The Physiology of Menopause




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НазваниеThe Physiology of Menopause
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Menopause Management for the MillenniumCME

Abstract


In the year 2000, an estimated 31.2 million women will be undergoing the menopausal transition. Although menopause is a normal developmental process, the resulting decline in endogenous estrogen levels can have serious clinical sequelae. Estrogen deficiency has been implicated in an increased risk for vasomotor symptoms, osteoporosis, cardiovascular disease, urogenital atrophy, cognitive decline, and Alzheimer's disease. This clinical management module provides an overview of the physiology of menopause, considers women's perceptions of menopause, and presents a detailed review of available and coming therapeutic options for the management of menopausal symptoms and the long-term effects of estrogen deficiency. A critical and individualized approach to menopause management is emphasized, because no intervention is suitable for every woman, and each option has a different risk/benefit profile.

Introduction


The age of menopause has not changed over the past few centuries, but there has been a gradual increase in life expectancy. Whereas in previous centuries women were not expected to live beyond menopause, women now spend one third to one half of their life after menopause. The total group of postmenopausal women in the United States is increasing. In the year 2000, there will be an estimated 31.2 million women older than 55 years, compared with 28.7 in 1990. By the year 2020, the size of this group is estimated to be 45.9 million.

This clinical management module presents a comprehensive overview of the most current data, thinking, and therapeutic strategies relating to the principal clinical consequence of menopause, estrogen deficiency.

The Physiology of Menopause


Clinically, menopause is defined as the cessation of menstrual cycles and results from either follicular depletion ("natural" menopause) or surgical removal of the ovaries ("induced," or "surgical," menopause). The secretion of the ovarian hormones estrogen and progesterone ends with menopause. However, menstrual cycles seldom cease abruptly; there is an interval termed the "perimenopause" or "menopausal transition," during which there are considerable hormonal fluctuations. The perimenopause usually begins a few years before the last menstrual cycle; the cycles become irregular, and there are often symptoms suggesting a decline in estrogen concentration. Estrogen levels can even swing higher than normal early in the perimenopause, but an abrupt decline in estrogen occurs 6 months before menopause. The perimenopause also extends for a few years after the last menstrual cycle; during this time, transient and episodic bursts of ovarian activity may occur, which may result in some vaginal bleeding.

Natural menopause occurs at a median age of 51.4 years, with a Gaussian distribution ranging from 40-58 years. A number of factors appear to determine the onset of menopause. The age at onset of natural menopause and the risk for surgical menopause both seem to be determined by familial factors as well as by genetic polymorphisms of the estrogen receptor (ER).[1] There also appears to be a relation between childhood cognitive function and the timing of natural menopause.[2] Multiparity and increased body mass index (BMI) are associated with later onset,[3,4] whereas smoking,[3,5,6] nulliparity,[3] medically treated depression,[7] toxic chemical exposure,[8] and treatment of childhood cancer with abdominal-pelvic radiation and alkylating agents[9] have been associated with a younger age at onset. Premature, or early, menopause (age < 40 years) has been linked to both familial and nonfamilial X-chromosome abnormalities.[10-13]

Reproductive Decline and Menopause


The time from the decline in reproductive capacity onward is often referred to as the climacteric. Reproductive aging occurs rapidly after the third decade, and fecundity is extremely low before menopause. Follicular atresia accelerates at about 37.5 years.[14] Thus, reproductive aging precedes menopause by 5-10 years, at a "young" chronologic age. This is signified by an increase in the serum follicle-stimulating hormone (FSH) level in the early follicular phase of regular cycles and a decrease in the circulating inhibin B level. The elevation in FSH drives the accelerated follicle depletion.[15] In late perimenopause, levels of estradiol (E2) and inhibin A also decrease, inhibin B levels remain low, and FSH is markedly increased.[16]

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