Sex Hormones and Blood PCSK9 Levels

This study has been completed.
Sponsor:
Collaborator:
Heart and Stroke Foundation of Ontario
Information provided by:
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00848276
First received: February 19, 2009
Last updated: December 7, 2010
Last verified: December 2010
  Purpose

This study measures a recently discovered protein named PCSK9 (Proprotein convertase subtilisin kexin 9) in blood to see if it is influenced by male and female sex hormones. PCSK9 has recently been shown to control cholesterol and triglyceride levels by diminishing the ability of liver cells to remove cholesterol from blood leading to high blood cholesterol levels.

It was found in previous studies that there was a relationship between blood levels of PCSK9 and cholesterol in men but not in women. This gender difference is a new finding and it raises the question of whether male and female hormones might influence PCSK9's role as a blood cholesterol regulator.

The study requires a pre-treatment fasting blood sample and another sample 3 months after starting hormone therapy.


Condition
Hypercholesterolemia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Human Studies On Gender Differences In PCSK9 Function In Lipoprotein Metabolism

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Biospecimen Retention:   Samples Without DNA

Serum


Enrollment: 61
Study Start Date: July 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Hypogonadal Men before and after starting testosterone replacement therapy
2
Post-menopausal women before and after starting Estrogen Replacement Therapy

Detailed Description:

Proprotein convertase subtilisin kexin 9 (PCSK9) is a secreted glycoprotein that was first demonstrated to play a role in lipoprotein metabolism in 2003 when several gain-of-function single nucleotide polymorphisms (SNPs) in PCSK9 were shown to associate with autosomal dominant hypercholesterolemia (ADH). Soon after, loss-of-function nonsense and missense SNPs in PCSK9 were shown to associate with hypocholesterolemia. Much is still not known about PCSK9's mechanism of action, its substrate(s), its regulation, and factors affecting its function, but we do know that PCSK9 decreases LDL clearance through degradation of LDL receptors. We examined plasma PCSK9 and serum lipids in182 normolipidemic subjects (98 men, 84 women) and found with Spearman analysis a significant correlation between plasma PCSK9 and total cholesterol (TC), LDL-C, and TC/HDL-C in men but not in women, suggesting a gender difference in PCSK9 regulation and/or function.

Following on our unexpected but novel and exciting observation, we hypothesize: that serum levels of testosterone and estradiol would be significantly correlated with plasma PCSK9 levels, that testosterone and 17-B estradiol replacement therapies in men and women respectively would result in changes in the levels of plasma PCSK9, that testosterone and estradiol modify the effect of PCSK9 on serum lipids in different ways, explaining at least in part, the gender dichotomy in PCSK9 function, and that a significant percentage of the effect of hormone replacement therapy on lipids is mediated through PCSK9 function.

Cohort #1 will be 60 hypogonadal men and cohort #2 will be 60 postmenopausal (hypoestrogenic) women before and after testosterone and estrogen replacement therapy respectively. They will undergo measurements of plasma PCSK9, serum testosterone in men or estradiol in women and TC, triglycerides, HDL-C and LDL-C before and 3 months after starting on replacement therapy. These panel studies will allow us to evaluate whether (a) hormone replacement therapy has an effect on PCSK9, and (b) whether resulting changes in PCSK9 are then associated with lipid response.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Primary care clincs

Criteria

Inclusion Criteria:

Males:

  • 18 years of age and older for hypogonadal males/males with prostate cancer
  • Prior clinical decision to start on testosterone therapy

Females:

  • 30 years of age and older for post-menopausal women
  • Prior clinical decision to start on estrogen therapy

Exclusion Criteria:

  • Cognitive impairment, active or chronic hepatic or renal disease, diagnosed diabetes mellitus,alcohol consumption greater than 4 drinks/day
  • receiving or needing progestogen therapy for women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00848276

Locations
Canada, Ontario
Ottawa Hospital Riverside Campus
Ottawa, Ontario, Canada, K1H 7W9
Sponsors and Collaborators
Ottawa Hospital Research Institute
Heart and Stroke Foundation of Ontario
Investigators
Principal Investigator: Teik Chye Ooi, MBBS Ottawa Hospital Research Institute
  More Information

No publications provided

Responsible Party: T.C. Ooi, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00848276     History of Changes
Other Study ID Numbers: 2008138-01H
Study First Received: February 19, 2009
Last Updated: December 7, 2010
Health Authority: Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
PCSK9
Lipoprotein metabolism
testosterone
estradiol

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 21, 2014