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Try out PMC Labs and tell us what you think. Learn More. The age at the final menstrual period holds intrinsic clinical and public health interest because the age at which natural menopause occurs may be a marker of aging and health. In addition, women who have undergone bilateral oophorectomy under the age of 45 years have been observed to be at increased risk of mortality from cardiovascular disease, particularly if they were not treated with estrogen.

Although menopause is a universal phenomenon among women, the timing of the onset and the duration of the menopausal transition and the timing of the final menstrual period are not. Thus, until recently, much of the knowledge about the timing of the natural final menstrual period has been affected by the nature of the samples of women studied and a of other methodologic differences in the studies of this phenomenon, which must be considered in comparing and summarizing their .

Most studies of the menopausal transition have been cross-sectional, rather than longitudinal, in de, providing an opportunity for distortion of the true picture of the timing of the final natural menstrual period, particularly for understanding factors that precede and may affect the timing of menopause.

Further, definitions of menopause or the final menstrual period have varied from study to study in terms of the of months of amenorrhea considered to represent in retrospect the final menstrual period. Studies have also varied with regard to which factors have been included in multivariable analyses that control simultaneously for the effects of multiple variables, which also makes the studies not directly comparable. The analysis of age at natural menopause in a of studies has been calculated as a simple mean, rather than using the less-biased survival or multivariable time-to-event analytic approaches.

These last two approaches include more information and observations for every woman studied, because all women are included but withdrawn or censored when they experience surgical menopause, start using menopausal hormone therapy or oral contraceptives OC; which generally masks the natural cessation of menses , or are still premenopausal.

Menopause is defined as the cessation of menstruation which reflects cessation of ovulation owing to a loss of ovarian follicles, which in turn in reduced ovarian production of estradiol, the most biologically active form of estrogen, 37 , 38 as well as increased circulating concentrations of follicle-stimulating hormone FSH and decreased concentrations of inhibin, which inhibits the release of FSH.

As circulating estrogen concentrations decline during the menopausal transition, variations in the regularity, timing, and nature of menstrual bleeding may occur. Lack of a corpus luteum, resulting in estrogen secretion even hyperestrogenicity 45 , 47 unopposed by progesterone, may lead to profuse bleeding. The nature and timing of bleeding may vary both within and between women. What is known about the host, environmental, or lifestyle factors that may affect such variation is summarized herein.

Although some factors have been identified that are associated with early age at natural menopause, the relation of many has not been examined, and most have not been examined in relation to duration of the perimenopause. from cross-sectional studies have indicated that endocrine changes characteristic of the onset of the perimenopause begin at around age Several studies have indicated that women living in developing countries including Latin America, Indonesia, Singapore, Pakistan, Chile, and Peru experience natural menopause several years earlier than those in developed countries.

Some studies have reported that African American 59 and Latina 58 , 60 women have natural menopause about 2 years earlier than white women. However, 1 small study in Nigeria reported the average age at menopause to be Mayan women, despite their high parity see Reproductive History , have been reported to experience natural menopause fairly early, at about age A of studies have observed that lower social class, as measured by the woman's educational attainment or by her own or her husband's occupation, is associated with an earlier age at natural menopause.

The age at which the final natural menstrual period occurs may be a marker for hormonal status or changes earlier in life. Increasing parity, particularly among women of higher SES, has also been associated with later age at natural menopause, 50 — 52 , 55 , 57 , 58 , 61 , 90 , 91 , 93 — 96 consistent with the theory that natural menopause occurs after oocytes have been sufficiently depleted. A of studies have reported that women who have used OCs have a later age at natural menopause.

However, the finding has not been wholly consistent across studies, because 1 study reported that this delay became nonificant after a time-dependent adjustment for when OCs were used, 52 and another study reported that OC users had a ificantly earlier natural menopause than nonusers, although this association was not consistent across 5-year age groups. Several studies have examined the relation of body mass to age at menopause, with inconsistent findings.

Some studies have reported that both increased BMI indicated by weight over height squared and upper body fat distribution indicated by waist-to-hip ratio were associated with later age at natural menopause 50 , 57 , 96 , 99 , and increased sex hormone concentrations. One study reported earlier natural menopause in women on weight reduction programs or who had gained more than 26 pounds between the ages of 20 and 45 years. Some of these apparently inconsistent findings may be explained by differences in study de cross-sectional or retrospective vs prospective or analysis eg, inadequate or varying control of confounding variables or survival analysis vs.

In general, the better deed and analyzed studies have shown no relation of body mass or body fat distribution to age at the final natural menstrual period. Although body mass and composition may be related to age at natural menopause, they are also related inversely to physical activity, alcohol consumption, and education, and positively related to infertility and parity.

In recent years, studies of factors related to age at natural menopause have begun to focus on genetic factors that may be related. One European genome-wide association study of nearly women identified 6 single nucleotide polymorphisms in 3 loci on chromosomes 13, 19, and 20 associated with age at natural menopause. A of analyses have been conducted on prospective data collected across the lifespan from a nationally representative birth cohort of nearly British women born in and followed to age 53 years, the Medical Research Council National Survey of Health and Development.

These analyses have revealed that women who had a low weight at 2 years of age had an earlier natural menopause, whereas those who were heaviest at 2 years of age had a later natural menopause. Further, additional findings from the British birth cohort indicate that women whose parents divorced early in their lives had an earlier natural menopause than other women, suggesting that early life stressors may also be related to early menopause.

Perhaps the single most consistently shown environmental effect on age at menopause is that women who smoke stop menstruating 1 to 2 years earlier than comparable nonsmokers. If the dose—response effect is a true effect, the apparent paradox might partly be explained by fewer years of smoking and thus toxic exposure to the ovaries in former smokers than in current smokers of similar age. The polycyclic aromatic hydrocarbons in cigarette smoke are known to be toxic to ovarian follicles , and thus could result in premature loss of ovarian follicles and early natural menopause among smokers.

Because drug metabolism is enhanced in smokers, estrogen also may be more rapidly metabolized in the livers of smokers, which could lead to an earlier reduction of estrogen levels. Although almost nothing is known about the relations of occupational or other environmental factors to age at the final natural menstrual period and duration of the menopausal transition, occupational exposures and stressors such as shift work, hours worked, hours spent standing, and heavy lifting have been related to increased risk of adverse pregnancy outcomes — and changes in menstrual cycle length and variability as well as fecundability.

One study showed a modest effect on age at natural menopause in women in Seveso, Italy, who were exposed to 2,3,7,8-tetrachlorobenzo-p-dioxin, a halogenated compound that may affect ovarian function, during a chemical plant explosion in Physical activity is associated with a of changes in hormonal parameters [estradiol, progesterone, prolactin, luteinizing hormone LH , and FSH , both during and after intense physical activity.

One early study from Papua, New Guinea, suggested that malnourished women ceased menstruation about 4 years earlier than well-nourished women, consistent with other studies showing that women with greater weight 62 , 69 and height 89 may have a later age at natural menopause. Findings regarding the relationship of specific dietary patterns to age at menopause have been inconsistent. For example, vegetarians were observed to have an earlier age at natural menopause in 1 study, whereas another study in Japan reported that higher green and yellow vegetable intake was ificantly associated with later age at natural menopause.

A couple of studies have reported that increased meat or alcohol consumption is ificantly associated with later age at menopause, after adjusting for age and smoking. Premenopausal women administered soy have shown increased plasma estradiol concentrations and follicular phase length, delayed menstruation, and suppressed midcycle surges of LH and FSH. Despite important methodologic differences, the limitations in the study des used and the populations studied in the accumulating literature regarding factors that affect the age at which the natural final menstrual period is experienced, an interesting and complex picture is emerging.

Smoking, lower parity, and lower SES have been found fairly consistently to be associated with earlier menopause, an indicator of reduced longevity. Other relationships remain largely unexplored eg, passive smoke exposure and occupational and other environmental exposures. Therefore, much remains to be learned about how these factors affect follicular atresia and hormone levels and thus determine the onset and potentially the duration of the perimenopause and the timing of the final menstrual period.

Increasing knowledge about these relationships ultimately offers women and their health care providers enhanced understanding and choices, based on greater knowledge, to deal with the individual presentations of menopause. Dr Gold was supported by AG National Center for Biotechnology Information , U. Obstet Gynecol Clin North Am. Author manuscript; available in PMC Sep 1. Ellen B. Gold , PhD. Author information Article notes Copyright and information Disclaimer.

Copyright notice. See other articles in PMC that cite the published article. Factors Related to Timing of Menopause from cross-sectional studies have indicated that endocrine changes characteristic of the onset of the perimenopause begin at around age Sociodemographic Differences International and geographic differences Several studies have indicated that women living in developing countries including Latin America, Indonesia, Singapore, Pakistan, Chile, and Peru experience natural menopause several years earlier than those in developed countries.

Differences by socioeconomic status A of studies have observed that lower social class, as measured by the woman's educational attainment or by her own or her husband's occupation, is associated with an earlier age at natural menopause. Health-Related Influences Menstrual and reproductive history The age at which the final natural menstrual period occurs may be a marker for hormonal status or changes earlier in life. Body mass and composition Several studies have examined the relation of body mass to age at menopause, with inconsistent findings.

Familial, genetic, and early childhood factors In recent years, studies of factors related to age at natural menopause have begun to focus on genetic factors that may be related. Environmental Influences Active and passive smoke exposure Perhaps the single most consistently shown environmental effect on age at menopause is that women who smoke stop menstruating 1 to 2 years earlier than comparable nonsmokers. Diet One early study from Papua, New Guinea, suggested that malnourished women ceased menstruation about 4 years earlier than well-nourished women, consistent with other studies showing that women with greater weight 62 , 69 and height 89 may have a later age at natural menopause.

Table 1 Factors related to earlier and later age at natural menopause. Open in a separate window. Age at natural menopause and mortality. Ann Epidemiol. Menopause: the aging of multiple pacemakers. Is early natural menopause a biologic marker of health and aging? Am J Public Health. Age at menopause, cause-specific mortality and total life expectancy.

Age at natural menopause and all-cause mortality: a year follow-up of 19, Norwegian women. Am J Epidemiol. Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. Age at menopause as a risk factor for cardiovascular mortality. Does age at natural menopause affect mortality from ischemic heart disease? J Clin Epidemiol. Age at natural menopause and risk of cardiovascular disease.

Arch Intern Med. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Relationships of age at menarche and menopause, and reproductive year with mortality from cardiovascular disease in Japanese postmenopausal women: the JACC study. J Epidemiol. Lifetime estrogen exposure versus age at menopause as mortality predictor.

Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study. Age at natural menopause and risk of ischemic stroke The Framingham Heart Study. Early menopause predicts angina after myocardial infarction. Population-based study of age at menopause and ultrasound assessed carotid atherosclerosis: the Tromso Study.

Menopause, menstrual and reproductive history, and bone density in northern Italy. J Epidemiol Community Health. Early menopause, of reproductive years, and bone mineral density in postmenopausal women. Early menopause: increased fracture risk at older age. Osteoporos Int. Reproductive factors and breast cancer. Epidemiol Rev. Early age at menopause and breast cancer: are leaner women more protected?

A prospective analysis of the Dutch DOM cohort. Breast Cancer Res Treat. Age at menarche and menopause of uterine cancer patients. Pooled analysis of 3 European case-control studies of ovarian cancer: II. Age at menarche and at menopause. Int J Cancer. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. Menstrual and reproductive factors and endometrial cancer risk: from a population-based case-control study in urban Shanghai. Increased cardiovascular mortality after early bilateral oophorectomy.

The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Memory functioning among midlife women: observations for the Seattle Midlife Women's health Study. Influence of gonadal hormones on neurotransmitters, receptor, cognition and mood.

Clin Neuropharmacol. Cognitive function across the life course and the menopausal transition in a British birth cohort. World Health Organization. Research on the menopause in the s. World Health Organization; Geneva Switzerland : Skolnick AA. At third meeting, menopause experts make the most of insufficient data.

Looking for the one 40 50 and natural

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