The pathophysiologic consequences of menopause may be best understood by considering that the ovary is a women’s only source of oocytes, her primary source of estrogen and progesterone, and a major source of androgens. Menopause results in infertility secondary to oocyte depletion. Ovarian cessation of progesterone production appears to have no clinical consequences except for the increased risk of endometrial proliferation, hyperplasia, and cancer associated with continued endogenous estrogen production or administration of unopposed estrogen therapy in menopausal women. The possible effects of declining androgen concentrations that occur with aging are an area of controversy and active investigation.
The major consequences of menopause are related primarily to estrogen deficiency. It is very difficult to distinguish the consequences of estrogen deficiency from those of aging, as aging and menopause are inextricably linked. Studying the effects of estrogen deficiency and replacement in young women with ovarian failure or of drugs that suppress estrogen synthesis (such as gonadotropin-releasing hormone antagonists) helps to distinguish between the effects of aging and estrogen deficiency. These models are imperfect, though, and differ from natural menopause in many ways.
Principal health concerns of menopausal women include vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, cognitive decline, and sexual problems. Options for caring for menopausal women have increased greatly since hormone therapy was first introduced in the 1960s. With respect to hormone use, there are many choices of hormone type, dose, and method of administration. In addition to hormones, estrogen agonistantagonists, centrally acting agents, and bisphosphonates are available to treat menopausal health concerns. Women are requesting more information on complementary and alternative therapies, which are being studied more carefully. The many options now available make caring for the postmenopausal woman more challenging and more rewarding.
Vasomotor symptoms affect up to 75% of perimenopausal women. Symptoms last for 1 to 2 years after menopause in most women, but may continue for up to 10 years or longer in others. Hot ﬂashes are the primary reason women seek care at menopause. Hot ﬂashes disturb women at work, interrupt daily activities and disrupt sleep (5). Many women report difficulty concentrating and emotional lability during the menopausal transition. Treatment of vasomotor symptoms should improve these cognitive and mood symptoms if they are secondary to sleep disruption and its resulting daytime fatigue. The incidence of thyroid disease increases as women age; therefore, thyroid function tests should be performed if vasomotor symptoms are atypical or resistant to therapy.
The physiologic mechanisms underlying hot ﬂashes are incompletely understood. A central event, probably initiated in the hypothalamus, drives an increased core body temperature, metabolic rate, and skin temperature; this reaction results in peripheral vasodilation and sweating in some women. The central event may be triggered by noradrenergic, serotoninergic, and/or dopaminergic activation. Although an LH surge often occurs at the time of a hot ﬂash, it is not causative, because vasomotor symptoms occur in women who had their pituitary glands removed. In symptomatic postmenopausal women, hot ﬂashes likely are triggered by small elevations in core body temperature acting within a narrow thermoneutral zone (6). Exactly how estrogen and alternative therapies play a role in modulating these events is unknown. Vasomotor symptoms are a consequence of estrogen withdrawal, not simply estrogen deficiency. For example, a young woman with primary ovarian insufficiency resulting from Turner syndrome will have a very high FSH level and low estrogen levels, but she will not experience hot ﬂashes until she is treated with estrogens and then therapy is withdrawn.