Reproductive Health of Young Adult Women Who Have Sickle Cell Disease

项目摘要 医疗保健的进步使镰状细胞病(SCD)从一种儿童疾病转变为一种 长期的慢性病。随着患有SCD的人成年，为人父母成为一个重要的人生目标 对许多人来说，但人们对它们的生殖潜力知之甚少。羟基脲是治疗SCD的一种常见方法，它有 与精子数量减少有关，但对成年女性卵巢储备的平行研究没有 是存在的。随着女性接近更年期，卵巢储备自然减少，但性腺激素治疗可能会 加速绝经，缩短生育时间，提早生育 出现更年期后遗症，如性功能障碍、心血管疾病和低骨密度。 输血也是SCD的一种重要治疗方法，但反复输血(慢性或发作性)会导致 铁超载，铁在某些器官和组织中积聚。在患有输血依赖型β的女性中- 地中海贫血，这与卵巢储备减少有关，这可能反映了体内铁的积累 卵巢。此外，铁对脑垂体前叶的毒性可能会损害性腺激素的产生。关于……的研究 青少年系统性红斑狼疮患者的铁超载及输血依赖型β-地中海贫血妇女的研究 似乎支持这种可能性。此外，在患有输血依赖型β-地中海贫血的妇女中， 性腺激素减退、性腺机能减退和闭经发生率高。因此，存在一些合理的机制，通过这些机制 SCD的治疗和并发症可能缩短SCD妇女的生殖窗口，并影响她们的 生育率很高，但几乎没有关于这一弱势群体生殖健康的研究。我们将解决 这一差距通过以下目标：1)我们将确定患有SCD的女性是否卵巢储备较低 2)我们将确定患有SCD的女性是否有更高的不孕风险 与未患SCD的女性相比。我们将通过铁超载状态和通过治疗来评估这些目标 羟基脲。我们处于独特的地位，可以完成拟议的工作，因为我们将从 Grady医院综合SCD诊所，为全国最大的SCD患者提供服务。 此外，我们将建立在我们先前研究癌症幸存者和 患有狼疮的女人。患有SCD的女性，主要是居住在大都市亚特兰大的非裔美国女性， 将与居住在亚特兰大大都市的以人口为基础的非裔美国女性样本进行比较 我们之前招募的。我们将根据血清抗苗勒氏激素来评估卵巢储备。不孕不育会 有几种定义，包括在正常的、无保护的性交12个月后不怀孕。 我们先前开展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尿素、铁超载和SCD护理信息。研究结果将 为医生提供循证信息，为女性提供有关SCD护理如何影响她们 生殖健康。

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.