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Stockpiling of Ovarian Follicles and the Response to Rosiglitazone

From the Department of Medicine, University of Alabama Birmingham, Division of Endocrinology, Birmingham, Alabama

Address correspondence to Tom Brooks Vaughan, UAB Department of Medicine, Division of Endocrinology, Faculty Office Tower, Suite 758, 510 20th St. S., Birmingham, AL 35294. E-mail: brooks{at}uab.edu

A 46-year-old woman of Euroasian descent had been treated for 2 years with 500 mg metformin twice daily for polycystic ovarian disease (PCO). While menarche occurred at age 12 years, she had no more than two to three menstrual periods per year except on two occasions in her 20s when, following a 9- to 10-kg weight loss, she achieved regular menstrual periods, became pregnant, and delivered two healthy infants with no complications.

While being treated with metformin, the woman was diagnosed as having diabetes based on two fasting serum glucoses tests >7 mmol/l. She was switched to a combination tablet containing 2-mg rosiglitazone and 500 mg metformin twice daily. Following this change, her serum total testosterone dropped from 2.5 to 1.12 nmol/l and her menstrual periods became regular for 4 months, after which she became amenorrheic. Because of her age and history of PCO, this did not cause concern, even though she had no menopausal symptoms. Six months later, after presenting with abdominal pain, it was discovered by ultrasonography that she was 30 weeks’ pregnant. Metformin and rosiglitazone were discontinued, and she was started on insulin therapy. At 36 weeks’ gestation she became hypertensive and at 37 weeks delivered a healthy 3.4-kg baby girl without neonatal complications.

Spontaneous pregnancy in this age range is unusual and has been estimated to be near 0% (1). The average age of last conception in a stable North American population (Hutterites) not practicing contraception was 40.9 years (1). This age-related decrease in fertility is attributed to loss of oocytes through years of ovulation. However, it has recently been noted that there is an increase in primary follicles in polycystic ovaries, a phenomenon described as "stockpiling," possibly due to anovulation or stasis (2). We suggest that in PCO patients, even in the age range where the rate of spontaneous pregnancy is low, utilization of thiazolidinediones should be accompanied by concurrent contraceptive use. These patients may achieve a more favorable hormonal milieu for ovulation in the setting of "stockpiled" ovarian follicles.

This case is also unique in that the patient was older and the length of rosiglitazone exposure longer than in the previous two reports of rosiglitazone exposure during pregnancy. Despite the known presence of rosiglitazone in fetal tissue, three reports have now documented normal fetal outcomes (3–5).

References

1. Tarlatzis B, Zepiridis L: Perimenopausal conception. Ann N Y Acad Sci 997:93–104, 2003[Abstract/Free Full Text]
   
2. Maciel G, Baracat E, Benda J, Markham S, Hensinger K, Chang J, Erickson G: Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome. J Clin End Met 89:5321–5327, 2004[Abstract/Free Full Text]
   
3. Yaris F, Yaris E, Kadioglu M, Ulku C, Kesim M, Kalyoncu N: Normal pregnancy outcome following inadvertent exposure ot rosiglitazone, gliclazide, and atorvostatin in a diabetic and hypertensive woman. Reprod Toxicol 18:619–621, 2004[Medline]
   
4. Kalyoncu N, Yaris F, Ulku C, Kadioglu M, Kesim M, Unsal M, Dikici M, Yaris E: A case of rosiglitazone exposure in the second trimester of pregnancy. Reprod Toxicol 19:563–564, 2005[Medline]
   
5. Chan L, Yeung J, Lau T: Placental transfer of rosiglitazone in the first trimester of human pregnancy. Fertil Steril 83:955–958, 2005[Medline]
   

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This article has been cited by other articles:

				A. B. Guirguis, R. M. Malone, P. R. Chelminski, and M. Pignone Conception as a Potential Consequence of Diabetes Treatment Clin. Diabetes, April 1, 2008; 26(2): 83 - 84. [Full Text] [PDF]

				T. A. Elhadd, T. Fiad, and L. Meer Ovarian Stockpiling in Polycystic Ovary Syndrome, Infertility, and the Combined Use of Rosiglitazone and Metformin Diabetes Care, October 1, 2006; 29(10): 2330 - 2331. [Full Text] [PDF]

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaughan, T. B. Articles by Bell, D. S.H. Search for Related Content PubMed PubMed Citation Articles by Vaughan, T. B. Articles by Bell, D. S.H. Social Bookmarking                What's this?