Zain A Al-Safi1, Huayu Liu1, Nichole E Carlson1, Justin Chosich1, Jennifer Lesh1, Celeste Robledo1, Andrew P Bradford1, Nancy A Gee1, Tzu Phang1, Nanette Santoro1, Wendy Kohrt1, Alex J Polotsky1. 1. Department of Obstetrics and Gynecology (Z.A.A., J.C., J.L., C.R., A.P.B., N.S., W.K., A.J.P.), University of Colorado School of Medicine, Aurora, Colorado 80045; Department of Biostatistics and Informatics (H.L., N.E.C., T.P.), Colorado School of Public Health, Aurora, Colorado 80045; Center for Health and the Environment and California National Primate Research Center (N.A.G.), University of California, Davis, California 95616; and Department of Medicine (W.K.), University of Colorado School of Medicine, Aurora, Colorado 80045.
Abstract
CONTEXT: Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines. OBJECTIVE: We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity. DESIGN, SETTING, AND PARTICIPANTS: This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women. INTERVENTION: A frequent blood-sampling study and one month of daily urinary collection were performed before and after administration of transdermal estradiol 0.1 mg/d for one entire menstrual cycle. MAIN OUTCOME MEASURES: Serum LH and FSH before and after GnRH stimulation, and urinary estrogen and progesterone metabolites were measured. RESULTS: E2 increased LH pulse amplitude and FSH response to GnRH (P = .048, and P < .03, respectively) in obese but not NW women. After E2 priming, ovulatory obese but not NW women had a 25% increase in luteal progesterone (P = .01). Obese women had significantly higher baseline IL-6, IL-10, TGF-β, and IL-12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL-1β, -21% for IL-8, -5% for TGF-β, -5% for IL-12; all P < .05) in obese but not in NW women. CONCLUSIONS: E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.
CONTEXT: Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines. OBJECTIVE: We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity. DESIGN, SETTING, AND PARTICIPANTS: This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women. INTERVENTION: A frequent blood-sampling study and one month of daily urinary collection were performed before and after administration of transdermal estradiol 0.1 mg/d for one entire menstrual cycle. MAIN OUTCOME MEASURES: Serum LH and FSH before and after GnRH stimulation, and urinary estrogen and progesterone metabolites were measured. RESULTS: E2 increased LH pulse amplitude and FSH response to GnRH (P = .048, and P < .03, respectively) in obese but not NW women. After E2 priming, ovulatory obese but not NW women had a 25% increase in luteal progesterone (P = .01). Obesewomen had significantly higher baseline IL-6, IL-10, TGF-β, and IL-12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL-1β, -21% for IL-8, -5% for TGF-β, -5% for IL-12; all P < .05) in obese but not in NW women. CONCLUSIONS: E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obesewomen. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.
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