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Menopause is the permanent cessation of menstruation due to loss of ovarian follicular function. It is diagnosed retrospectively after 12 months of amenorrhea. The average age at menopause is 51 years among U.S. women. Perimenopause refers to the time period preceding menopause, when fertility wanes and menstrual cycle irregularity increases, until the first year after cessation of menses. The onset of perimenopause precedes the final menses by 2 to 8 years, with a mean duration of four years. Smoking accelerates the menopausal transition by 2 years.

Although the peri- and postmenopausal transitions share many symptoms, the physiology and clinical management differ. Low-dose oral contraceptives have become a therapeutic mainstay in perimenopause, whereas postmenopausal hormone therapy (HT) has been a common method of symptom alleviation after menstruation ceases.


Ovarian mass and fertility decline sharply after age 35 and even more precipitously during perimenopause; depletion of primary follicles, a process that begins before birth, occurs steadily until menopause (Chap. 347). In perimenopause, intermenstrual intervals shorten significantly (typically by 3 days) due to an accelerated follicular phase. Follicle-stimulating hormone (FSH) levels rise due to altered folliculogenesis and reduced inhibin secretion. In contrast to the consistently high FSH and low estradiol levels seen in menopause, perimenopause is characterized by "irregularly irregular" hormone levels. The propensity for anovulatory cycles can produce a hyperestrogenic, hypoprogestagenic environment that may account for the increased incidence of endometrial hyperplasia or carcinoma, uterine polyps, and leiomyoma observed among women of perimenopausal age. Mean serum levels of selected ovarian and pituitary hormones during the menopausal transition are shown in Fig. 348-1. With transition into menopause, estradiol levels fall markedly, whereas estrone levels are relatively preserved, reflecting peripheral aromatization of adrenal and ovarian androgens. FSH levels increase more than those of luteinizing hormone (LH), presumably because of the loss of inhibin, as well as estrogen feedback.

Figure 348-1

Mean serum levels of ovarian and pituitary hormones during the menopausal transition. FSH, follicle-stimulating hormone; LH, luteinizing hormone. (From JL Shifren, I Schiff: J Womens Health Gend Based Med 9 Suppl 1:S3, 2000, with permission.)

Diagnostic Tests

Because of their extreme intraindividual variability, FSH and estradiol levels are imperfect diagnostic indicators of perimenopause in menstruating women. However, a low FSH in the early follicular phase (days 2 through 5) of the menstrual cycle is inconsistent with a diagnosis of perimenopause. FSH measurement can also aid in assessing fertility; levels of <20 mIU/mL, 20 to <30 mIU/mL, and 30 mIU/mL measured on day 3 of the cycle indicate a good, fair, and poor likelihood of achieving pregnancy, respectively.


Determining whether symptoms that develop in midlife are due to ovarian senescence or to other age-related changes is difficult. There is strong evidence that the menopausal transition can cause hot flashes, night sweats, irregular bleeding, and ...

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