Kling Juliana M, Dowling N Maritza, Bimonte-Nelson Heather A, Gleason Carey E, Kantarci Kejal, Manson JoAnn E, Taylor Hugh S, Brinton Eliot A, Lobo Rogerio A, Cedars Marcelle I, Pal Lubna, Neal-Perry Genevieve, Naftolin Frederick, Harman S Mitchell, Miller Virginia M
Division of Women's Health Internal Medicine, Mayo Clinic, Scottsdale, Arizona.
Department of Acute and Chronic Care, School of Nursing, Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, D.C.
Am J Physiol Regul Integr Comp Physiol. 2019 Dec 1;317(6):R912-R920. doi: 10.1152/ajpregu.00234.2019. Epub 2019 Oct 30.
Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of postmenopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45 ± 2.49 yr of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE; = 109), transdermal 17β-estradiol (t-E2; = 107), or placebo ( = 146). Androstenedione, testosterone, 17β-estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum before (baseline) and 48 mo after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE, t-E2, and placebo on these hormone levels at 48 mo, adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 mo within treatment groups. As expected, at 48 mo of treatment, hormone levels differed between women in the two active treatment groups compared with placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups compared with placebo. Associations among testosterone, 17β-estradiol, FSH, and LH differed between the o-CEE group compared with t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and interhormonal associations in recently menopausal women. These interactions provide the basis for future studies investigating the impact of hormonal modulation of aging, including cognitive decline in women.
围绝经期过渡期间垂体 - 卵巢激素的变化具有多种生理后果。然而，对于绝经后主要类型的激素疗法（HT）如何影响垂体 - 卵巢激素关系，我们知之甚少。本研究在Kronos早期雌激素预防研究（KEEPS）中，对近期绝经的女性（年龄52.45±2.49岁）进行了评估，这些女性接受了口服结合马雌激素（o - CEE；n = 109）、经皮17β - 雌二醇（t - E2；n = 107）或安慰剂（n = 146）的随机双盲治疗。在随机分组接受治疗前（基线）和治疗48个月后，测定血清中的雄烯二酮、睾酮、17β - 雌二醇、雌酮、促卵泡激素（FSH）和促黄体生成素（LH）。对激素水平进行了描述性总结，并使用多元回归分析来检验o - CEE、t - E2和安慰剂在48个月时对这些激素水平的影响，并对基线水平进行了校正。网络分析研究了治疗组内48个月内激素水平变化的协方差。正如预期的那样，在治疗48个月时，与安慰剂相比，两个活性治疗组女性的激素水平存在差异，并且网络分析表明，与安慰剂相比，t - E2组和o - CEE组中激素水平之间的关系更强。与t - E2组和安慰剂组相比，o - CEE组中睾酮、17β - 雌二醇、FSH和LH之间的关联有所不同。因此，两种常见的HT方案会不同程度地改变垂体 - 卵巢激素水平，改变近期绝经女性的反馈循环和激素间关联。这些相互作用为未来研究激素调节衰老的影响提供了基础，包括女性认知能力下降。
