Androgens in Human Evolution. A New Explanation of Human Evolution
Copyright ã 2001, James Michael Howard and Rivista di Biologia / Biology Forum 2001; 94: 345-362
(This chart is not part of my publication. This chart supports my hypothesis and was published in 2003.)
Regarding Increased Breast Size in Humans: It is my hypothesis that increased testosterone in female hominids / humans caused phenomena which differentiates humans from the (other) apes. One of these phenomena is the enlarged breasts of humans compared to the apes. Estradiol is approximately the same in human and chimpanzee females, so, what causes the difference? It is increased testosterone in human females. Human females produce more testosterone than chimpanzee females.
“Testosterone was significantly positively associated with %DBV [ percentage of dense breast volume] and ADBV [absolute dense breast volume].” Cancer Epidemiol Biomarkers Prev. 2014”\: “Endogenous sex hormones and breast density in young women.,” Jung, et al.,
Voilà, increased female testosterone in humans causes the increased breast volume.
New, strong support of my explanation of human evolution: According to my explanation of the effects of prenatal testosterone in human evolution, prenatal testosterone in Bonobos should be less than humans but higher than chimpanzees: "We observed the expected sex difference in 2D:4D, and substantially higher, more human-like, 2D:4D in bonobos than chimpanzees." (J Hum Evol 2009; 56(4): 361-5)
Very strong support of my explanation of human evolution:
"Interactive Effects of Dehydroepiandrosterone and Testosterone on
Cortical Thickness during Early Brain Development," The Journal of
Neuroscience, June 26, 2013 • 33(26):10840 –10848. This also includes the connection of adrenarche. "Androgens in Human Evolution," of 2001 is not mentioned.
Human evolution consists of chronological changes in gene regulation of a continuous and relatively stable genome, activated by hormones, the production of which are intermittently affected by endogenous and exogenous forces. Periodic variations in the gonadal androgen, testosterone, and the adrenal androgen, dehydroepiandrosterone (DHEA), significantly participated in all hominid transformations. The hominid characteristics of early Australopithecines are primarily a result of increased testosterone. The first significant cold of the early Pleistocene resulted in an increase in DHEA that simultaneously produced Homo and the robust Australopithecines. Subsequent Pleistocene climatic changes and differential reproduction produced changes in DHEA and testosterone ratios that caused extinction of the robust Australopithecines and further changes in "Homo." Changes in testosterone and DHEA produce allometric and behavioral changes that are identifiable and vigorous in modern populations.
Humans and chimpanzees differ in hormones that produce significant effects on anatomy, physiology, and behavior. Human males and females produce more testosterone than chimpanzee males and females, respectively (Winter et al., 1980). Chimpanzee and human females produce similar levels of estradiol (Winter et al., 1980) and progesterone (Hobson et al., 1976). I suggest early differences in testosterone levels started species divergence and promoted hominid evolution.
Estradiol and testosterone support different functions in females. Estradiol stimulates genital displays that advertise ovulation in monkeys (Wilson, 1977), gibbons (Nadler et al., 1993), chimpanzees (Ozasa & Gould, 1982) and gorillas (Nadler, 1980), but not women. Estradiol and testosterone both peak near ovulation in female orangutans, gorillas, chimpanzees and humans. Estradiol and testosterone act synergistically to maximize reproduction. Estradiol prepares the sexual apparatus for coitus and impregnation; testosterone stimulates sexual activity.
While it "is a general trend in Western societies to blame psychosocial factors for diminished sexuality in women," diminished sexual drive and other aspects of sexual dysfunction, in androgen-deficit women, are primarily improved by testosterone therapy (Davis, 1998; Kaplan & Owett, 1993). In postmenopausal women, combined estrogen-androgen therapy significantly improves "sexual desire, satisfaction and frequency," whereas estrogen alone, or estrogen-progestin therapies do not, leading to the conclusions that "androgens play a pivotal role in sexual function" and "estrogens are not a significant factor determining levels of sexual drive and enjoyment" (Sarrel et al., 1998). Because estrogens prepare female genitalia for coitus, it is best to treat sexual dysfunction in women with testosterone and estradiol (Davis et al., 1995). Nevertheless, libido is primarily an effect of testosterone. In sexually functional women, testosterone treatment produces a "statistically significant increase in genital responsiveness" and "subjective reports of ‘genital sensations’ and ‘sexual lust’" (Tuiten et al., 2000). Supplementary testosterone not only corrects deficiencies in sexual desire, it intensifies normal sex drive.
Estradiol levels in women and chimpanzees are optimal. Therefore, increasing testosterone to estradiol ratios in hominids increases sexuality proportionately. As testosterone increases, so does the sexual activity of the female. This increases male attendance and reproduction. These females have an advantage in representation in future generations.
Increasing the testosterone to estradiol ratio reduces the effects of estradiol. Human female fetal external genitalia contain AR (androgen receptors) and ER (estrogen receptors), while male external genitalia lack ER (Kalloo et al., 1993). The AR in the female external genitalia "were strikingly similar to that in the male." In women, increased testosterone competes with the effects of estradiol on external genitalia. As the testosterone to estradiol ratio increases, the labial display decreases. This is why humans do not produce a labial display. (Adrenal androgens stimulate male and female pubic hair just prior to puberty and probably act through the common AR in both sexes.) The primary sexual signal of female chimpanzees is the labial display. In women the primary display of sexual maturity is the breast. Chimpanzee mothers and small breasted women produce ample nutrition for nursing offspring. I suggest the increased size of the human breast is a sexual signal. Breasts are estradiol-dependent structures. Breast enlargement is a signal of maturing estradiol levels, and may also be a signal of maturing testosterone levels and, therefore, of increased sexual arousal.
Fat tissues capture steroid hormones, including testosterone. Testosterone is aromatized to estradiol in fat tissues. While breast fat is not as active as axillary fat in converting testosterone into estradiol, "results indicate a possible role of adipose tissue as a significant extra-gonadal source of estrogens" (Nimrod & Ryan, 1975). This increased level of estradiol in the breast could increase breast size. Aromatization of testosterone occurs in normal female breast tissue and in gynecomastia in men. Breast tissue from five out of six men with gynecomastia aromatized testosterone into estradiol (Perel et al., 1981). (Gynecomastia is true breast development in men, vis-à-vis pseudogynecomastia caused by fat deposits.) Conversion of testosterone into estradiol in human breast fat augments breast development and size. Testosterone and estrogen both inhibit human hair production, in vitro (Kondo et al., 1990). Increasing testosterone levels in hominids reduced hair production in both sexes. The combined effects of testosterone and estradiol further reduce hair growth in women. This increases the prominence of the breast. The female human breast is a signal of mature estrogen and testosterone production. The female human breast is largest among primates due to increased testosterone.
The pubic bones of male mice are shorter and thicker than those of female mice. Neonatal testosterone treatment of female mice produces "pubic bones shorter and thicker than those of age-matched females" and "Pubes in male mice castrated at the day of birth were thinner than those of intact males." (Iguchi et al., 1989). Androgens directly affect bone growth in women (Gasperino, 1995). Testosterone is involved in bone growth and produces changes in the female pelvis. Increasing testosterone in hominid females would change growth and development of the pelvis with time. Essentially all tissues produce androgen receptors, therefore growth and development of all tissues in emerging hominids were affected by testosterone. The muscles that control upright walking increased in strength as a result of increased testosterone. The large size of the gluteus maximus "is one of the most characteristic features of the muscular system in man, connected as it is with the power he has of maintaining the trunk in the erect posture." (Gray, 1966).
The brain also enlarged as a response to the effects of increasing testosterone. The brain produces androgen receptors throughout. Testosterone exposure of the male human brain, in utero, results in increased head circumference of male brains at birth (Liebermen L.S., 1982). Androgen treatment of female monkeys increased performance to male levels, on an "object discrimination task." Both male and female performance levels were adversely affected by lesions in the orbital prefrontal cortex, indicating that "gonadal hormones may play an inductive role in the differentiation of higher cortical function in nonhuman primates." (Clark & Goldman-Rakic, 1989).
The single phenomenon of increasing testosterone produced the hominid characteristics of Australopithecus. The single phenomenon of increased testosterone production participated in every hominid characteristic, simultaneously. Testosterone increased female sexual activity, reduced female genital display, reduced hair growth, increased breast size, changed pelvic growth, and produced increases in brain size. These combined changes accelerated the advent of upright, bipedal locomotion and larger brains. (Male and female pubic hair is visually different. It may be that pubic hair was the first appreciable change in sexual display as body hair and the labial display digressed in Australopithecus.)
The canine teeth of Australopithecus were smaller, and less "projecting" than contemporary primates. However, in living monkeys, testosterone increases large canine teeth. The canines are larger in males and prenatal exposure of females to testosterone increases the size of their canines (Zingeser & Phoenix, 1978). This appears to present a quandary for this explanation of human evolution. Humans produce more testosterone, yet the canine teeth are small.
In hominids the effects of testosterone, on brain size, teeth, and other tissues, are due to changes in availability of DHEA. I suggest DHEA is involved in growth and maintenance of all tissues, especially the brain, and is paramount in the formation of the robust Australopithecines and Homo. DHEA is proven to positively affect growth and function of many tissues, including the brain. "Dehydroepiandrosterone and its sulphate ester are neuroactive and are both imported into the brain from the circulation and produced in the nervous system. These neurosteroids have neurotrophic and excitatory effects." (Baulieu, 1999). (The enlargement of neural tissue during primitive evolution may be due to increased absorption and production of DHEA.) Testosterone evolved after DHEA; testosterone is a conversion product of androstenedione, which is a direct conversion product of DHEA. Therefore growth before testosterone relied on DHEA. Testosterone evolved because its molecular structure affected DNA in an advantageous manner. My principal hypothesis is DHEA optimizes transcription and replication of DNA. Therefore, a subordinate hypothesis suggests the advantage of testosterone is that it directs DHEA use for genes that are targets of testosterone action. Testosterone increases the rate of DHEA use. (Males produce more testosterone, therefore, in males, testosterone-target-tissues are larger, e.g., muscle, bone, etc., or grow at different rates, producing different structures from the same beginning tissues, e.g., genitalia, or differences in final brain function, e.g. male-female differences in the brain. Testosterone is not the male hormone, males simply produce more.)
That testosterone affects levels of DHEA is supported by reductions of DHEA during increased levels of testosterone in some nonhuman primates. The following references support a pattern of decline of DHEA levels when testosterone levels increase. In the crab-eating monkey, "DHA [DHEA] levels were high during the first months, decreased at about 1 year, remained stable during infancy and prepuberty and then declined again during puberty. At about 5 years, the values were 28% of those in neonates." (Meusy-Dessolle & Dang, 1985). "By contrast the serum prolactin and dehydroepiandrosterone levels showed an inverse pattern achieving their highest levels in spring, during the period of reduced testicular function." (Wickings & Nieschlag, 1980). "Serum testosterone levels rose during male development; however, there was a progressive decrease in dehydroepiandrosterone sulfate levels indicating the absence of adrenarche." (Crawford et al., 1997). The decline in DHEA when testosterone is increased in these examples could indicate that DHEA is being utilized in tissues, therefore reducing measurable levels in blood.
In the Australopithecines, as in the primates above, a limited amount of DHEA was directed toward one tissue at the expense of another. As testosterone increased in Australopithecus, the brain increased use of DHEA. When testosterone increased use of DHEA for the brain, the available DHEA for growth and development of canine teeth was reduced. (The brain may be the paramount tissue in vertebrate evolution because it is able to capture DHEA better than other tissues.) The brain increased slightly and the canines decreased slightly. Brain tissue simply takes more of the supply of DHEA; canines do not grow as large in response. (Measurable levels of DHEA are very high in monkeys, much lower in humans, with chimpanzees levels very similar to humans. I suggest this is an indication of relative use of DHEA by the respective brains.)
The cold periods of the Pleistocene epoch directly caused changes in hominid evolution. Homo and the robust Australopithecines are the results of the first, large cold increase around 2.5 mya. A common phenomenon occurred in both. This particular cold selected for individuals that produced more DHEA. Increased DHEA is an advantage during cold. DHEA treatment in rats "affected body weight, body composition and utilization of dietary energy by both impairing fat synthesis and promoting fat-free tissue deposition and resting heat production." (Tagliaferro et al., 1986). This effect of DHEA is due to increased thermogenesis (Bobyleva et al., 1993). Individuals who produce more DHEA derive more heat from the same nutrition. As cold decreased available nutrition, individuals that could derive more benefit from sparse nutrition had a survival advantage. The ratio of DHEA to testosterone in hominids started to change at this time. (Increased DHEA may have been involved in early mammalian evolution. That is, increased ability to make DHEA may have been the reason mammals survived events that caused extinction of the dinosaurs.)
The Australopithecines remained relatively unchanged during the upper Pliocene. The change from A. afarensis to A. africanus was probably due to increasing testosterone. A noticeable change occurred in the Australopithecines during the first cold of the early Pleistocene. The robust Australopithecines appeared, i.e., robustus and boisei. Robustus and boisei differed from afarensis and africanus mainly in teeth size and facial size, little in body size. Pronounced sexual dimorphism continued in the Australopithecines, including the robust types. That is, the survival strategy of these groups continued to mainly depend on increased testosterone in males. The levels of testosterone did not increase much, so brain size did not increase much. The cold selected for individuals of higher DHEA in this group. Therefore, increased availability of DHEA increased effects on testosterone-target-tissues. Teeth and facial structures are testosterone-target-tissues. The available DHEA, not used in thermogenesis, caused increased size in the teeth and facial structures. The testosterone levels of the males did not change significantly, so their brain size did not change significantly.
Homo differs from Australopithecus mainly in a small increase in brain size at the time of separation of the two. I suggest separation of Homo from Australopithecus occurred as a result of increased testosterone in Homo females. It is in Homo that the true effects of increased testosterone began to increase rapidly. The breast would increase in Homo and increase selection pressure for those changes that produce more efficient bipedal locomotion. As testosterone increased in Homo females, brain size continued to increase over that of Australopithecus. When this increase in testosterone first began in Homo, there should be transitional forms with larger brains, but which continued to exhibit small bodies and sexual dimorphism, such as Homo rudolfensis and Homo habilis. H. rudolfensis and habilis developed contemporaneously with A. robustus and boisei.
As testosterone and DHEA increased during this time period, increases in growth continued in the brain and began to affect growth of the body. Homo began to increase in overall size. The effects of these two hormones increased as the climate began to warm. (There is no selection pressure to reduce testosterone and DHEA levels by relative warmth.) Reduced use of DHEA for thermogenesis increased availability for body and brain growth. Homo ergaster and H. erectus emerged at this time. It is the increase in females of higher testosterone that produced Homo. It is first identifiable in Homo erectus/ergaster. Sexual dimorphism declined in Homo erectus as a result of increased female size, not a decline in male size. This increase in testosterone in both sexes, and the increase in DHEA, would increase bone growth and length.
Treatment of rats with DHEA increases bone mineral density. "Treatment with DHEA caused a 4-fold stimulation of serum alkaline phosphatase, a marker of bone formation, while the urinary excretion of hydroxyproline, a marker of bone resorption, was decreased by DHEA treatment." (Martel et al., 1998). DHEA treatment of postmenopausal women stimulates increases in serum osteocalcin, another marker of bone formation (Labrie, 1997). Adrenarche is the beginning of the measurable increase of DHEA in humans that begins around five- or six-years-of-age and increases rapidly until about age twenty. Adrenarche continues for years prior to puberty. A significant amount of bone growth occurs prior to the growth spurt of puberty. "Premature adrenarche" produces an acceleration of bone age that was greater in males, and the appearance of premature pubic hair in 93.8% of both sexes (Likitmaskul et al., 1995). The testosterone conversion product, dihydrotestosterone (DHT), produces no qualitative differences in bone growth, only a more rapid increase in bone growth in vitro. DHEA and DHT both stimulated "cell proliferation and differentiated functions, but the gonadal androgen DHT was significantly more potent than DHEA." (Kasperk et al., 1997). Years of bone growth due to DHEA occurs prior to puberty; testosterone rapidly increases and finalizes body growth at puberty during the growth spurt. Testosterone and estradiol rapidly increase the final development of bone. A direct connection of increased bone formation in individuals of higher testosterone exists. Serum testosterone, estradiol and bone density are higher in black women than white women (Perry et al., 1996). Testosterone is significantly higher in black college students than white college students (Ross et al., 1986). Black males and females consistently exhibit greater mean levels of "areal and volumetric bone mineral density" "at all skeletal sites" than Asians, Hispanics, and whites (Bachrach et al., 1999). Increased testosterone increases bone growth. As testosterone and DHEA increased in Homo, growth in size and length of bones increased.
Homo erectus existed during a time of relative warmth. This climate change means that its DHEA could be used for purposes other than thermogenesis. The brain of H. erectus doubled that of Australopithecus. There was less sexual dimorphism in H. erectus than in the Australopithecines, but still more than that of later hominids. Musculoskeletal development was very robust, another consequence of additional DHEA for growth, not used by the brain or for thermogenesis. The anterior teeth were larger and the molar teeth smaller than those of Australopithecus. The decrease in posterior teeth results from an increase in development of anterior parts of the brain. Brain forming later, during the time of formation of posterior teeth, reduces available DHEA for those teeth, therefore, they are smaller. Again, the brain takes DHEA at the expense of other tissues.
The return of cold later in the Pleistocene returned selection for increased DHEA. Neandertal habitat was characterized by relative containment. The cold and containment increased DHEA and testosterone in Neandertal. Neandertal continued to increase in brain size. The teeth and facial structures and brain development of Neandertal are exaggerated due to increased testosterone and DHEA. The large teeth and brains indicate there was plenty of DHEA for sharing between various tissues. However, this large brain was increased in posterior regions, not in anterior areas. This would be consistent with early puberty.
High testosterone and high DHEA could cause early puberty. Increased androgen receptors in the brains of individuals of higher testosterone increase use of DHEA for brain growth during childhood. This accelerates the onset of puberty, because the brain structures that control puberty mature early. This shortens the time to hypothalamic stimulation of testosterone production by the gonads. As testosterone-target-tissues grow and begin to increase use of DHEA, competition for available DHEA increases. Therefore, early puberty reduces available DHEA for growth of anterior parts of the cerebrum. Large bodies and early puberty reduce final (anterior) brain development. That is, early puberty reduces the time of basic growth and development of the brain that occurs under the influence of DHEA.
Effects of low testosterone on craniofacial growth and statural height have been demonstrated in boys with delayed puberty. "These results show that statural height and craniofacial dimensions are low in boys with delayed puberty. Low doses of testosterone accelerate statural and craniofacial growth, particularly in the delayed components, thus leading towards a normalization of facial dimensions." (Verdonck et al., 1999). Osteoporosis in vertebrae, the diaphysis of the radius, and neck of the femur in male leprosy patients were "significantly correlated with [reduced] FT [free testosterone] in all three regions of the skeleton." (Ishikama et al., 1999). Assuming sufficient DHEA is available, too much testosterone increases bone size and prognathism; too little has the opposite effect.
Continued cycling of cold during the upper Pleistocene and changes in containment areas selected for hominids with different ratios of DHEA and testosterone. Some combination of testosterone and DHEA occurred that favored increased use of DHEA for brain growth. A change in the ratio of DHEA and testosterone can slow the onset of puberty and increase anterior brain size. Producing less DHEA reduces the effects of testosterone. Reduced containment (testosterone) or reduced nutrition will slow the pace of puberty. (Increased nutrition should favor those with early puberty.) The percentage of high testosterone individuals would decrease and average size of the forebrain would increase. This began in H. antecessor and H. heidelbergensis. Delayed puberty and increased brain size produced Homo sapiens. Increased brain growth in H. sapiens occurred in the anterior portion of the brain, the prefrontal lobes. This produces the high forehead.
Another shift downward in testosterone levels in a population could occur rapidly. Testosterone compromises the immune system. The effects are especially dangerous when trauma is involved. "Male gender is associated with a dramatically increased risk of major infections following trauma . This effect is most significant following injuries of moderate severity and persists in all age groups." (Offner et al., 1999). "Castration before soft-tissue trauma and hemorrhagic shock maintains normal immune function in male mice, but sham-castrated male mice show significant immunodepression. The maintenance of immune function by androgen deficiency does not seem to be related to changes in the release of corticosterone. We conclude that male sex steroids are involved in the immunodepression observed in after trauma-hemorrhage. Thus, the use of testosterone-blocking agents following trauma-hemorrhage should prevent the depression of immune functions and decrease the susceptibility to sepsis under those conditions." (Wiehmann et al., 1996). These negative effects of testosterone on immunity could increase the probability of infectious epidemics that could radically change the percentage of individuals of higher testosterone in a population. This is very possibly the mechanism involved in extinctions of the robust Australopithecines and various Homo populations.
Once a population is reduced in high testosterone individuals, a stable population could exist for some time. However, due to the influence of testosterone on reproduction, most populations will regain their high levels of testosterone in time. Every positive increase in nutrition would increase the probability of increasing the percentage of high testosterone individuals. Therefore, a "cycling" of high testosterone populations should occur. This may have occurred at the end of the Upper Paleolithic, through the Neolithic, when body size in males and females clearly declined (Frayer, 1984). A reduction in body size indicates that individuals of high testosterone levels in the population died. Body size then increased into the Middle Ages during which epidemics occurred with some frequency. Increased availability of food increases the rate of these cycles, but does not cause them. People of high testosterone simply reproduce faster when more food is available.
Homo sapiens exhibit a constellation of characteristics that separate sapiens from other hominids. Postcranial skeleton, teeth, and craniofacial size are all reduced coincidentally with changes in brain growth, that is, increases in size in the frontal areas. Earlier, I suggested that canines are reduced in size in Australopithecus because the brain is using DHEA for growth at the expense of these teeth. The part of the brain that increased in Australopithecus reduced growth of front teeth. These are increases mainly in the posterior parts of the brain. Posterior growth of the brain retards growth of anterior teeth because they occur concurrently. Many hominids exhibit increased posterior brain size and reduced anterior teeth. The increase in brain growth of Homo sapiens includes the posterior and the anterior parts of the cerebrum. Therefore, in Homo sapiens, both the anterior and posterior teeth compete for DHEA during times of brain growth. This is why the entire dentition is reduced in Homo sapiens.
There are two dentitions in humans. DHEA levels are very high at birth, then decline to very low levels within a year and remain low for some time. Around age five to six, DHEA levels increase rapidly (adrenarche) and peak around age twenty, at levels about half as much as that of the levels at birth. The brain is using so much DHEA for growth and development during early childhood that measurable levels of DHEA are very low. From age twenty, DHEA levels begin to decline, reaching very low levels in old age. The high levels of DHEA at birth stimulate growth of deciduous teeth. This period of high levels of DHEA declines rapidly to very low levels in the first year. This decline of DHEA of early childhood is so low that it does not support continued maintenance of the deciduous teeth, and they are lost. The permanent dentition occurs as a result of increasing DHEA beginning at adrenarche. Adrenarche begins as the brain begins to finalize growth. These teeth are supported until DHEA begins to decline in old age, unless something interferes with DHEA. This explains human dentition. This implies that teeth are very sensitive to DHEA levels. With the simple assumption that the bone of the mandible is less sensitive to reduced DHEA, the reduction of the size of the anterior teeth produces the chin.
Australopithecus and Homo evolved as consequence of differential gene regulation, in continuous, relatively comparable genomes, resulting mainly from chronological differences in production of the androgenic hormones, testosterone and dehydroepiandrosterone (DHEA). The cold periods of the Pleistocene epoch selected for individuals of higher DHEA, which interacted with levels of testosterone that varied according to behavioral advantages. The two principal events of hominid evolution are 1) increased testosterone in females, that stimulated increased testosterone in males, and 2) the amplification of testosterone-directed characteristics by increased DHEA. The effects of these events resulted in bipedal, upright locomotion, breasts as sexual displays, larger brains, and the effects of increased use of DHEA by larger brains throughout the body.
Individuals who produce large amounts of testosterone are vulnerable to infections. Moreover, high testosterone individuals may act as carriers of infectious agents. Testosterone and puberty are directly connected to "establishment and maintenance of the carrier state" of an infectious virus in horses (McCollum et al., 1994; Holyoak et al., 1993). This may have caused past epidemics, when populations were composed of high percentages of high testosterone individuals in dense populations. The end result would be a new population reduced in the testosterone to DHEA ratio. This may have produced the first population of Homo sapiens and, thereafter, periodically reduced the percentages of individuals of high testosterone in later populations.
Increased amounts of DHEA for relatively lengthy, slower development of the brain results in larger brains in the remaining population. These types of events increase during times of higher population density due to increased nutrition. This phenomenon is identifiable as the decline in body size that occurred from the upper Paleolithic through the Neolithic periods. That is, increased food increases reproduction rates and concentrates high testosterone individuals into population centers. When testosterone reaches supra-optimal levels, infection rates increase. Body size increased in the Middle Ages, which frequently included epidemics. Learning disabilities are "significantly associated" with high testosterone levels (Kirkpatrick et al., 1993). The Renaissance followed the Middle Ages. Populations will periodically cycle through times of increased and reduced percentages of high testosterone individuals. Civilizations evolve in this manner. I suggest the increase in percentage of individuals of higher testosterone produces the "secular trend," in populations. The secular trend is real, identifiable, and vigorous in the U.S.A., at this time (Freedman et al., 2000).
This is a new explanation of human evolution. It accounts for all aspects of human evolution, including the formation and declines of Australopithecus and Homo, formation and declines of civilization, and is identifiable in current populations.
Bachrach, L.K., Hastie, T., Wang, M.C., Narasimhan, B., & Marcus, R. (1999). Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. J. Clin. Endocrinol. Metab. 84, 4702-12.
Baulieu, E.E. (1999). Neuroactive neurosteroids: dehydroepiandrosterone (DHEA) and DHEA sulphate. Acta. Paediatr. Suppl. 88, 78-80.
Bobyleva, V., Kneer, N., Bellei, M., & Lardy, H.A. (1993). Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone. J. Bioenerg. Biomembr. 25, 313-21.
Clark, A.S. & Goldman-Rakic, P.S. (1989). Gonadal hormones influence the emergence of cortical function in nonhuman primates. Behav. Neurosci. 103, 1287-95.
Crawford, B.A., Harewood, W.J. & Handelsman, D.J. (1997). Growth and hormone characteristics of pubertal development in the hamadryas baboon. J. Med. Primatol. 26, 153-63.
Davis S.R., McCloud, P., Strauss, B.J. & Burger, H. (1995). Testosterone enhances estradiol’s effects on postmenopausal bone density and sexuality. Maturitas 21, 227-36.
Davis, S.R. (1998). The clinical use of androgens in female sexual disorders. J. Sex. Marital Ther. 24, 153-63.
Frayer, D.W. (1984). Biological and cultural change in the european late pleistocene and early holocene. In (Smith, F. H. & Spencer, F., Eds.) The Origins of Modern Humans. A World Survey of the Fossil Evidence, New York, Alan R. Liss, Inc., pages 211-50.
Freedman, D.S., Khan, L.K., Serdula, M.K., Srinivasan, S.R., & Berenson, G.S. (2000). Secular Trends in Height Among Children During 2 Decades. The Bogalusa Heart Study. Arch. Pediatr. Adolesc. Med. 154, 155-61.
Gasperino, J. (1995). Androgenic regulation of bone mass in women. A review. Clin. Orthop. 311, 278-86.
Gray, H. (1966). Anatomy of the Human Body, (Goss, C.M., Ed.). Philadelphia, Lea & Fegiber, page 500.
Hobson, W., Coulston, F., Faiman, C., Winter, J.S. & Reyes, F. (1976). Reproductive endocrinology of female chimpanzees: a suitable model of humans. J. Toxicol. Environ. Health 1, 657-68.
Holyoak, G.R., Little, T.V., McCollam, W. H., & Timoney, P.J. (1993). Relationship between onset of puberty and establishment of persistent infection with equine arteritis virus in the experimentally infected colt. J. Comp. Pathol. 109, 29-46.
Iguchi, T., Irisawa, S., Fukazawa, Y., Uesugi, Y. & Takasugi, N. (1989). Morphometric analysis of the development of sexual dimorphism of the mouse pelvis. Anat. Rec. 224, 490-4.
Ishikawa, S., Ishikawa, A., Yoh, K., Tanaka, H.. & Fujiwara, M. (1999). Osteoporosis in male and female leprosy patients. Calcif. Tissue Int. 64, 144-7.
Kalloo N.B., Gearhart J.P., & Barrack E.R. (1993). Sexually dimorphic expression of estrogen receptors, but not of androgen receptors in human fetal external genitalia. J. Clin. Endocrinol. Metab. 77, 692-8.
Kaplan, H.S. & Owett, T. (1993). The female androgen deficiency syndrome. J. Sex. Marital Ther. 19, 3-24.
Kasperk, C H., Wakley, G.K., Hierl, T., & Ziegler, R. (1997). Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro. J. Bone Miner. Res. 12, 464-71.
Kirkpatrick, S.W., Campbell, P.S., Wharry, R.E. & Robinson, S.L. (1993). Salivary testosterone in children with and without learning disabilities. Physiol. Behav. 53, 583-6.
Kondo, S., Hozumi, Y. & Aso, K. (1990). Organ culture of human scalp hair follicles: effect of testosterone and oestrogen on hair growth. Arch. Dermatol. Res. 282, 442-5.
Labrie, F., Diamond, P., Cusan, L., Gomez, J.L., Belanger, A., & Candas, B. (1997). Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J. Clin. Endocrinol. Metab. 82, 3498-505.
Lieberman, L.S. (1982). Normal and abnormal sexual dimorphic patterns of growth and development. In (R.L. Hall, Ed.) Sexual Dimorphism in Homo Sapiens. A Question of Size, New York: Praeger, page 281.
Likitmaskul, S., Cowell, C.T., Donaghue, K., Kreutzmann, D.J., Howard, N.J., Blades, B., & Silink, M. (1995). ‘Exaggerated adrenarche’ in children presenting with premature adrenarche. Clin. Endocrinol. (Oxf). 42, 265-72.
Martel, C., Sourla, A., Pelletier, G., Labrie, C., Fournier, M., Picard, S., Li, S., Stojanovic, M., & Labrie, F. (1998). Predominant androgenic component in the stimulatory effect of dehydroepiandrosterone on bone mineral density in the rat. J. Endocinol. 157, 433-42.
McCollum, W.H., Little, T.V., Timoney, P.J., & Swerczek, T.W. (1994). Resistance of castrated male horses to attempted establishment of the carrier state with equine arteritis virus. J. Comp.Pathol. 111, 383-8.
Meusy-Dessolle, N. & Dang, D.C. (1985). Plasma concentrations of testosterone, dihydrotestosterone, delta 4-androstenedione, dehydroepiandrosterone and oestradiol-17 beta in the crab-eating monkey (Macaca fascicularis) from birth to adulthood. J. Reprod. Fertil. 74, 347-59.
Nadler, R.D. (1980). Reproductive physiology and behaviour of gorillas. J. Reprod. Fertil. Suppl. 28, 79-89.
Nadler, R.D., Dahl, J.F. & Collins, D.C. (1993). Serum and urinary concentrations of sex hormones and genital swelling during the menstrual cycle of the gibbon. J. Endocrinol. 136, 447-55.
Nimrod, A. & Ryan, K.J. (1975). Aromatization of androgens by human abdominal and breast fat tissue. J. Clin. Endocrinol. Metab. 40, 367-72.
Offner, P.J., Moore, E.E. & Biffl, W.L. (1999). Male gender is a risk factor for major infections after surgery. Arch. Surg. 134, 935-8.
Ozasa, H. & Gould, K.G. (1982). Demonstration and characterization of estrogen receptor in chimpanzee sex skin: correlation between nuclear receptor levels and degree of swelling. Endocrinology 111, 125-31.
Perel, E., Davis, S. & Killinger, D.W. (1981). Androgen metabolism in male and female breast tissue. Steroids 37, 345-52.
Perry, H.M., 3rd., Horowitz, M., Morley, J.E., Fleming, S., Jensen, J., Caccione, P., Miller, D.K., Kaiser, F.E., & Sundarum, M. (1996). Aging and bone metabolism in African American and Caucasian women. J. Clin. Endocrinol. Metab. 81, 1108-17.
Ross, R., Bernstein, L., Judd, H., Hanisch, R., Pike, M., & Henderson, B. (1986). Serum testosterone levels in healthy young black and white men. J. Natl. Cancer Inst. 76, 45-8.
Sarrel, P., Dobay B.J., & Wiita, B. (1998). Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses. Reprod. Med. 43, 847-56
Tagliaferro, A.R., Davis, J.R., Truchon, S., & Van Hamont, N. (1986). Effects of dehydroepiandrosterone acetate on metabolism, body weight and composition of male and female rats. J. Nutr. 116, 1977-83.
Tuiten A., Van Honk J., Koppeschaar, H., Bernaards C., & Verbaten, R. (2000). Time course of effects of testosterone administration on sexual arousal in women. Arch. Gen. Psychiatry 57, 149-53.
Verdonck, A. Gaethofs, M., Carels, C., & de Zegher, F. (1999). Effect of low-dose testosterone treatment on craniofacial growth in boys with delayed puberty. Eur. J. Orthod. 21, 137-43.
Wickings, E.J. & Nieschlag, E. (1980). Seasonality in endocrine and exocrine testicular function of the adult rhesus monkey (Macaca mulatta). Int. J. Androl. 3, 87-104.
Wiehmann, M.W., Zellweger, R., DeMaso, C.M., Ayala, A. & Chaudry, I.H. (1996). Mechanism of immunosuppression in males following trauma-hemorrhage. Critical role of testosterone. Arch. Surg. 131, 1186-91.
Wilson, M.I. (1977). A note on the external genitalia of female squirrel monkeys (Saimiri sciureus). J. Med. Primatol. 6, 181-5.
Winter, J.S.D., Faiman, C., Hobson, W.C. & Reyes, F.I. (1980). The endocrine basis of sexual development in the chimpanzee. In (R.V. Short & B.J. Weir, Eds.) The Great Apes of Africa, Text-fig. 2 (testosterone, males), page 134, Text-fig. 5 (testosterone, females), page 137, and Text-fig. 3, page 135, (estradiol, females). J. Reprod. Fertil. Suppl. 28.
Zingeser, M.R. & Phoenix, C.H. (1978). Metric characteristics of the canine dental complex in prenatally androgenized female rhesus monkeys (Macaca mulatta). Am. J. Phys. Anthropol. 49, 187-92.