Female reproductive senescence is characterized by the so‐called menopausal transition taking place between the ages of 40 and 60 years. The major event of menopausal transition is menopause itself, which is biomedically defined as the cessation of menstrual function and the irreversible termination of female reproductive capability. Recent human females experience a postreproductive period from about 30 years. Such a long postreproductive period is absolutely uncommon among animals. Consequently, human menopause is still an evolutionary puzzle and several theories to explain the evolutionary basis of menopause have been presented. Menopausal transition, however, is also seen as a period of increased somatic and psychic symptoms which make this phase of life quite uncomfortable for affected women. In the present study, menopause and climacteric complaints are discussed from the viewpoint of evolutionary anthropology.
- human evolution
- climacteric symptoms
- reproductive senescence
2. Human life history theory
As pointed out above, according to the biogenetic imperative and natural selection theory, menopause should be rare in nature. Among
Every species has evolved its own patterns of ontogeny of the individual organism from conception to death. This species typical process contains somatic growth, development, maturation, reproduction, and senescence—all of them are energetically costly events . Life history theory tries to explain the evolution of these patterns of growth and reproduction by identifying trade‐offs . An important trade‐off is between somatic growth and the maintenance on the one hand and successful reproduction on the other. For most organisms, it is not possible to provide enough energy to grow and to reproduce simultaneously. Therefore many organisms have evolved a timely separation between growth and reproduction. A period where energy is provided for growth and development is followed by a period where energy is used for successful reproduction. Human life history differs from that of other social mammals in several puzzling details. Even our next living relatives, the nonhuman primates, exhibit marked differences in certain features of life history . In detail, human infants are weaned relatively early, on average by age 36 months, but after weaning human children depend on their mothers or other older group members for food and protection much longer than do the offspring of any other mammal, usually until they age about 7 years [12, 13]. From the viewpoint of evolutionary anthropology and human life history theory, the period between weaning and age of 7 years is defined as childhood stage, which is characterized by a set of biological and behavioral traits. This life history definition of childhood differs from the commonly used term childhood which refers to any time between birth and sexual maturation. It is assumed that the life history stage of childhood evolved about 2 million years ago among
3. Reproductive senescence among animals
As pointed out above, human females experience the cessation of reproductive function long before they die. Some signs of reproductive ageing are found among invertebrates in particular tephritid fruit flies  and the nematode
4. Physiology of menopause: proximate approach
In the first step, we have to analyze the proximate or physiological basis of female reproductive senescence. From a proximate viewpoint, menopause results from follicular atresia that starts extremely early in female ontogeny, i.e., during intrauterine phase and continues until menopause [23, 30]. In the female embryo, primordial germ cells originating from the yolk sac develop into oogonia, immature sex cells. Germ cell numbers peak at approximately3 × 105–7 × 106 by the fifth month of fetal development . Oogonia develop to oocytes. Oocyte formation, however, ceases by the time a female fetus is 5 months old. Consequently, human females are unable to continue to produce oocytes past their fifth month in utero. At this time process of follicular degeneration and resorption from 3.4 to 7 million germ cells to less than 1000 remaining follicles at the time of menopausal transition, starts. The exorbitantly high number of 7 million oogonia declines to about 2 million oocytes at the time of birth and to about 400000 at pubertal onset. Oocytes are embedded in follicular cells. The vast majority of follicles are nonproliferating, produces steroids and succumb to atresia by apoptosis . Only few follicles develop to preovulatory follicles with a thick layer of granulosa and theca cells, consequently only few oocytes undergo ovulation. The majority of follicles and oocytes, which are developmental units, degenerates before ovulation. Fertility declines in human females before total depletion of oocytes. A gradual decline in fertility is observable between the ages 35 and 40 years, after this period the decline accelerates. This reduced fertility from about 35 years onward is mainly due to defects in oocytes . Oocyte or follicular depletion accelerates as menopause got closer. At the time of menopause, the activity of the few remaining follicles declines drastically .
The follicular decline results in marked hormonal disturbances typical of perimenopause and postmenopause . The main feature of menopausal transition is the dramatic decline in estrogen levels [32, 33]. These hormonal disturbances are caused by the depletion of follicular cells. The theca and the granulosa cells of the follicle, however, are essential for estrogen synthesis in the ovary. Consequently, estrogens are no longer converted from androgen in the granulosa cells during menopausal transition . The decrease of estrogen secretion resulted in consecutive disturbances of the hypothalamus‐pituitary‐gonad axis (HPO‐axis). During reproductive phase, menstrual cycle patterns are regulated by this hormonal axis. The hypothalamus secretes gonadotropin releasing hormone (GnRh) directly to the anterior pituitary. The secretion patterns of GnRh are modified by neurotransmitters such as dopamine, serotonin, epinephrine, or endorphin. Receptors in the anterior pituitary sense the pulse frequency and amplitude of GnRh and direct the production of the gonadotropins, follicle stimulating hormone (FSH), and lutenizing hormone (LH), which are essential for reproduction. FSH stimulates follicle development, LH the estrogen synthesis in the ovaries. Both stimulate ovulation and LH induces corpus luteum development and in this way progesterone synthesis. FSH binds to specific hormone receptors on the membrane of the granulosa cells, whereas LH binds to receptors of the granulose and theca cells. Androgens are secreted under LH stimulation from the theca cells, in the granulosa cells these androgens are converted into estradiol. The hormone secretion of the HPO‐axis is regulated by a negative feedback mechanism. During reproductive phase, female sex hormone secretion underlies dramatic cyclic fluctuations [32, 33].
Menopausal transition is characterized by marked endocrine changes which are mainly induced by changes within the ovary but also central neuroendocrine changes. The reduction of ovarian follicles during perimenopause results in declining levels of inhibin B, a dimeric protein, and a rise of follicle stimulating hormone (FSH) and lutenizing hormone (LH) levels. During perimenopause, estradiol levels remain relatively unchanged presumably in response to the elevated FSH levels [32, 33]. As the follicular supply is exhausted, estradiol (E2) and estrone (E) decrease dramatically; FSH and LH, however, remain elevated. Estradiol, the most physiologically active estrogen, declines most markedly, whereas estrone continues to be produced through the conversion of androstenedione to estrone in muscle, adipose, and other tissues. Consequently, the hypothalamus‐pituitary gonad axis (HPG‐axis) is irreversible disturbed. Beside the decline in estrogens and progesterone (P), a decrease of testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA‐S), and sex hormone binding globulin (SHBG) levels after menopausal transition was observed [32, 33]. Additionally, thyroxine (t4) and triiodothyronine (t3) levels as well as growth hormone (GH) decrease as a result of the general ageing process. This dramatic hormonal transition is often associated with weight gain and changes in body composition, in particular fat distribution patterns [34–41]. We can summarize from a proximate viewpoint that menopausal transition is caused by the final depletion of germ cells and it is characterized by marked hormonal disturbances which are associated with significant changes in body composition and fat patterning.
5. Evolutionary explanations of menopause: ultimate approach
According to Theodosius Dobzhansky, “nothing in biology makes sense except in the light of evolution” . Consequently, we have to analyze menopausal transition from an ultimate or evolutionary viewpoint. There is no doubt that menopause is clearly a biological phenomenon and consequently, we can assume that menopause has an evolutionary origin [43–45]. The majority of women in First world countries experience menopause usually between 47 and 55 years of life . Considering an average life expectancy of about 80 years among females in First world countries, female postreproductive phase thus lasts on the average of 30 years. The potential maximum life span of recent
Since 1970s, several evolutionary scenarios of human menopause were proposed to explain the phenomenon of female reproductive senescence and in particular menopause; however, there is still no consensus about which of these hypotheses should be preferred [31, 45, 47, 48]. In general, two different types of evolutionary explanations of menopause can be distinguished: nonadaptive or by‐product hypotheses and adaptive hypotheses . Consequently, we have to ask that whether menopause is an adaption or an epiphenomenon .
At a first glimpse, the so‐called by‐product hypothesis seems comprehensible. The by‐product hypothesis is based on the assumption that life expectancy increased dramatically during the last few centuries. In former times, however, the life expectancy was much shorter. Consequently, women did simply not live long enough to experience menopause for most time of our evolution and history. From a physiological point of view, menopause occurs when all oocytes are depleted. The maximum number of germ cells which is produced until fifth month in utero is adapted to a life expectancy of less than 50 years. According to the by‐product hypothesis, it was assumed that in our past only few women lived until 50 years and beyond. Therefore, postmenopausal women did not exist. Consequently, menopause is not an adaptation, it is nothing else than a by‐product of increased life span and therefore a very recent phenomenon [50, 51].
In contrast to by‐product hypotheses, the adaptive hypotheses consider menopause itself as a fitness advantage . The most important question is, how natural selection came to favor prolonged postreproductive phase in human life history? The antagonistic pleiotropy hypothesis—first proposed by Williams in 1957—suggests that if a gene caused both increased reproduction in early life and aging in later life, then reproductive senescence can be interpreted as adaptive. In case of menopause, it was assumed that follicular depletion may cause both more regular cycles in early life and loss of fertility in later life through menopause. Consequently, its early benefits may outweigh its late costs .
From the perspective of life history, the main question is, when in our evolution an extended postreproductive period occurred for the first time? At the moment, it seems that life circumstances of our ancestors changed dramatically about 2 or 1.8 million years ago at the time when
Human females are unable to reproduce after menopause; however, they invest in the offspring of their daughters and sons. In this way, a prolonged postreproductive span may have increased inclusive fitness of postmenopausal women. This point of view resulted in the introduction of the so‐called grandmother hypothesis, which suggested increased fitness of women who stop reproduction and invest in their grandchildren [55, 61, 63–65]. The grandmother hypothesis is mainly based on the results of Kirsten Hawkes extensive fieldwork among Hadza hunter‐gatherers northern Tanzania in eastern Africa [55, 60]. Nevertheless, the grandmother hypotheses have been criticized by several authors .
Beside the grandmother hypothesis, the so‐called good mother hypothesis tries to explain the evolutionary benefit of an extended postreproductive phase in female
Recently, some new approaches to solve the evolutionary puzzle of menopause have been provided. According to the mate‐choice hypothesis, male mating preference for younger females may lead to the accumulation of mutations deleterious to female fertility and thus lead to the evolution of an extended postreproductive period in human females . Takahashi et al.  tried to explain the origin and evolution of menopause by combining a genetic basis, behavioral factors such as mating behavior, a life history perspective, and social changes in human evolution.
Although many different theories to explain the origin and evolution of menopause have been presented, human menopause remains as an unsolved evolutionary puzzle.
6. Climacteric syndrome from the viewpoint of evolutionary anthropology
As pointed out above, menopause is a common experience of all human females who lived until about 50 years of age and beyond [23, 46, 69]. From a biological viewpoint, menopause simply reflects reproductive senescence, the end of childbearing phase and is therefore a natural part of female life history . Consequently, menopause is not pathology because all human females who live long enough experience menopausal transition and the cessation of reproductive capability. Despite this fact, menopause was increasingly interpreted as a pathological condition since early nineteenth century. This medicalization of menopause within biomedical practice has affected the way menopause is viewed within society until today. Of special importance in this case is the work of the British gynecologist E.J. Tilt, who introduced the phenomenon of menopause in British Gynecology in 1857 . In continental Europe and North America, biomedicine practitioners began to think of menopause as a disease‐like state by the 1930s. As endocrinology improved and as synthetic estrogens became readily available in the 1960s, menopause was treated as a hormone deficiency disease, comparably to diabetes . As a consequence, the medical (pathological) viewpoint dominates menopause research for a long time.
Two different approaches to this medical viewpoint can be distinguished: on the one hand, menopause is interpreted as an own deficiency disease or endocrinopathy. According to this view, hormonal deficiency results in symptoms of the so called climacteric syndrome [6, 71, 72]. This medicalization of menopause is mainly due to the fact that many women experience a large variety of symptoms, such as hot flushes and night sweats, and also psychic problems such as depression, irritability, or insomnia during peri‐ and postmenopause. This symptom complex is commonly called climacteric syndrome, which make peri‐ and postmenopause very uncomfortable for many women. In western societies, 60–70% of menopausal women reported hot flushes and night sweats [46, 69]. Climacteric symptoms seem to be strongly related to the menopause‐specific decline of estrogen levels [32, 33]. However, not all climacteric women suffer from climacteric symptoms and the interpretation of the individual symptoms varies between individuals according to culture and society [46, 73–76]. Quite different is the alternative approach: menopause is not seen as a disease by itself but menopause is interpreted as a major risk factor for the development of other diseases such as osteoporosis, cardiovascular disease, some cancers such as breast cancer, and also Alzheimer disease [4, 77]. Additionally, the decline of estrogen levels after menopause enhances the risk of cardiovascular disease such as hypertension . Consequently, the risk of stroke, myocard infarct, and heart failure increases after menopause. Furthermore, menopause also seems to increase the risk of the development of certain cancers such as breast cancer [79, 80].
From the viewpoint of evolutionary anthropology, the so‐called climacteric syndrome can be interpreted in an evolutionary sense. Of course, potential climacteric complaints cannot be reconstructed from fossil bones and it is not possible to search for climacteric complaints among nonhuman primates or other social mammals. However, different attitudes toward menopausal transition and climacteric symptoms are found in different cultural settings [73, 75, 76].
The climacteric syndrome, however, can also be interpreted from the viewpoint of evolutionary medicine [81, 82]. Evolutionary medicine was formalized in early 1990s, most notably by the evolutionary biologist George C. Williams and psychiatrist Randolph Nesse who tried to understand why natural selection has left the human body so vulnerable to diseases . According to their concept, many medical conditions that are clearly pathological today have been adaptive in the ancestral environment in which
As pointed out above, we can assume that menopause and prolonged postmenopausal phase occurred first among members of
During the twentieth and twenty-first century lifestyle changed again dramatically. Urbanization, technical advances, and general modernization resulted in a marked transition in human life style. Advances in medicine reduced human morbidity and mortality and lead to increased life expectancy. The daily energy effort to gather and prepare food is reduced nearly to zero, since only few individuals are working on food production. Mechanized transportation, sedentary jobs, and labor‐saving household technologies reduce physical activity too. On the other hand, more than enough energy providing food, mainly consisting of sugar and fat is easily available [91, 92]. Consequently, a dramatic mismatch between current environment and human body evolved in the environment of our evolutionary adaptedness can be observed. In 99% of our evolutionary history, we have survived as foragers following a highly mobile life style in small groups. Obesity and noncommunicable diseases were quite unknown. Our gene pool was shaped by natural and sexual selection toward an optimal adaptation to these environments and life circumstances. Our recent environments, however, differ dramatically from that in which our ancestors evolved. There is no doubt that also some genetic changes had occurred since the Neolithic transition; however natural selection works slowly and our genome changed to a certain degree only. Therefore, we are still often adapted to a habitat that since more than 10,000 years no longer exists [83, 93–95].
Recent health problems such as climacteric complaints, cardiovascular disease, osteoporosis, or even postmenopausal breast cancer can be interpreted primarily as the results of a dramatic change in life style of women in contemporary societies. As pointed out above, the rapid decline in estrogen levels associated with menopause experienced by recent women in industrialized societies enhances climacteric symptoms such as hot flushes [23, 32, 33, 96]. These hormonal disturbances may be the result of our recent life style patterns. We have to be aware that life history patterns of contemporary women are unique within human evolution . We can assume that female life history patterns in our environment of evolutionary adaptedness resemble those of contemporary hunter gatherer societies . Recent female hunter gatherers reach sexual maturation quite late. Their reproductive span is characterized by many cycles of pregnancy, long periods of lactation, and early menopause. Consequently, the number of ovulatory cycles is quite low and about 100 ovulatory cycles are assumed during reproductive span. Therefore life‐time estrogen levels were quite low . These low levels of estrogens during adult life are caused by high levels of physical activity, a diet characterized by low fat contents, a low amount of body fat, and low body weight [79, 97]. Consequently, lifetime estrogen exposition was quite low in the environment of evolutionary adaptedness. Life history patterns of women in recent developed countries are quite different. Menarche occurs early and first pregnancy becomes late. In Austria, for example, first menstrual bleeding occurs at the age of 12 years on average, first birth, however, occurs at the age of 29.7 years . This means a period of nearly 18 years between sexual maturation and first reproduction. Reproductive span of contemporary women living in First world countries is characterized by extremely few pregnancies, few births, and short periods of lactation. It can be assumed that a woman experiences about 400 cycles on the average. Menopause occurs late and hormone supply via hormonal contraceptives or hormone replacement therapy is usual. Consequently, life estrogen exposition is long and estrogen levels are high . During menopausal transition, estrogen levels drop down very fast resulting in rapid hormone deficiency, which may lead to climacteric symptomatology [32, 33, 69].
Among recent traditional societies, following quite different life style patterns such as women in rural India or Maya women in Yucatan estrogen levels are very low during menopausal transition; nevertheless, climacteric symptoms are rarely reported. Traditional lifestyle is characterized by low life time estrogen levels. The decline of estrogen secretion during menopausal transition is therefore not as dramatic as among women in western societies. Sometimes, last lactational amenorrhea—characterized by low estrogen levels—switches to menopause . Consequently, climacteric complaints as a reaction of a sudden drastic estrogen decline are prevented. The high prevalence of climacteric symptoms in western societies may therefore be interpreted as a result our recent life style.
Additionally, a high rate of physical activity and a traditional diet poor in fat reduce estrogen levels through reproductive phase and even during and shortly after menopausal transition. Estrogens are converted from androgens in adipose tissue. Consequently, a higher amount of body fat increase the estrogen levels during reproductive phase and even during menopausal transition. This positive association between body fat and estrogen levels increases also the probability to develop breast cancer during peri‐ and postmenopause. A sedentary life style, high fat contents in diet, high life time estrogen levels, and high rates of overweight and obesity during middle age increase the risk of several diseases associated with menopausal transition such as breast cancer, cardiovascular disease, and also osteoporosis .
From the viewpoint of evolutionary anthropology, menopause is a natural part of female life history and therefore not a pathology. Several theories have been proposed to explain the evolutionary basis of menopausal transition, although there is still no consensus. The climacteric syndrome—mainly caused by estrogen deficiency—may be interpreted as the result of a mismatch between recent life style and reproductive patterns and life circumstances in the environment in which our ancestors evolved.