Ovaries out of control – hormonal strategies

Abstract

The perimenopausal transition represents a therapeutic challenge for clinicians as the follicular activity of the ovaries does not decline gradually and evenly, but is accompanied by a pronounced up and down of hormone production. The female menstrual cycle involves a highly regulated chain of neuro-endocrine phenomena, maintained by a constant dialogue between the hypothalamus, the pituitary gland and the ovaries. Besides FSH, LH, estradiol and progesterone, other components of this dialogue are inhibin A and B, AMH as well as the KNDy neurons in the arcuate nucleus. Approaching menopause the number of primordial follicles declines to a critically low level. As a result a series of endocrine changes occur and the highly coordinated feed-back loops between the regulating levels is increasingly disturbed. The pituitary-ovarian axis is no longer subject to the laws of the fertile phase: Follicular activity fluctuates and there are periods of estrogen excess alternating with periods of estrogen deficiency. Luteal insufficiencies and anovulation increasingly occur and asynchronous maturation of follicles can lead to so-called "LOOP-events" = "luteal out of phase-events. The strongly fluctuating levels of steroidal hormones can lead to pronounced bleeding disorders and may be responsible for sleep disturbances and depressive moods, both typical symptoms of the early and mid perimenopausal transition.