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Menopause without symptoms: The endocrinology of menopause among rural Mayan Indians
Menopause without symptoms: The endocrinology of menopause among rural Mayan Indians Mary C. Martin, MD," Jon E. Block, PhD," Sarah D. Sanchez, MSc,c Claude D. Arnaud, MD,c and Yewoubdar Beyene, PhDd San Francisco, California OBJECTIVE: Our purpose was to determine the characteristics of menopause among Mayan women who did not have menopausal symptoms. STUDY DESIGN: A cross-sectional study of Mayan women from Chichimila, Mexico, was performed. Demographic information, history and physical examination, hormone concentrations, and radial bone density measurement were obtained. RESULTS: Fifty-two postmenopausal women were compared with 26 premenopausal women. Menopause occurred at 44.3 ± 4.4 years. None of the women admitted to hot flushes and did not recall significant menopausal symptoms. Hormone levels included elevated follicle-stimulating hormone (66.6 ± 29 mIU/ml), low estradiol and estrone (9.4 ± 8.3 and 13.3 ± 7.8 pg/ml), estrone greater than estradiol levels, normal levels of testosterone and androstenedione (0.17 ± 0.14 and 0.31 ± 0.17 ng/ml). Bone mineral density declined with age, but height did not. Clinical evidence of osteoporosis was not detected. CONCLUSIONS: Lack of symptoms during the menopausal transition is not attributable to a difference in endocrinology. Postmenopausal Mayan women are estrogen deprived and experience age-related bone demineralization but do not have a high incidence of osteoporotic fractures. (AM J OBSTET GVNECOL 1993;168: 1839-45.)
Key words: Menopause, hot flushes, osteoporosis
Menopause is both an objective hormonal event and a subjectively perceived endocrine transition. The degree of symptomatology experienced by an individual woman can be influenced by a number of factors, including age at menopause and psychosocial attitudes toward menopause, but it is usually estimated that 65% to 76% of women will experience hot flushes during the perimenopause.'· 2 After the menopause there can be significant adverse health consequences, including osteoporosis.' These health consequences are known to be determined by multiple factors such as nutrition, activity level, parity, and genetics! Among the Mayan Indians of Yucatan, Mexico, who have high gravidity and use minimal contraception, menopause is accompanied by minimal negative connotations. 5 Menopause
From the Departments of Obstetrics, Gynecology, and Reproductive Sciences: Radiology, b Medicine,' and the Division of Medical Anthropology, the Department of Epidemiology and Biostatistics! Supported in part by National Institutes of Health grant No. AG07619. Presented by invitation at the Fifty-ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Ojai, California, October 11-18, 1992. Reprint requests: Mary C. Martin, MD, UCSF, Department of Obstetrics, Gynecology, and Reproductive Sciences, Parnassus Ave., San Francisco, CA 94143-1032. Copyright © 1993 by Mosby-Year Book, Inc. 0002-9378/93 $1.00 + .20 6/6/45358
is welcomed as a favorable transition to a new niche in the village life-style, characterized by relief from childbearing, acceptance as a respected elder, and a surrendering of many household chores to the wives of married sons. 5 Menopause occurs for the majority of Mayan Indians in the Yucatan at a relatively early age, usually between ages 41 and 45. A tropical climate would be expected to maximize the incidence of hot flushes, yet Mayan women in the perimenopausal interval do not complain of hot flushes. 5 Even with specific questioning it has not been possible to elicit familiarity with the symptom of hot flushes. In spite of a longevity that permits most women to live at least 30 years after menopause, there is no reported increase in the incidence of osteoporosis. Elderly women do not typically have kyphosis or experience fractures (Beyene Y. Unpublished data). These aspects of the menopause, the absence of hot flushes and the apparent protection against osteoporosis, led us to explore whether the menopausal transition is endocrinologically different among these women. We hypothesized that Mayan women after the menopause have higher levels of endogenous estrogen or maintain higher levels of androgens. Most of the women are short but stocky with a high body mass index, and it was postulated that by greater peripheral conversion of androgen precursors they might maintain greater concentrations of estrone. 1839
1840 Martin et al.
June 1993 Am J Obstet Gynecol
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Table I. Demographic data comparing mean values for premenopausal and postmenopausal women (mean ± SD)
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Age, yr
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70
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7.1 4.5 9.4 3.1 2.6
Postmenopausal 55 143 54 7.1 4.4
52
± 8.9
± 3.7
± 9.9 ± 4.0 ± 3.1
80
Fig. 1. Distribution of FSH values by age and menopausal status by history. ..., Premenopausal; ., postmenopausal.
Material and methods
The study was approved by the Committee on Human Research at the University of California, San Franciso. A preliminary screening was undertaken in Chichimila, Yucatan, Mexico, a village with a population of about 3000, primarily long-term residents of Mayan descent. Villagers were notified of the study by the assistance of local health personnel, announcements in the village church, and door-to-door visits. An interview was then conducted with those who volunteered to participate. Only women verified to be long-term residents ofthe village, and therefore probably members of the same major tribe of Mayans, were included in the study. A brief history and physical examination was performed, and blood samples and a radial bone density measurement were obtained. One hundred fourteen women participated and 107 completed all phases of the study; seven women had failed phlebotomy or refused venipuncture; two of the 107 women were eliminated from analysis because of abnormal laboratory findings. Fifty-two of the 105 women were postmenopausal by history, 26 were premenopausal with normal cycles by history, and the remainder, 27, were either pregnant, lactating, or experiencing irregular cycles. The history included a determination of general health, past medical history, gynecologic and obstetric history, and menstrual history. Physical examination included measurement of height and weight and blood pressure and a brief cardiopulmonary examination. For many of the residents the interview was conducted in Mayan through an interpreter who was fluent in Spanish and Mayan. For those women who were menopausal, specific information about their menopausal transition experience was sought. Blood samples were obtained, serum separated by centrifugation, and the tubes initially refrigerated at 4° F, then frozen. The frozen samples were shipped to
the University of California, San Francisco and stored frozen until assayed. Pituitary gonadotropins (luteinizing hormone, follicle-stimulating hormone [FSHD, prolactin, estradiol, estrone, androstenedione, and testosterone were measured by standard radioimmunoassays performed in the University of California, San Francisco Reproductive Endocrinology Center. 6 -S Intraassay and interassay coefficients of variation for these assays were luteinizing hormone 6% and lO%; FSH 4% and 8%; prolactin 10% and 9.6%, estradiol 5% and 11% high range, 9% and 14% low range, estrone 8% and 8% high range, 9% and 16% low range; androstenedione lO% and 10%; and testosterone 10 and 14%. A bone density measurement of the distal radius was made with a single-photon absorptiometer (Norland 2780, Norland, Fort Atkinson, Wis.) with standardization and calibration according to manufacturer's specifications with all measurements performed by the same investigator (J. B.). Comparison of means of premenopausal and postmenopausal values, for both endocrine and bone density measurements, was made by means of the two-tailed Student t test. Results
Of the 54 women classified by history as postmenopausal, two were excluded from data analysis after determination of the hormonal profile: one woman stated she had experienced menopause at the age of 30 but when studied at the age of 42 had normal to low gonadotropins consistent with hypothalamic amenorrhea, and one woman was found to have markedly elevated androgens. The 27 women who were lactating or pregnant are not included in this analysis. Table I provides demographic information on the two comparison groups, 26 premenopausal women having regular cycles and 52 postmenopausal women. The average age at which menopause occurred by history was 44.3 ± 4.4 years; this is reflected in the distribution of FSH values by age, as shown in Fig. 1. The shift to elevated FSH values occurs in the early 40s. The results of other endocrine measurements were generally consistent with the menstrual histories. Endo-
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180
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1841
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POST
135 0.6
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90
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AGE GROUPS
Fig. 2A Mean (± SD) values of estradiol and estrone by age for premenopausal and postmenopausal women. [ZI, Estradiol; III. estrone.
Fig. 2B. Mean (± SD) values of androstenedione and testosterone by age for premenopausal and postmenopausal women. r?l Androstenedione; •. Intosterone.
Table II. Mean values of endocrine measurements and bone density in premenopausal.and postmenopausal women (mean ± SD) Premenopausal age (yr)
20-29 No.
Prolactin 14 Luteinizing hor13 mone (mIU/m!) FSH (mIU/ml) 6.5 Estradiol (pglml) 97 Estrone (pg/ml) 61 0.68 Androstenedione (ng/ml) Testosterone 0.24 (ng/ml) Bone mineral 0.678 density (gm/cm2)
11 ± 18* ± 11
± ± ± ±
3 76 34 0.5
± 0.1
I
30-39 11 10 ± 3 16 ± 10 12 78 55 0.54
± ± ± ±
6 72 41 0.3
0.24 ± 0.1
I
Postmenopausal age (yr)
>40 4 13 ± 8 9.5 ± 1 8.5 61 48 0.38
± ± ± ±
2 32 40 0.1
0.17 ± 0.07
40-49 16 7 ± 2 53 ± 22 61 12 14 0.31
± ± ± ±
22 13 9 0.1
0.14 ± 0.1
I
50-59 15 7 ± 3 58 ± 31 70 8 14 0.34
± ± ± ±
J
60-69 17 9 ± 10* 44 ± 21
I
>70 4 8 ± 2 89 ± 72
31 3 11 0.3
62 ± 25 7±2 12 ± 6 0.27 ± 0.1
90 8 16 0.39
0.17 ± 0.1
0.18 ± 0.2
0.19 ± 0.1
± ± ± ±
60 2 4 0.2
± 0.045 0.718 ± 0.048 0.722 ± 0.034 0.643 ± 0.089 0.574 ± 0.082 0.459 ± 0.090 0.440 ± 0.047
*One woman with hyperprolactinemia included in analysis.
crine and bone mineral density data are shown in Table II. The distribution of estrogens and androgens by 10-year age groups is illustrated in Figs. 2A and 2B. Means of premenopausal and postmenopausal values for luteinizing hormone (13.9 ± 9.8 vs 55.7 ± 31.4 mIU/ml), FSH (9.1 ± 5.3 vs 66.6 ± 29.1 mIU/ml), estradiol (84.3 ± 68.9 vs 9.4 ± 8.3 pg/ml), estrone (56.4 ± 36.5 vs 13.3 ± 7.8 pg/ml), androstenedione (0.58 ± 0.39 vs 0.31 ± 0.17 ng/ml), and bone mineral density (0.701 ± 0.048 vs 0.546 ± 0.116 gm/cm2) were all significantly different with p < 0.0001. Mean values of prolactin (12.5 ± 12.3 vs 7.6 ± 6.2 ng/ml) and testosterone (0.2 ± 0.1 vs 0.18 ± 0.2 ng/ml) were not different between groups. Expressed as either a function of age (Fig. 3A), menopausal status (Fig. 3B), or years since menopause
(Fig. 3C), bone mineral density declined markedly with time. These levels were noted to be qualitatively lower than normative standards for women in the United States.9 Evidence for 0steoporotic fractures was sought by examining height as a function of age, but the cross-sectional data did not reveal a significant decline with age, as seen in Fig. 4A or 4B. Comment
Our initial hypothesis, that menopause in rural Mayan women was endocrinologically different from the menopausal transition in women in the United States, was based on two observations: first, that Mayan women do not experience the most characteristic symptom of the Western menopause, the hot flush; and second, that the population and individual histories
1842 Martin et al.
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Fig. 3A. Bone mineral density (BMD) as function of age.
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June 1993 Am J Obstet Gynecol
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20-29 30-39 40-49
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Age Group Fig. 3B. Mean (:tSD) bone mineral density (BM) by age groups for premenopausal and postmenopausal women.
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•
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Yrs Since Menopause
35
40
Fig. 3C. Bone mineral density (BMD) in postmenopausal women as function of years since menopause.
suggest a relative lack of osteoporosis. s Our hypothesis was not substantiated, because the endocrine changes are similar to those reported for women in the United States. 6 The classification of women as premenopausal or postmenopausal was based on their reported men-
Fig. 4B. Mean (:tSD) height by age groups for premenopausal and postmenopausal women.
strual history, and endocrine determinations were not used to assign women to one or the other category. The two women with endocrine disorders were excluded because the androgen levels or the prolonged amenorrhea associated with the hypothalamic amenorrhea are known to affect bone density and might have altered interpretation of these measurements. In contrast, the two women with hyperprolactinemia gave menstrual histories similar to their age cohorts, and there was therefore no apparent justification for excluding them from analysis. In general, estrogen levels in Mayan postmenopausal women were at or below the values expected for women in the United States, II with a typical postmenopausal reversal of the estradiol to estrone relationship. Ovarian androgens have been shown to be less affected by the menopause, IO and mean values of testosterone in Mayan women were not significantly different between age groups. The bone density measurements revealed that, in fact, bone demineralization does occur, as would be predicted by the estrogen-deprived status of these women, although this was not suggested by the lack of osteoporosis by history.
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Alternative explanations for the observed differences in signs and symptoms of the menopause must be sought. The inability to elicit symptoms of the menopause might have been caused by difficulties in translation, but the primary interviewer was a Mayan woman who had completed a 3-month health aid course and functioned as a nurse's aide in the village. She was fluent in Spanish and Mayan and was a friend of many of the women in the study. The expected incidence of hot flushes, on the basis of other populations studied, was 60% to 80% of menopausal women' and the observed incidence in this population was zero. It is possible that the cultural advantages of completing the menopause for these women diminished the subjective recall of the experience but would be more likely to diminish the perceived incidence rather than eliminate the complaint of hot flushes. We considered whether the tropical climate, with the constant high temperature, simply obviated the marked temperature sensations associated with the menopause. However, Mayan women who have moved to a more urban environment nearby do admit to experiencing hot flushes (unpublished observations), suggesting that the climate is not an absolute determinant. Finally, it has been observed that Mayan women will frequently experience the menopausal transition while breast-feeding or shortly after their final gestation, so that they move into the menopause without marked hormonal fluctuations. This would again account for a reduced incidence in numbers of women with perceived hot flushes but would not explain the apparent universal lack of this symptom. The fact that bone mineral density declines so markedly is somewhat surprising, again because there are relatively few elderly women with histories of osteoporotic fractures. The Mexican health care system allows access to physician care for these patients, so it is unlikely that fractures of the radius or hip would be neglected or unreported. In addition, it was anticipated that some decline in height would be seen in these cross-sectional data, but that it would be difficult to determine whether younger women were taller as a result of improved nutrition or older women became shorter with age. '2 In fact, older women were not shown to be shorter. Because bone mineral density is not maintained, a protective effect of the relative obesity of the population could only be as mechanical cushioning, not as a promoter of bone mineralization. These factors are undergoing further study by comparison with an urban Mayan population from the city of Velledolid, 5 km from Chichimila. Because many of these women share a similar genetic heritage but experience different dietary factors, activity patterns, and cultural values, some comparison of possible influential factors can be made. We conclude that the same endocrine event, the menopausal transition, can result in markedly different
1843
symptoms in differing patient populations and that the ultimate consequences of estrogen deprivation on bone can result in different clinical manifestations, which is mediated by other as yet undetermined factors. We thank the office of the State of Yucatan Health Department (Salubridad), Merida, without whose assistance this study could not have been accomplished; Dr. Jose Leopolo Garcia Revero, Clinica Valladolid, Valladolid; Dona Gilda Osorio Rejon, Chichimila; Dr. David Sanchez, University of California, San Francisco, UCMEXUS coordinator; and Alicia Sagasay, who performed the hormone assays under the direction of Elizabeth Schriock, MD. REFERENCES
1. Hannan JH. The fiushings of the menopause. London: Bailliere, Tindall and Cox, 1927: 1. 2. Neugarten BL, Kraines RJ. Menopausal symptoms in women of various ages. Psychosom Med 1965;27:266. 3. Jaffe, Robert B. The menopause and perimenopausal period. In: Yen SSC, Jaffe RB, eds. Reproductive endocrinology. Philadelphia, WB Saunders, 1991:392-401. 4. Pollitzer WS, Anderson JJ. Ethnic and genetic differences in bone mass: a review with a hereditary vs environmental perspective. Am J Clin Nutr 1989;50: 1244-59. 5. Beyene Y. The cultural significance and physiological manifestation of menopause: a biocultural analysis. Cult Med Psychiatry 1986;10;47-71. 6. Midgley AR Jr, Jaffe RB. Regulation of human gonadotropins. X. Episodic fluctuations of LH during the menstrual cycle. J Clin Endocrinol Metab 1971 ;33:962-9. 7. Monroe SE, Blumenfeld Z, Andreyko JR, Schriock E, Henzl MR, Jaffe RB. Dose dependent inhibition of pituitary-ovarian function during administration of a GnRH agonistic analog (nafarelin). J Clin Endocrinol Metab 1986;63: 1334-41. 8. Abraham GE, Manlomis FS, Garza R. Radioimmunoassay of steroids. In: Abraham GE, ed. Handbook of radioimmunoassays. New York: Marcel Dekker, 1977:591-656. 9. Mazess RB, Cameron JR. Bone mineral content in normal U.s. whites. In: Proceedings of the international conference on bone mineral measurement. Washington: US Department of Health, Education, and Welfare, 1975; DHEW publication no (NIH) 75-683. 10. Yen SSe. The biology of menopause. J Reprod Med 1977;18:287. 11. Judd HL, Lucas WE, Yen SSC. Serum 17f3-estradiol and estrone levels in postmenopausal women with and without endometrial cancer. J Clin Endocrinol Metab 1976;43: 272-8. 12. Davies KM, Recker RR, Stegman MR, Heaney RP. Tallness versus shrinkage: do women shrink with age or grow taller with recent birth data? J Bone Miner Res 1991;6: 1115-20.
Discussion
Paradise Valley, Arizona. Martin et al. have presented an intriguing study. Two of the classic findings of the menopause, hot flushes and osteoporosis, are apparently absent in Mayan women, in spite of a demonstrated hypoestrogenic state with laboratory values similar to those found in women in Western industrialized societies. First let us consider the Mayan view of the menopause. One of the coauthors of this study is Dr. Yewoubdar Beyene, who in 1989 published a book based DR. DAVID PENT,
1844 Martin et al.
on her doctoral thesis which compares various aspects of reproductive life among Mayan women in Chichimila in the Yucatan and Greek women in the rural village of Stira. 1 The attitudes of Mayan women toward cessation of menses is quite different from attitudes of women in industrialized societies. In addition to those mentioned in the study-relief from childbearing, acceptance as a respected elder, and the end of household choresthere is also the freedom from the taboos associated with menstruation, because a menstruating woman is believed to carry an evil wind and is a danger to others. Such a woman avoids passing by an area where men are digging wells, because she can cause a cave in. There is also the problem of the menstrual flow soaking through the rags used for protection (sanitary napkins are considered too expensive) and soiling the white dress that is the standard garment worn by Mayan women. Furthermore, as Beyene points out, Mayan women do not have cultural knowledge and anticipations relating to the onset of the menopause other than the cessation of menses. This contrasts with the view in our youthoriented society that looks on menopause as a giant step forward into old age and the beginning of the end of a woman's useful life . Parenthetically, in spite of these great differences there are striking similarities. Beyene notes that the major stresses in a Mayan woman's life are her husband's and son's drinking, money, work load, pregnancy, and her mother-in-law. However, Beyene concludes on the basis of her comprehensive study of Mayan and Greek women that the presence or absence of physiologic symptoms cannot be explained in terms of role changes at midlife or by the removal of cultural taboos. What about the complete lack of hot flushes, the symptom considered pathognomonic for the menopause? It would seem that the next logical step would be to evaluate these women by means of sleep studies measuring skin resistance, skin temperature, and other parameters to more accurately and objectively evaluate this apparent total absence of hot flushes. The finding of bone loss in the distal radius, which would be expected to occur after spinal bone loss, is surprising because of the lack of kyphosis or a decrease in stature. Of interest is the Mayan diet, which is associated with a high incidence of vitamin deficiency and anemia but has a good supply of calcium. This comes not only from the chaya, a green, leafy plant often eaten, but also from the drinking water, because of the abundant lime in the soil, and from tortillas. The lime water is used to soak maize before grinding it into masa for tortillas, and Mexicans get > 500 mg of calcium per day from tortillas alone. I believe it would be of value to carry out computed tomographic scans of the spine in these patients, who, incidentally, have almost none of the risk factors generally associated with osteoporosis. I look forward to the results of the continuing study with an urban Mayan population. I find it very inter-
June 1993 Am J Obstet Gynecol
esting that some of the women who have moved to an urban area have experienced hot flushes. Clearly menopause is a biocultural experience, and research should, as these authors note, consider genetics, environment, diet, activity patterns, fertility patterns, and cultural values. Beyene felt her study was an ethnography of menopause and notes that rather than "studying people" ethnography means "learning from people." This is clearly the approach that is needed. REFERENCE 1. Beyene Y. From menarche to menopause - reproductive lives of peasant women in two cultures. Albany: State University of New York Press, 1989. DR. RALPH HALE, Honolulu, Hawaii. You did not mention the age of menarche. What impact would the age of menarche, especially a delayed menarche, have? I am not aware of data in the literature on osteoporosis that indicates that padding has anything to do with preventing fractures. Fractures are caused by a force that exceeds the bone's resistance. Can you explain your finding of a consistently high level of bone mineral density? You had women in their 30s and 40s that were still in the 600 to 700 mg/cm2 range, a range higher than I have ever seen in several thousand bone densities in cross-cultural evaluations. You also recorded an unusually low rate of bone loss, somewhere between 0.5% to 2% per year. If this is true, these women would reach in their late 60s, well beyond the age that you indicated as their life expectancy, a level of 300 to 350, which we consider to be the level where osteoporotic fractures can occur. Do you think we are dealing with a genetic effect on bone metabolism? DR. DONALD MINKLER, San Francisco, California. Many years ago, before modern assays were available, Dr. Jelliffe coined the term "maternal depletion syndrome," a concept based largely on clinical observations of African women who had suffered from repeated cycles of childbearing and lactation. Do you have data comparing women of high and low parity? Such data might shed light on the influence of the "maternal depletion syndrome" on postmenopausal life. DR. HOWARD JUDD, Los Angeles, California. I reiterate Dr. Pent's comment on the lack of measurements of hot flushes; it's necessary to test for hot flushes with objective techniques before saying that the Mayan women do not have them. You report no women in extreme old age, and that may be a major contributing factor to the lack of fractures. Can you tell us why these women die at younger ages than North American women do? DR. PURVIS MARTIN, San Diego, California. Because these women do not live as long as North American women, I wonder if their cardiovascular status could be improved by estrogen therapy. Because they seem to undergo the same endocrine changes as North American women do, do you think estrogen therapy could improve their quality of life and extend their life span? May I also suggest that fractures are uncommon among
Volume 168, Number 6, Part I Am J Obstet Gynecol
these women because they are so short that they do not have far to fall? DR. TAWFIK RIZKALLAH, Phoenix, Arizona. The lifestyles of these women are different. They are working people who exercise every day, working in the fields and doing other physically demanding chores. If menopausal women are placed on a walking exercise for I year, accompanied with a diet with about 800 mg of calcium per day, there is no decrease in bone density. I Dr. Pent mentioned that these women are getting enough calcium through their diet. With that in mind, I am not surprised to see that there is no decrease in bone density. REFERENCE 1. Nelson ME, Fisher EC, Dilmanian FA, et al. A I-year walking program and increased dietary calcium in postmenopausal women: effects on bone. Am J Clin Nutr 1991;53: 1304-11.
DR. MARTIN (Closing). Dr. Pent and Dr. Judd, we hope to continue the study with definitive and objective measurements of hot flushes. Our initial intention was to provide a biochemical explanation for the clinical observation of the absence of hot flushes. Failing in that effort, I agree that it is critical to define whether these women experience hot flushes but are not perturbed by them or whether they do not in fact have them. We did find that when we went to a city about 5 km from Chichimila and conducted a similar study we met Mayan women who experienced hot flushes. We are examining the dietary, life-style, and hormonal differences in these two populations. Dr. Pent mentioned using computed tomographic scans for study of trabecular bone. Dual energy scans would be highly desirable, but unfortunately one of the major difficulties we encountered during our study was simply getting a bone densitometer across the border and through Mexican customs. Our single energy bone density determinations of the distal radius were compared with data collected with similar equipment in women in the United States and mean values in Mayan women were at or below age-corrected normative values for the women in the United States. These are being analyzed separately. Dr. Hale's questions were incisive and raised significant issues. The age of menarche in these populations is between 12 and 13. They marry at 15 years old and begin their reproductive careers usually before 20. Most women have relatively few intervals of repetitive menstrual cycles and usually experience lactational amenorrhea after each pregnancy and delivery. I am also unaware of any studies that have demonstrated a protective effect of padding on osteoporosis. It is known, however, that osteoporotic fractures are a consequence of the balance between bone mineraliza-
Martin et al.
1845
tion or strength and the extent of trauma that the women experience. For women who have osteoporosis, with "weak" bones, the risk of fractures can be reduced by eliminating some of the factors that might contribute to falling or to trauma with falls. We hypothesize that these women have endogenous protective padding similar to the pads that allow a football player to withstand considerable force without sustaining fracture. It is probable that there are genetic factors that are the dominant factors in any protective effect of their bone architecture. Dr. Minkler, our data do not yet let us determine the potential effect of the separate variable parity on bone density. Continuing the study with a population in the urban community will give us greater power to do this, because women in the urban environment use contraception and their parity is lower. Dr. Judd, the lack of hot flushes that we determined by history needs to be validated and verified by use of objective measures, such as thermisters. The oldest patient that we studied was 74 years old. This would be 30 years after menopause and thus equivalent to someone in the United States population in the early 80s. By asking the physicians in the nearby community what diseases they treat in these women we found that most deaths in postmenopausal women are from cardiovascular disease, stroke, or heart attack. These women do experience the consequences of estrogen deprivation. I have learned a great deal from Dr. Martin, one of the foremost contributors to the study of menopause, and I appreciated his question. I think these women would definitely benefit from estrogen replacement, both to improve the quality of their lives and to avoid the vascular consequences that ultimately lead to their death. It is actually not unreasonable to postulate that their short stature leads to minimal trauma with falls and again fits with the observation of decreased fractures in spite of bone demineralization. Dr. Rizkallah, our original intention in traveling to this village was to verifY our hypothesis that these women have dense bones. We had considered as possible explanations the high calcium in their diet and their activity - they carry burdens such as firewood on their heads; they do a lot of walking, sometimes carrying several children; they obtain their water from wells (the ones that the menstruating women have not collapsed) and carry it back to their houses. So they have lots of weight-bearing activities that would lead to high bone density. To our surprise, we found that the bone density decreases significantly in the postmenopausal era. We hope to continue our investigation into the balance between the factors that might be expected to preserve bone mineral content and the obvious consequences of estrogen deprivation.
Key words: Menopause, hot flushes, osteoporosis
Menopause is both an objective hormonal event and a subjectively perceived endocrine transition. The degree of symptomatology experienced by an individual woman can be influenced by a number of factors, including age at menopause and psychosocial attitudes toward menopause, but it is usually estimated that 65% to 76% of women will experience hot flushes during the perimenopause.'· 2 After the menopause there can be significant adverse health consequences, including osteoporosis.' These health consequences are known to be determined by multiple factors such as nutrition, activity level, parity, and genetics! Among the Mayan Indians of Yucatan, Mexico, who have high gravidity and use minimal contraception, menopause is accompanied by minimal negative connotations. 5 Menopause
From the Departments of Obstetrics, Gynecology, and Reproductive Sciences: Radiology, b Medicine,' and the Division of Medical Anthropology, the Department of Epidemiology and Biostatistics! Supported in part by National Institutes of Health grant No. AG07619. Presented by invitation at the Fifty-ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Ojai, California, October 11-18, 1992. Reprint requests: Mary C. Martin, MD, UCSF, Department of Obstetrics, Gynecology, and Reproductive Sciences, Parnassus Ave., San Francisco, CA 94143-1032. Copyright © 1993 by Mosby-Year Book, Inc. 0002-9378/93 $1.00 + .20 6/6/45358
is welcomed as a favorable transition to a new niche in the village life-style, characterized by relief from childbearing, acceptance as a respected elder, and a surrendering of many household chores to the wives of married sons. 5 Menopause occurs for the majority of Mayan Indians in the Yucatan at a relatively early age, usually between ages 41 and 45. A tropical climate would be expected to maximize the incidence of hot flushes, yet Mayan women in the perimenopausal interval do not complain of hot flushes. 5 Even with specific questioning it has not been possible to elicit familiarity with the symptom of hot flushes. In spite of a longevity that permits most women to live at least 30 years after menopause, there is no reported increase in the incidence of osteoporosis. Elderly women do not typically have kyphosis or experience fractures (Beyene Y. Unpublished data). These aspects of the menopause, the absence of hot flushes and the apparent protection against osteoporosis, led us to explore whether the menopausal transition is endocrinologically different among these women. We hypothesized that Mayan women after the menopause have higher levels of endogenous estrogen or maintain higher levels of androgens. Most of the women are short but stocky with a high body mass index, and it was postulated that by greater peripheral conversion of androgen precursors they might maintain greater concentrations of estrone. 1839
1840 Martin et al.
June 1993 Am J Obstet Gynecol
200
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Table I. Demographic data comparing mean values for premenopausal and postmenopausal women (mean ± SD)
•
150
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100
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#
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"'... 10
20
30
...
40
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No. Age (yr) Height (em) Weight (kg) Gravidity Parity
, ••
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50
Age, yr
60
70
26 31.2 ± 145 ± 54.7 ± 4.7 ± 3.4 ±
7.1 4.5 9.4 3.1 2.6
Postmenopausal 55 143 54 7.1 4.4
52
± 8.9
± 3.7
± 9.9 ± 4.0 ± 3.1
80
Fig. 1. Distribution of FSH values by age and menopausal status by history. ..., Premenopausal; ., postmenopausal.
Material and methods
The study was approved by the Committee on Human Research at the University of California, San Franciso. A preliminary screening was undertaken in Chichimila, Yucatan, Mexico, a village with a population of about 3000, primarily long-term residents of Mayan descent. Villagers were notified of the study by the assistance of local health personnel, announcements in the village church, and door-to-door visits. An interview was then conducted with those who volunteered to participate. Only women verified to be long-term residents ofthe village, and therefore probably members of the same major tribe of Mayans, were included in the study. A brief history and physical examination was performed, and blood samples and a radial bone density measurement were obtained. One hundred fourteen women participated and 107 completed all phases of the study; seven women had failed phlebotomy or refused venipuncture; two of the 107 women were eliminated from analysis because of abnormal laboratory findings. Fifty-two of the 105 women were postmenopausal by history, 26 were premenopausal with normal cycles by history, and the remainder, 27, were either pregnant, lactating, or experiencing irregular cycles. The history included a determination of general health, past medical history, gynecologic and obstetric history, and menstrual history. Physical examination included measurement of height and weight and blood pressure and a brief cardiopulmonary examination. For many of the residents the interview was conducted in Mayan through an interpreter who was fluent in Spanish and Mayan. For those women who were menopausal, specific information about their menopausal transition experience was sought. Blood samples were obtained, serum separated by centrifugation, and the tubes initially refrigerated at 4° F, then frozen. The frozen samples were shipped to
the University of California, San Francisco and stored frozen until assayed. Pituitary gonadotropins (luteinizing hormone, follicle-stimulating hormone [FSHD, prolactin, estradiol, estrone, androstenedione, and testosterone were measured by standard radioimmunoassays performed in the University of California, San Francisco Reproductive Endocrinology Center. 6 -S Intraassay and interassay coefficients of variation for these assays were luteinizing hormone 6% and lO%; FSH 4% and 8%; prolactin 10% and 9.6%, estradiol 5% and 11% high range, 9% and 14% low range, estrone 8% and 8% high range, 9% and 16% low range; androstenedione lO% and 10%; and testosterone 10 and 14%. A bone density measurement of the distal radius was made with a single-photon absorptiometer (Norland 2780, Norland, Fort Atkinson, Wis.) with standardization and calibration according to manufacturer's specifications with all measurements performed by the same investigator (J. B.). Comparison of means of premenopausal and postmenopausal values, for both endocrine and bone density measurements, was made by means of the two-tailed Student t test. Results
Of the 54 women classified by history as postmenopausal, two were excluded from data analysis after determination of the hormonal profile: one woman stated she had experienced menopause at the age of 30 but when studied at the age of 42 had normal to low gonadotropins consistent with hypothalamic amenorrhea, and one woman was found to have markedly elevated androgens. The 27 women who were lactating or pregnant are not included in this analysis. Table I provides demographic information on the two comparison groups, 26 premenopausal women having regular cycles and 52 postmenopausal women. The average age at which menopause occurred by history was 44.3 ± 4.4 years; this is reflected in the distribution of FSH values by age, as shown in Fig. 1. The shift to elevated FSH values occurs in the early 40s. The results of other endocrine measurements were generally consistent with the menstrual histories. Endo-
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Volume 168. Number 6. Part 1 Am J Obstet Gynecol
180
PRE
1841
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POST
135 0.6
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90
01
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20-29 30-39 40-49 40-49 50-59 60-69 70-79
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Age Groups
AGE GROUPS
Fig. 2A Mean (± SD) values of estradiol and estrone by age for premenopausal and postmenopausal women. [ZI, Estradiol; III. estrone.
Fig. 2B. Mean (± SD) values of androstenedione and testosterone by age for premenopausal and postmenopausal women. r?l Androstenedione; •. Intosterone.
Table II. Mean values of endocrine measurements and bone density in premenopausal.and postmenopausal women (mean ± SD) Premenopausal age (yr)
20-29 No.
Prolactin 14 Luteinizing hor13 mone (mIU/m!) FSH (mIU/ml) 6.5 Estradiol (pglml) 97 Estrone (pg/ml) 61 0.68 Androstenedione (ng/ml) Testosterone 0.24 (ng/ml) Bone mineral 0.678 density (gm/cm2)
11 ± 18* ± 11
± ± ± ±
3 76 34 0.5
± 0.1
I
30-39 11 10 ± 3 16 ± 10 12 78 55 0.54
± ± ± ±
6 72 41 0.3
0.24 ± 0.1
I
Postmenopausal age (yr)
>40 4 13 ± 8 9.5 ± 1 8.5 61 48 0.38
± ± ± ±
2 32 40 0.1
0.17 ± 0.07
40-49 16 7 ± 2 53 ± 22 61 12 14 0.31
± ± ± ±
22 13 9 0.1
0.14 ± 0.1
I
50-59 15 7 ± 3 58 ± 31 70 8 14 0.34
± ± ± ±
J
60-69 17 9 ± 10* 44 ± 21
I
>70 4 8 ± 2 89 ± 72
31 3 11 0.3
62 ± 25 7±2 12 ± 6 0.27 ± 0.1
90 8 16 0.39
0.17 ± 0.1
0.18 ± 0.2
0.19 ± 0.1
± ± ± ±
60 2 4 0.2
± 0.045 0.718 ± 0.048 0.722 ± 0.034 0.643 ± 0.089 0.574 ± 0.082 0.459 ± 0.090 0.440 ± 0.047
*One woman with hyperprolactinemia included in analysis.
crine and bone mineral density data are shown in Table II. The distribution of estrogens and androgens by 10-year age groups is illustrated in Figs. 2A and 2B. Means of premenopausal and postmenopausal values for luteinizing hormone (13.9 ± 9.8 vs 55.7 ± 31.4 mIU/ml), FSH (9.1 ± 5.3 vs 66.6 ± 29.1 mIU/ml), estradiol (84.3 ± 68.9 vs 9.4 ± 8.3 pg/ml), estrone (56.4 ± 36.5 vs 13.3 ± 7.8 pg/ml), androstenedione (0.58 ± 0.39 vs 0.31 ± 0.17 ng/ml), and bone mineral density (0.701 ± 0.048 vs 0.546 ± 0.116 gm/cm2) were all significantly different with p < 0.0001. Mean values of prolactin (12.5 ± 12.3 vs 7.6 ± 6.2 ng/ml) and testosterone (0.2 ± 0.1 vs 0.18 ± 0.2 ng/ml) were not different between groups. Expressed as either a function of age (Fig. 3A), menopausal status (Fig. 3B), or years since menopause
(Fig. 3C), bone mineral density declined markedly with time. These levels were noted to be qualitatively lower than normative standards for women in the United States.9 Evidence for 0steoporotic fractures was sought by examining height as a function of age, but the cross-sectional data did not reveal a significant decline with age, as seen in Fig. 4A or 4B. Comment
Our initial hypothesis, that menopause in rural Mayan women was endocrinologically different from the menopausal transition in women in the United States, was based on two observations: first, that Mayan women do not experience the most characteristic symptom of the Western menopause, the hot flush; and second, that the population and individual histories
1842 Martin et al.
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AGE, yr
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Fig. 4A. Height as function of age.
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-
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Fig. 3A. Bone mineral density (BMD) as function of age.
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June 1993 Am J Obstet Gynecol
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J:
139
500 450 400
20-29 30-39 40-49
40-48 5Q·SSt 60·81 70.7'
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Age Group Fig. 3B. Mean (:tSD) bone mineral density (BM) by age groups for premenopausal and postmenopausal women.
900
..
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800
r . 0.64 P = 0.0001
•
700
• •
600 500 400
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300 200 0
5
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15
20
25
40-49 50-59 60-69 70-79
30
Yrs Since Menopause
35
40
Fig. 3C. Bone mineral density (BMD) in postmenopausal women as function of years since menopause.
suggest a relative lack of osteoporosis. s Our hypothesis was not substantiated, because the endocrine changes are similar to those reported for women in the United States. 6 The classification of women as premenopausal or postmenopausal was based on their reported men-
Fig. 4B. Mean (:tSD) height by age groups for premenopausal and postmenopausal women.
strual history, and endocrine determinations were not used to assign women to one or the other category. The two women with endocrine disorders were excluded because the androgen levels or the prolonged amenorrhea associated with the hypothalamic amenorrhea are known to affect bone density and might have altered interpretation of these measurements. In contrast, the two women with hyperprolactinemia gave menstrual histories similar to their age cohorts, and there was therefore no apparent justification for excluding them from analysis. In general, estrogen levels in Mayan postmenopausal women were at or below the values expected for women in the United States, II with a typical postmenopausal reversal of the estradiol to estrone relationship. Ovarian androgens have been shown to be less affected by the menopause, IO and mean values of testosterone in Mayan women were not significantly different between age groups. The bone density measurements revealed that, in fact, bone demineralization does occur, as would be predicted by the estrogen-deprived status of these women, although this was not suggested by the lack of osteoporosis by history.
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Volume 168, Number 6, Part I Am J Obstet Gynecol
Alternative explanations for the observed differences in signs and symptoms of the menopause must be sought. The inability to elicit symptoms of the menopause might have been caused by difficulties in translation, but the primary interviewer was a Mayan woman who had completed a 3-month health aid course and functioned as a nurse's aide in the village. She was fluent in Spanish and Mayan and was a friend of many of the women in the study. The expected incidence of hot flushes, on the basis of other populations studied, was 60% to 80% of menopausal women' and the observed incidence in this population was zero. It is possible that the cultural advantages of completing the menopause for these women diminished the subjective recall of the experience but would be more likely to diminish the perceived incidence rather than eliminate the complaint of hot flushes. We considered whether the tropical climate, with the constant high temperature, simply obviated the marked temperature sensations associated with the menopause. However, Mayan women who have moved to a more urban environment nearby do admit to experiencing hot flushes (unpublished observations), suggesting that the climate is not an absolute determinant. Finally, it has been observed that Mayan women will frequently experience the menopausal transition while breast-feeding or shortly after their final gestation, so that they move into the menopause without marked hormonal fluctuations. This would again account for a reduced incidence in numbers of women with perceived hot flushes but would not explain the apparent universal lack of this symptom. The fact that bone mineral density declines so markedly is somewhat surprising, again because there are relatively few elderly women with histories of osteoporotic fractures. The Mexican health care system allows access to physician care for these patients, so it is unlikely that fractures of the radius or hip would be neglected or unreported. In addition, it was anticipated that some decline in height would be seen in these cross-sectional data, but that it would be difficult to determine whether younger women were taller as a result of improved nutrition or older women became shorter with age. '2 In fact, older women were not shown to be shorter. Because bone mineral density is not maintained, a protective effect of the relative obesity of the population could only be as mechanical cushioning, not as a promoter of bone mineralization. These factors are undergoing further study by comparison with an urban Mayan population from the city of Velledolid, 5 km from Chichimila. Because many of these women share a similar genetic heritage but experience different dietary factors, activity patterns, and cultural values, some comparison of possible influential factors can be made. We conclude that the same endocrine event, the menopausal transition, can result in markedly different
1843
symptoms in differing patient populations and that the ultimate consequences of estrogen deprivation on bone can result in different clinical manifestations, which is mediated by other as yet undetermined factors. We thank the office of the State of Yucatan Health Department (Salubridad), Merida, without whose assistance this study could not have been accomplished; Dr. Jose Leopolo Garcia Revero, Clinica Valladolid, Valladolid; Dona Gilda Osorio Rejon, Chichimila; Dr. David Sanchez, University of California, San Francisco, UCMEXUS coordinator; and Alicia Sagasay, who performed the hormone assays under the direction of Elizabeth Schriock, MD. REFERENCES
1. Hannan JH. The fiushings of the menopause. London: Bailliere, Tindall and Cox, 1927: 1. 2. Neugarten BL, Kraines RJ. Menopausal symptoms in women of various ages. Psychosom Med 1965;27:266. 3. Jaffe, Robert B. The menopause and perimenopausal period. In: Yen SSC, Jaffe RB, eds. Reproductive endocrinology. Philadelphia, WB Saunders, 1991:392-401. 4. Pollitzer WS, Anderson JJ. Ethnic and genetic differences in bone mass: a review with a hereditary vs environmental perspective. Am J Clin Nutr 1989;50: 1244-59. 5. Beyene Y. The cultural significance and physiological manifestation of menopause: a biocultural analysis. Cult Med Psychiatry 1986;10;47-71. 6. Midgley AR Jr, Jaffe RB. Regulation of human gonadotropins. X. Episodic fluctuations of LH during the menstrual cycle. J Clin Endocrinol Metab 1971 ;33:962-9. 7. Monroe SE, Blumenfeld Z, Andreyko JR, Schriock E, Henzl MR, Jaffe RB. Dose dependent inhibition of pituitary-ovarian function during administration of a GnRH agonistic analog (nafarelin). J Clin Endocrinol Metab 1986;63: 1334-41. 8. Abraham GE, Manlomis FS, Garza R. Radioimmunoassay of steroids. In: Abraham GE, ed. Handbook of radioimmunoassays. New York: Marcel Dekker, 1977:591-656. 9. Mazess RB, Cameron JR. Bone mineral content in normal U.s. whites. In: Proceedings of the international conference on bone mineral measurement. Washington: US Department of Health, Education, and Welfare, 1975; DHEW publication no (NIH) 75-683. 10. Yen SSe. The biology of menopause. J Reprod Med 1977;18:287. 11. Judd HL, Lucas WE, Yen SSC. Serum 17f3-estradiol and estrone levels in postmenopausal women with and without endometrial cancer. J Clin Endocrinol Metab 1976;43: 272-8. 12. Davies KM, Recker RR, Stegman MR, Heaney RP. Tallness versus shrinkage: do women shrink with age or grow taller with recent birth data? J Bone Miner Res 1991;6: 1115-20.
Discussion
Paradise Valley, Arizona. Martin et al. have presented an intriguing study. Two of the classic findings of the menopause, hot flushes and osteoporosis, are apparently absent in Mayan women, in spite of a demonstrated hypoestrogenic state with laboratory values similar to those found in women in Western industrialized societies. First let us consider the Mayan view of the menopause. One of the coauthors of this study is Dr. Yewoubdar Beyene, who in 1989 published a book based DR. DAVID PENT,
1844 Martin et al.
on her doctoral thesis which compares various aspects of reproductive life among Mayan women in Chichimila in the Yucatan and Greek women in the rural village of Stira. 1 The attitudes of Mayan women toward cessation of menses is quite different from attitudes of women in industrialized societies. In addition to those mentioned in the study-relief from childbearing, acceptance as a respected elder, and the end of household choresthere is also the freedom from the taboos associated with menstruation, because a menstruating woman is believed to carry an evil wind and is a danger to others. Such a woman avoids passing by an area where men are digging wells, because she can cause a cave in. There is also the problem of the menstrual flow soaking through the rags used for protection (sanitary napkins are considered too expensive) and soiling the white dress that is the standard garment worn by Mayan women. Furthermore, as Beyene points out, Mayan women do not have cultural knowledge and anticipations relating to the onset of the menopause other than the cessation of menses. This contrasts with the view in our youthoriented society that looks on menopause as a giant step forward into old age and the beginning of the end of a woman's useful life . Parenthetically, in spite of these great differences there are striking similarities. Beyene notes that the major stresses in a Mayan woman's life are her husband's and son's drinking, money, work load, pregnancy, and her mother-in-law. However, Beyene concludes on the basis of her comprehensive study of Mayan and Greek women that the presence or absence of physiologic symptoms cannot be explained in terms of role changes at midlife or by the removal of cultural taboos. What about the complete lack of hot flushes, the symptom considered pathognomonic for the menopause? It would seem that the next logical step would be to evaluate these women by means of sleep studies measuring skin resistance, skin temperature, and other parameters to more accurately and objectively evaluate this apparent total absence of hot flushes. The finding of bone loss in the distal radius, which would be expected to occur after spinal bone loss, is surprising because of the lack of kyphosis or a decrease in stature. Of interest is the Mayan diet, which is associated with a high incidence of vitamin deficiency and anemia but has a good supply of calcium. This comes not only from the chaya, a green, leafy plant often eaten, but also from the drinking water, because of the abundant lime in the soil, and from tortillas. The lime water is used to soak maize before grinding it into masa for tortillas, and Mexicans get > 500 mg of calcium per day from tortillas alone. I believe it would be of value to carry out computed tomographic scans of the spine in these patients, who, incidentally, have almost none of the risk factors generally associated with osteoporosis. I look forward to the results of the continuing study with an urban Mayan population. I find it very inter-
June 1993 Am J Obstet Gynecol
esting that some of the women who have moved to an urban area have experienced hot flushes. Clearly menopause is a biocultural experience, and research should, as these authors note, consider genetics, environment, diet, activity patterns, fertility patterns, and cultural values. Beyene felt her study was an ethnography of menopause and notes that rather than "studying people" ethnography means "learning from people." This is clearly the approach that is needed. REFERENCE 1. Beyene Y. From menarche to menopause - reproductive lives of peasant women in two cultures. Albany: State University of New York Press, 1989. DR. RALPH HALE, Honolulu, Hawaii. You did not mention the age of menarche. What impact would the age of menarche, especially a delayed menarche, have? I am not aware of data in the literature on osteoporosis that indicates that padding has anything to do with preventing fractures. Fractures are caused by a force that exceeds the bone's resistance. Can you explain your finding of a consistently high level of bone mineral density? You had women in their 30s and 40s that were still in the 600 to 700 mg/cm2 range, a range higher than I have ever seen in several thousand bone densities in cross-cultural evaluations. You also recorded an unusually low rate of bone loss, somewhere between 0.5% to 2% per year. If this is true, these women would reach in their late 60s, well beyond the age that you indicated as their life expectancy, a level of 300 to 350, which we consider to be the level where osteoporotic fractures can occur. Do you think we are dealing with a genetic effect on bone metabolism? DR. DONALD MINKLER, San Francisco, California. Many years ago, before modern assays were available, Dr. Jelliffe coined the term "maternal depletion syndrome," a concept based largely on clinical observations of African women who had suffered from repeated cycles of childbearing and lactation. Do you have data comparing women of high and low parity? Such data might shed light on the influence of the "maternal depletion syndrome" on postmenopausal life. DR. HOWARD JUDD, Los Angeles, California. I reiterate Dr. Pent's comment on the lack of measurements of hot flushes; it's necessary to test for hot flushes with objective techniques before saying that the Mayan women do not have them. You report no women in extreme old age, and that may be a major contributing factor to the lack of fractures. Can you tell us why these women die at younger ages than North American women do? DR. PURVIS MARTIN, San Diego, California. Because these women do not live as long as North American women, I wonder if their cardiovascular status could be improved by estrogen therapy. Because they seem to undergo the same endocrine changes as North American women do, do you think estrogen therapy could improve their quality of life and extend their life span? May I also suggest that fractures are uncommon among
Volume 168, Number 6, Part I Am J Obstet Gynecol
these women because they are so short that they do not have far to fall? DR. TAWFIK RIZKALLAH, Phoenix, Arizona. The lifestyles of these women are different. They are working people who exercise every day, working in the fields and doing other physically demanding chores. If menopausal women are placed on a walking exercise for I year, accompanied with a diet with about 800 mg of calcium per day, there is no decrease in bone density. I Dr. Pent mentioned that these women are getting enough calcium through their diet. With that in mind, I am not surprised to see that there is no decrease in bone density. REFERENCE 1. Nelson ME, Fisher EC, Dilmanian FA, et al. A I-year walking program and increased dietary calcium in postmenopausal women: effects on bone. Am J Clin Nutr 1991;53: 1304-11.
DR. MARTIN (Closing). Dr. Pent and Dr. Judd, we hope to continue the study with definitive and objective measurements of hot flushes. Our initial intention was to provide a biochemical explanation for the clinical observation of the absence of hot flushes. Failing in that effort, I agree that it is critical to define whether these women experience hot flushes but are not perturbed by them or whether they do not in fact have them. We did find that when we went to a city about 5 km from Chichimila and conducted a similar study we met Mayan women who experienced hot flushes. We are examining the dietary, life-style, and hormonal differences in these two populations. Dr. Pent mentioned using computed tomographic scans for study of trabecular bone. Dual energy scans would be highly desirable, but unfortunately one of the major difficulties we encountered during our study was simply getting a bone densitometer across the border and through Mexican customs. Our single energy bone density determinations of the distal radius were compared with data collected with similar equipment in women in the United States and mean values in Mayan women were at or below age-corrected normative values for the women in the United States. These are being analyzed separately. Dr. Hale's questions were incisive and raised significant issues. The age of menarche in these populations is between 12 and 13. They marry at 15 years old and begin their reproductive careers usually before 20. Most women have relatively few intervals of repetitive menstrual cycles and usually experience lactational amenorrhea after each pregnancy and delivery. I am also unaware of any studies that have demonstrated a protective effect of padding on osteoporosis. It is known, however, that osteoporotic fractures are a consequence of the balance between bone mineraliza-
Martin et al.
1845
tion or strength and the extent of trauma that the women experience. For women who have osteoporosis, with "weak" bones, the risk of fractures can be reduced by eliminating some of the factors that might contribute to falling or to trauma with falls. We hypothesize that these women have endogenous protective padding similar to the pads that allow a football player to withstand considerable force without sustaining fracture. It is probable that there are genetic factors that are the dominant factors in any protective effect of their bone architecture. Dr. Minkler, our data do not yet let us determine the potential effect of the separate variable parity on bone density. Continuing the study with a population in the urban community will give us greater power to do this, because women in the urban environment use contraception and their parity is lower. Dr. Judd, the lack of hot flushes that we determined by history needs to be validated and verified by use of objective measures, such as thermisters. The oldest patient that we studied was 74 years old. This would be 30 years after menopause and thus equivalent to someone in the United States population in the early 80s. By asking the physicians in the nearby community what diseases they treat in these women we found that most deaths in postmenopausal women are from cardiovascular disease, stroke, or heart attack. These women do experience the consequences of estrogen deprivation. I have learned a great deal from Dr. Martin, one of the foremost contributors to the study of menopause, and I appreciated his question. I think these women would definitely benefit from estrogen replacement, both to improve the quality of their lives and to avoid the vascular consequences that ultimately lead to their death. It is actually not unreasonable to postulate that their short stature leads to minimal trauma with falls and again fits with the observation of decreased fractures in spite of bone demineralization. Dr. Rizkallah, our original intention in traveling to this village was to verifY our hypothesis that these women have dense bones. We had considered as possible explanations the high calcium in their diet and their activity - they carry burdens such as firewood on their heads; they do a lot of walking, sometimes carrying several children; they obtain their water from wells (the ones that the menstruating women have not collapsed) and carry it back to their houses. So they have lots of weight-bearing activities that would lead to high bone density. To our surprise, we found that the bone density decreases significantly in the postmenopausal era. We hope to continue our investigation into the balance between the factors that might be expected to preserve bone mineral content and the obvious consequences of estrogen deprivation.