Maternal Nutrition and Lactational Infertility, edited by J. Dobbing. Nestle Nutrition, Vevey/ Raven Press, New York © 1985. Maternal Nutrition and Lactational Amenorrhoea: Perceiving the Metabolic Costs Rose E. Frisch Harvard Center for Population Studies, Cambridge, Massachusetts 02138 The disruptive effects of undernutrition and intensive physical work on female reproductive ability are well documented. Undernutrition and weight loss delay menarche and cause cessation of already established ovulatory cycles (1—3). High- energy outputs also affect menstrual periodicity and the onset of menarche. Studies of ballet dancers (4,5) and women athletes (6-8) show that training at young ages before menarche delays menarche and that dancers and athletes have a high inci- dence of irregular cycles and amenorrhoea. The delay of menarche can be as much as 0.4 year (5 months) for every year of training (6). Some athletes and dancers had menarche as late as ages 19, 20, and 21 years (4-6). These disruptive effects of undernutrition and intensive exercise on female reproductive ability are reversible with weight gain (1,3,9,10) and/or cessation or reduction of physical activity after varying periods of time (5,6). The endocrinological basis for these findings is now also well documented. Studies of pituitary response to exogenous luteinizing hormone (LHRH) show that there is hypothalamic dysfunction associated with weight loss in the range of 10% to 15% of normal weight for height, as well as with the more extreme weight loss (30%) associated with anorexia nervosa (2,9). The degree of hypothalamic dys- function is directly related to the amount of weight loss (2,9). The endocrinological changes which are associated with the hypothalamic dysfunction are essentially a reversion to a prepubertal endocrinological state (11). What do these findings on dancers, runners, and too-thin women have to do with observations of varying length of lactational amenorrhoea? One connection is the unexplained differences in natural fertility (fertility of couples who do not volun- tarily control the number of births in any way) (12). The natural fertility of the Bush people of the Kalahari desert is four babies in a reproductive lifetime (13). In contrast, the natural fertility of the Hutterites, a well-to-do religious sect who do not believe in contraception, is 10 to 11 (14). Louis Henry, who first observed the differences in natural fertility in historical populations (12), explained the observed differences by differences in the birth interval. The birth interval differ- ence is also observed in many developing countries today, such as Bangladesh, and 65 66 NUTRITION, ACTIVITY, MENSTRUATION among the Bush people of the Kalahari. In the latter population the birth interval is almost 4 years (13); in Bangladesh it is approximately 3 years (15). A major component of this long birth interval is a long lactational amenorrhoea (13,15). No explanation was offered historically for the observed differences in natural fertility of populations other than the statement of the longer birth interval or general statements on differences in health and nutrition, without specification of the mechanism. NUTRITION AND THE REPRODUCTIVE SPAN The findings on the direct effect of undernutrition and physical activity on age of menarche and regular ovulatory cycles cited above suggested a direct pathway from food available per capita to fecundity to fertility (16-18), in addition to the classical pathway of Malthus through a rise in mortality (19). Gopalan and Naidu (20) suggested such a pathway in 1972. The average number of births to poor couples in many developing countries today is approximately six or seven (15,17), similar to that observed in the past for poor couples in countries which are now developed. As the result of the improvements in mortality following the proper introduction of public health mea- sures in developing countries, an average of six or seven children per couple results in a very rapid rate of population growth. However, paradoxically, this total fertility rate is far below the observed human maximum of an average of 10 to 11 children born to well-nourished, non-contracepting couples, such as the Hutterites. Historical data for women of mid-nineteenth-century England and Scotland showed that slow growth to maturity of women and men due to undernutrition, hard work, and disease is correlated with a reproductive span which is shorter and less efficient than that of a well-nourished population (17,18). The submaximally nourished females and males are identifiable by a later average age of completion of growth, 20 to 21 years and 23 to 25 years, respectively, compared with that of contemporary, well-nourished females and males who complete their growth by ages 16 to 18 years and 20 to 21 years, respectively. The historical data showed that the slower growing women subsequently differed reproductively from well-nourished females, not only in having longer birth inter- vals, but also in having shorter lengths of the entire reproductive span, in later ages of peak nubility, and in lower levels of age-specific fertility in the reproductive years (21). There is thus a biological syndrome as it were in which submaximal rates of growth to maturity in a population, or in some classes of a population, are subsequently associated with a pattern of late mean age of menarche, early mean age of menopause, longer birth intervals, and more relative and absolute sterility (18,21) (Figs. 1 and 2). Such a reproductive pattern is observed also among the poor populations of many developing countries today when data on age of menarche, age of menopause, length of birth intervals, and pregnancy wastage are available. The differences in the length of the reproductive span and the timing of each reproductive event have been published in detail (Figs. 1 and 2). New data now 20-24yr 100 . Peok . / Nubility 25-29 80 Peak _l Age 18 Nubilty Nubility / Stage I Age 22 Nubility t Stage I f- 60 Adolescent Subfecundity I 40 / Adolescent ' Subfecundity 20- Premenopausal Subfecundity 41 Age of last birth ^-Menopause I Menopause 15 20 25 30 35 40 45 50 AGE (YEARS) FIG. 1. The mid-nineteenth-century curve of female "procreative power" or reproductive ability (variation of the rate of child- bearing with age; maximum fertility rate, 100) compared with that of the well-nourished, non-contracepting modern Hutterites. The Hutterite fertility curve results in an average of 10 to 11 children; the 1850 to 1870 fertility curve in about 6 to 8 children. (From ref. 17.) 68 NUTRITION, ACTIVITY, MENSTRUATION Fatness (%fot) •—Weight .WelgJ>t —^-s "Height Peok Reproductive Ability =100 24 28 32 AGE-YEARS FIG. 2. The synchronization of peak female reproductive ability with the attainment of mature height, weight, and relative fatness. Timing and levels for 1950 to 1975. Slower growth to maturity is associated with a shortened, less efficient reproductive span, a later age of peak reproductive ability, and a decreased peak value. establish that fatter women have a later age of menopause (22) and that the mean age of menopause is now 52.0 years for United States women. There is thus evidence for a secular trend in age of menopause as well as for age of menarche. The strong association between differing rates of growth to maturity and differ- ential timing and efficiency of reproductive events makes it reasonable to hypoth- esize that the length of the lactational amenorrhoea is also affected by the previous rate of growth of the mother and her physical state as determined by nutritional intake and energy output. In addition, the physical demands of the infant must be included in the equation. Since the prepregnancy weight of the mother and, inde- pendently, her weight gain during pregnancy are the determinants of the infant birth weight, all of these factors are intercorrelated. ENERGY COSTS OF LACTATION Although the neuro-endocrinological control of lactation was not understood in the second half of the nineteenth century, there was widespread understanding of the energy costs of lactation and reproduction in general. Darwin noted that "it is difficult to get a cow to give much milk and to fatten readily." Darwin also observed that "hard living retards the period at which animals conceive" and that "domestic animals which have regular, plentiful food without working to get it are more fertile than the corresponding wild animals" (23). Darwin concludes from his list of NUTRITION, ACTIVITY, MENSTRUATION 69 examples: "All these facts may be merged under a more general principle, namely that natural selection is continually trying to economise in every part of the organization." The idea is "not to waste nutriment" (24). Estimates of the metabolic cost of lactation for present-day women make even clearer the importance of the concept that "the production of milk costs something" (25). Hytten and Thomson (25) further state: "Satisfactory lactation represents the greatest nutritional stress imposed by a physiological process on the human body." The required input, estimated at between 800 and 1,000 calories/day (25,26) above requirements for maintenance and activity, is more than the output because the conversion of nutriments from diet into milk is not 100% efficient. The production of a live infant also costs something: a human pregnancy requires approximately 50,000 calories over and above normal metabolic requirements (27). It is therefore physiologically improbable to assume that women who have grown up slowly because of marginal food supplies, physical labour, and/or disease and who have a late age of menarche (15-16 years) would have the same length of lactational amenorrhoea and the same birth interval as non-contracepting women who grew up rapidly on high levels of nutrition, both quantitatively and qualitatively (particularly approximately 40% calories from fat), even if the pattern of nursing were identical.