Study of Testosterone and Athlete Response

Athletic Performance Clinical Trial

— STAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03210558
• Other study ID #: 2016/1485-32
• Status: Completed
• Phase: Phase 2
• Start date: May 26, 2017
• Est. completion date: June 20, 2018

Study information

• Verified date: October 2022
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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:

1. Submaximal work on treadmill (oxygen uptake, ventilation, heart rate, blood lactate and subjective rate of exhaustion)

2. Anaerobic performance (Wingate test)

3. Muscle strength (Cybex apparatus, force transducer, counter movement jump)

4. Body composition (Dual X-ray Absorptiometry: muscle mass, fat mass, bone mass)

5. Behaviour and well-being (Quality of life, Profile of mood state, Confidence Questionnaire, Aggression Questionnaire)

6. Blood parameters (hemoglobin, hematocrit, reticulocytes, ferritin, CRP)

7. Steroid hormone profile in blood and urine

8. Gynecological evaluation (ovarian and endometrial variables on ultrasound)

9. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 20, 2018
• Est. primary completion date: June 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Testosterone cream 1% (Andro-Feme® )
Testosterone cream 10 mg (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.
• Placebo cream
Placebo cream (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.

Locations

Country	Name	City	State
Sweden	Department of Obstetrics and Gynecology, Karolinska University Hospital	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska University Hospital	The Swedish School of Sport and Health Sciences

Country where clinical trial is conducted

Sweden, 

References & Publications (23)

Bermon S, Garnier PY, Hirschberg AL, Robinson N, Giraud S, Nicoli R, Baume N, Saugy M, Fénichel P, Bruce SJ, Henry H, Dollé G, Ritzen M. Serum androgen levels in elite female athletes. J Clin Endocrinol Metab. 2014 Nov;99(11):4328-35. doi: 10.1210/jc.2014-1391. Epub 2014 Aug 19. — View Citation

Bermon S, Ritzén M, Hirschberg AL, Murray TH. Are the new policies on hyperandrogenism in elite female athletes really out of bounds? Response to "out of bounds? A critique of the new policies on hyperandrogenism in elite female athletes". Am J Bioeth. 2013;13(5):63-5. doi: 10.1080/15265161.2013.776129. — View Citation

Buss AH, Perry M. The aggression questionnaire. J Pers Soc Psychol. 1992 Sep;63(3):452-9. — View Citation

Chang WY, Knochenhauer ES, Bartolucci AA, Azziz R. Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups. Fertil Steril. 2005 Jun;83(6):1717-23. — View Citation

Davis S, Papalia MA, Norman RJ, O'Neill S, Redelman M, Williamson M, Stuckey BG, Wlodarczyk J, Gard'ner K, Humberstone A. Safety and efficacy of a testosterone metered-dose transdermal spray for treating decreased sexual satisfaction in premenopausal women: a randomized trial. Ann Intern Med. 2008 Apr 15;148(8):569-77. — View Citation

Davis SR, Hirschberg AL, Wagner LK, Lodhi I, von Schoultz B. The effect of transdermal testosterone on mammographic density in postmenopausal women not receiving systemic estrogen therapy. J Clin Endocrinol Metab. 2009 Dec;94(12):4907-13. doi: 10.1210/jc.2009-1523. Epub 2009 Oct 22. — View Citation

El-Hage G, Eden JA, Manga RZ. A double-blind, randomized, placebo-controlled trial of the effect of testosterone cream on the sexual motivation of menopausal hysterectomized women with hypoactive sexual desire disorder. Climacteric. 2007 Aug;10(4):335-43. — View Citation

Fénichel P, Paris F, Philibert P, Hiéronimus S, Gaspari L, Kurzenne JY, Chevallier P, Bermon S, Chevalier N, Sultan C. Molecular diagnosis of 5a-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism. J Clin Endocrinol Metab. 2013 Jun;98(6):E1055-9. doi: 10.1210/jc.2012-3893. Epub 2013 Apr 30. — View Citation

Fooladi E, Reuter SE, Bell RJ, Robinson PJ, Davis SR. Pharmacokinetics of a transdermal testosterone cream in healthy postmenopausal women. Menopause. 2015 Jan;22(1):44-9. doi: 10.1097/GME.0000000000000259. — View Citation

Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR. Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause. 2003 Sep-Oct;10(5):390-8. — View Citation

Gooren LJ, Bunck MC. Transsexuals and competitive sports. Eur J Endocrinol. 2004 Oct;151(4):425-9. Review. — View Citation

Hagmar M, Berglund B, Brismar K, Hirschberg AL. Hyperandrogenism may explain reproductive dysfunction in olympic athletes. Med Sci Sports Exerc. 2009 Jun;41(6):1241-8. doi: 10.1249/MSS.0b013e318195a21a. — View Citation

Huang G, Basaria S, Travison TG, Ho MH, Davda M, Mazer NA, Miciek R, Knapp PE, Zhang A, Collins L, Ursino M, Appleman E, Dzekov C, Stroh H, Ouellette M, Rundell T, Baby M, Bhatia NN, Khorram O, Friedman T, Storer TW, Bhasin S. Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial. Menopause. 2014 Jun;21(6):612-23. doi: 10.1097/GME.0000000000000093. — View Citation

Jovanovic H, Kocoska-Maras L, Rådestad AF, Halldin C, Borg J, Hirschberg AL, Nordström AL. Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study. Neuroimage. 2015 Feb 1;106:47-54. doi: 10.1016/j.neuroimage.2014.11.003. Epub 2014 Nov 11. — View Citation

Meriggiola MC, Jannini EA, Lenzi A, Maggi M, Manieri C. Endocrine treatment of transsexual persons: an Endocrine Society Clinical Practice Guideline: commentary from a European perspective. Eur J Endocrinol. 2010 May;162(5):831-3. doi: 10.1530/EJE-09-1091. Epub 2010 Feb 11. — View Citation

Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr Rev. 1987 Feb;8(1):1-28. Review. — View Citation

Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002 Apr;77 Suppl 4:S34-41. Review. — View Citation

Rickenlund A, Carlström K, Ekblom B, Brismar TB, von Schoultz B, Hirschberg AL. Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance. Fertil Steril. 2003 Apr;79(4):947-55. — View Citation

Slayden SM. Risks of menopausal androgen supplementation. Semin Reprod Endocrinol. 1998;16(2):145-52. Review. — View Citation

Turpeinen U, Linko S, Itkonen O, Hämäläinen E. Determination of testosterone in serum by liquid chromatography-tandem mass spectrometry. Scand J Clin Lab Invest. 2008;68(1):50-7. Epub 2007 Jun 24. — View Citation

Zang H, Carlström K, Arner P, Hirschberg AL. Effects of treatment with testosterone alone or in combination with estrogen on insulin sensitivity in postmenopausal women. Fertil Steril. 2006 Jul;86(1):136-44. Epub 2006 Jun 5. — View Citation

Zang H, Sahlin L, Masironi B, Eriksson E, Lindén Hirschberg A. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. J Clin Endocrinol Metab. 2007 Jun;92(6):2169-75. Epub 2007 Mar 6. — View Citation

Zethraeus N, Kocoska-Maras L, Ellingsen T, von Schoultz B, Hirschberg AL, Johannesson M. A randomized trial of the effect of estrogen and testosterone on economic behavior. Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6535-8. doi: 10.1073/pnas.0812757106. Epub 2009 Apr 6. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aerobic performance	Change in endurance exercise time to exhaustion on treadmill	Baseline and 10 weeks of treatment
Secondary	Submaximal work on treadmill	Change in oxygen uptake (L/min, mL/kg x min)	Baseline and 10 weeks of treatment
Secondary	Anaerobic performance (Wingate test)	Change in average power output on a cycle ergometer (W)	Baseline and 10 weeks of treatment
Secondary	Muscle strength (knee extension torque)	Change in peak muscle strength (N) and strength endurance (time)	Baseline and 10 weeks of treatment
Secondary	Functional power development-jump tests	Change in jump height (m) by squat jump and countermovement jump	Baseline and 10 weeks of treatment
Secondary	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
Secondary	Muscle mass	Change in muscle mass (g) by DXA	Baseline and 10 weeks of treatment
Secondary	Body fat percentage	Change in body fat (%) by DXA	Baseline and 10 weeks of treatment
Secondary	Bone mineral density	Change in bone mineral density (g/cm2) by DXA	Baseline and 10 weeks of treatment
Secondary	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
Secondary	Mood	Change in mood (POMS) score 0 (not at all) to 4 (very much)	Baseline and 10 weeks of treatment
Secondary	Confidence	Change in confidence (Confidence Questionnaire) score 1 (not at all) to 5 (very much)	Baseline and 10 weeks of treatment
Secondary	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
Secondary	Blood parameters	Change in blood parameters (hemoglobin, hematocrit, reticulocytes, ferritin, CRP)	Baseline and 10 weeks of treatment
Secondary	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, 5a androstane-3a, 17ß-diol 17-glucuronide, androst-5-ene-diol-3ß, 17ß-diol, testosterone, androstenedione, epitestosterone, androsterone, etiocholanolone).	Baseline and 10 weeks of treatment
Secondary	Gynecological evaluation	Change in ultrasound assessments of the endometrium (mm) and ovaries (volume)	Baseline and 10 weeks of treatment
Secondary	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