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Activin A and Follistatin in Menstrual Blood: Low Concentrations in Women With Dysfunctional Uterine Bleeding

Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil, Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy

Lívia L. Nascimento, MD

Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil

Anastasia Tsigkou, PhD

Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy

Márcia C. Ferreira, MD

Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil

Stefano Luisi, MD, PhD

Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy

Felice Petraglia, MD

Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy, petraglia{at}unisi.it

Activin A and follistatin are growth factors produced by several organs, comprising the endometrium, where they modulate cell and tissue differentiation. In this study, the authors tested whether activin A and follistatin are measurable in menstrual blood and whether their concentrations change in women with dysfunctional uterine bleeding (DUB). The authors evaluated healthy women with regular menstrual cycles (n = 15) and women with DUB (n = 12). Activin A and follistatin were measured in both menstrual and peripheral blood samples using highly sensitive enzyme immunoassays, whereas their respective mRNAs were quantified by real-time polymerase chain reaction in endometrial samples collected during the perimenstrual period. Activin A concentrations were 4-fold higher in menstrual than in peripheral serum of healthy women (mean ± SE, 4.24 ± 0.18 vs 1.00 ± 0.15 ng/mL, P < .001) and were significantly lower in women with DUB compared to healthy subjects (P < .001). Follistatin concentration was 8-fold higher in menstrual than in peripheral serum of healthy women (3.94 ± 0.49 vs 0.49 ± 0.04 ng/mL, P < .001) and was significantly lower in the menstrual serum of women with DUB compared to controls (P < .001). There was no correlation between menstrual and peripheral serum concentrations of both proteins. The endometrial expression of activin A and follistatin mRNA was lower in women with DUB compared to controls (P < .05). Both activin A and follistatin are measurable in high concentrations in human menstrual blood and are relatively lower in women with DUB. The quantitative assessment of activin A and follistatin in menstrual serum might be a putative clinical marker of endometrial function.

Key Words: Activin • follistatin • endometrium • menstruation.

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