Contraindications to hormone therapy use include known or suspected breast or endometrial cancer, undiagnosed abnormal genital bleeding, cardiovascular disease (including coronary heart disease, cerebrovascular disease, and thromboembolic disorders), and active liver or gallbladder disease. Relative contraindications include high-risk states for the above disorders.
Menopause, the permanent cessation of menstruation, occurs at a mean age of 51 years. Despite a great increase in the life expectancy of women, the age at menopause remains remarkably constant. A woman in the United States today will live approximately 30 years, or greater than a third of her life, beyond the menopause. The age at menopause appears to be genetically determined and is unaffected by race, socioeconomic status, age at menarche, or number of prior ovulations. Factors that are toxic to the ovary often result in an earlier age of menopause; women who smoke experience an earlier menopause, as do many women exposed to chemotherapy or pelvic radiation (1). Women who had surgery on their ovaries or had a hysterectomy, despite retention of their ovaries, may experience early menopause (2). Premature ovarian insufficiency, defined as menopause before the age of 40 years, occurs in approximately 1% of women. It may be idiopathic or associated with a toxic exposure, chromosomal abnormality, or an autoimmune disorder.
Although menopause is associated with changes in the hypothalamic and pituitary hormones that regulate the menstrual cycle, menopause is not a central event, but rather primary ovarian failure. At the level of the ovary, there is a depletion of ovarian follicles, most likely secondary to apoptosis or programmed cell death. The ovary, therefore, is no longer able to respond to the pituitary hormones, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), and ovarian estrogen and progesterone production ceases. The ovarian–hypothalamic– pituitary axis remains intact during the menopausal transition; thus, FSH levels rise in response to ovarian failure and the absence of negative feedback from the ovary. Atresia of the follicular apparatus, in particular the granulosa cells, leads to decreased production of estrogen and inhibin, resulting in elevated FSH levels, a cardinal sign of menopause. Antim¨ullerian hormone (AMH) is produced by small ovarian follicles, so levels decrease with declining ovarian reserve (3). Although still considered experimental, AMH may one day be used as a reliable marker of the menopause transition.
Androgen production from the ovary continues beyond the menopausal transition because of sparing of the stromal compartment. Androgen concentrations are lower in menopausal women than in women of reproductive age. This finding appears to be associated with aging and decreased functioning of the ovary and adrenal glands over time rather than with menopause per se. Menopausal women continue to have low levels of circulating estrogens, principally from peripheral aromatization of ovarian and adrenal androgens. Adipose tissue is a major site of aromatization, so obesity affects many of the sequelae of menopause.
Several staging systems were developed to describe the many changes that encompass the transition from reproductive life to postmenopause. The late reproductive years are characterized by regular menses associated with elevated FSH levels (4).
Menopausal transition is characterized by elevated FSH levels associated with variable cycle lengths and missed menses, whereas the postmenopausal period is marked by amenorrhea. The menopausal transition begins with variability in menstrual cycle length accompanied by rising FSH levels and ends with the final menstrual period.
Menopause is defined retrospectively as the time of the final menstrual period followed by 12 months of amenorrhea
Postmenopause describes the period following the final menses (4).