Reproductive Hormonal Alterations in Obesity

NCT01457703 | Completed Results

• 2 other identifiers: 09-0977U54HD058155
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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.

1. 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. 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)

Conditions

Obesity

Keywords

LH pulsatility; Obesity; Reproduction

Outcome Measures

Primary Outcomes (3)

• Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)

  Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.

  Measured hourly and averaged over the 12 hour study visit

• Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)

  Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.

  Measured hourly and averaged over the 12 hour study visit

• Changes in Pregnanediol Glucuronide (PdG) (Aim 2)

  Pregnanediol glucuronide (PdG) was collected daily over the course of one menstrual cycle and averaged.

  Averaged over the length of menstrual cycle

Secondary Outcomes (2)

• Changes in Follicle Stimulating Hormone (FSH) (Aim 1)

  Measured hourly and averaged over the 12 hour study visit

• Changes in Follicle Stimulating Hormone (FSH) (Aim 2)

  Measured hourly and averaged over the 12 hour study visit

Study Arms (2)

BMI ≥30 kg/m2

ACTIVE COMPARATOR

Group 2: * BMI ≥30 kg/m2 * History of regular menstrual cycles every 25-40 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.

Drug: Cetrorelix; Drug: Gonadorelin-GnRH; Drug: Recombinant LH; Drug: Letrozole

BMI 18-25 kg/m2

EXPERIMENTAL

* BMI 18-25 kg/m2 * History of regular menstrual cycles every 25-35 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.

Drug: Cetrorelix; Drug: Gonadorelin-GnRH; Drug: Recombinant LH; Drug: Letrozole

Interventions

Cetrorelix DRUG

Abolishes pituitary sensitivity to GnRH.

Also known as: Cetrotide

BMI 18-25 kg/m2; BMI ≥30 kg/m2

Gonadorelin-GnRH DRUG

GnRH is used to stimulate the pituitary gland to produce LH and FSH.

Also known as: Lutrepulse

BMI 18-25 kg/m2; BMI ≥30 kg/m2

Recombinant LH DRUG

Used to stimulate ovarian function in women.

Also known as: Luveris

BMI 18-25 kg/m2; BMI ≥30 kg/m2

Letrozole DRUG

An aromatase inhibitor.

Also known as: Femara

BMI 18-25 kg/m2; BMI ≥30 kg/m2

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Clinical Translational Research Center

Aurora, Colorado, 80045, United States

Location

Related Publications (5)

• 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.

  PMID: 17440019 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.

  PMID: 2818247 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.

  PMID: 18829008 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.

  PMID: 4729055 BACKGROUND

• 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.

  PMID: 23958434 DERIVED

Related Links

• PI Biographical data

MeSH Terms

Conditions

Obesity

Interventions

cetrorelix; Gonadotropin-Releasing Hormone; Luteinizing Hormone, beta Subunit; Letrozole

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Luteinizing Hormone; Gonadotropins, Pituitary; Gonadotropins; Pituitary Hormones, Anterior; Pituitary Hormones; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Research Regulatory Manager
• Organization: University of Colorado Denver

Chanel.mansfield@ucdenver.edu

303-724-6501

Study Officials

• Nanette Santoro, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2011
• First Posted: October 24, 2011
• Study Start: June 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: January 12, 2017
• Results First Posted: March 25, 2015

Record last verified: 2016-11

Locations

US (1)