ClinicalTrials.gov

History of Changes for Study: NCT03210558
Study of Testosterone and Athlete Response (STAR)
Latest version (submitted August 16, 2019) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's date link to see a rendering of the study for that version.
  • Edits or deletions will be displayed in red.
  • Additions will be displayed in green.
  • The yellow choices in the table indicate the study versions currently compared below. A yellow row indicates the study version being viewed.
  • Hover over the "
    Recruitment Status
    " to see how the study's recruitment status changed.
Study Record Versions
Version A B Submitted Date Changes
1 July 4, 2017 Nothing (earliest Version on record)
2 August 6, 2018
Recruitment Status
, Study Status, Contacts/Locations and Study Design
3 August 16, 2019 Outcome Measures, Study Status and Study Description
Comparison Format:

Scroll up to access the controls

Changes (Merged) for Study: NCT03210558
July 4, 2017 (v1) -- August 16, 2019 (v3)

Changes in: Study Status, Outcome Measures, Contacts/Locations, Study Design and Study Description

Study Identification
Unique Protocol ID: Version 7
Brief Title: Study of Testosterone and Athlete Response (STAR)
Official Title: Effects of Moderately Increased Testosterone Concentration on Physical Performance and Behaviour in Healthy Women - a Double-blind, Randomized, Placebo-controlled Study
Secondary IDs:
Study Status
Record Verification: June 2017 August 2019
Overall Status: Recruiting Completed
Study Start: May 26, 2017
Primary Completion: September 30, 2018 [Anticipated] June 20, 2018 [Actual]
Study Completion: December 31, 2018 [Anticipated] June 20, 2018 [Actual]
First Submitted: June 30, 2017
First Submitted that
Met QC Criteria:
July 4, 2017
First Posted: July 7, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
July 4, 2017 August 16, 2019
Last Update Posted: July 7 August 20, 2017 2019 [Actual]
Sponsor/Collaborators
Sponsor: Karolinska University Hospital
Responsible Party: Principal Investigator
Investigator: Angelica Lindén Hirschberg
Official Title: Professor
Affiliation: Karolinska University Hospital
Collaborators: The Swedish School of Sport and Health Sciences
Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Study Description
Brief 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 ( endurance 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.

Detailed Description:
Conditions
Conditions: Athletic Performance
Testosterone
Women's Health: Female Athlete/Female Athlete Triad
Keywords: female athletes, testosterone, physical performance, body composition
Study Design
Study Type: Interventional
Primary Purpose: Basic Science
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: QuadrupleParticipant, Care Provider, Investigator, Outcomes Assessor
Allocation: Randomized
Enrollment: 50 [Anticipated] 48 [Actual]
Arms and Interventions
Arms Assigned Interventions
Active Comparator: Group A
Testosterone cream 1% (Andro-Feme® )
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 Comparator: Group B
Placebo cream
Drug: Placebo cream
Placebo cream (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.
Outcome Measures
Primary Outcome Measures:
1. Aerobic performance
Change in endurance exercise time to exhaustion on bicycle treadmill

[Time Frame: Baseline and 10 weeks of treatment]
Secondary Outcome Measures:
2. Submaximal work on treadmill
Change in oxygen uptake (L/min, mL/kg x min)

[Time Frame: Baseline and 10 weeks of treatment]
3. Contractive functions Anaerobic performance (Wingate test)
Change in peak torque (Nm/sec) Change in average power output on a cycle ergometer (W)

[Time Frame: Baseline and 10 weeks of treatment]
4. Muscle strength and endurance Muscle strength (knee extension torque)
Change in peak muscle strength (N) and strength endurance (time)

[Time Frame: Baseline and 10 weeks of treatment]
5. Functional power development-jump tests
Change in peak power output (N) Change in jump height (m) by squat jump and countermovement jump

[Time Frame: Baseline and 10 weeks of treatment]
6. Physical activity during one week before treatment and one week before the end of treatment
Change in accelerometer counts

[Time Frame: Baseline and 10 weeks of treatment]
7. Muscle mass
Change in muscle mass (g) by DXA

[Time Frame: Baseline and 10 weeks of treatment]
8. Mood Body fat percentage
Change in mood body fat ( POMS %) by DXA

[Time Frame: Baseline and 10 weeks of treatment]
9. Wellbeing Bone mineral density
Change in wellbeing (PGWB) Change in bone mineral density (g/cm2) by DXA

[Time Frame: Baseline and 10 weeks of treatment]
10. Psychological General Well-Being
Change in Psychological General Well-Being (PGWB) score 0 (poor quality of life) and 110 (good quality of life)

[Time Frame: Baseline and 10 weeks of treatment]
11. Mood
Change in mood (POMS) score 0 (not at all) to 4 (very much)

[Time Frame: Baseline and 10 weeks of treatment]
12. Confidence
Change in confidence (Confidence Questionnaire) score 1 (not at all) to 5 (very much)

[Time Frame: Baseline and 10 weeks of treatment]
13. Aggression
Change in aggression (Aggression Questionnaire) score 1 (does not fit in with me at all) to 5 (totally fits in with me)

[Time Frame: Baseline and 10 weeks of treatment]
14. Blood parameters
Change in blood parameters (hemoglobin, hematocrit, reticulocytes, ferritin, CRP)

[Time Frame: Baseline and 10 weeks of treatment]
15. 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).

[Time Frame: Baseline and 10 weeks of treatment]
16. Gynecological evaluation
Change in ultrasound assessments of the endometrium (mm) and ovaries (volume)

[Time Frame: Baseline and 10 weeks of treatment]
17. 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)

[Time Frame: Baseline and 10 weeks of treatment]
Eligibility
Minimum Age: 18 Years
Maximum Age: 35 Years
Sex: Female
Gender Based:
Accepts Healthy Volunteers: Yes
Criteria:

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.

Contacts/Locations
Central Contact: Angelica Lindén Hirschberg
Telephone: + 46 70 255 99 24
Email: angelica.linden-hirschberg@sll.se
Study Officials: Angelica Lindén Hirschberg
Principal Investigator
Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden
Locations: Sweden
Department of Obstetrics and Gynecology, Karolinska University Hospital
[Recruiting]
Stockholm, Sweden, 171 76
Contact: Angelica L Hirschberg, Professor +46 8 517 733 26 angelica.linden-hirschberg@karolinska.se
IPDSharing
Plan to Share IPD: No
References
Citations: 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. PubMed 23557056
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. PubMed 25137421
Buss AH, Perry M. The aggression questionnaire. J Pers Soc Psychol. 1992 Sep;63(3):452-9. PubMed 1403624
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. PubMed 15950641
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. PubMed 18413618
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. PubMed 19850682
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. PubMed 17653960
Fénichel P, Paris F, Philibert P, Hiéronimus S, Gaspari L, Kurzenne JY, Chevallier P, Bermon S, Chevalier N, Sultan C. Molecular diagnosis of 5α-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. PubMed 23633205
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. PubMed 24845394
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. PubMed 14501599
Gooren LJ, Bunck MC. Transsexuals and competitive sports. Eur J Endocrinol. 2004 Oct;151(4):425-9. Review. PubMed 15476439
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. PubMed 19461542
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. PubMed 20150325
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. PubMed 24281237
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. PubMed 25462800
Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr Rev. 1987 Feb;8(1):1-28. Review. PubMed 3549275
Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002 Apr;77 Suppl 4:S34-41. Review. PubMed 12007900
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. PubMed 12749436
Slayden SM. Risks of menopausal androgen supplementation. Semin Reprod Endocrinol. 1998;16(2):145-52. Review. PubMed 9711680
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. PubMed 17852804
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. PubMed 16750207
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. PubMed 17341565
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. PubMed 19366676
Hirschberg AL, Elings Knutsson J, Helge T, Godhe M, Ekblom M, Bermon S, Ekblom B. Effects of moderately increased testosterone concentration on physical performance in young women: a double blind, randomised, placebo controlled study. Br J Sports Med. 2019 Oct 15. pii: bjsports-2018-100525. doi: 10.1136/bjsports-2018-100525. [Epub ahead of print] PubMed 31615775
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services