Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women

J Clin Endocrinol Metab. 2015 Nov;100(11):4372-81. doi: 10.1210/jc.2015-1946. Epub 2015 Oct 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Cytokines / metabolism*
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Estrogens / urine
  • Female
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / metabolism
  • Gonadotropins / physiology*
  • Humans
  • Hypogonadism / metabolism
  • Hypogonadism / physiopathology
  • Hypothalamo-Hypophyseal System / drug effects
  • Luteinizing Hormone / blood
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Progesterone / urine
  • Young Adult


  • Cytokines
  • Estrogens
  • Gonadotropins
  • Gonadotropin-Releasing Hormone
  • Progesterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone