Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)
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|ClinicalTrials.gov Identifier: NCT02959853|
Recruitment Status : Completed
First Posted : November 9, 2016
Results First Posted : January 30, 2020
Last Update Posted : January 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hypogonadism Severe Obesity||Drug: Anastrazole Behavioral: weight loss||Phase 4|
After the age of 40, testosterone (T) production in men gradually decreases at a rate of 1.6% per year for total and to 2-3% per year for bioavailable T. Because of the age-related increase in sex hormone binding globulin, the magnitude of the decrease in bioavailable T in men is even greater than the decline in total T levels. This reduction in T production in men parallels the age-associated loss of muscle mass that leads to sarcopenia and impairment of function and the age-associated loss of bone mass that leads to osteopenia and fracture risk. Hypogonadism is a condition associated with multiple symptom complex including fatigue, depressed mood, osteoporosis, increased fat mass, loss of libido and reduced muscle strength, all of which deeply affect patient's quality of life. The prevalence of hypogonadismamong obese men ranges between 29.3% to 78.8%, with levels of androgens decreasing proportionately to the degree of obesity. This decline in T levels is exacerbated among obese patients due the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens (E) which in turn exerts a negative feedback on hypothalamus and pituitary, inhibiting the production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) and, as a consequence, of T by the testis resulting in hypogonadotropic hypogonadism (HH). Considering the high aromatase expression in the adipose tissue, the administration of T among obese men with HH could increase the conversion of the substrate T to estradiol (E2) and fuels the negative feedback on the hypothalamus and pituitary, producing a greater suppression of GnRH and gonadotropins.
Thus, men with obesity induced HH may benefit from other treatment strategies that target the pathophysiology of the disease. Weight loss intervention which improves hormonal and metabolic abnormalities related to obesity may also be considered a logical approach to improve obesity-induced HH.
One possible approach consists of the use of aromatase inhibitors (AI) to stop the conversion of T to E2 thereby interrupting the vicious cycle of E2 inhibition of the hypothalamic-pituitary-gonadal axis and restoring T production to normal levels. Increased T and reduced E2 levels have been reported in men with low levels of T after AI administration, even though very few studies investigated clinical outcomes.
We believe that AI use could promote positive changes on hypogonadal symptoms and body composition in HH severely obese patients, acting at the physiopathology of the disease without necessarily causing bone loss.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)|
|Actual Study Start Date :||June 2016|
|Actual Primary Completion Date :||November 20, 2018|
|Actual Study Completion Date :||December 20, 2018|
Placebo Comparator: weight loss
Patients given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent
Behavioral: weight loss
Experimental: aromatase inhibitor (anastrazole) plus weight loss
Patient placed on an aromatase inhibitor anastrazole 1 mg daily plus given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent
Other Name: Arimidex
Behavioral: weight loss
- Percent Change in Muscle Strength as Assessed by Knee Extension and Knee Flexion [ Time Frame: baseline and 6 months ]
Muscle strength was assessed using Biodex System 4 Isokinetic Dynamometer (Shirley, NY). Peak torque for isokinetic knee extension and flexion was measured at baseline, 6 months on the right leg. During the testing, participants sat with their hips flexed at 120 degrees, secured with thigh and pelvic straps. Testing was performed at an angular velocity of 60 degrees per second. The best result of 3 maximal voluntary efforts for each knee flexion and extension was used as the measure of absolute strength and reported as peak torque at 60 degrees in Newton-meter (N*m) units.
The higher the measured Newton-meter (N*m), the greater the measured muscle strength.
- Change in Symptoms Score of Hypogonadism [ Time Frame: baseline, 3 and 6 months ]
Symptoms of androgen deficiency were measured with 3 validated questionnaires done at baseline, 3 and 6 months.
- The Quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire uses questions from a scale of 1-5. The final summation yields a total score between 10 (most symptomatic) and 50 (least symptomatic).
- The second questionnaire used was the International Index of Erectile Function (IIEF). Total score ranges from 5 to 25, with 5 being severe erectile dysfunction and 25 being no erectile dysfunction.
- The third questionnaire used was the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-lite). Total score ranges from 31 to 155, with 31 being least symptomatic and 155 being the most symptomatic.
Score change at 3 months calculated by: total score at 3 months minus total score at baseline
Score change at 6 months calculated by: total score at 6 months minus total score at baseline
- Change in Fat Mass (in Kilograms) [ Time Frame: baseline and 6 months ]change in fat was measured by Dual-energy X-ray absorptiometry (DXA) scan at baseline and 6 months only.
- Change in Visceral Adipose Tissue (in Grams) [ Time Frame: baseline and 6 months ]Change in absolute visceral adipose tissue as measured by DXA scan, done at baseline and 6 months.
- Percent Change in Bone Mineral Density [ Time Frame: baseline and 6 months ]Percent change in bone mineral density as measured by DXA scan, done at baseline and 6 months
- Percent Change in Bone Quality [ Time Frame: baseline and 6 months ]Percent change in bone quality as measured by high resolution peripheral quantitative computed tomography scan (HR-pQCT), at baseline and 6 months
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 ClinicalTrials.gov identifier (NCT number): NCT02959853
|United States, Texas|
|Michael E. DeBakey Veterans Affairs Medical Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Reina Villareal, MD||Baylor College of Medicine|