Trial With Metformin in Women With Polycystic Ovary Syndrome

Study Description

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Brief Summary:

The investigators wanted to elucidate the effects of metformin in Polycystic Ovary Syndrome (PCOS) by performing a randomized, double-blinded, placebo-controlled cross-over study.

Condition or disease	Intervention/treatment	Phase
Polycystic Ovary Syndrome	Drug: Metformin; Drug: Placebo	Phase 4

Detailed Description:

Eligible women who gave written informed consent were assigned to 6 months of treatment with either 850 mg of metformin or placebo twice daily, followed by a wash-out period of 3 months before cross-over to the alternate treatment for another 6 months. Randomization defining treatment sequence was done at inclusion by random number tables. The appearance of the tablets was identical, and patients and investigators were blinded to treatment allocation. The randomization code was stored in a closed envelope until all participants had finished the treatment. Participants were seen by one of the investigators before inclusion and every second month during treatment periods, always in the morning after an overnight fast of at least 8 h. They were weighed wearing light clothing. Waist circumference was measured at the umbilical level and hip circumference at the trochanter region. Systolic and diastolic blood pressure was measured with a semiautomatic blood pressure monitor and a blood sample was drawn for immediate analysis without respect to bleeding periods. All participants registered their bleeding periods in a calendar during both study periods and the 3 months wash-out period. Calculation of sample size was based on the assumption that at least 50% of the women would experience at least 30% more menstrual periods on metformin than on placebo. Based on a power of 90 (b = 0.10) to detect a significant difference [two-sided P-value of 0.05], the minimum sampling size was calculated to 44 subjects.

We also assumed a 10% drop-out rate, and thus aimed at including 50 women. As drop-out rate quickly rose higher than expected, we decided to include 60 women. In the intention-to-treat analysis, the values of each participant after 6 months of metformin or placebo were compared with the baseline values. Linear regression analysis with the changes in testosterone and homeostasis model assessment (HOMA) index as dependent variables was performed to examine potential relations between the changes. The per protocol analysis included data from participants completing both study periods, i.e. the difference between the values of each participant after placebo and metformin, respectively, was calculated, and a significance test performed on the differences.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	56 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Double (Participant, Care Provider)
Primary Purpose:	Treatment
Official Title:	Randomized, Cross-over Trial With Metformin in Women With Polycystic Ovary Syndrome
Study Start Date :	September 2001
Actual Primary Completion Date :	December 2002
Actual Study Completion Date :	December 2002

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: Metformin; Metformin 850 mg x 2 in six months	Drug: Metformin; Metformin 1500 mg (=2 pills) per day in six months
Placebo Comparator: Placebo; Placebo 2 tablets daily for six months	Drug: Placebo; 2 pills per day in six months; pills look like metformin pills

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Testosterone (Levels of free testosterone) [ Time Frame: six months ]
   Levels of free testosterone

Secondary Outcome Measures :

1. Insulin sensitivity (measured homeostasis model assessment (HOMA) index) [ Time Frame: Six months ]
   Insulin sensitivity measured homeostasis model assessment (HOMA) index

Other Outcome Measures:

1. Body weight change [ Time Frame: Six months ]
   Body weight changes

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 45 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• testosterone value above the upper normal limit and
• oligo- or amenorrhea,

Exclusion Criteria:

• periclimacteric gonadotrophin values,
• hyperprolactinaemia,
• diabetes mellitus,
• impaired thyroid,
• renal or hepatic function,
• hormonal treatment,
• pregnancy,
• lactation or a wish for fertility treatment.

Contacts and Locations

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Locations

Denmark
Gynecology Dept. Herning Hospital
Herning, Denmark, 7400

Sponsors and Collaborators

Herning Hospital

GEA A/S Denmark

Investigators

Principal Investigator:	Finn F Lauszus, MD, PhD	Gyn Dept. Herning Hospital, Herning, Denmark

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Trolle B, Flyvbjerg A, Kesmodel U, Lauszus FF. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Hum Reprod. 2007 Nov;22(11):2967-73. Epub 2007 Aug 31.

Trolle B, Lauszus FF, Frystyk J, Flyvbjerg A. Adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a randomized controlled study. Fertil Steril. 2010 Nov;94(6):2234-8. doi: 10.1016/j.fertnstert.2010.01.057. Epub 2010 Mar 2.

Greibe E, Trolle B, Bor MV, Lauszus FF, Nexo E. Metformin lowers serum cobalamin without changing other markers of cobalamin status: a study on women with polycystic ovary syndrome. Nutrients. 2013 Jul 5;5(7):2475-82. doi: 10.3390/nu5072475.

Madsen HN, Lauszus FF, Trolle B, Ingerslev HJ, Tørring N. Impact of metformin on anti-Müllerian hormone in women with polycystic ovary syndrome: a secondary analysis of a randomized controlled trial. Acta Obstet Gynecol Scand. 2015 May;94(5):547-51. doi: 10.1111/aogs.12605. Epub 2015 Mar 4.

Responsible Party:	Finn Friis Lauszus, Senior Consultant, Herning Hospital
ClinicalTrials.gov Identifier:	NCT02280057 History of Changes
Other Study ID Numbers:	2166-00
First Posted:	October 31, 2014
Last Update Posted:	February 23, 2017
Last Verified:	February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Finn Friis Lauszus, Herning Hospital:

PCOS; metformin; obesity; randomized controlled trial

Additional relevant MeSH terms:

Syndrome; Polycystic Ovary Syndrome; Disease; Pathologic Processes; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases	Adnexal Diseases; Genital Diseases, Female; Gonadal Disorders; Endocrine System Diseases; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs