Clinical trial NCT01457703: Reproductive Hormonal Alterations in Obesity
Official title: Reproductive Hormonal Alterations in Obesity, AIMS #1 & #2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: LH pulsatility
Obesity
Reproduction
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2011-10-24
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief 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)

Detailed description: AIM 1: test the hypothesis that reduced pituitary sensitivity to GnRH-induced LH and FSH secretion causes the relative hypogonadotropic hypogonadism of obesity AIM 2: test the hypothesis that the hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity

Eligibility criteria: Inclusion Criteria:

* Aged 18-40 at study entry
* BMI either 18-25 kg/m2 or ≥30 kg/m2
* prolactin (PRL) and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
* Baseline hemoglobin \>11 gm/dl
* History of regular menstrual cycles every 25-35 days if BMI 18-25 kg/m2
* History of regular menstrual cycles every 25-40 days if BMI ≥30 kg/m2

Exclusion Criteria:

* History of chronic disease affecting hormone production, metabolism or clearance
* Use of medications that are known to alter or interact with reproductive hormones (e.g., thiazolidinediones, metformin)
* Use of hormones within three months of enrollment
* Excessive exercise (\>4 hours per week)
* Pregnancy, breast-feeding or current active attempts to conceive

Primary outcomes:
measure: Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
timeFrame: Measured hourly and averaged over the 12 hour study visit
measure: Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)
timeFrame: Measured hourly and averaged over the 12 hour study visit
measure: Changes in Pregnanediol Glucuronide (PdG) (Aim 2)
timeFrame: Averaged over the length of menstrual cycle
Secondary outcomes:
measure: Changes in Follicle Stimulating Hormone (FSH) (Aim 1)
timeFrame: Measured hourly and averaged over the 12 hour study visit
measure: Changes in Follicle Stimulating Hormone (FSH) (Aim 2)
timeFrame: Measured hourly and averaged over the 12 hour study visit
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Clinical Translational Research Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Nanette Santoro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.