Gonadotropin response to insulin and lipid infusion reproduces the reprometabolic syndrome of obesity in eumenorrheic lean women: a randomized crossover trial
Autor: | Angela J. Fought, Andrew P. Bradford, Katherine Kuhn, Sara Babcock-Gilbert, Irene E. Schauer, Nanette Santoro |
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Rok vydání: | 2021 |
Předmět: |
Adult
0301 basic medicine endocrine system medicine.medical_specialty medicine.drug_class medicine.medical_treatment 03 medical and health sciences 0302 clinical medicine Bolus (medicine) Thinness Internal medicine medicine Hyperinsulinemia Humans Insulin Obesity Phospholipids Metabolic Syndrome Cross-Over Studies 030219 obstetrics & reproductive medicine business.industry Area under the curve Obstetrics and Gynecology Luteinizing Hormone medicine.disease Crossover study Soybean Oil 030104 developmental biology Endocrinology Reproductive Medicine Emulsions Female Follicle Stimulating Hormone Gonadotropin business Luteinizing hormone Hormone |
Zdroj: | Fertility and Sterility. 116:566-574 |
ISSN: | 0015-0282 |
DOI: | 10.1016/j.fertnstert.2021.03.005 |
Popis: | Objective To study the reprometabolic syndrome in normal-weight, eumenorrheic women by infusing a combination of insulin and lipid. Women with obesity have been shown to have reduced gonadotropins and impaired luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (GnRH). Design Randomized crossover. Setting Academic medical center. Participant(s) Fifteen women, median age 32 (interquartile ranged [IQR] 26, 36) years and body mass index 21.9 (IQR 20.2, 22.9) kg/m2 were recruited. Intervention(s) Early follicular phase, 6-hour infusions of insulin (20–40 mU/m2 per minute) and lipid (Intralipid)—insulin/lipid infusion; or saline infusion (controls). The first 4 hours of each study assessed endogenous gonadotropins; at 4 hours, GnRH (75 ng/kg) bolus was administered and sampling continued until 6 hours. Main Outcome Measure(s) Linear mixed model analysis was used to determine differences between insulin/lipid and saline influence on endogenous LH pulse amplitude (primary outcome), mean FSH, and area under the curve (AUC) response to GnRH (secondary outcomes). Result(s) Twelve women completed both intended studies and an additional 3 women completed only 1 of the 2 studies. LH pulse amplitude, mean FSH, and both AUC responses to GnRH were reduced by insulin/lipid, mean FSH and AUC for LH were at or near statistical significance. LH response to GnRH was significantly reduced when 1 participant with very high LH and antimullerian hormone levels was excluded. Conclusion(s) Acute infusion of insulin/lipid to eumenorrheic, normal-weight women recapitulated the reprometabolic syndrome of obesity. These findings imply that specific circulating factors in obese women contribute to their subfertility and thus may be amenable to discovery and treatment. Clinical Trial Registration Number NCT02653092. |
Databáze: | OpenAIRE |
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