Klinefelter&apos s Syndrome Knowledge Length Life Lupus Measures Medical Medical Records Menopause Oncology Oocytes Organ Osteoporosis Ovary Parents Patients Physicians Pituitary Gland Population Positioning Attribute Pregnancy Pregnancy Complications Pregnancy Outcome Premature Menopause Prevalence Production Quality of life Recommendation Recording of previous events Reporting Reproductive Health Reproductive Medicine Research Risk Sampling Serum Sexual Dysfunction Sickle Cell Anemia Societies Sperm Count Procedure Spermatogenesis Time Time Study Tissues Toxic effect Transfusion Unsafe Sex Vulnerable Populations Woman Women&apos s Group Work adverse pregnancy outcome aged base beta Thalassemia common treatment comparison group diminished ovarian reserve early onset evidence base experience fertility preservation hydroxyurea hypothalamic pituitary ovarian axis interest involuntary childlessness man men metropolitan mullerian-inhibiting hormone ovarian reserve patient population population based pregnant public health relevance recruit reproductive reproductive hormone sickling young adult

项目摘要

Project Summary Improvements in medical care have transitioned sickle cell disease (SCD) from a disease of childhood into a long-term chronic illness. As people who have SCD become adults, parenthood becomes an important life goal for many, but little is known about their reproductive potential. Hydroxyurea, a common treatment for SCD, has been associated with decreased sperm count, but parallel studies of ovarian reserve in adult women do not exist. Ovarian reserve decreases naturally as women approach menopause, but gonadotoxic treatments may accelerate the onset of menopause resulting in a shortened period in which to have children as well as earlier onset of menopause sequelae such as sexual dysfunction, cardiovascular disease, and low bone density. Blood transfusion is also an important therapy for SCD, but repeated transfusions (chronic or episodic) result in iron overload, the accumulation of iron in some organs and tissues. In women with transfusion-dependent β- thalassemia, this has been associated with decreased ovarian reserve, which may reflect iron accumulation in the ovary. Further, iron toxicity to the anterior pituitary may impair production of gonadal hormones. A study of iron overload in adolescents with SCD and studies of women with transfusion-dependent β-thalassemia appear to support this possibility. Further, in women with transfusion-dependent β-thalassemia, the prevalence of hypogonadotropic hypogonadism and amenorrhea are high. Thus, there are plausible mechanisms by which SCD treatments and complications may shorten the reproductive window of women with SCD and affect their fertility, but there are almost no studies of reproductive health in this vulnerable population. We will address this gap through the following aims: 1) We will determine whether women with SCD have lower ovarian reserve than women without SCD and 2) We will determine whether women with SCD are at increased risk of infertility compared with women without SCD. We will evaluate these aims by iron overload status and by treatment with hydroxyurea. We are uniquely positioned to complete the proposed work because we will recruit women from the Grady Hospital Comprehensive SCD Clinic, which serves the largest SCD patient population in the country. Further, we will build on our extensive prior experience studying reproductive health in cancer survivors and in women with lupus. Women with SCD, predominately African American women living in metropolitan Atlanta, will be compared with a population-based sample of African American women living in metropolitan Atlanta that we recruited previously. We will assess ovarian reserve based on serum anti-Müllerian hormone. Infertility will be defined several ways including as not getting pregnant after 12 months of regular, unprotected intercourse. Our previously developed, in-depth interview will provide information on infertility and potential confounders. We will abstract hydroxyurea, iron overload, and SCD care information from medical records. Study results will provide physicians with evidence-based information to counsel women about how SCD care affects their reproductive health.

项目概要医疗保健的进步已将镰状细胞病 (SCD) 从一种儿童疾病转变为一种常见疾病随着 SCD 患者成年，为人父母成为一个重要的人生目标。对于许多人来说，但对其生殖潜力知之甚少。羟基脲是 SCD 的常见治疗方法。与精子数量减少有关，但对成年女性卵巢储备的平行研究并未发现当女性接近更年期时，卵巢储备自然减少，但性腺毒性治疗可能存在。加速更年期的到来，导致生育时间缩短以及提前出现性功能障碍、心血管疾病、骨密度低等更年期后遗症。输血也是 SCD 的重要治疗方法，但反复输血（慢性或偶发性）会导致铁超载，即患有输血依赖性β-的女性某些器官和组织中铁的积累。地中海贫血，这与卵巢储备功能下降有关，这可能反映了体内铁的积累此外，铁对垂体前叶的毒性可能会损害性腺激素的产生。患有 SCD 的青少年铁超负荷以及对输血依赖性 β 地中海贫血女性的研究此外，在患有输血依赖性β-地中海贫血的女性中，患病率似乎也支持这种可能性。促性腺激素低下性腺功能减退症和闭经的发生率很高，因此，存在可能的机制。 SCD 治疗和并发症可能会缩短 SCD 女性的生育窗口并影响她们的生育能力。生育率，但几乎没有针对这一弱势群体的生殖健康的研究。通过以下目标来弥补这一差距：1) 我们将确定患有 SCD 的女性卵巢储备功能是否较低与没有 SCD 的女性相比，并且 2) 我们将确定患有 SCD 的女性不孕的风险是否增加与没有 SCD 的女性相比，我们将通过铁过载状态和治疗来评估这些目标。我们具有独特的优势来完成拟议的工作，因为我们将从中招募女性。格雷迪医院综合 SCD 诊所为全国最大的 SCD 患者群体提供服务。此外，我们将利用我们之前研究癌症幸存者和生殖健康的丰富经验。患有狼疮的女性，主要是居住在亚特兰大大都市的非裔美国女性，将与居住在亚特兰大大都市的非裔美国女性的人口样本进行比较我们将根据血清抗苗勒氏管激素来评估卵巢储备。定义有多种，包括在 12 个月的定期、无保护性交后未怀孕。我们之前开发的深入访谈将提供有关不孕症和潜在混杂因素的信息。我们将从医疗记录中提取羟基脲、铁过载和 SCD 护理信息。向医生提供基于证据的信息，向女性提供关于 SCD 护理如何影响她们的建议生殖健康。