Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Bone and muscle structure and function in relation to exercise and oestrogen replacement: a randomised double-blind placebo-controlled one-year-trial
Acronym
Ex/HRT-study
Study hypothesis
Deterioration of bone and muscle properties may occur after menopause. High-impact, power training and oestrogen-containing hormonal replacement therapy (HRT) may reverse these deteriorations. Combined treatments with both training and HRT may have additional effects.
Ethics approval
Ethical Committee of the Central Hospital of Central Finland has approved this study on 11th June 1996 (ref: Dnro1053/04/046/06). The study was re-evaluated concerning the use of DNA-samples and approved on the 18th October 2005.
Study design
Randomised double-blind placebo-controlled one-year-trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Osteopenia, sarcopenia
Intervention
Exercise (Ex): 1-year progressive physical training programme that included a supervised circuit training session twice a week and a series of exercises at home 4 days per week. Training was high-impact power training consisting of circuit training periods for 8 - 11 weeks, interrupted by three high-impact aerobic dance periods for 2 weeks and a summer pause for 5 weeks. They also used placebo tablets.
HRT: the combined oestradiol (2 mg) and noretisterone acetate (1 mg) product (Kliogest®, Novo Nordisk) was administered continously, one tablet per day for one year. The administration of HRT was conducted double-blinded.
Ex+HRT: participants conducted the training program and used HRT.
CO: control arm participants did not recieve any treatment, but they used placebo and were asked not to change their daily physical activities.
Total duration of the treatment was 12 months; the 12-month measurements were performed within a week of ending the treatments. This part of the trial was completed on the 30th August 1997.
A 10-year follow-up measurement was also performed for the participants who were willing to come back to the lab (n = 47). These measurements were performed from the 15th September to 24th November 2007. End of analysis and follow-up will be on the 31st December 2013.
Intervention type
Drug
Phase
Not Applicable
Drug names
Oestradiol, noretisterone acetate (Kliogest®)
Primary outcome measure
1. Developing methods for the testing of material and structural changes in the trabecular and cortical bone sites of the lower leg in relation to high-impact exercise and hormone replacement:
1.1. Single photon absorption method
1.2. Computed tomography
1.3. Elastic wave propagation
1.4. Ultrasonography
2. The effects of a high-intensity, explosive-type physical training and hormonal replacement on lower leg muscle mass, structure and performance in post-menopausal women:
2.1. Ultrasonography
2.2. Computed tomography
2.3. Muscle biopsies
2.4. Maximal isometric strength measurements with dynamometer chair
2.5. Measurement of explosive muscle power; ability to elevate the body's centre of gravity during vertical jumps onto a contact mat
2.6. Muscle performance; maximal running speed over 20 m distance
All measurements were done at baseline (0 months), at mid-point (6 months) and after completion of the treatments (12 months).
Secondary outcome measures
1. Examining the molecular mechanism responding to high-intensity, explosive-type physical training and hormonal replacement by using muscle biopsies, taken at baseline, after 0.5 years of study onset and after 1 year of study onset, by microarray and other applicable molecular methods
2. Examining the adaptation of bone collagen metabolism and the different types of muscle fibres to altered force transmission and oestrogen status (using serum and urine samples to determine the content of deoxypyridinoline in overnight (10 hour) samples and using immunohistochemical methods with respective antibodies
All measurements were done at baseline (0 months), at mid-point (6 months) and after completion of the treatments (12 months).
Overall trial start date
01/09/1996
Overall trial end date
31/12/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. No serious medical conditions
2. No current or previous use of medications including oestrogen, fluoride, calcitonin, biophosphonates or steroids
3. Last menstruation at least 0.5 years but not more than 5 years ago
4. Follicle-stimulating hormone leves greater than 30 iu/litre
5. No contra-indications for exercise and HRT
6. Aged 50 - 57, caucasian post-menopausal women
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
80
Participant exclusion criteria
1. Serious medical conditions
2. Current or previous use of medications including oestrogen, fluoride, calcitonin, biophosphonates or steroids
3. Currently menstruating or having last menstruation within 0.5 years of the onset of study or longer than 5 years ago
4. Follicle-stimulating hormone leves less than 30 iu/litre
5. Contra-indications for exercise and HRT
Recruitment start date
01/09/1996
Recruitment end date
31/12/2013
Locations
Countries of recruitment
Finland
Trial participating centre
PO Box 35
Jyväskylä
40014
Finland
Sponsor information
Organisation
University of Jyvaskyla (Finland)
Sponsor details
Department of Health Sciences
P.O.Box 35
Jyväskylä
FI-40014
Finland
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Finnish Academy (Finland) - 1st January 1996 - 1st January 2001
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Finnish Funding Agency for Technology and Innovation (TEKES) (Finland) - 1st January 1996 - 1st January 2001
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Finnish Ministry of Education (Finland) (ref: 98/772/2002)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Protocol and methods:
1. 2000 developing methods for assessing changes in bone results in http://www.ncbi.nlm.nih.gov/pubmed/10893682
2. 2002 developing methods for testing the material changes and turnover in bone results in http://www.ncbi.nlm.nih.gov/pubmed/12073156
Results:
1. 1999 ultrasound and bone mineral density assessment results in http://www.ncbi.nlm.nih.gov/pubmed/10499970
2. 2001 initial results in http://www.ncbi.nlm.nih.gov/pubmed/11473488
3. 2002 bone mass distribution results in http://www.ncbi.nlm.nih.gov/pubmed/12110425
4. 2004 lower-body muscle power results in http://www.ncbi.nlm.nih.gov/pubmed/15161458
5. 2005 muscle attenuation results in http://www.ncbi.nlm.nih.gov/pubmed/16117734
6. 2007 muscular transcriptome results in http://www.ncbi.nlm.nih.gov/pubmed/17985945
Publication citations
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Developing methods for assessing changes in bone results
Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Väänänen HK, Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption., J. Bone Miner. Res., 2000, 15, 7, 1337-1345, doi: 10.1359/jbmr.2000.15.7.1337.
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Developing methods for testing the material changes and turnover in bone results
Halleen JM, Ylipahkala H, Alatalo SL, Janckila AJ, Heikkinen JE, Suominen H, Cheng S, Väänänen HK, Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other markers of bone turnover and bone mineral density., Calcif. Tissue Int., 2002, 71, 1, 20-25, doi: 10.1007/s00223-001-2122-7.
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Ultrasound and bone mineral density assessment results
Cheng S, Suominen H, Ollikainen S, Goll J, Sipilä S, Taaffe D, Fuerst T, Njeh CF, Genant HK, Comparison of ultrasound and bone mineral density assessment of the calcaneus with different regions of interest in healthy early menopausal women., J Clin Densitom, 1999, 2, 2, 117-126.
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Initial results
Sipilä S, Taaffe DR, Cheng S, Puolakka J, Toivanen J, Suominen H, Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study., Clin. Sci., 2001, 101, 2, 147-157.
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Bone mass distribution results
Cheng S, Sipilä S, Taaffe DR, Puolakka J, Suominen H, Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women., Bone, 2002, 31, 1, 126-135.
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Muscle attenuation results
Taaffe DR, Sipilä S, Cheng S, Puolakka J, Toivanen J, Suominen H, The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention., Clin Physiol Funct Imaging, 2005, 25, 5, 297-304, doi: 10.1111/j.1475-097X.2005.00628.x.
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Muscular transcriptome results
Pöllänen E, Ronkainen PH, Suominen H, Takala T, Koskinen S, Puolakka J, Sipilä S, Kovanen V, Muscular transcriptome in postmenopausal women with or without hormone replacement., Rejuvenation Res, 2007, 10, 4, 485-500, doi: 10.1089/rej.2007.0536.
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Sipilä S, Koskinen SO, Taaffe DR, Takala TE, Cheng S, Rantanen T, Toivanen J, Suominen H, Determinants of lower-body muscle power in early postmenopausal women., J Am Geriatr Soc, 2004, 52, 6, 939-944, doi: 10.1111/j.1532-5415.2004.52261.x.