title: Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Zain A
authors.initials: ZA
authors.lastname: Al-Safi
authors.affiliation: 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.
authors.forename: Huayu
authors.initials: H
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Nichole E
authors.initials: NE
authors.lastname: Carlson
authors.affiliation: 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.
authors.forename: Justin
authors.initials: J
authors.lastname: Chosich
authors.affiliation: 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.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lesh
authors.affiliation: 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.
authors.forename: Celeste
authors.initials: C
authors.lastname: Robledo
authors.affiliation: 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.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Bradford
authors.affiliation: 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.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Gee
authors.affiliation: 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.
authors.forename: Tzu
authors.initials: T
authors.lastname: Phang
authors.affiliation: 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.
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.affiliation: 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.
authors.forename: Wendy
authors.initials: W
authors.lastname: Kohrt
authors.affiliation: 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.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Polotsky
mesh_terms: D015502:Absorptiometry, Photon; D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000652:urine; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000502:physiology*; D006801:Humans; D007006:Hypogonadism / Q000378:metabolism / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D011374:Progesterone / Q000652:urine; D055815:Young Adult
chemical_list: D016207:Cytokines; D004967:Estrogens; D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone