Johannes D. Veldhuis, MD


March 15, 2000

In This Article


The World Health Organization has defined the perimenopause as the interval preceding cessation of menses through 1 year after the last spontaneous bleeding cycle, which, according to the findings of the Massachusetts's Women's Health Study, is a mean span of about 3 1/2 years. There is still no known biochemical signal that reliably indicates the onset of menopause. However, serum FSH levels tend to rise in regularly menstruating late-premenopausal women (42-50 years of age). The pulsatility and the orderliness of LH release also change before menstrual cyclicity falters.[1] Estrogen secretion in the perimenopause is variable, and includes intervals of increased production. A greater stimulation by FSH may increase follicular aromatase activity and induce estrogen excess. Inhibin concentrations fall perimenopausally and contribute to heightened FSH release.

Hot flushes may precede the onset of anovulatory cycles in the perimenopause. Physical complaints, such as breast tenderness, irregular menstrual bleeding, hot flushes, and dyspareunia; and emotional concerns, such as disrupted sleep, fatigue, tension, and irritability, are equally represented among menopausal women in North America.[24] Some of the relevant physiologic effects of estrogen that ameliorate the consequences of menopause may be exerted via the 10 or more membrane (nongenomic) binding sites for estradiol, which regulate ion flow and kinase signaling. In addition, the alpha and recently cloned beta isoforms of the estrogen receptor mediate classical DNA-dependent interactions within the target cell. New designer estrogens, such as raloxifene (Evista), which act as selective estrogen-receptor modulators (SERMs), may or may not confer the same neurobiologic effects as estrogen.[5]