Study of Testosterone and Athlete Response

Study Overview
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Brief Summary
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Trial objectives and purpose: The primary aim is to study the effects of moderately increased testosterone concentration on aerobic performance (endurance running time to exhaustion), and secondary aims to investigate the effects on submaximal work on treadmill, anaerobic capacity, muscle strength, body composition, behaviour and well-being, blood parameters, steroid hormone profile, gynecological parameters and skeletal muscle parameters in young healthy women in a double-blind, randomized, placebo-controlled trial. Treatment: Ten weeks of transdermal treatment with testosterone cream 10 mg daily or placebo cream in a randomized design (1:1). Primary outcome: Aerobic performance (running time to exhaustion on treadmill) Secondary outcomes: Submaximal work on treadmill (oxygen uptake, ventilation, heart rate, blood lactate and subjective rate of exhaustion) Anaerobic performance (Wingate test) Muscle strength (Cybex apparatus, force transducer, counter movement jump) Body composition (Dual X-ray Absorptiometry: muscle mass, fat mass, bone mass) Behaviour and well-being (Quality of life, Profile of mood state, Confidence Questionnaire, Aggression Questionnaire) Blood parameters (hemoglobin, hematocrit, reticulocytes, ferritin, CRP) Steroid hormone profile in blood and urine Gynecological evaluation (ovarian and endometrial variables on ultrasound) Skeletal muscle morphology, metabolic enzymes and muscle protein synthesis Study population: Fifty healthy menstruating women will be included in the study and randomized to treatment with testosterone or placebo. Inclusion criteria: 18-35 yrs of age; body mass index (BMI) 19-25; non-smoking; a moderate to high self-reported level of recreational physical activity; not taking hormonal contraception and willing to use highly efficient non-hormonal contraception during the study (intrauterine device, bilateral tubal occlusion, vasectomised partner, same-sex partner, or sexual abstinence); accepting to not participate in any sports competitive event during the study period plus one month. Exclusion criteria: the presence of cardiovascular, liver, biliary or renal disease; hyperlipidemia; uncontrolled high blood pressure; endocrinological disorder; oligomenorrhea (menstrual intervals of more than 6 weeks) or amenorrhea (no menstruation for at least 3 months); pregnancy; a history of thromboembolic disorder; any malignancy; and intake of hormonal contraception the last two months prior to the study.

Official Title
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Effects of Moderately Increased Testosterone Concentration on Physical Performance and Behaviour in Healthy Women - a Double-blind, Randomized, Placebo-controlled Study

Conditions
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Athletic Performance, Testosterone, Women's Health: Female Athlete/Female Athlete Triad

Intervention / Treatment
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* Drug: Testosterone cream 1% (Andro-Feme® )
* Drug: Placebo cream


Participation Criteria
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Eligibility Criteria
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Inclusion criteria are: healthy menstruating women; 18-35 yrs of age; BMI 19-25; non-smoking; having a moderate to high self-reported level of recreational physical activity (minimum of three hours of endurance and/or strength training per week); not taking hormonal contraception; and willing to use highly efficient non-hormonal contraception during the study such as: Intrauterine device Bilateral tubal occlusion Vasectomised partner Same-sex partner Sexual abstinence Exclusion criteria are: the presence of cardiovascular, liver, biliary or renal disease; hyperlipidemia; uncontrolled high blood pressure; endocrinological disorder; oligomenorrhea (menstrual intervals of more than 6 weeks) or amenorrhea (no menstruation for at least 3 months); pregnancy; a history of thromboembolic disorder; any malignancy; and intake of hormonal contraception the last two months prior to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A double-blind, randomized, placebo-controlled, phase II trial of in total 50 women randomized to two parallel groups (1:1): Group A treated with transdermal testosterone or Group B treated with placebo for ten weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Testosterone cream 1% (Andro-Feme® ) | Drug: Testosterone cream 1% (Andro-Feme® )<br>* Testosterone cream 10 mg (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.<br>|
| Placebo Comparator: Group B<br>Placebo cream | Drug: Placebo cream<br>* Placebo cream (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aerobic performance | Change in endurance exercise time to exhaustion on treadmill | Baseline and 10 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Submaximal work on treadmill | Change in oxygen uptake (L/min, mL/kg x min) | Baseline and 10 weeks of treatment | 
| Anaerobic performance (Wingate test) | Change in average power output on a cycle ergometer (W) | Baseline and 10 weeks of treatment | 
| Muscle strength (knee extension torque) | Change in peak muscle strength (N) and strength endurance (time) | Baseline and 10 weeks of treatment | 
| Functional power development-jump tests | Change in jump height (m) by squat jump and countermovement jump | Baseline and 10 weeks of treatment | 
| Physical activity during one week before treatment and one week before the end of treatment | Change in accelerometer counts | Baseline and 10 weeks of treatment | 
| Muscle mass | Change in muscle mass (g) by DXA | Baseline and 10 weeks of treatment | 
| Body fat percentage | Change in body fat (%) by DXA | Baseline and 10 weeks of treatment | 
| Bone mineral density | Change in bone mineral density (g/cm2) by DXA | Baseline and 10 weeks of treatment | 
| Psychological General Well-Being | Change in Psychological General Well-Being (PGWB) score 0 (poor quality of life) and 110 (good quality of life) | Baseline and 10 weeks of treatment | 
| Mood | Change in mood (POMS) score 0 (not at all) to 4 (very much) | Baseline and 10 weeks of treatment | 
| Confidence | Change in confidence (Confidence Questionnaire) score 1 (not at all) to 5 (very much) | Baseline and 10 weeks of treatment | 
| Aggression | Change in aggression (Aggression Questionnaire) score 1 (does not fit in with me at all) to 5 (totally fits in with me) | Baseline and 10 weeks of treatment | 
| Blood parameters | Change in blood parameters (hemoglobin, hematocrit, reticulocytes, ferritin, CRP) | Baseline and 10 weeks of treatment | 
| Steroid hormone profile in blood and urine | Change in steroid hormones and metabolites in blood (testosterone, dihydrotestosterone, androstenedione, estradiol, dehydroepiandrosterone and its sulfate, cortisol, progesterone, other reproductive hormones (LH, FSH, AMH), binding protein (SHBG) and steroid hormones and metabolites in urine (estrone, estrone sulfate, androsterone glucuronide, 5α androstane-3α, 17β-diol 17-glucuronide, androst-5-ene-diol-3β, 17β-diol, testosterone, androstenedione, epitestosterone, androsterone, etiocholanolone). | Baseline and 10 weeks of treatment | 
| Gynecological evaluation | Change in ultrasound assessments of the endometrium (mm) and ovaries (volume) | Baseline and 10 weeks of treatment | 
| Skeletal muscle | Change in morphology and concentration of metabolic enzymes (HAD, SC), markers of muscle protein synthesis (mTOR, p70), as well as markers from the muscle atrophy pathway (MABbx, MuRF-1) | Baseline and 10 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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female athletes, testosterone, physical performance, body composition