Baseline Sexual Function, Cognitive Function, Body Composition and Muscle Parameters and Pharmacokinetics of Transdermal Testosterone Gel in Women With Hypopituitarism

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by Charles Drew University of Medicine and Science.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Charles Drew University of Medicine and Science
ClinicalTrials.gov Identifier:
NCT00144404
First received: September 1, 2005
Last updated: February 23, 2009
Last verified: February 2009
  Purpose

The purpose of this study is to determine the blood levels of testosterone gel administered for a week to women with hypopituitarism and determine if this leads to testosterone replacement in a normal range for women. An additional objective is to determine the baseline laboratory abnormalities and physical, brain function, emotional and sexual symptomatology of these women with hypopituitarism.


Condition Intervention Phase
Panhypopituitarism
Drug: Transdermal Testosterone Gel
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Baseline Sexual Function, Cognitive Function, Body Composition and Muscle Parameters and Pharmacokinetics of Transdermal Testosterone Gel in Women With Hypopituitarism

Resource links provided by NLM:


Further study details as provided by Charles Drew University of Medicine and Science:

Primary Outcome Measures:
  • The purpose of this study is to determine the pharmacokinetics of testosterone gel 2 mg/d administered for a week to women with hypopituitarism and determine if this leads to testosterone replacement in a physiologic range. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • An additional objective is to determine the baseline laboratory abnormalities and physical, cognitive, emotional and sexual symptomatology of these women with hypopituitarism. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: August 2002
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Pharmacokinetic study of transdermal testosterone gel-study groups of (8 pumps, 12 pumps, 16 pumps)
Drug: Transdermal Testosterone Gel
2.0 mg per pump of testosterone gel (8 pumps, 12 pumps, 16 pumps). Pharmacokinetic study

Detailed Description:

The ovaries and the adrenal glands contribute to the daily production of 300 micrograms of testosterone in healthy, menstruating women. The physiologic role of testosterone in women, however, remains poorly understood. Previous studies of testosterone supplementation, largely in surgically or naturally menopausal women, have reported improvements in subjective measures of sexual function, sense of well being, and variable changes in markers of bone formation and resorption. However, many of these previous studies used supraphysiologic doses of testosterone, and insensitive assays for the measurement of total and free testosterone levels that lacked precision and accuracy in the low range prevalent in women. The effects of testosterone in women on body composition, muscle performance and physical function have not been studied. Therefore, the clinical significance of androgen deficiency in women remains unclear. Thus, we do not know whether physiologic testosterone replacement of women with androgen deficiency can produce clinically meaningful improvements in sexual and cognitive functions, fat-free mass, and muscle performance, without virilizing side effects.

Women with hypopituitarism represent an excellent model to study the effects of physiologic replacement as these patients have severely diminished androgen production from both the adrenal glands and the ovaries. Estrogen administration, by increasing sex hormone binding globulin (SHBG) in these women leads to further reduction in free testosterone concentrations. In fact, a recent study demonstrated very low levels of total and free testosterone, dehydroepiandrosterone sulfate (DHEAS), its parent steroid dehydroepiandrosterone (DHEA), and androstenedione in women with hypopituitarism. Therefore, it is postulated that many women with hypopituitarism suffer from decreased libido, altered body composition, and impaired quality of life, symptoms possibly related to androgen deficiency. However, these parameters have not been properly studied in a well-defined group of women with hypopituitarism. These baseline studies are needed prior to undertaking a study on treating women with hypopituitarism with a testosterone preparation.

Prior to investigating testosterone replacement in a large study of women with hypopituitarism, we must first determine in this pilot study the amount and interval of testosterone administration.

Currently, the only FDA-approved drug for testosterone in women is Estratest, which contains methyl testosterone, a compound that when given orally is associated with liver toxicity in animals and humans. Until recently, most hypogonadal men received biweekly intramuscular injections of testosterone. This regimen gives variable serum testosterone levels depending on the time of the blood sampling compared to the time of injection. Many male hypogonadal patients now receive their testosterone replacement via either transdermal testosterone gel or patch, with much more uniform serum testosterone levels. We have chosen transdermal testosterone gel for use in this study for several reasons:

  1. Recent studies have shown that stable, reproducible levels of serum testosterone can be obtained irrespective of application site in hypogonadal men. No skin irritation (which can be problematic with the testosterone patch) was observed.
  2. Graded Double-blinded dosing can easily be implemented.

Thus, we will use transdermal testosterone gel as it provides predictable and physiologic levels of testosterone.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women age 18-55
  • Hypopituitarism with documented central adrenal and gonadal deficiencies. Serum testosterone level of < 20 ng/dl or free testosterone <1.5 pg/ml on conjugated equine estrogen replacement
  • No other significant medical condition
  • Weight between 80 and 150% of ideal body weight
  • Able to provide informed consent
  • All races and ethnicities
  • All patients regardless of marital status and relationship status

Exclusion Criteria:

  • Physical disabilities that would prevent them from participating in the study
  • Current use of testosterone or other androgenic steroids. Patients who are taking testosterone, DHEA or other androgen precursors will discontinue these medications/supplements three months prior to the study.
  • Significant cardiopulmonary disease, renal disease (creatinine > 1.5 mg/dL), diabetes mellitus, uncontrolled hypertension, malignancy (other than basal cell skin carcinoma) or major psychiatric disease. Patients with depression or anxiety on a stable dose of medication will be allowed to enroll.
  • Current abuse of illicit drugs or heavy ethanol use
  • History of breast or uterine cancer
  • Those with significant liver function abnormalities defined as SGOT, SGPT or alkaline phosphatase value of greater than one and one-half times the upper limit of normal in our Clinical Pathology Laboratory or serum bilirubin levels of greater than 2 mg/dl will be excluded.
  • Those with history of hyperandrogenic disorders such as hirsutism and polycystic ovary disease will be excluded. These conditions are rare in women with hypopituitarism. Testosterone administration to these patients may exacerbate the underlying disorder.
  • Women who are pregnant, seeking to become pregnant in the next 6 months, or breast feeding
  • Those who have previously experienced intolerance to other transdermal systems
  • Drugs known to alter testosterone production such as Megace or ketoconazole
  • Patients with untreated hyperprolactinemia or active Cushing's disease. Patients with treated prolactinoma or Cushing's disease will be allowed to participate in the study.
  • Hematocrit > 50%
  • Male sex
  • Not willing to answer all questions on surveys
  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: NCT00144404

Contacts
Contact: Erik Zuckerbraun, M.D. 310.668.8754 erzucker@cdrewu.edu
Contact: Christian Gastelum, M.D. 310.668.8754 christiangastelum@cdrewu.edu

Locations
United States, California
Charles R. Drew University Recruiting
Los Angeles, California, United States, 90059
Contact: Erik Zuckerbraun, M.D.    310-668-8754    erzucker@cdrewu.edu   
Contact: Christian Gastelum, M.D.    310.668.8754    christiangastelum@cdrewu.edu   
Principal Investigator: Ted C Friedman, M.D., Ph.D.         
Sponsors and Collaborators
Charles Drew University of Medicine and Science
Investigators
Principal Investigator: Ted C Friedman, M.D., Ph.D. Charles Drew University of Medicine and Science
  More Information

Additional Information:
No publications provided

Responsible Party: Theodore C. Friedman, M.D., Ph.D. Principal Investigator, Charles Drew University of Medicine and Science
ClinicalTrials.gov Identifier: NCT00144404     History of Changes
Other Study ID Numbers: 02-04-376-07
Study First Received: September 1, 2005
Last Updated: February 23, 2009
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Pituitary Diseases
Hypopituitarism
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on July 22, 2014