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.
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.)
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 vaginal dryness, and moderate evidence that it can cause sleep disturbances in some women. There is inconclusive or insufficient evidence that ovarian aging is a major cause of mood swings, depression, impaired memory or concentration, somatic symptoms, urinary incontinence, or sexual dysfunction. In one U.S. study, nearly 60% of women reported hot flashes in the 2 years before their final menses. Symptom intensity, duration, frequency, and effects on quality of life are highly variable.
For women with irregular or heavy menses or hormone-related symptoms that impair quality of life, low-dose combined oral contraceptives are a staple of therapy. Static doses of estrogen and progestin (e.g., 20 μg of ethinyl estradiol and 1 mg of norethindrone acetate daily for 21 days each month) can eliminate vasomotor symptoms and restore regular cyclicity. Oral contraceptives provide other benefits, including protection against ovarian and endometrial cancers and increased bone density, although it is not clear whether use during perimenopause decreases fracture risk later in life. Moreover, the contraceptive benefit is important, given that the unintentional pregnancy rate among women in their forties rivals that of adolescents. Contraindications to oral contraceptive use include cigarette smoking, liver disease, a history of thromboembolism or cardiovascular disease, breast cancer, or unexplained vaginal bleeding. Progestin-only formulations (e.g., 0.35 mg norethindrone daily) or medroxyprogesterone (Depo-Provera) injections (e.g., 150 mg IM every 3 months) may provide an alternative for the treatment of perimenopausal menorrhagia in women who smoke or have cardiovascular risk factors. Although progestins neither regularize cycles nor reduce the number of bleeding days, they reduce the volume of menstrual flow.
Nonhormonal strategies to reduce menstrual flow include use of nonsteroidal anti-inflammatory agents such as mefenamic acid (initial dose of 500 mg at start of menses, then 250 mg qid for 2–3 days) or, when medical approaches fail, endometrial ablation. It should be noted that menorrhagia requires an evaluation to rule out uterine disorders. Transvaginal ultrasound with saline enhancement is useful for detecting leiomyomata or polyps, and endometrial aspiration can identify hyperplastic changes.
For sexually active women using contraceptive hormones to alleviate perimenopausal symptoms, the question of when and if to switch to HT must be individualized. Doses of estrogen and progestogen (either synthetic progestins or natural forms of progesterone) in HT are lower than those in oral contraceptives and have not been documented to prevent pregnancy. Although a 1-year absence of spontaneous menses reliably indicates ovulation cessation, it is not possible to assess the natural menstrual pattern while a woman is taking an oral contraceptive. Women willing to switch to a barrier method of contraception should do so; if menses occur spontaneously, oral contraceptive use can be resumed. The average age of final menses among relatives can serve as a guide for when to initiate this process, which can be repeated yearly until menopause has occurred.
One of the most complex health ...