Condition category
Pregnancy and Childbirth
Date applied
29/01/2018
Date assigned
05/02/2018
Last edited
05/02/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Polycystic ovary syndrome (PCOS) is the most condition that affects the ovaries. Its main characteristics are hyperandrogenism (high levels of male horomones), chronic anovulation (not ovulating) and polycystic ovaries (ovaries covered with cysts). Obesity and hyperinsulinemia (high levels of insulin) are also highly prevalent among women with PCOS. These issues can negatively affect endometrial function (the lining of the uterus). Impaired endometrial function is leading to implantation failure and endometrial abnormalities, such as hyperplasia (the enlargement of organs) and cancer. The aim of this study is to investigate whether weight loss and improved menstrual function can affect the expression of hormonal receptors that are of important for endometrial function in women with PCOS.

Who can participate?
Women aged 18-40 years old who have PCOS.

What does the study involve?
Participants are allocated to groups based on their weight. Participants are provided with individualized diet plans that are high in protein and low in carbohydrates. It is dietician supervised. Participants who are overweight are provided with a membership to a local exercise facility. Recommendations regarding the type, duration and frequency of training were individualized on the basis of interest, experience and present condition, with a weekly average of 2 or 3 45-min sessions of aerobic activity and verification by the staff of the gym. Participants are assessed before the intervention and on days 6-8, 21-24 of their menstruation cycle. Blood samples are taken from participants and analyzed. Endometrial biopsies are taken and transvaginal ultrasounds are done. Participants record their menstrual bleedin in a diary.

What are the possible benefits and risks of participating?
All patients participating in the study undergo general health check as well as gynecological examination. Taking part in the lifestyle intevention can result in improvement of general health. The risks of participating in the study are judged to be small. Endometrial biopsy and blood sampling are clinical routine examinations and rarely cause greater discomfort or complications. The overall risk is judged to be small in relation to the benefit of participating in the study.

Where is the study run from?
1. Swedish Research Council (Sweden)
2. Swedish Cancer Society (Sweden)
3. Karolinska Institutet (Sweden)

When is the study starting and how long is it expected to run for?
January 2008 to December 2012

Who is funding the study?
1. Swedish Research Council (Sweden)
2. The Swedish Cancer Society (Sweden)
3. Karolinska Institutet (Sweden)
4. Regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet (ALH, LS) (Sweden)

Who is the main contact?
Prof Angelica Lindén Hirschberg (Scientific)
angelica.linden-hirschberg@sll.se

Trial website

Contact information

Type

Scientific

Primary contact

Prof Angelica Lindén Hirschberg

ORCID ID

Contact details

Department of Women's and Children's Health
Karolinska Institutet
Stockholm
17176
Sweden

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Dnr 2008/865-32

Study information

Scientific title

Hormonal and metabolic effects of diet and physical activity in women with polycystic ovary syndrome (PCOS) - a lifestyle intervention study

Acronym

Study hypothesis

Lifestyle intervention aiming at weight loss could improve reproductive and metabolic health including endometrial function in overweight/obese women with PCOS.

Ethics approval

Regional Ethics Committee Stockholm, 2008/06/18, ref: Dnr 2008/865-32

Study design

Prospective lifestyle intervention study

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

Polycystic ovary syndrome (PCOS)

Intervention

The three-month individualized intervention involved changes in lifestyle designed to achieve weight loss. The diet was high in protein with little carbohydrate (40E% carbohydrates, 30E% fat and 30E% proteins). The dietician supervised and recommended the participants to intake three major meals and two or three snacks daily. Each participant reported her food intake, which was adjusted if necessary. In order to increase physical activity, all overweight women with PCOS are provided with membership in a local exercise facility (Friskis & Svettis). Recommendations regarding the type, duration and frequency of training were individualized on the basis of interest, experience and present condition, with a weekly average of 2 or 3 45-min sessions of aerobic activity and verification by the staff of the gym.

The group of overweight/obese women with PCOS are examined before and immediately after the intervention, on days 6-8 and 21-23 of the menstrual cycle (assessed on the basis of spontaneous menstruation or bleeding induced by administration of 10 mg medroxyprogesterone acetate daily for 7 days). The women of normal weight with PCOS and all controls are examined once on days 6-8 and 21-23 of the same menstrual cycle.

While still fasting, a blood sample was taken from a peripheral vein at the same time each morning. Serum collected by centrifugation was stored at -70° C for later analyses. All gynecological examinations, including transvaginal ultrasound, are performed with the Sonoline SL-250 apparatus (Siemens Healthcare Diagnostics) by a single investigator. Under local anesthesia, endometrial biopsies were taken with a suction curette (Pipet Curet, CooperSurgical, USA).

During the intervention, the women in the OB-PCOS group recorded their menstrual bleedings in a diary and their ovulation are monitored (serum progesterone > 17 nmol/l). Alteration from amenorrhea to oligomenorrhea/regular menstruation or from oligomenorrhea to regular menstruation was defined as improvement.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measure

Weight change is measured using the body weight at baseline and 12 weeks.

Secondary outcome measures

1. Menstrual function is evaluated using recordings of menstrual pattern and blood sampling of hormones during the intervention. The menstrual function is considered to be improved from baseline to 12 weeks when there is a shift from amenorrhea to oligomenorrhea/regular menstruation or from oligomenorrhea to regular menstruation and/or ovulation is confirmed by increased serum progesterone >17 nmol/L
2. Insulin sensitivity of the endometrium is measured using determination of gene and protein levels of molecules involved in insulin signaling at baseline and 12 weeks
3. Endometrial hormone receptor expression is measured using determination of gene and protein levels of hormone receptors at baseline and 12 weeks

Overall trial start date

01/01/2008

Overall trial end date

31/12/2012

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. All Rotterdam criteria for the diagnosis of PCOS should be met (anovulation, hyperandrogenism, polycystic ovaries)
2. 18-40 years
3. BMI >27
4. No medication or hormone-containing contraceptives for 3 months before beginning the study
5. Willing to sign informed consent

Healthy controls:
Women with normal weight with PCOS

Participant type

Mixed

Age group

Adult

Gender

Female

Target number of participants

50 women with complete investigations

Participant exclusion criteria

1. Pregnancy or lactation during preceding 12 months
2. Smoking
3. Use of hormone-containing contraceptives
4. Current disease
5. Regular medication including insulin-sentizing drugs
6. Eating disorder

Recruitment start date

01/07/2008

Recruitment end date

31/12/2011

Locations

Countries of recruitment

Sweden

Trial participating centre

Karolinska University Hospital
Stockholm
171 76
Sweden

Sponsor information

Organisation

Karolinska Institutet

Sponsor details

Solnavägen 1
Stockholm
17176
Sweden
+46 08 524 800 00
registrator@ki.se

Sponsor type

University/education

Website

http://ki.se

Funders

Funder type

Not defined

Funder name

Swedish Research Council

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Cancerfonden

Alternative name(s)

Swedish Cancer Society

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

Sweden

Funder name

Karolinska Institutet

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Three papers from the study have been published. There are plans to publish three more papers in high-impact peer reviewed journals.

IPD Sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from Angelica Lindén Hirschberg: angelica.linden-hirschberg@sll.se

Intention to publish date

05/02/2019

Participant level data

Available on request

Basic results (scientific)

Publication list

1. 2014 results in https://www.ncbi.nlm.nih.gov/pubmed/24842895
2. 2016 results in https://www.ncbi.nlm.nih.gov/pubmed/26649621
3. 2017 results in https://www.ncbi.nlm.nih.gov/pubmed/28388727

Publication citations

Additional files

Editorial Notes