DHEA Replacement in Adrenalectomized/Hypoadrenal Patients

Assessing the Effects of Dehydroepiandrosterone Replacement on the Mood of Adrenalectomised/Hypoadrenal Subjects

The role of dehydroepiandosterone (DHEA) and its sulphated ester (DHEAS) [together known as DHEA(S)] in humans remains to be fully elucidated. They are the most abundant circulating steroid hormones in humans with the principle source of production being the adrenal glands. In adrenalectomised or hypoadrenal subjects it is not standard clinical practice to replace this hormone. Whilst this lack of DHEA(S) is clearly not life threatening, the published literature on the psychological effects of replacement in this population has shown some benefit in quality of life but data concerning the metabolic effects is conflicting and incomplete. We wish to carry out a study to measure the effect of DHEA(S) replacement in a group of adrenalectomised / hypoadrenal subjects and measure the outcome of a number of psychological and metabolic parameters both prior to and after twelve weeks of 50 mg/day DHEA(S) in a double blind randomised cross over design.

Mood, quality of life and sexual well being will be assessed using validated questionnaires. In addition, we will utilise the GCRC facility to measure body composition using total body water and DEXA. We will measure insulin sensitivity, exercise performance, muscle fatigability and VO2 max. Pre- and post- intervention muscle biopsies will assess DHEA(S) effects on myosin heavy chain isoform expression; skeletal muscle mitochondrial ATP production and be used to assess muscle enzyme levels.

Study Overview

• Status: Completed
• Conditions: Aging; Dehydroepiandosterone Replacement; DHEA Replacement
• Intervention / Treatment: Procedure: DHEA Replacement

• Study Type: Interventional
• Enrollment: 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

• Subjects who have been adrenalectomised or have been hypoadrenal (from whatever cause) for > 24 months;
• Subjects who have been on a steady glucocorticoid replacement regime for >12 months;
• Women of child bearing age in whom oestrogen status has been steady for > 6 months - i.e. either on or off the oral contraceptive pill for that time;
• Subjects on other forms of hormone replacement therapy (e.g. thyroxin) in whom dose has remained the same for > 6 months.

Exclusion criteria:

• BMI >35 Kg/m2;
• Individuals with fasting blood glucose above 120mg/dl;
• A history of sex hormone dependant malignancy;
• A history of liver disease;
• Renal failure;
• Cardiovascular disease (other than hypertension);
• Polycythaemia;
• Pregnancy or breastfeeding;
• Cerebrovascular disorders;
• Neurological disorders;
• PSA levels above the age related reference range;
• Use of drugs known to alter mood within the 6 months prior to enrolment;
• Any drug known to affect hepatic biotransformation;
• Evidence of psychiatric disease or dementia;
• Postmenopausal women who have been on hormone replacement therapy for less than six months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
quality of life
physical performance (VO2 peak, muscle strength as measured by chest press, double knee extension, and isokinetic knee extension
muscle protein synthesis
body composition
glucose and insulin metabolism

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institutes of Health (NIH); National Institute on Aging (NIA)
• Investigators: Principal Investigator: K. Sreekumaran Nair, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Dhatariya KK, Greenlund LJ, Bigelow ML, Thapa P, Oberg AL, Ford GC, Schimke JM, Nair KS. Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function. Mayo Clin Proc. 2008 Nov;83(11):1218-25. doi: 10.4065/83.11.1218.

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): June 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: January 18, 2006
• First Submitted That Met QC Criteria: January 18, 2006
• First Posted (Estimate): January 20, 2006

Study Record Updates

• Last Update Posted (Estimate): May 23, 2011
• Last Update Submitted That Met QC Criteria: May 20, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Other Study ID Numbers: 669-02; P01AG014383 (U.S. NIH Grant/Contract)