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
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
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
Trusts, charities, foundations (both public and private)
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
4. 2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/31389293 (added 09/08/2019)