Inhibins, Activins, and Follistatin in the Aging Female and Male

Joshua M. Hurwitz, M.D.; Nanette Santoro, M.D


Semin Reprod Med. 2004;22(3) 

In This Article

Abstract and Introduction

Dimeric inhibins, activins, and follistatin (FS) were all initially characterized as reproductive endocrine hormones that regulate follicle-stimulating hormone (FSH) secretion. This model, however, has expanded under the weight of current medical evidence. Activin appears to play a central auto/paracrine role in reproductive and nonreproductive tissues. Inhibin and FS each have important counterregulatory functions in activin signaling. With reproductive aging, inhibin B declines along with the follicular pool and disturbs the dynamics of the normal menstrual cycle of midreproductive age. The loss of inhibin restraint of FSH secretion appears to be the initiating endocrine event that leads to menstrual cycle shortening and some of the hormonal unpredictability of the late reproductive years. It may also be related to the decline in fertility that occurs in reproductive aging. In men, inhibin B is an excellent marker for gonadal competence, and the decline of inhibin B with age reflects decreased gonadal reserve in both sexes. Circulating activin increases with aging, but its effect on reproduction in women and men is not clear. FS does not appear to change greatly with aging in men or women. The age-related fluctuations in this delicately balanced regulatory triad influence reproductive capacity and the sequelae of chronological aging. Elucidation of the molecular pathways responsible for the action of these hormones may allow closer integration with their current conceptual roles in aging.

The regulatory triangle of dimeric inhibin, activin, and follistatin (FS) has been explored by both observational and molecular techniques to delineate their roles in the human menstrual cycle. Several investigations have centered on the changes of these hormones in older ovulatory women and support a role for the inhibin-activin-FS axis in reproductive aging in women[1,2,3,4,5,6,7,8] and men.[9,10,11,12,13,14] This article attempts to synthesize the existing evidence for the dynamics of these chronological changes in women and men and examine their possible implications.