Adrenal Suppression and Adrenal Recovery Induced by Megestrol Acetate

Evaluation of the Time Course of Adrenal Suppression and Adrenal Recovery After Ingestion of Megestrol Acetate

Megestrol Acetate (MA) is a progesterone-like hormone that has been utilized as a birth control agent, chemotherapeutic drug, and more recently, to induce appetite and weight gain in patients malnourished as a result of radiation therapy, chemotherapy, cystic fibrosis, AIDS, or dementia. The mechanism of MA-stimulated appetite and weight gain is unknown.

Although only approved to combat weight loss associated with AIDS and cancer, MA is frequently prescribed for long periods of time to prevent or reverse weight loss in nursing home residents and in elderly patients with serious illnesses in the community. Little data is available to support this practice. Among its many properties, MA acts as a partial glucocorticoid agonist, and long term and short term use of MA may results in adrenal suppression. The rapidity of the onset of MA-induced adrenal suppression and the time course of resumption of normal adrenal function after discontinuation of MA is completely unknown. As a consequence, it is unclear whether MA can be given safely for short periods of time or whether glucocorticoid administration is necessary after abruptly stopping MA treatment. The increased use of MA in the frail elderly, where even partial adrenal insufficiency may pose a substantial risk of adrenal crisis after an illness, requires a clear understanding of these issues. To address these concerns, we will evaluate adrenal function before, during, and after MA administration in healthy volunteers between the ages of 60 and 85 years.

Study Overview

• Status: Completed
• Conditions: Adrenal Insufficiency
• Intervention / Treatment: Drug: megestrol acetate

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Elderly males and females
• Age 65-80 years
• With stable (no history of urgent/ emergent care visits with health care provider/s in the preceding 2 months), medical conditions

Exclusion Criteria:

Subjects will be excluded if they have a history of (H/O):

• Dementia
• Adrenal disease
• Thromboembolism
• Diabetes mellitus
• Liver disease
• Electrolyte abnormalities; or
• Vaginal bleeding
• Hypertriglyceridemia
• CAD with CHF
• Unstable depression
• Schizophrenia; and
• Morbidly obese subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: megace treatment; Study subjects will be given 600mg of MA for oral ingestion per day for duration of 8 weeks. They will be monitored every week clinically for the development of adrenal insufficiency by review of symptoms, physical exam, body weight, pulse, and blood pressure. Subjects also will undergo biochemical evaluation of adrenal status every two weeks by measurement of serum electrolytes, serum cortisol, serum adrenocorticotropic hormone(ACTH) levels, and the adrenal response to a low dose ACTH (1µgm) stimulation test(see methods).

Drug: megestrol acetate; 600 mg by mouth daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adrenal Insufficiency	Number of participants with adrenal insufficiency after treatment with megestrol acetate assessed by ACTH stimulated cortisol levels less than normal (21 ug/dl) measured weekly for 8 weeks or when adrenal insufficiency is clinically encountered	stimulated acth stimulated cortisol levels weekly for 8 weeks or until adrenal insufficiency is encountered
Time Required for Recovery From Adrenal Suppression to Normal Adrenal Function	the number of weeks required for participants to recover from adrenal suppression as assessed by a normal ACTH stimulation test (cortisol level >21 mcg/dl)	weekly for up to 6 weeks

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: donald l bodenner, Associate Professor

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): December 1, 2004

Study Registration Dates

• First Submitted: December 13, 2007
• First Submitted That Met QC Criteria: December 14, 2007
• First Posted (Estimate): December 17, 2007

Study Record Updates

• Last Update Posted (Estimate): August 29, 2011
• Last Update Submitted That Met QC Criteria: July 27, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: megestrol acetate; adrenal insufficiency; adrenal suppression
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Appetite Stimulants; Megestrol; Megestrol Acetate
• Other Study ID Numbers: 26835