Study of Testosterone and Athlete Response

NCT03210558 | Completed Phase 2

• 1 other identifier: 2016/1485-32
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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 (running time to exhaustion on treadmill) Secondary outcomes:

1. 1.Submaximal work on treadmill (oxygen uptake, ventilation, heart rate, blood lactate and subjective rate of exhaustion)
2. 2.Anaerobic performance (Wingate test)
3. 3.Muscle strength (Cybex apparatus, force transducer, counter movement jump)
4. 4.Body composition (Dual X-ray Absorptiometry: muscle mass, fat mass, bone mass)
5. 5.Behaviour and well-being (Quality of life, Profile of mood state, Confidence Questionnaire, Aggression Questionnaire)
6. 6.Blood parameters (hemoglobin, hematocrit, reticulocytes, ferritin, CRP)
7. 7.Steroid hormone profile in blood and urine
8. 8.Gynecological evaluation (ovarian and endometrial variables on ultrasound)
9. 9.Skeletal muscle morphology, metabolic enzymes and muscle protein synthesis

Conditions

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

Keywords

female athletes, testosterone, physical performance, body composition

Outcome Measures

Primary Outcomes (1)

• Aerobic performance

  Change in endurance exercise time to exhaustion on treadmill

  Baseline and 10 weeks of treatment

Secondary Outcomes (16)

• Submaximal work on treadmill

  Baseline and 10 weeks of treatment

• Anaerobic performance (Wingate test)

  Baseline and 10 weeks of treatment

• Muscle strength (knee extension torque)

  Baseline and 10 weeks of treatment

• Functional power development-jump tests

  Baseline and 10 weeks of treatment

• Physical activity during one week before treatment and one week before the end of treatment

  Baseline and 10 weeks of treatment

Study Arms (2)

Group A

ACTIVE COMPARATOR

Testosterone cream 1% (Andro-Feme® )

Drug: Testosterone cream 1% (Andro-Feme® )

Group B

PLACEBO COMPARATOR

Placebo cream

Drug: Placebo cream

Interventions

Testosterone cream 1% (Andro-Feme® ) DRUG

Testosterone cream 10 mg (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.

Group A

Placebo cream DRUG

Placebo cream (1 ml) daily, supplied every evening via a dose applicator to the upper outer thigh for 10 weeks.

Group B

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Intrauterine device
• Bilateral tubal occlusion
• Vasectomised partner
• Same-sex partner
• Sexual abstinence

Sponsors & Collaborators

• Karolinska University Hospital: lead
• The Swedish School of Sport and Health Sciences: collaborator

Study Sites (1)

Department of Obstetrics and Gynecology, Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Related Publications (26)

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  PMID: 23557056 BACKGROUND

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  PMID: 25137421 BACKGROUND

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• 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. doi: 10.1016/j.fertnstert.2005.01.096.

  PMID: 15950641 BACKGROUND

• 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. doi: 10.7326/0003-4819-148-8-200804150-00001.

  PMID: 18413618 BACKGROUND

• 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.

  PMID: 19850682 BACKGROUND

• 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. doi: 10.1080/13697130701364644.

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• Fenichel P, Paris F, Philibert P, Hieronimus S, Gaspari L, Kurzenne JY, Chevallier P, Bermon S, Chevalier N, Sultan C. Molecular diagnosis of 5alpha-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.

  PMID: 23633205 BACKGROUND

• 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.

  PMID: 24845394 BACKGROUND

• 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. doi: 10.1097/01.GME.0000060256.03945.20.

  PMID: 14501599 BACKGROUND

• Gooren LJ, Bunck MC. Transsexuals and competitive sports. Eur J Endocrinol. 2004 Oct;151(4):425-9. doi: 10.1530/eje.0.1510425.

  PMID: 15476439 BACKGROUND

• 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.

  PMID: 19461542 BACKGROUND

• 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.

  PMID: 20150325 BACKGROUND

• 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.

  PMID: 24281237 BACKGROUND

• Jovanovic H, Kocoska-Maras L, Radestad AF, Halldin C, Borg J, Hirschberg AL, Nordstrom 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.

  PMID: 25462800 BACKGROUND

• Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr Rev. 1987 Feb;8(1):1-28. doi: 10.1210/edrv-8-1-1.

  PMID: 3549275 BACKGROUND

• Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002 Apr;77 Suppl 4:S34-41. doi: 10.1016/s0015-0282(02)02968-0.

  PMID: 12007900 BACKGROUND

• Rickenlund A, Carlstrom 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. doi: 10.1016/s0015-0282(02)04850-1.

  PMID: 12749436 BACKGROUND

• Slayden SM. Risks of menopausal androgen supplementation. Semin Reprod Endocrinol. 1998;16(2):145-52. doi: 10.1055/s-2007-1016265.

  PMID: 9711680 BACKGROUND

• Turpeinen U, Linko S, Itkonen O, Hamalainen E. Determination of testosterone in serum by liquid chromatography-tandem mass spectrometry. Scand J Clin Lab Invest. 2008;68(1):50-7. doi: 10.1080/00365510701496496. Epub 2007 Jun 24.

  PMID: 17852804 BACKGROUND

• Zang H, Carlstrom 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. doi: 10.1016/j.fertnstert.2005.12.039. Epub 2006 Jun 5.

  PMID: 16750207 BACKGROUND

• Zang H, Sahlin L, Masironi B, Eriksson E, Linden Hirschberg A. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. J Clin Endocrinol Metab. 2007 Jun;92(6):2169-75. doi: 10.1210/jc.2006-2171. Epub 2007 Mar 6.

  PMID: 17341565 BACKGROUND

• 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.

  PMID: 19366676 BACKGROUND

• Horwath O, Moberg M, Hirschberg AL, Ekblom B, Apro W. Molecular Regulators of Muscle Mass and Mitochondrial Remodeling Are Not Influenced by Testosterone Administration in Young Women. Front Endocrinol (Lausanne). 2022 Apr 14;13:874748. doi: 10.3389/fendo.2022.874748. eCollection 2022.

  PMID: 35498440 DERIVED

• Elings Knutsson J, Andersson A, Baekken LV, Pohanka A, Ekstrom L, Hirschberg AL. Disposition of Urinary and Serum Steroid Metabolites in Response to Testosterone Administration in Healthy Women. J Clin Endocrinol Metab. 2021 Mar 8;106(3):697-707. doi: 10.1210/clinem/dgaa904.

  PMID: 33274381 DERIVED

• 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. 2020 May;54(10):599-604. doi: 10.1136/bjsports-2018-100525. Epub 2019 Oct 15.

  PMID: 31615775 DERIVED

MeSH Terms

Conditions

Female Athlete Triad Syndrome

Condition Hierarchy (Ancestors)

Relative Energy Deficiency in Sport; Feeding and Eating Disorders; Mental Disorders

Study Officials

• Angelica Lindén Hirschberg

  Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The testosterone cream and the placebo cream will be of identical appearance and will have the same texture to maintain double blind treatment.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 7, 2017
• Study Start: May 26, 2017
• Primary Completion: June 20, 2018
• Study Completion: June 20, 2018
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)