Condition category
Urological and Genital Diseases
Date applied
09/09/2004
Date assigned
15/10/2004
Last edited
06/07/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://groups.stakes.fi/THP/FI/hankkeet/kayEPHTtrial.htm

Contact information

Type

Scientific

Primary contact

Prof Elina Hemminki

ORCID ID

Contact details

Lintulahdenkuja 4
Helsinki
00530
Finland
+358 (0)9 3967 2307
Elina.Hemminki@stakes.fi

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

308901

Study information

Scientific title

Acronym

EPHT

Study hypothesis

The Estonian Postmenopausal Hormone Therapy (EPHT) trial is a randomised controlled trial, having blind and non-blind groups. By carrying out this trial comparing combined continuous postmenopausal Hormone Therapy (HT) to placebo or no drugs we will study:
1. Health effects of HT on the risk of cancers, coronary heart disease, cardiovascular disease, bone fractures
2. Immediate and long-term effects on well-being and quality of life
3. Effects on the experience of the climacteric and aging and partner relationship
4. Effects on the use of health services
5. Placebo effect and trial effect by means of the design as well as its effect on recruitment, adherence and trial outcomes

Outcome data have been collected by annual questionnaires to the women, from national health registers (cancer register, death register, sickness insurance), and patient records. The analysis is by intention to treat: the women could opt out from the randomised treatment, but they remain in the study until they die or are lost to follow-up.

In terms of long-term effects we assume that PHT will increase the incidence of breast cancer and decrease fractures. In terms of other diseases, we have no hypothesis on the direction of the effect. We assume that PHT will have beneficial effects to those of women who have menopausal symptoms, but regarding the direction of the effect on symptoms and well being in older women we have no a priori hypothesis. The impact on different dimensions is likely to vary. The same is true for social effects. We assume that PHT will increase the use of health services and result in more gynaecological interventions, including hysterectomy.

In terms of feasibility, the hypotheses are:
1. The non-blind arm will have better recruitment, fewer drop-outs, and will be cheaper
2. The blind trial will not be fully blind (women will guess the therapy because of drug effects), and will be less contaminated later in the trial, when PHT is likely to be more common in Estonia. Cost in the non-blind arm will be reduced both by anticipated fewer visits and less need for a thorough study of spotting and other bleeding.

Ethics approval

Ethics approval received from local research ethics committee (Tallinna Meditsiinieetika komitee) on the 22nd January 1998 (Signed Pavel Bogovski, Chief of the Ethical Committee).

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Menopausal disorders

Intervention

Blind group: The active drug is orally administered conjugated oestrogen 0.625 mg plus Medroxyprogesterone Acetate (MPA) 2.5 mg, taken every day (women within 3 years of their last period will receive an additional 2.5 mg of MPA), or matched placebo.

Non-blind group: Open label conjugated oestrogen 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg, taken every day. Women within 3 years of their last period will receive an additional 2.5 mg of MPA.

Control group: No intervention

Intervention type

Drug

Phase

Not Specified

Drug names

Oestrogen, medroxyprogesterone acetate

Primary outcome measures

1. Health effects:
1.1. The sum of major ischaemic heart diseases events (fatal and non-fatal myocardial infarction and sudden coronary death) and of stroke
1.2. The sum of major fractures
1.3. Mortality and incidence of breast cancer and other cancers. In case of breast cancer the stage and type of cancer will be specified
1.4. Deaths from all causes
2. Immediate and long-term effects on well-being and quality of life: data from the annual questionnaires including Women's Health Questionnaire (WHQ), EQ-5D scores, self-rated health status, list of symptoms
3. Effects on the experience of the climacteric and aging and partner relationship: data from the annual questionnaires
4. Effects on health services:
4.1. Inpatient health care costs
4.2. Outpatient health care costs
4.3. Costs of prescribed drugs
4.4. Costs of sickness leaves
4.5. Total number of health care visits
4.6. Number of visits to gynaecologists
4.7. Number of visits to family practitioners
4.8. Number of hospital care days
4.9. Number of hospitalisations
4.10. Number of days on sickness leave
4.11. Number of selected medical procedures
5. Methodological outcomes:
5.1. Recruitment rates
5.2. Adherence rates
5.3. Differences between the trial arms regarding outcomes in health effects, quality of life, health care use, well-being, symptoms and social effects

Secondary outcome measures

No secondary outcome measures

Overall trial start date

13/01/1999

Overall trial end date

30/04/2004

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women aged 50 - 64 years
2. Last period at least 12 months before recruitment

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1823

Participant exclusion criteria

Women with the following characteristics and health problems, as reported by women themselves or reported in patient records or health registers or found during the clinical examination are excluded from the study:
1. Current HT in last six months
2. Menstrual period within the last 12 months
3. Untreated endometrial adenomatosis or atypical hyperplasia of endometrium
4. Breast cancer, endometrial cancer, ovarian cancer
5. Any cancer treated less than 5 years ago
6. History of meningioma
7. Myocardial infarction within the last 6 months
8. History of hepatitis (not hepatitis A) or liver functional disorders during last 3 months
9. History of deep vein thrombosis, pulmonary embolism, cerebral infarction
10. Porphyria
11. Hypertension in spite of medication more than 170/110 mmHg
12. Endometriosis

Recruitment start date

13/01/1999

Recruitment end date

30/04/2004

Locations

Countries of recruitment

Estonia

Trial participating centre

Lintulahdenkuja 4
Helsinki
00530
Finland

Sponsor information

Organisation

National Research and Development Centre for Welfare and Health (STAKES) (Finland)

Sponsor details

Lintulahdenkuja 4
Helsinki
00530
Finland
+358 (0)9 39 671
Vappu.Taipale@stakes.fi

Sponsor type

Research organisation

Website

http://www.stakes.fi/EN/index.htm

Funders

Funder type

Research organisation

Funder name

National Research and Development Centre for Welfare and Health (STAKES) (Finland) (ref: 308901)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Academy of Finland (Finland) (refs: 48117, 201490)

Alternative name(s)

Academy of Finland

Funding Body Type

government organisation

Funding Body Subtype

federal

Location

Finland

Funder name

Ministry of Education in Finland (Finland)

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

Results - basic reporting

Publication summary

Results in:
1. 2005 progress report on patient recruitment in http://www.ncbi.nlm.nih.gov/pubmed/15826311
2. 2005 progress report on treatment adherence in http://www.ncbi.nlm.nih.gov/pubmed/16055284
3. 2006 results in http://www.ncbi.nlm.nih.gov/pubmed/16504428
4. 2006 results on cost effectiveness in http://www.ncbi.nlm.nih.gov/pubmed/16813745
5. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17355268
6. 2008 results on symptom reporting and quality of life in http://www.ncbi.nlm.nih.gov/pubmed/18366766
7. 2008 progress report in http://www.ncbi.nlm.nih.gov/pubmed/18366766
8. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19505307

Academic dissertations' at:
1. http://acta.uta.fi/pdf/951-44-6629-2.pdf
2. http://acta.uta.fi/pdf/978-951-44-7134-6.pdf

Publication citations

  1. Progress report on patient recruitment

    Hovi SL, Hakama M, Veerus P, Rahu M, Hemminki E, Who wants to join preventive trials?--Experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]., BMC Med Res Methodol, 2005, 5, 12, doi: 10.1186/1471-2288-5-12.

  2. Progress report on treatment adherence

    Vorobjov S, Hovi SL, Veerus P, Pisarev H, Rahu M, Hemminki E, Treatment adherence in the Estonian postmenopausal hormone therapy (EPHT) trial [ISRCTN35338757]., Maturitas, 52, 3-4, 286-295, doi: 10.1016/j.maturitas.2005.05.001.

  3. Results

    Veerus P, Hovi SL, Fischer K, Rahu M, Hakama M, Hemminki E, Results from the Estonian postmenopausal hormone therapy trial [ISRCTN35338757]., Maturitas, 2006, 55, 2, 162-173, doi: 10.1016/j.maturitas.2006.01.012.

  4. Results on cost effectiveness

    Veerus P, Fischer K, Hovi SL, Hakama M, Rahu M, Hemminki E, Postmenopausal hormone therapy increases use of health services: experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]., Am. J. Obstet. Gynecol., 2006, 195, 1, 62-71, doi: 10.1016/j.ajog.2005.12.037.

  5. Results

    Veerus P, Fischer K, Hovi SL, Karro H, Hemminki E, Does hormone replacement therapy affect the use of prescription medicines in postmenopausal women: experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]., BJOG, 2007, 114, 5, 548-554, doi: 10.1111/j.1471-0528.2007.01292.x.

  6. Results on symptom reporting and quality of life

    Veerus P, Fischer K, Hovi SL, Karro H, Rahu M, Hemminki E, Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial., BMC Womens Health, 2008, 8, 5, doi: 10.1186/1472-6874-8-5.

  7. Progress report

    Veerus P, Fischer K, Hovi SL, Karro H, Rahu M, Hemminki E, Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial., BMC Womens Health, 2008, 8, 5, doi: 10.1186/1472-6874-8-5.

  8. Results

    Hemminki E, Veerus P, Pisarev H, Hovi SL, Topo P, Karro H, The effects of postmenopausal hormone therapy on social activity, partner relationship, and sexual life - experience from the EPHT trial., BMC Womens Health, 2009, 9, 16, doi: 10.1186/1472-6874-9-16.

Additional files

Editorial Notes