Sex Hormones and Blood PCSK9 Levels

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00848276
Recruitment Status : Completed
First Posted : February 20, 2009
Last Update Posted : December 8, 2010
Heart and Stroke Foundation of Ontario
Information provided by:
Ottawa Hospital Research Institute

Brief Summary:

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 or disease

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.

Study Type : Observational
Actual Enrollment : 61 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Human Studies On Gender Differences In PCSK9 Function In Lipoprotein Metabolism
Study Start Date : July 2008
Actual Primary Completion Date : September 2010
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Hypogonadal Men before and after starting testosterone replacement therapy
Post-menopausal women before and after starting Estrogen Replacement Therapy

Biospecimen Retention:   Samples Without DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Primary care clincs

Inclusion Criteria:


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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00848276

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: T.C. Ooi, Ottawa Hospital Research Institute Identifier: NCT00848276     History of Changes
Other Study ID Numbers: 2008138-01H
First Posted: February 20, 2009    Key Record Dates
Last Update Posted: December 8, 2010
Last Verified: December 2010

Keywords provided by Ottawa Hospital Research Institute:
Lipoprotein metabolism

Additional relevant MeSH terms:
Lipid Metabolism Disorders
Metabolic Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs