Reproductive Hormonal Alterations in Obesity

Summary

The purpose of this study is to determine why obese women have lower hormone levels and less fertility than women of normal body weight. The proposal will examine the reproductive system at the level of the brain and the ovary to define the changes that happen leading to lowered hormone production. Women will be studied throughout a menstrual cycle and given medications that will test how well their pituitary gland can make hormones that stimulate the ovary (luteinizing hormone (LH) and follicle stimulating hormone (FSH)). They will also be given a medication to abolish estrogen production in the body and their response to this medication will be assessed. Finally, the ovary's ability to produce progesterone after ovulation will be examined. --Hypotheses: 1. Obese women have reduced pituitary sensitivity to exogenous gonadotropin-releasing hormone (GnRH), but normal clearance of exogenous LH. (comparative study of obese compared to normal weight women) 2. Obese women have abnormally increased sensitivity to estradiol negative feedback which will be reversed by an aromatase inhibitor. (comparative study of obese compared to normal weight women)

Timeline

Start

2010-06

Primary completion

2013-07

Completion

2013-07

Publications

• Background Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. doi: 10.1210/jc.2006-2274. Epub 2007 Apr 17.
• Background Haynes G, Bailey MK, Davis S, Mahaffey JE. Use of methylprednisolone in epidural analgesia. Arch Neurol. 1989 Nov;46(11):1167-8. doi: 10.1001/archneur.1989.00520470017014. No abstract available.
• Background Rochester D, Jain A, Polotsky AJ, Polotsky H, Gibbs K, Isaac B, Zeitlian G, Hickmon C, Feng S, Santoro N. Partial recovery of luteal function after bariatric surgery in obese women. Fertil Steril. 2009 Oct;92(4):1410-1415. doi: 10.1016/j.fertnstert.2008.08.025. Epub 2008 Sep 30.
• Background Santen RJ, Bardin CW. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest. 1973 Oct;52(10):2617-28. doi: 10.1172/JCI107454.
• Roth LW, Allshouse AA, Lesh J, Polotsky AJ, Santoro N. The correlation between self-reported and measured height, weight, and BMI in reproductive age women. Maturitas. 2013 Oct;76(2):185-8. doi: 10.1016/j.maturitas.2013.07.010. Epub 2013 Aug 16.

Drugs

Indications