LEVAY CRITIQUE *Neuroscience or Nonsense* Written by Sandy Zetlan, Ph.D.Neurosciences zetlan@wiscmacc (Bitnet) zetlan@wisc.macc.edu (Internet) Women's Studies Program University of Wisconsin 209 North Brooks St Madison, WI 53706 INTRODUCTION In August of 1991 Simon LeVay published an article in the interdisciplinary journal Science (A difference in hypothalamic structure between heterosexual and homosexual men. Science 253:1034-1037, 1991). LeVay's conclusion from this work, was that *sexual orientation has a biological substrate*. This research study met with rapid and voluminous accolade in the media and little critique from the scientific community. The article is short and fairly accessible, and I recommend that anyone interested in this topic read it in its entirety. Much of the following analysis, and my understanding of this subject, has been formed by discussions with William Byne MD,PhD, a current psychiatric resident and neuroscientist at Columbia University, New York City and former doctoral student of Dr. Ruth Bleier, Marsha Segerberg PhD Neurosciences, Postdoctoral Fellow in Physiology at the University of Arizona, Tucson, and Mariamne Whatle PhD, Chair of the Women's Studies Program at the University of Wisconsin, Madison. However, none of them should be held at all accountable for my ramblings! I review LeVay's background assumptions and methodology, and offer a critique of both. The following discussion is unreferenced. Quotes are between *stars*. Unlike LeVay, I will use GM for males in the homosexual male group (because it is clearer) and, like LeVay, I use M for males in the heterosexual male group. SECTION ONE :What did LeVay do? Using autopsied brain material, Simon LeVay measured the volume that different cell groups takes up within the hypothalamus. He reported that the volume of one group of cells, called INAH3 (the third interstitial nucleus of the anterior hypothalamus) was on average 2x larger in the M subject group than in the homosexual male (GM) or female subject (F) groups. He found no differences in nearby groups designated INAH 1,2 or 4. LeVay's conclusion from this work, was that *sexual orientation has a biological substrate*. The results have been interpreted as evidence that the reason that GM sexual behavior is *more like* female behavior than M behavior is due to corresponding differences in INAH3. ***FYI: The human hypothalamus is about the size of a pea, and the INAH3 is about the size of a grain of sand.*** SECTION TWO: I suggest that there are major methodological flaws in this study which invalidate LeVay's conclusions. In addition, LeVay, and other researchers, make highly contestable assumptions regarding the biological basis of human sexual orientation that are based primarily on inappropriate animal models. I will first critique the methodology and then the background assumptions. SECTION THREE: What are some methodological problems in the LeVay study? 1. LeVay obtained inadequate information on the sexual background of his subjects. The sexual orientation of the 6 females was not known. The sexual orientation of the males in M was PRESUMED, based on the numerical preponderance of males in the population. It was not clear on what basis men in G were so labeled. LeVay never defines the criteria for sexual orientation. What constitutes sexual experience? How many times did you have to do IT? Does fantasy *count*? What if one's sexual orientation changed over time? That LeVay never defines the criteria for sexual orientation is a major problem, since separating groups with clearly defined sexual orientation is the basis for this study. However, since sexual orientation seems to be an elusive blend of physical, mental and emotional properties, a uniform definition that is applicable to each subject within each group may be an unachievable goal. 2. LeVay obtained inadequate information on the medical background of his subjects.. All GM (n=19) died of AIDS related opportunistic diseases. Six M subjects died of complications of AIDS, and 10 of other causes. Males contracting AIDS from sexual exposure, IV needle use, or blood transfusions may incur different opportunistic diseases and treatments, as well as varying exposure time before detection (perhaps as a result of differential interaction with the health care system), any of which might affect the INAH3 volume. 3. Brain material was processed a variable length of time (one to two weeks). While resulting differential artifacts may or may not be negligible, nervous tissue can undergo distortion during fixation, and all tissue should be processed identically, if possible. 4. Even if his three groups were actually representative of people with different sexual orientations, it would be impossible to discern if INAH3 volume differences are the *cause* of certain sexual behaviors or the *result* of certain sexual behaviors or other unknown and uncontrolled variables. The brain is incredibly plastic, and can be physically altered by life experience, even in adults. 5. In light of the volume of research which suggests that sexual orientation appears greatly influenced by social factors, it seems naive to expect that there would be a direct relationship between hypothalamic structure and sexual behavior. This position is supported by the overlap of INAH3 volumes between the subjects of all three groups. In other words, given the size of a particular INAH3, it would be impossible to predict into which sexual orientation group a subject would fall. SECTION FOUR: Background information: Hormones, behavior, and brain. Rodents have provided much of the information used to construct the current biological model of human sexuality. Normally male rats (and male humans) are exposed to high levels of androgens secreted from their own testes during development, while female rats (and female humans) are not. In RATS, androgens (eg: testosterone) affect sex differences in reproductive motor behavior and in hypothalamic structure and function. There is no evidence that androgens have these effects in humans. The arguments are explained in greater detail below. a) To a large extent, male and female rats do have different stereotypic reproductive behaviors which can be altered by varying levels of androgens during development. Male rats tend to mount other rats more than do female rats. Females rats tend to display lordosis (back arched) behavior more than male rats and allow themselves to be mounted at certain times in their cycle. Male rats in which androgen levels were decreased experimentally during development tend to show decreased mounting frequency and allow themselves to be mounted more frequently (so called male *homosexual* behavior in rats). Female rats exposed to increased androgen levels will tend to increase mounting frequency (so called female *homosexual* behavior in rats). These effects of androgen levels on reproductive posture and motor behavior in rats form the basis of theories on human homosexuality. b) In rats, exposure to androgens during fetal development alters the ability of the hypothalamus to regulate the release of the hormone LH. In response to natural ovarian or administered estrogen, the adult female rat hypothalamus signals the the pituitary gland to release leutinizing hormone (LH is the hormone that causes ovulation in female rats). Adult male rats who have been exposed to androgens secreted from their own testes during development cannot release a surge of LH in response to administered estrogen. In addition, female rats exposed to experimentally induced high levels of androgen during their development will not have an LH surge in response to estrogen. In other words, the after exposure to high levels of androgens during fetal development, the hypothalamus no longer has the ability to mediate the positive feedback of estrogen. Androgen exposure has a permanent effect on the hypothalamus. Some researchers say that *brain* has been permanently *organized, masculinized or defeminized* by androgens. I like to say disorganized. Of course the word *brain* , in this instance, means a region of the hypothalamus, probably serving a specific hormonal function. c) Parts of the rat hypothalamus are structurally different in males and females. These areas are called the sexually dimorphic nuclei, or SDN. The functions of these areas are not known. SECTION FIVE: Why shouldn't LeVay (or anyone else) extrapolate an androgen theory of rodent sexual behavior to models of sexuality in humans? Because... 1. Applying a rodent model of sexual behavior to human sexual orientation requires several highly contestable assumptions. a. That reproductively linked posturing behavior (mounting and lordosis) is somehow representative of sexual orientation in rats AND in humans. b. That human male heterosexuality is characterized by *masculine or male-typical* behavior (eg:mounting), and that human female heterosexuality is characterized by *feminine or female-typical* behavior (eg: lordosis) during sexual encounters. c. That human male homosexuality is characterized by * feminine or female-typical* behavior (eg: lordosis and lack of mounting) and human female homosexuality is characterized by *masculine or male-typical* behavior (eg: mounting and lack of lordosis), sexual encounters. In addition, I object to the terminology *masculinization* and *feminization* as applied to to the brain since they give the misleading impression that stereotypical masculine and feminine human behaviors are already known to be a consequence of brain structure and function. 2. There is evidence that, unlike in rats, the non-human primate and human hypothalamus is NOT permanently altered by exposure to androgens during development. In other words, there is no corresponding evidence in humans for a *male* and *female* brain. (Aside: Nevertheless, differential levels of androgen exposure to the brain during development are also often cited as the basis of any presumed cognitive sex differences in humans.) 3. There are no replicated studies in humans which correlate level of androgens and sexual orientation. High levels of testosterone during development in human females and low levels of testosterone in human males do NOT correspond with an incidence of homosexuality. 4. Attempts to replicate reported sex dimorphic structural differences in the human hypothalamus have not been successful. There is no evidence in humans that an area of the hypothalamus directs sexual activity. There is not evidence that INAH3 has a function similar to sex dimorphic areas in the rat hypothalamus, which may or may not be correlated with sexual activity in the rat. SECTION SIX: Summary of major arguments against LeVay's conclusions and assumptions. 1. LeVay's method of separating male subjects into heterosexal and homosexual groups is highly contestable. 2. The length of exposure to AIDS, type of opportunistic infection or other disease acquired, or type of medicative or other treatment was not reported for any subject. 3. The impact of disease state, treatment, or length of exposure to AIDS on the INAH3 volume is unknown. 4. Sex and sexuality differences research is currrently hampered by poor reproducibity of results. Until LeVay's work is improved and replicated, it stands unsupported. 5. Androgen exposure during development has not been shown to affect human brain function or structure. 6. Androgen exposure during development has not been shown to correlate with later sexual orientation. 7. Androgen levels in adults have not been shown to correlate with self reported adult sexual orientation. 8. Rat motor patterns of copulation cannot be extrapolated to human sexual orientation or sexual activity. 9. The ability of the hypothalamus to mediate positive feedback of estrogen is blocked by early androgen exposure in rats but not in primates. That is, there may be *male and female brains* in rats, but this has not been shown to be true in humans. 10. The function of the sexually dimorphic nucleus (SDN) of the rat brain is not known and there is no convincing evidence that the SDN in rats corresponds structurally to the INAH3 in humans. Thus, there is no evidence that sexual orientation in humans has a *biological substrate* similar to that suggested for sexual posturing in rats. Therefore, as far as I can tell, LeVay has not found a biological substrate for sexual orientation. All LeVay has reported is that in groups of people with unknown medical and sexual histories there is a significant difference in the size of a structure whose function is not known. SECTION SEVEN: addendum The assumptions LeVay makes in his work are those made by many other researchers in the field. The critiques presented here are those that should be applied to any scientific study. I attribute the exorbitant amount of press coverage to the idea that the media has finally found something even sexier than biological theories on cognitive differences between the sexes. I attribute the exorbitant amount of latitude allowed LeVay by the scientific community to the belief, as expressed by one scientist, that such results were *not unexpected*.