Possible metformin effect on adrenal androgens during pretreatment and IVF cycle in women with polycystic ovary syndrome

Kjøtrød, Sigrun B.; Sunde, Arne; von Düring, Vidar; Carlsen, Sven M.

doi:10.1016/j.fertnstert.2007.11.069

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Volume 91, Issue 2 , Pages 500-508, February 2009

Possible metformin effect on adrenal androgens during pretreatment and IVF cycle in women with polycystic ovary syndrome

Sigrun B. Kjøtrød, M.D.
- IVF Unit, Department of Obstetrics and Gynaecology, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway
- Reprint requests: Sigrun Kjøtrød, M.D., IVF-Unit, Department of Obstetrics and Gynaecology, St. Olavs Hospital, Trondheim University Hospital, Olav Kyrres gt 17, N-7006 Trondheim, Norway (FAX: +47 72573901).
Arne Sunde, Ph.D.
- IVF Unit, Department of Obstetrics and Gynaecology, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway
- Department of Laboratory Medicine, Women's and Children's Health, Norwegian University of Science and Technology, Trondheim, Norway
Vidar von Düring, M.D.
- IVF Unit, Department of Obstetrics and Gynaecology, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway
Sven M. Carlsen, M.D., Ph.D.
- Department of Endocrinology, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway
- Department of Laboratory Medicine, Women's and Children's Health, Norwegian University of Science and Technology, Trondheim, Norway

Received 17 September 2007; received in revised form 19 November 2007; accepted 19 November 2007. published online 26 February 2008.

Objective

To determine the effects of metformin treatment on serum androgen levels ahead of and during the IVF cycle in infertile polycystic ovary syndrome (PCOS) women.

Design

A prospective, double-blind, placebo-controlled study.

Setting

Single-center, university IVF clinic.

Patients

Sixty-three PCOS women.

Intervention(s)

Treatment with metformin 2,000 mg/day or identical placebo tablets for at least 14 weeks before and then during IVF treatment, ending on the day of hCG injection.

Main Outcome Measure(s)

Serum levels of dehydroepiandrosterone, dehydroepiandrosterone sulphate (DHEAS), androstenedione, free testosterone index (FTI), dihydrotestosterone, and the androgen metabolite 5α-androstane-3α, 17β-diol-glucuronide were measured at five time points ending on the day of ovum collection.

Result(s)

During metformin pretreatment DHEAS increased, wheres other androgens were unaffected. During the IVF procedure androgens were unaffected by metformin treatment. Within 36 hours after the study medication was withdrawn the levels of androstenedione and FTI increased in the metformin group, whereas DHEAS decreased.

Conclusion(s)

In infertile PCOS women metformin treatment increased DHEAS levels. During the IVF cycle androgen levels were unaffected by metformin, whereas there was a “rebound” effect when stopping metformin treatment.

Key Words: Polycystic ovary syndrome, metformin, hyperandrogenemia, free testosterone index, dehydroepiandrosterone sulphate