tag:theconversation.com,2011:/au/topics/androgen-12385/articlesAndrogen – The Conversation2020-11-12T19:50:05Ztag:theconversation.com,2011:article/1491742020-11-12T19:50:05Z2020-11-12T19:50:05ZFierce female moles have male-like hormones and genitals. We now know how this happens.<figure><img src="https://images.theconversation.com/files/368987/original/file-20201112-23-1ourijf.jpg?ixlib=rb-1.1.0&rect=0%2C5%2C4000%2C2652&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Moles live a tough life underground. As a result, they’ve evolved helpful adaptations, such as excavator-like claws. Female moles in particular have evolved an unusual strategy: high levels of the male hormone testosterone. </p>
<p>This is an evolutionary advantage. It produces stronger muscles for digging and foraging and aggression, to help mothers defend themselves and their young. </p>
<p>Most of the year, female moles look and behave like males. They have masculinised genitals, with no external vagina and an enlarged clitoris. But when mating season comes, testosterone levels drop and a vagina is formed; mating and birth follow.</p>
<p>How they accomplish this remained a mystery for a long time. But now, the <a href="https://science.sciencemag.org/content/370/6513/208.abstract">complete sequencing</a> of the mole genome has revealed the genetic tweaks underpinning this strange cycle in female moles, by which reproductive organs (gonads) develop and hormones are produced.</p>
<h2>Gonads and hormones</h2>
<p>Male development in humans and other mammals is determined by chromosomes (the structures within cells of living things that contain genes). Females have two copies of an X chromosome. Males have a single X and a male-specific Y chromosome. </p>
<p>In XY embryos, a gene called <em>SRY</em> on the Y chromosome intervenes in a network of another 60 genes. <em>SRY</em> turns on testis genes and turns off ovary genes to transform a ridge of cells into a testis. </p>
<p>In the testis, one cell type becomes specialised to make sperm and another (Leydig cells) makes male hormones, including testosterone. </p>
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<a href="https://theconversation.com/what-makes-you-a-man-or-a-woman-geneticist-jenny-graves-explains-102983">What makes you a man or a woman? Geneticist Jenny Graves explains</a>
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<p>Testosterone is responsible for the most visible sex differences in males, such as bigger bodies, more muscle mass, male genitalia and more aggression. In XX embryos, an alternate pathway makes an ovary, which pumps out oestrogen.</p>
<p>So in mammals, different genetic pathways drive the same patch of embryonic tissue to become either an ovary or a testis. Generally, there’s no in-between. </p>
<p>But female moles have a patch of testis within their ovaries.</p>
<h2>An evolutionary balancing act</h2>
<p><a href="https://dev.biologists.org/content/118/4/1303">In 1993</a>, it was discovered the basis for “intersex development” in female moles is a gonad with both ovarian and testicular tissue. </p>
<p>Like other male mammals, male moles have a Y chromosome, bearing the <em>SRY</em> gene which directs testis formation. </p>
<p>Also like other mammals, female moles lack a Y chromosome. Curiously, however, instead of developing ovaries they develop “ovotestes”, with ovarian tissue at one end and testicular tissue at the other. </p>
<p>The ovarian tissue makes eggs and gets larger during breeding, then regresses. The testicular tissue is full of Leydig cells that make testosterone (but not sperm). Outside of breeding season, it expands until it’s larger than the ovarian end. </p>
<p>This explains why female moles have male-like genitalia, and are muscular and aggressive. But how does a patch of testis form in female moles if they have no <em>SRY</em> gene to trigger the process?</p>
<h2>Genetic tweaks behind ovotestis development</h2>
<p>To look for genetic changes that could allow this to happen, a global consortium of scientists <a href="https://science.sciencemag.org/content/370/6513/208.abstract">sequenced the entire mole genome</a>.</p>
<p>They found no differences between moles and other mammals in the protein products of the 60-odd genes involved in sex determination. However, they did discover mutations that altered the <em>regulation</em> of two of these genes in female moles.</p>
<p>One difference was found in the DNA sequences of a gene that’s vital for developing testes: <em>FGF9</em>. In all mammals, this gene switches on testis growth in XY embryos and inhibits genes that determine ovarian development. </p>
<p>In females of other mammals, the <em>FGF9</em> gene is turned off in the absence of <em>SRY</em>, but in female moles it stays on. </p>
<p>Genome sequencing revealed why: a big patch of DNA just upstream of <em>FGF9</em> is flipped around in moles. This inversion removes the usual control sequences from the gene, allowing it to stay on for longer in XX embryos.</p>
<p>The other gene impacted in female moles is <em>CYP17A1</em>, which codes for an enzyme that’s key to producing androgens (male hormones). In female moles, this gene and its surrounds have two extra copies, which increases testosterone output. </p>
<p>To show these genomic changes were indeed responsible for masculinising female moles, the researchers introduced them into mice, causing sex reversal and higher testosterone levels.</p>
<p>It’s important to note these evolutionary changes are in the <em>regulation</em> of gene activity, rather than in the regulation of protein products — which could compromise other normal functions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Clownfish (_Amphiprioninae_)." src="https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=416&fit=crop&dpr=1 600w, https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=416&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=416&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=522&fit=crop&dpr=1 754w, https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=522&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/368997/original/file-20201112-19-gi6jel.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=522&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Other than mammals, many marine animals have gender-bending tendencies. Clownfish always begin life as hermaphrodites carrying both female and male reproductive organs. Later in life, males can become female on an as-needed basis to mate with other males.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/szipiszopi/4919095469/in/photolist-8uFDGR-d6iqgf-2pEgAR-a3xGB7-4t985n-a3uQ4i-5cadh1-8ECGaX-3L8UN5-up9Mh-3L8UYN-Cu66xD-9pfPTN-8GLsLd-4kL2uD-4J1u8d-8FsdQs-dzruc-5DpDBY-5GUkSb-4kQ5YW-4kL38D-8WkdZn-KozKd7-qnrwnJ-coksCs-a6fGi2-2wMpjF-FPVyZy-38dWFC-PGX7c4-Kc29n9-gRkLPn-xDeEWy-EjqyJJ-6Y189v-rGsD6c-34WhVy-6YA5ez-gRkSs5-4g9oXn-pjBqbJ-6XX1Zc-nfKMRT-4kL1Ke-4J1sGC-5j4jKU-5LYxz4-aad1RH-ayLz3G">Istvan/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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Read more:
<a href="https://theconversation.com/what-we-learn-from-a-fish-that-can-change-sex-in-just-10-days-129063">What we learn from a fish that can change sex in just 10 days</a>
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<h2>What this means for sex and evolution</h2>
<p>Since mammals, including humans, develop as either males or females, we’ve been accustomed to regard testis or ovary development in the embryo as strict alternatives, depending on an on/off switch (the presence or absence of the Y chromosome and <em>SRY</em> gene). </p>
<p>But we now know there’s a complex gene network full of checks and balances that is the basis for alternate pathways of sexual development.</p>
<p>There are many studies of human babies born with <a href="http://theconversation.com/boy-girl-or-dilemmas-when-sex-development-goes-awry-49359">mutations in one of these genes</a>. This points to a more complex picture of the wiring behind the “switch” responsible for variation in human sexual development. </p>
<p>There are fierce females in other mammal species, too. Female spotted hyenas are <a href="https://www.sciencedirect.com/science/article/abs/pii/S0018506X00916349">bigger and more dominant</a> than males and have male-like genitalia. We don’t know how this change works at a genetic level. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A female spotted hyena in the wold." src="https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/368992/original/file-20201112-17-1axmrqx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">The spotted hyena, <em>Crocuta crocuta</em> (also known as the ‘laughing hyena’) is native to sub-Saharan Africa. In females such as this one, the clitoris is shaped and positioned like a penis that can become erect.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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<p>The downside of this is that mating is tricky. Cubs are birthed through the female’s narrow phallus. Mothers and/or cubs often die during this fraught process.</p>
<p>So while these larger, more aggressive females rule the hyena roost and get first pick at meals, like most things in nature, it seems this comes at a price.</p>
<p>Big fierce female moles and hyenas remind us the natural world, as always, features unique evolutionary differences — enlightening our view on human variation.</p><img src="https://counter.theconversation.com/content/149174/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves receives funding from the Australian research Council. </span></em></p>Female moles evolved to have high testosterone levels, making them fiercer diggers and mothers. Female hyenas share this trait, but it means they must give birth through a male-like phallus.Jenny Graves, Distinguished Professor of Genetics and Vice Chancellor's Fellow, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1387672020-06-09T12:20:27Z2020-06-09T12:20:27ZCOVID-19’s deadliness for men is revealing why researchers should have been studying immune system sex differences years ago<figure><img src="https://images.theconversation.com/files/339316/original/file-20200602-133902-dka80w.jpg?ixlib=rb-1.1.0&rect=72%2C0%2C5613%2C3712&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Reports show that the mortality rate among men with COVID-19 is higher than women. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/mattia-guarneri-lies-on-a-bed-in-coma-connected-to-a-news-photo/1219161924?adppopup=true">Marco Mantovani/Getty Images</a></span></figcaption></figure><p>When it comes to surviving critical cases of COVID-19, it appears that men draw the short straw. </p>
<p>Initial reports from China revealed the early evidence of increased male mortality associated with COVID. According to the <a href="https://globalhealth5050.org/covid19/sex-disaggregated-data-tracker/">Global Health 50/50 research initiative</a>, nearly every country is now reporting significantly higher COVID-19-related mortality rates in males than in females as of June 4. Yet, current data suggest similar infection rates for men and women. In other words, while men and women are being infected with COVID-19 at similar rates, a significantly higher proportion of men succumb to the disease than women, across groups of similar age. Why is it then that more men are dying from COVID-19? Or rather, should we be asking why are more women surviving? </p>
<p><a href="https://cvm.msu.edu/research/faculty-research/comparative-gastro-intestinal-research/moeser/gsbl-team">I am an immunologist</a>, and <a href="https://cvm.msu.edu/research/faculty-research/comparative-gastro-intestinal-research/moeser">I explore how stress and biological sex can impact a person’s vulnerability to immune-mediated disease</a>. I study a specific immune cell called the mast cell. Mast cells play a pivotal role in our immune systems as they act as first responders to pathogens and orchestrate immune responses that help clear the invading pathogens.</p>
<p>Our research shows that <a href="https://doi.org/10.1186/s13293-016-0113-7">mast cells from females are able to initiate a more active immune response</a>, which may help females fight off infectious diseases better than men. But the trade-off may be that <a href="https://theconversation.com/whos-stronger-an-immunological-battle-of-the-sexes-111334">women are at higher risk for allergic and inflammatory diseases</a>. Recent evidence indicates that mast cells are activated by SARS-CoV-2 which causes COVID-19.</p>
<p>Some clues to why females have higher survival rates may be found in our current understanding of differences in the <a href="https://theconversation.com/whos-stronger-an-immunological-battle-of-the-sexes-111334">immune systems of men versus women</a>. </p>
<h2>Could sex differences in immune system play a role?</h2>
<p>In general, females have a more robust immune response than men which may help females fight off infections better than males. This could be a result of genetic factors or sex hormones such as estrogen and testosterone. </p>
<p>Biological females have two copies of the X chromosome, which contains more immune genes. While the genes on one X chromosome are mostly inactive, some immune genes can escape this inactivation, leading to double the number of immune-related genes and thus double the quantity of certain immune proteins compared with biological men who have only one X chromosome. </p>
<p>Sex hormones such as estrogen and testosterone can also impact the immune response. In one study, researchers showed that <a href="https://doi.org/10.4049/jimmunol.1601896">activating the estrogen receptor in female mice provided them protection</a> against SARS-CoV. And there is an approved clinical trial that will examine the effects of <a href="https://clinicaltrials.gov/ct2/show/NCT04359329">estrogen patches on the severity of COVID-19 symptoms</a>. </p>
<p>It is, however, interesting that the current data showing that women have better survival rates than men applies to even men and women in the 80-plus age group, when hormone levels in both sexes equalize. This suggests that factors other than adult sex hormone levels are contributing to sex differences in COVID-19 mortality.</p>
<p>Androgens, a group of hormones - including testosterone - that are best known to stimulate the development of male characteristics and can cause hair loss, have also received recent attention as a risk factor for COVID-19 in males. In a study conducted in Italy, prostate cancer diagnosis increased the risk for COVID-19. However, prostate cancer patients who were receiving androgen-deprivation therapy (ADT), a treatment that suppresses the production of androgens which fuels prostate cancer cell growth, <a href="http://doi.org/10.1016/j.annonc.2020.04.479">had a significantly lower risk for SARS-CoV-2 infection</a>. This suggests that blocking androgens in men was protective against SARS-CoV-2 infection. </p>
<p>It is unknown how ADT works to reduce infection rates in men and whether this has been shown in other countries has yet to be determined. Testosterone, which is an androgen hormone has immune-suppressive effects so one explanation could be that ADT might boost the immune system to combat SARS-CoV-2 infection.</p>
<p>There is also evidence that males and females have different quantities of certain receptors that recognize pathogens or that serve as an invasion point for viruses like SARS-CoV-2. One example is the quantity of <a href="https://theconversation.com/what-is-the-ace2-receptor-how-is-it-connected-to-coronavirus-and-why-might-it-be-key-to-treating-covid-19-the-experts-explain-136928">angiotensin converting enzyme 2 (ACE2) receptors,</a> which SARS-CoV-2 binds to in order to infect cells. While there is currently no conclusive evidence for a role of ACE2 receptors impacting sex differences and the severity of COVID-19 disease, it remains a potential contributing factor. </p>
<h2>Gender, sex and COVID-19 risk</h2>
<p>A number of factors can interact with biological sex to increase or decrease one’s susceptibility to COVID-19. Another major factor is gender, which refers to social behaviors or cultural norms that society deems appropriate. <a href="http://doi.org/10.1186/s13293-020-00304-9">Males may be at increased risk for severe disease</a>, because in general, they tend to smoke and drink more, wash their hands less frequently and often delay seeking medical attention. All of these gender specific behaviors may put men at higher risk. While there is no current data yet on how gender plays a role in COVID-19, it will be a critically important factor to account for in order to understand sex differences in mortality.</p>
<p>Age, psychological stress level, coexisting conditions such as obesity, diabetes and cardiovascular disease can also interact with biological sex to increase disease.</p>
<p>While COVID-19 highlights the importance of biological sex in disease risk, sex biases in disease in general is not a new concept. COVID-19 is just another example of a disease that will be added to the growing list of diseases for which males or females are at increased risk. </p>
<h2>A history of male-biased research</h2>
<p>You might be wondering that if biological sex is so important, then why don’t we know what is causing disparities in disease prevalence between the sexes and why are there no sex-specific therapies? </p>
<p>One major reason is when it comes to being included in scientific research, it is mostly males who have been studied. </p>
<p>This disparity between biological sex differences in research has only recently been remedied. It has only been in the last five years that the National Institutes of Health <a href="https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-102.html">has required sex difference data to be collected</a> for all newly funded preclinical research grants. </p>
<p>While there may be several reasons for choosing one sex over the other in research, the huge disparity that now exists is likely a major reason why we still know relatively little about sex differences in immunity, including the current COVID-19 pandemic. </p>
<p>This has clearly hindered advancement of women’s health, but also has negative consequences for men’s health. For example, given the biological differences between the sexes, it is very possible that drugs and therapies will have different effects in females than males. </p>
<p>Biological sex is clearly a major factor determining disease outcomes in COVID-19. Precisely how your biological sex makes you more or less resilient to diseases such as COVID-19 remains to be elucidated. Future basic research with animals and clinical trials in people need to consider biological sex as well as interactions with gender as an important variable. </p>
<p>[<em>Get facts about coronavirus and the latest research.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=upper-coronavirus-facts">Sign up for The Conversation’s newsletter.</a>]</p><img src="https://counter.theconversation.com/content/138767/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Moeser receives funding from The National Institutes of Health </span></em></p>Why does COVID-19 hit men harder than women? Is the disparity in mortality rates due to male hormones or an underlying difference in the male versus female immune system?Adam Moeser, Matilda R. Wilson Endowed Chair, Associate Professor of Large Animal Clinical Sciences, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1227642019-09-03T13:40:36Z2019-09-03T13:40:36ZStop calling it a choice: Biological factors drive homosexuality<figure><img src="https://images.theconversation.com/files/290563/original/file-20190902-175705-15kuqu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Biological factors shape sexual preference.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/lgbt-lesbian-couple-moments-happiness-concept-575079754?src=-1-53">Rawpixel.com/SHutterstock.com</a></span></figcaption></figure><p><a href="https://doi.org/10.1126/science.aat7693">Across cultures, 2% to 10% of people report having same-sex relations</a>. In the U.S., <a href="https://www.statista.com/topics/1249/homosexuality/">1% to 2.2% of women and men</a>, respectively, identify as gay. Despite these numbers, <a href="https://www.pewresearch.org/global/2013/06/04/the-global-divide-on-homosexuality/">many people still consider homosexual behavior to be an anomalous choice</a>. However, biologists have <a href="https://us.macmillan.com/books/9780312253776">documented homosexual behavior in more than 450 species</a>, arguing that same-sex behavior is not an unnatural choice, and may in fact play a vital role within populations.</p>
<p>In <a href="https://doi.org/10.1126/science.aat7693">a 2019 issue of Science magazine</a>, geneticist Andrea Ganna at the Broad Institute of MIT and Harvard, and colleagues, described the largest survey to date for genes associated with same-sex behavior. By analyzing the DNA of nearly half a million people from the U.S. and the U.K., they concluded that genes account for between 8% and 25% of same-sex behavior. </p>
<p><a href="https://www.nature.com/news/sex-redefined-1.16943">Numerous studies have established that sex is not just male or female</a>. Rather, it is a continuum that emerges from a person’s genetic makeup. Nonetheless, misconceptions persist that same-sex attraction is a choice that warrants condemnation or <a href="https://www.apa.org/pi/lgbt/resources/just-the-facts">conversion</a>, and leads to discrimination and persecution.</p>
<p><a href="https://wjsulliv.wixsite.com/sullivanlab">I am a molecular biologist</a> and am interested in this new study as it further illuminates the genetic contribution to human behavior. As the author of the book, <a href="https://www.penguinrandomhouse.com/books/608709/pleased-to-meet-me-by-bill-sullivan/9781426220555/">“Pleased to Meet Me: Genes, Germs, and the Curious Forces That Make Us Who We Are,”</a> I have done extensive research into the biological forces that conspire to shape human personality and behavior, including the factors influencing sexual attraction.</p>
<h2>The hunt for ‘gay genes’</h2>
<p>The new finding is consistent with multiple earlier studies of twins that indicated same-sex attraction is a heritable trait.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1200&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1200&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1200&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290580/original/file-20190902-175663-baya3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A new study suggests that genes are responsible for between 8% and 25% of same-sex preference.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/dna-multi-color-isolated-on-white-717211195?src=-1-47">Guru 3D</a></span>
</figcaption>
</figure>
<p>The 2019 study is the latest in a hunt for “gay genes” that began in 1993, when Dean Hamer <a href="https://doi.org/10.1126/science.8332896">linked male homosexuality to a section of the X chromosome</a>. As the ease and affordability of genome sequencing increased, additional gene candidates have emerged with potential links to homosexual behavior. So-called <a href="https://doi.org/10.1038/s41598-017-15736-4">genome-wide association studies identified a gene called <em>SLITRK6</em></a>, which is active in a brain region called the diencephalon that differs in size between people who are homosexual or heterosexual.</p>
<p>Genetic studies in mice have uncovered additional gene candidates that could influence sexual preference. A 2010 study <a href="https://doi.org/10.1186/1471-2156-11-62">linked sexual preference to a gene called fucose mutarotase</a>. When the gene was deleted in female mice, they were attracted to female odors and preferred to mount females rather than males. </p>
<p>Other studies have shown that <a href="https://doi.org/10.1038/nature06089">disruption of a gene called <em>TRPC2</em></a> can cause female mice to act like males. <a href="https://doi.org/10.1126/science.1069259">Male mice lacking <em>TRPC2</em></a> no longer display male-male aggression, and they initiate sexual behaviors toward both males and females. Expressed in the brain, <em>TRPC2</em> functions in the recognition of pheromones, chemicals that are released by one member of a species to elicit a response in another.</p>
<p>With multiple gene candidates being linked to homosexuality, it seemed highly unlikely that a single “gay” gene exists. This idea is further supported by <a href="https://doi.org/10.1126/science.aat7693">the new study</a>, which identified five new genetic loci (fixed positions on chromosomes) correlating with same-sex activity: two that appeared in men and women, two only in men, and one only in women.</p>
<h2>How might these genes influence same-sex behavior?</h2>
<p>I find it intriguing that some of the genes from men identified in Ganna’s study are associated with olfactory systems, a finding that has parallels to the work in mice. Ganna’s group found other gene variants that may be linked with sex hormone regulation, which other scientists have previously suggested plays a large role in shaping the brain in ways that influence sexual behavior. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=846&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=846&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=846&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1063&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1063&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290575/original/file-20190902-175691-1l5i9pk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1063&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Conditions in the uterus during pregnancy are thought to influence the sexual preferences of the child.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/beautiful-pregnant-woman-shopping-bags-outdoors-503149633?src=-1-18">Anna Om/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Males with a genetic condition called <a href="https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome">androgen insensitivity syndrome</a> can develop female genitalia and are usually brought up as girls, despite being genetically male – with an X and Y chromosome – and they are attracted to men. This suggests that testosterone is needed to “masculinize” a prenatal brain; if that doesn’t happen, the child will grow up to desire men. </p>
<p>Similarly, girls who have a genetic condition called <a href="https://www.nichd.nih.gov/health/topics/cah">congenital adrenal hyperplasia</a> are exposed to unusually high levels of male hormones like testosterone while in the womb, which may masculinize their brain and increase the odds of lesbianism. </p>
<p>It’s also possible that hormonal shifts during pregnancy could affect how a fetus’ brain is configured. In rats, <a href="https://doi.org/10.1210/en.2011-0277">manipulation of hormones during pregnancy</a> produces offspring that exhibit homosexual behavior.</p>
<h2>Why does homosexual behavior exist?</h2>
<p>Several hypotheses have been advanced to explain how homosexuality can be beneficial in perpetuating familial genes. One idea involves the concept of kin selection, whereby people work to ensure the passage of their family’s genes into subsequent generations. Gay uncles and aunts, for example, are “<a href="https://doi.org/10.1177/0956797609359623">helpers in the nest</a>” that help raise other family members’ children to nurture the family tree.</p>
<p>Another idea suggests that homosexuality is a “trade-off trait.” For example, certain genes in women help increase their fertility, but <a href="https://doi.org/10.1111/j.1743-6109.2008.00944.x">if these genes are expressed in a male</a>, they predispose him toward homosexuality.</p>
<p>Sexual behavior is widely diverse and governed by sophisticated mechanisms throughout the animal kingdom. As with other complex behaviors, it is not possible to predict sexuality by gazing into a DNA sequence as if it were a crystal ball. Such behaviors emerge from constellations of hundreds, perhaps thousands, of genes, and how they are regulated by the environment.</p>
<p>While there is no single “gay gene,” there is overwhelming evidence of a biological basis for sexual orientation that is programmed into the brain before birth based on a mix of genetics and prenatal conditions, none of which the fetus chooses.</p>
<p>[ <em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=youresmart">You can read us daily by subscribing to our newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/122764/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Sullivan does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A new study of nearly 500,000 individuals finds that many genes affect same-sex behavior, including newly identified candidates that may regulate smell and sex hormones.Bill Sullivan, Professor of Pharmacology & Toxicology, Indiana University School of MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1135872019-04-16T09:29:51Z2019-04-16T09:29:51ZTestosterone: why defining a ‘normal’ level is hard to do<figure><img src="https://images.theconversation.com/files/267612/original/file-20190404-123413-1emyzsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/509354542?size=medium_jpg">Marc Bruxelle/Shutterstock</a></span></figcaption></figure><p>Testosterone is the main sex hormone in men. It’s best known for its role in the development of male sexual characteristics and physical features, but there are also many surprising and lesser known functions of testosterone that make it an important hormone in health and disease. Identifying whether someone has too much or too little testosterone can predict future diseases and even treat them. But knowing what is high, low or normal for an individual isn’t straightforward.</p>
<p>Testosterone plays an important role in how male reproductive tissues – such as the testicles and the prostate – develop, as well as promoting what are known as secondary sexual characteristics, such as increased muscle, bigger bones, deep voice and the growth of body hair – all the things we associate with being male. Females also produce testosterone, although in much lower amounts. It helps with the growth and maintenance of a woman’s reproductive tissue, strengthens bones and can influence mood and behaviour. </p>
<p>As with many hormones, the importance of testosterone becomes even more apparent when we look at people who don’t have enough. </p>
<p>Doctors measure testosterone in nanomoles per litre (nmol/l) and the reported “normal” healthy range in males is anywhere from <a href="https://academic.oup.com/jcem/article/102/4/1161/2884621">9.2 to 31.8 nmol/L</a>. It is about ten times lower in females, with “normal” levels considered to be between <a href="https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/83686">0.3 and 2.4 nmol/L</a>. Despite these lower levels in women, testosterone circulates in the blood at higher concentrations than oestrogen, the typical female hormone.</p>
<p>But it is difficult to know what is the right level of testosterone, and these ranges are often <a href="https://www.ncbi.nlm.nih.gov/pubmed/17100942?dopt=Abstract&holding=npg">not agreed on</a> by experts from different societies, countries or laboratories. </p>
<p>Nevertheless, low levels of testosterone in men can result in a lack of energy and strength, a reduced sex drive and putting on weight. Many of these symptoms are actually the same in women who also have low testosterone, and now research suggests that low testosterone can be a risk factor for developing heart disease, diabetes and obesity in both men and women.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/267618/original/file-20190404-123397-1edkq1s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Low testosterone can increase the risk of obesity, in men and women.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1212097219?size=medium_jpg">India Picture/Shutterstock</a></span>
</figcaption>
</figure>
<h2>The Goldilocks zone</h2>
<p>Really high testosterone levels in men tend not to occur naturally, but it is known that male athletes abusing testosterone or other similar steroids for performance gains often have problems with their heart. Likewise, certain diseases in women that result in high testosterone also lead to similar risks for heart disease. This means that testosterone appears to be best for health when it stays within a certain range: not too high and not too low. </p>
<p>Complicating this matter is the fact that testosterone levels don’t stay the same through life, through the year or even through the day – at least in men. Testosterone levels change throughout the day in men, peaking at around <a href="https://www.sciencedirect.com/science/article/pii/0039128X73901104">4-8am and falling to their lowest at about 12 hours later</a>. They can also vary across the year, although these seasonal highs and lows will differ around <a href="https://www.ncbi.nlm.nih.gov/pubmed/22790643">the world</a>. These daily and seasonal variations can see levels change by as much as 19%.</p>
<p>Men’s testosterone levels in the blood are thought to fall with age, although this may actually be more related to diseases that occur with age. Women’s testosterone levels are a bit more stable, without any known daily or yearly changes. As with men, however, they also decrease a little with age. And it is these falling levels that increase the risk of disease. </p>
<p>Complicating matters even further is the fact that everybody is different, particularly in the way that testosterone works. </p>
<h2>Approximations of the truth</h2>
<p>Testosterone takes action when it joins onto its receptor in any particular cell in our body. But how well it does this to bring about the functions mentioned above differs from person to person, which is influenced by genetics. So what might be considered a low level for one person may actually be OK if they have a more sensitive receptor capable of carrying out testosterone’s actions at lower concentrations. In fact, when we look at some diseases in men that are thought to result from low testosterone, not everyone below the normal range develops the disease.</p>
<p>It is unclear whether it is also due to similar genetic factors, but testosterone can also be different depending on where you <a href="https://www.nature.com/articles/s41559-018-0567-6">live and how wealthy you are</a>. So a universal “normal range” may not apply to all groups of people. </p>
<p>Establishing a “normal” level is complex, and measuring testosterone on its own may not be enough to estimate what is the correct level to have in the blood for any one person. Still, research tries to define levels that are healthy, and levels that may be related to disease so patients can be identified and treated. Still, these are approximations of the truth in specific populations with specific genetics, backgrounds and disease. Like the story of the <a href="https://www.allaboutphilosophy.org/blind-men-and-the-elephant.htm">blind men feeling different parts of an elephant</a>, we can only build up a picture of the truth from small parts in the search to find the answers.</p>
<p>Using average levels of testosterone from lots of people from different populations to establish normal ranges is useful to help identify people outside of this range with a related disease. But many factors have to be considered when deciding whether someone has normal testosterone or not and whether there truly is a “normal” testosterone level at all.</p><img src="https://counter.theconversation.com/content/113587/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Daniel Kelly does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>So-called normal levels of testosterone are approximations, but can help researchers investigate disease and treatments.Daniel Kelly, Lecturer in Biochemistry, Sheffield Hallam UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/629352016-08-15T10:14:17Z2016-08-15T10:14:17ZSo what if some female Olympians have high testosterone?<p>On August 12, Dutee Chand became just the second female sprinter to represent India at the Olympic Games. Her road to Rio has been anything but easy.</p>
<p>In 2014, the International Association of Athletic Federations banned her from competition on the grounds that her body naturally produced too much testosterone, a condition called hyperandrogenism. It wasn’t her fault, the organization explained. But her condition gave her an unfair edge over other female athletes, according to the IAAF policy.</p>
<p>Chand appealed the ruling, and in July 2015, the Court of Arbitration for Sport determined <a href="http://www.tas-cas.org/fileadmin/user_upload/Media_Release_3759_FINAL.pdf">that the IAAF</a>:</p>
<blockquote>
<p>“was unable to conclude that hyperandrogenic female athletes may benefit from such a significant performance advantage that it is necessary to exclude them from competing in the female category.” </p>
</blockquote>
<p>Arbitrators gave the IAAF two years to produce enough evidence to justify its policy. Until then, the organization must suspend the hormone test. The International Olympic Committee also complied, allowing Chand and other hyperandrogenic women to compete at the 2016 Olympic Games without having to lower their hormone levels.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"761493947285774336"}"></div></p>
<p>The Chand case is the just the latest chapter in the long history of sex-testing female athletes in elite sport, something <a href="http://www.press.uillinois.edu/books/catalog/58ctr3rx9780252038167.html">I’ve been studying</a> for a while. Although the tests have changed over the years, the intent – to ensure that female athletes are sufficiently female – has not. </p>
<p>With all due respect, I think asking if elevated levels of testosterone give female athletes a competitive advantage is the wrong question. Instead, we should ask: “So what?” </p>
<h2>The long history of sex-testing female athletes</h2>
<p>As the prestige of international athletics grew during the 20th century, critics worried that male athletes might commit “gender fraud” in pursuit of sporting glory. In 1946, for example, the <a href="http://dx.doi.org/10.1016/j.endeavour.2010.09.005">IAAF required</a> female competitors to submit medical certificates to verify their sex. </p>
<p>At the European Athletics Championship in 1966, the IAAF subjected female competitors to a “nude parade” past three gynecologists. This was because, as Life magazine <a href="https://books.google.com/books?id=jFYEAAAAMBAJ&pg=PA63&lpg=PA63&dq=%E2%80%9Cthere+had+been+persistent+speculation+through+the+years+about+women+who+turn+in+manly+performances.%E2%80%9D&source=bl&ots=jAZWikIlN_&sig=TgyZcnJJrnAPsMkz8aW0LON0V6U&hl=en&sa=X&ved=0ahUKEwiY1ou91ajOAhUJ34MKHeDvCX4Q6AEIITAB#v=onepage&q=%E2%80%9Cthere%20had%20been%20persistent%20speculation%20through%20the%20years%20about%20women%20who%20turn%20in%20manly%20performances.%E2%80%9D&f=false">reported</a>, “there had been persistent speculation through the years about women who turn in manly performances.” That same year female athletes at the Commonwealth Games had to undergo gynecological exams to prove their sex. British pentathlete Mary Peters <a href="https://www.amazon.com/Mary-Autobiography-Wooldridge-Ian-Peters/dp/0099123304">would later refer to it as</a> “the most crude and degrading experience I have ever known in my life.” </p>
<p>In 1967 the IAAF <a href="http://dx.doi.org/10.1001/jama.1972.03200220032008">turned to a</a> “simpler, objective and more dignified” laboratory-based chromosome assessment, typically obtained by swabbing the inside of every female athlete’s cheek (the IOC followed suit for the 1968 Olympic Games). An XX result effectively established femaleness. Anything else spelled an end to the woman’s career. But there are a host of genetic and biological variations that complicate the seemingly tidy split between male and female.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=484&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=484&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=484&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=608&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=608&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133864/original/image-20160811-11853-1gl46tp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=608&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Ewa Klobukowska.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/smithsonian/5494508884/in/photolist-9nwN4N">Smithsonian Institution</a></span>
</figcaption>
</figure>
<p>Polish sprinter Ewa Klobukowska, for instance, was summarily dismissed from sport in 1967 because she had “one chromosome too many.” The IAAF nullified all of her victories, struck her name from the record books, and rescinded her medals, including the gold and bronze from the 1964 Olympics, all because of a naturally occurring condition that probably had little bearing on her success. </p>
<p>At 21 years old, her athletic career was over. “It’s a dirty and stupid thing to do to me,” she said at the time. “I know what I am and how I feel.”</p>
<p>Then there are women with XY chromosomes, such as Spanish hurdler <a href="http://www.thelancet.com/pdfs/journals/lancet/PIIS0140673605678415.pdf">María José Martínez-Patiño</a>. She successfully challenged her 1985 disqualification on the grounds that she also has androgen insensitivity syndrome, a condition in which her body cannot respond to testosterone, either natural or synthetic. </p>
<h2>Objections to mandatory testing grow</h2>
<p>The results of the tests are supposed to be confidential, so we don’t know exactly how many women have been drummed out of sport as a result. Researchers <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1478807/">estimate</a> that <a href="http://rua.ua.es/dspace/handle/10045/15015">between 1972 and 1990</a>, sex-testing procedures disqualified approximately one in 504 elite athletes. An untold number of women competing at the lower levels of sport met a similar fate, or else abandoned competition altogether based on fears that they might not meet the standards for femaleness. </p>
<p>From the beginning, there were protests about the ethics, validity and reliability of the tests. By the early 1990s, objections had <a href="http://www.tandfonline.com/doi/pdf/10.1080/00336297.2011.10483678?needAccess=true&redirect=1">reached a fever pitch</a> and, in May 1992, the IAAF announced an end to systematic chromosomal testing. The IOC did the same in 1999. However, both organizations reserved the right examine athletes if someone were to “challenge” their femaleness. The ostensibly progressive protocol ultimately discriminates against women who do not look or perform in accordance with certain “feminine” ideals. This is what happened to South African runner <a href="http://link.springer.com/chapter/10.1007/978-0-230-36746-3_28#page-1">Caster Semenya</a> in 2009 and to Dutee Chand in 2014. </p>
<h2>Caster Semenya and Dutee Chand</h2>
<p>Just hours before Semenya cruised to victory in the finals of the 800-meter race at the 2009 World Championships in Athletics, the IAAF <a href="https://books.google.com/books?id=e-7kAgAAQBAJ&pg=PA118&lpg=PA118&dq=jaime+schultz+%22concerns+that+she+does+not+meet+the+requirements+to+compete+as+a+woman%22&source=bl&ots=fc9EPAcz_p&sig=5imIubO9b21ex7v2dVX-9QfgonY&hl=en&sa=X&ved=0ahUKEwigkduM0r7OAhUG9x4KHQzDALAQ6AEIIjAB#v=onepage&q=jaime%20schultz%20%22concerns%20that%20she%20does%20not%20meet%20the%20requirements%20to%20compete%20as%20a%20woman%22&f=false">confirmed</a> “concerns that she does not meet the requirements to compete as a woman.”</p>
<p>Never clarifying what those requirements were, officials requested Semenya abstain from competition. She obliged for a <a href="http://www.bbc.com/sport/olympics/36991646">disquieting 11 months</a>, during which experts worked to determine her sex. She was noticeably slower upon returning to the track (although she won a silver medal in the women’s 800 meter at the London Games in 2012), leading to speculation that she must have undergone some intervention to lower her testosterone. The IAAF’s subsequent <a href="https://www.iaaf.org/news/iaaf-news/iaaf-to-introduce-eligibility-rules-for-femal-1">policy on hyperandrogenism</a> bolstered those opinions. </p>
<p>This new policy ruled any female athlete exhibiting <a href="https://www.iaaf.org/news/press-release/hyperandrogenism-regulations-cas-dutee-chand">10 or more nanomoles</a> of functional testosterone per liter of blood (which they consider the lower end of “normal” male range) ineligible for competition.</p>
<p>Women could apply for reinstatement if they sufficiently reduced their testosterone levels below the 10 nanomole threshold. This can be done surgically, often through the removal of internal testes, with hormone-suppressing medication or through a combination of both. Women with androgen insensitivity syndrome are exempt from this policy.</p>
<p>These guidelines took the place of the earlier “gender verification policy.” Indeed, the IAAF, IOC and affiliated federations erased all mention of sex testing from their rule books and instead initiated the hormone test “to protect the health of the athlete.” </p>
<p>It’s worth noting that male athletes don’t seem to need similar protection. There is no upper limit to the levels of natural testosterone allowed in their bodies. In fact, male athletes with low testosterone can apply for a “<a href="https://www.wada-ama.org/en/what-we-do/science-medical/therapeutic-use-exemptions">Therapeutic Use Exemption</a>” that allows them to take medically prescribed steroids to augment their androgen levels. </p>
<p>The Court of Arbitration for Sport’s decision in Dutee Chand’s case suspends, <a href="https://www.theguardian.com/sport/2016/aug/11/caster-semenya-sebastian-coe-iaaf-cas-testosterone-olympics?CMP=share_btn_fb">at least</a> for the 2016 Olympic Games, any testing or exclusion of women on the basis of hyperandrogenism. This creates an incredible amount of interest in the performances of Chand and Semenya and, quite possibly, any female athlete who does not conform to the traditional standards of femininity.</p>
<h2>Question of testosterone is missing the point</h2>
<p>Dutee Chand <a href="http://www.thehindu.com/sport/other-sports/rio-olympics-2016-brief-glimpse-of-olympics-but-all-worth-it-for-dutee-chand/article8984186.ece">did not win medal in Rio</a>, but Caster Semenya, who has grown increasingly faster in past months, is an odds-on favorite to take home the gold in the 800-meter race. </p>
<p>So does excess testosterone actually confer a competitive advantage? </p>
<p>My question is if it does, so what?</p>
<p>Elite sport is built on the back of inequality. We love the myth of a level playing field, but it doesn’t exist. Of the 207 nations competing in Rio, 75 have never won a medal. Wealthy, powerful countries dominate the Olympic Games, while conflicted, war-torn, impoverished countries simply lack the resources to promote sport to the level that will produce Olympic champions. That’s a clear disparity that raises little outcry.</p>
<p>But what we’re talking about in the case of hyperandrogenism is an innate condition that potentially enhances athletic performance. And, as scientists are just beginning to understand, elite sport is riddled with similar endowments. </p>
<p>Researchers associate physical performance with over <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993978/">200 different genetic variations</a>. More than 20 of those variants relate to elite athleticism. These performance-enhancing polymorphisms – PEPs – can affect height, blood flow, metabolic efficiency, muscle mass, muscle fibers, bone structure, pain threshold, fatigue resistance, power, speed, endurance, susceptibility to injury, psychological aptitude, and respiratory and cardiac functions, to name just a few. </p>
<p>We don’t disqualify athletes with these types of predispositions. We celebrate them.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=500&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=500&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133862/original/image-20160811-28926-gxs06d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=500&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Eero Mantyranta at the Innsbruck Olympic Games in 1964.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File%3AEeroMantyranta.jpg">Jussi Pohjakallio, via Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>With seven Olympic medals, Finland’s Eero Mäntyranta, for example, is among the all-time greats of Nordic skiing. It’s a sport that requires incredible stamina – a trait assisted by an abundance of red blood cells, which carry oxygen to the muscles. That’s why so many endurance athletes try to boost their hemoglobin by training at high altitudes, sleeping in altitude chambers, or through illegal measures like blood doping or taking a synthetic version of the hormone erythropoietin (EPO).</p>
<p>Mäntyranta, who died in 2013, didn’t need any of that. He had a condition called primary familial and congenital polycythemia, associated with a variation in the EPOR gene, which caused his body to produce 65 percent more red blood cells than the average male. David Epstein, author of “<a href="http://thesportsgene.com/">The Sports Gene</a>,” calls Mäntyranta’s EPOR variant a “gold medal mutation.”</p>
<p>How is this different from a woman’s body that naturally produces more testosterone? Why is primary familial and congenital polycythemia a genetic gift and hyperandrogenism a disqualifying curse? Unless athletic authorities want to take on all conditions that might result in an unfair advantage – biological, genetic, social or otherwise – it seems arbitrary to focus on testosterone in female athletes.</p><img src="https://counter.theconversation.com/content/62935/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jaime Schultz does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Some women naturally produce high levels of testosterone. Why is this innate condition treated differently from other conditions that potentially enhance athletic performance?Jaime Schultz, Associate Professor of Kinesiology, Penn StateLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/601562016-06-21T04:23:13Z2016-06-21T04:23:13ZFair play at the Olympics: testosterone and female athletes<figure><img src="https://images.theconversation.com/files/124531/original/image-20160531-7695-1gb743m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Caster Semenya was withdrawn from competition in 2009 on the basis that her higher-than-normal testosterone level conferred a performance advantage.</span> <span class="attribution"><span class="source">Reuters/Mike Hutchings</span></span></figcaption></figure><p>There are performance differences between the sexes in elite sport. It has long been assumed that contrasting <a href="http://www.livestrong.com/article/286883-muscular-endurance-men-vs-women/">levels of testosterone</a> in <a href="http://www.nytimes.com/2012/06/18/sports/olympics/the-line-between-male-and-female-athletes-how-to-decide.html">men and women</a> can largely account for that gap, but <a href="https://www.researchgate.net/publication/260522903_Endocrine_Profiles_in_693_Elite_Athletes_in_the_Post-Competition_Setting">new scientific studies</a> are <a href="https://www.researchgate.net/publication/264558402_Natural_Selection_for_Genetic_Variants_in_Sport_The_Role_of_Y_Chromosome_Genes_in_Elite_Female_Athletes_with_46XY_DSD">bringing that into question</a>.</p>
<p>This emerging research is also important for a practical reason: until recently, women with higher-than-expected testosterone levels were declared ineligible to take part in track and field athletics. Sporting authorities were under the impression these female athletes had an unacceptable performance advantage. </p>
<h2>Androgens, women and sport</h2>
<p>Androgens are a sex hormone. Among these is testosterone. </p>
<p>Typically, men and women have a different range of testosterone levels, but some women present with much higher than the norm. This is <a href="http://www.ncbi.nlm.nih.gov/pubmed/16772149">known medically as hyperandrogenism</a>.</p>
<p>A key cause of hyperandrogenism is androgen insensitivity syndrome (AIS). It occurs when an embryo is born XY (male) but resistant to male hormones, subsequently developing with some or all of the conventional physical traits of a woman. Babies with this presentation are routinely raised as girls and develop into women according to prevailing social norms.</p>
<p>However, in developed countries there typically comes a point at which they are diagnosed as having AIS, such as by an investigation for the absence of menstruation, or infertility. </p>
<p>Those with AIS may have different gender identities; should they choose, hormonal treatments can be used to better reflect that disposition. Some may also consider surgery in scenarios where health and psychological outcomes are beneficial.</p>
<p>Women who have AIS are not “obvious” by way of physical appearance. Many are tall and slim, just as women without the syndrome. Most – like Spanish hurdler <a href="http://www.thelancet.com/pdfs/journals/lancet/PIIS0140673605678415.pdf">Maria Jose Martinez-Patino</a>, who failed a <a href="http://www.ncbi.nlm.nih.gov/pubmed/8272686">chromosome test</a> in 1986 – had no idea their status as an adult woman was anything but conventional. </p>
<p>Women with severe AIS are resistant to androgens such as testosterone. Thus, it cannot confer any athletic “advantage”. </p>
<h2>The ‘hyperandrogenism’ rule</h2>
<p>In 2009, South African runner Caster Semenya was <a href="http://www.telegraph.co.uk/sport/othersports/athletics/7873240/Caster-Semenya-given-all-clear-after-gender-test-row.html">withdrawn from competition</a> on the basis of claims that – as a woman – she had a higher-than-normal testosterone level that conferred a performance advantage.</p>
<p>Two years later, the International Association of Athletics Federations (IAAF) announced a “hyperandrogenism” rule that was intended to counter concerns about female athletes with <a href="http://www.iaaf.org/news/iaaf-news/iaaf-to-introduce-eligibility-rules-for-femal-1">excessive production of testosterone</a>.</p>
<p>The rule had serious consequences for <a href="http://www.ncbi.nlm.nih.gov/books/NBK1429/">women with AIS</a>, which typically results in very high serum testosterone levels. In order to be classified as “women” in a sport contest, medical intervention was deemed necessary. Reportedly, <a href="http://press.endocrine.org/doi/abs/10.1210/jc.2012-3893">four elite athletes</a> were persuaded to undergo surgery on genitalia or sex organs and to accept estrogen-replacement therapy.</p>
<p>Even though these procedures involved informed consent, the need for such significant interventions raised <a href="https://www.researchgate.net/publication/270909133_Medical_and_Ethical_Concerns_Regarding_Women_With_Hyperandrogenism_and_Elite_Sport">serious ethical issues</a> for women who wished to continue with sport but were persuaded that their bodies needed alteration in order to do so.</p>
<p>In 2015, however, the Court of Arbitration for Sport (CAS) upheld Indian sprinter Dutee Chand’s appeal against the <a href="https://ussporthistory.com/2015/09/17/hyperandrogenism-regulations-in-sport/">“hyperandrogenism” rule</a>. It concluded there was no convincing scientific evidence that women with elevated testosterone levels had a performance advantage over others. </p>
<p>The path was now clear for those who had previously been declared ineligible to compete in the 2016 Olympic Games. </p>
<p>The CAS decision has generated much debate, but <a href="https://sociallitigator.com/2016/05/08/sporting-integrity-gender-and-human-dignity-dutee-chand-and-what-her-case-means-for-rio/">these</a> <a href="http://fittish.deadspin.com/banning-testosterone-limits-makes-womens-athletics-unfa-1722603560">discussions</a> have ignored the significant scientific evidence that supported the rule being struck out.</p>
<h2>Why was the rule flawed?</h2>
<p>After the Semenya case in 2009, the IAAF had convened a working group to advise on how to manage female athletes with elevated testosterone levels. </p>
<p>Among that group was Liz Ferris, a medical doctor and former Olympian, who was advocating on behalf of athletes. She sought the advice of Peter Sonksen, the lead author of this article. Coincidentally, he was part of a research team that was investigating the hormone profiles of female and male athletes.</p>
<p>This study <a href="https://www.researchgate.net/publication/260522903_Endocrine_Profiles_in_693_Elite_Athletes_in_the_Post-Competition_Setting">measured hormone profiles</a>, including testosterone, from a sample of 693 elite athletes across 15 sporting categories. There were many unexpected findings. </p>
<p>For example, 16.5% of men had a testosterone level below 8.4 nanomole per litre (the lower limit of the normal male reference range). Some were unmeasurably low. And 13.7% of the elite female athletes had a level higher than 2.7nmol/l, the upper limit of the normal reference range for women. Some were in the high male range.</p>
<p>Thus, there was a complete overlap of testosterone levels between male and female elite athletes. This challenged existing knowledge, which had assumed there was no such overlap.</p>
<p>Frustratingly for Ferris, the IAAF working group ignored this research. Instead, it proceeded to introduce its flawed – but now suspended – “hyperandrogenism” rule. </p>
<p>CAS has given the IAAF two years to present scientific evidence to justify its position. If it cannot do so the rule will be declared void. </p>
<h2>An unfair advantage?</h2>
<p>It appears likely that women with AIS are more commonly Olympic athletes than one would expect by chance alone. They often have an “athletic” body configuration. This has recently been attributed to a number of <a href="https://www.researchgate.net/publication/264558402_Natural_Selection_for_Genetic_Variants_in_Sport_The_Role_of_Y_Chromosome_Genes_in_Elite_Female_Athletes_with_46XY_DSD">genes on the Y chromosome</a>, but not the presence of the high serum testosterone level – to which they are physiologically unable to respond.</p>
<p>Sonksen’s research team <a href="https://www.researchgate.net/publication/260522903_Endocrine_Profiles_in_693_Elite_Athletes_in_the_Post-Competition_Setting">found</a> the gaps in world records between <a href="http://www.ajol.info/index.php/sasma/article/view/50506">men and women</a> for various track and field events are in keeping with the differences in their lean body mass. The study showed men to have approximately 10kg greater lean body mass than women. </p>
<p>The researchers concluded this contrast was: </p>
<blockquote>
<p>… sufficient to account for … differences in strength and aerobic performance seen between the sexes without the need to hypothesise that [elite sport] performance is … determined by … testosterone levels.</p>
</blockquote>
<p>Chand just missed out on the qualifying time for <a href="http://www.firstpost.com/sports/dutee-chand-shatters-national-record-misses-2016-rio-olympic-qualification-by-0-01-second-2755600.html">Olympic selection</a>, but Semenya will be at Rio, as is her right. The scientific evidence outlined here should be borne in mind by those watching Semenya or competing against her at the Olympics.</p><img src="https://counter.theconversation.com/content/60156/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Sonksen received funding for the GH-2000 Project from the European Union (Biomed 2: BMH4 CT950678 ) and the International Olympic Committee.</span></em></p><p class="fine-print"><em><span>Daryl Adair does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Until recently, women with higher-than-expected testosterone levels were declared ineligible to take part in track and field athletics.Peter Sonksen, Emeritus Professor of Endocrinology, St Thomas' Hospital and King's College, London; Visiting Professor, University of SouthamptonDaryl Adair, Associate Professor of Sport Management, University of Technology SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/569492016-04-06T10:59:11Z2016-04-06T10:59:11ZThe high cost of publicly funded cancer drugs<figure><img src="https://images.theconversation.com/files/116637/original/image-20160329-13709-30gfrw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">yari2000/Shutterstock</span></span></figcaption></figure><p>Patients with prostate cancer in England and Wales <a href="http://www.bbc.co.uk/news/health-35861202">will now have</a> early access to <a href="http://prostatecanceruk.org/prostate-information/treatments/abiraterone">abiraterone</a>, a drug which can delay the need for chemotherapy. The drug previously cost £3,000 a month, and was not considered “<a href="https://www.nice.org.uk/nice-appraisal-of-earlier-treatment-with-abiraterone-for-prostate-cancer">cost-effective</a>” for the NHS until cancers were more advanced – even though patients in Scotland <a href="http://www.dailymail.co.uk/health/article-3278615/Prostate-cancer-sufferers-denied-wonder-pill-s-widely-available-Scots.html">had access</a> to it.</p>
<p>The U-turn comes after a lower price was agreed with the manufacturer Janssen – making abiraterone affordable for widespread use. Janssen is also said to have submitted <a href="https://www.nice.org.uk/news/press-and-media/nice-recommends-abiraterone-for-prostate-cancer">fresh data</a> about the drug’s effectiveness to the National Institute for Health and Care Excellence (NICE), <a href="http://www.cancerresearchuk.org/about-cancer/cancers-in-general/cancer-questions/what-is-nice-and-how-does-it-work">which decides which drugs and treatments are available</a> on the NHS in England and Wales.</p>
<p>This change in price now means that abiraterone can be given to prostate cancer patients who have mild symptoms but evidence of the disease spreading. The drug will also be used in patients who have not previously responded to hormone therapy and have not undergone radiotherapy. </p>
<p>While this new widespread use of the drug is great news for cancer patients, why has it taken so long to get things to this point? It does not seem entirely clear what this <a href="https://www.nice.org.uk/guidance/GID-TAG434/documents/final-appraisal-determination-document">new data</a> is, or why the current, <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1209096">published data</a> was considered to be insufficient. And it’s not the first time decisions on life-saving drugs have come into question.</p>
<h2>Dying for treatment</h2>
<p>There are a wide and generally effective range of treatment options for prostate cancer available. The main one is hormone therapy, which is aimed at blocking androgen (testosterone) production. </p>
<p>The rationale for this treatment is that most prostate tumours, especially in the earlier stages of the disease, require <a href="http://prostatecanceruk.org/prostate-information/treatments/hormone-therapy">androgens</a> for their continued growth and survival, in much the same way that some breast cancers are dependent on oestrogen. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/ygoQ_kWf5ZQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Prostate Cancer kills one man every hour in the UK.</span></figcaption>
</figure>
<p>The original treatment for depriving prostate tumours of androgen was the removal of the testicles, giving rise to the delightful term “<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935714/">castration resistant prostate cancer</a>”. </p>
<p>Abiraterone delays the need for chemotherapy by helping to overcome the problem of “castration resistant tumours” – where the cancer cells become more and more sensitive to androgen in response to its reduced levels after hormone therapy.</p>
<p>Castration was subsequently replaced with drug-based therapy, with abiraterone developed in the early 1990s by scientists at <a href="http://www.icr.ac.uk/news-features/latest-features/abiraterone-a-story-of-scientific-innovation-and-commercial-partnership">Cancer Research UK’s</a> Centre for Cancer Therapeutics – using money donated by cancer survivors, the families of cancer patients, and numerous other individuals and organisations.</p>
<p>And yet the final product has until recently been prohibitively expensive, to the point where thousands of men may have missed out on its potential benefits, and it has <a href="http://www.dailymail.co.uk/health/article-2627653/Prostate-cancer-pill-extend-life-years-delay-need-chemotherapy-set-ban-not-cost-effective.html">severely strained NHS budgets</a>.</p>
<h2>Drug of choice</h2>
<p>Abiraterone has long been considered to be one of the most effective treatments for prostate cancer as it almost completely blocks testosterone production. This has been supported by a number of large <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1209096">clinical trials</a>, including one that recruited 1,088 men and revealed that abiraterone increased the average time taken for prostate cancer to spread from eight months to 16.5 months.</p>
<p>Despite this, NICE refused to approve the use of abiraterone for prostate cancer on the grounds that its cost was not justified by its proven clinical benefits. </p>
<p>While NICE have now reversed this decision, it still doesn’t take away from the fact that for so long, so many men have been unable to access an effective treatment for prostate cancer, which could have helped to delay the spread of the disease.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/116640/original/image-20160329-13718-1b6yaom.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">One in seven men will be diagnosed with prostate cancer during their lifetime.</span>
<span class="attribution"><span class="source">Image Point Fr/Shutterstock</span></span>
</figcaption>
</figure>
<p>Of course, hormone therapy is not without side effects – it can (and usually does) lead to varying degrees of feminisation, alongside erection problems, hot flushes and breast tenderness. However, these side effects are generally far less severe than those associated with therapies used when tumours fail to respond to hormone treatment. </p>
<p>This type of treatment includes conventional chemotherapy with <a href="http://www.evidence.nhs.uk/formulary/bnf/current/8-malignant-disease-and-immunosuppression/81-cytotoxic-drugs/side-effects-of-cytotoxic-drugs">cytotoxic drugs</a> that are generally designed to selectively kill rapidly dividing cells. </p>
<p>Many normal adult cells also need to divide quickly though – for example those involved in replacing the lining of the gut or in generating new blood cells – meaning this type of chemotherapy can have a broad and significant range of unpleasant side effects including hair loss, mouth ulcers, nausea and vomiting as well as increased chance of infection from the drop in white blood cells.</p>
<p>When you consider the debilitating side effects associated with chemotherapy, and the fact that prostate cancer is the most common male-specific cancer with around <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer#heading-Zero">35,000 new cases</a> and about <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer#heading-Zero">10,000 deaths</a> every year in the UK, the fact that drug therapy is withheld in treatment is very concerning.</p>
<p>But abiraterone is not the first anti-cancer drug to prove prohibitively expensive. Consider the small sum of <a href="http://www.bbc.co.uk/news/health-34831197">£90,000</a> required for a course of the breast cancer drug Kadcyla. Or the <a href="http://www.theguardian.com/business/2015/sep/23/uk-cancer-patients-being-denied-drugs-due-to-inflated-prices-say-experts">£24,000</a> cost per patient per year for another breast cancer drug, lapatinib. </p>
<p>Then there is also growing disquiet about the regional differences in the cost of drugs with lapatinib costing considerably less in a number of <a href="http://www.theguardian.com/business/2015/sep/23/uk-cancer-patients-being-denied-drugs-due-to-inflated-prices-say-experts">other countries</a>. </p>
<p>Questions need to be asked around drug costs and accessibility across the whole of the UK. Because although abiraterone isn’t the first high-cost cancer drug, sadly it won’t be the last.</p><img src="https://counter.theconversation.com/content/56949/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Morgan does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The cost of cancer drugs is killing patients and it needs to stopRichard Morgan, Professor of Molecular Oncology, University of BradfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/473492015-11-15T19:17:29Z2015-11-15T19:17:29ZHow cancer doctors use personalised medicine to target variations unique to each tumour<figure><img src="https://images.theconversation.com/files/99119/original/image-20151021-32235-1gvxijl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Understanding the DNA of tumours allows researchers to target treatment to each individual.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/akire_yrko/3573644189/in/photolist-6rMRUZ-kaeMjj-ks75Wi-o8Dufm-kh2cVC-6Zq5td-o5GPqG-ng8ZAw-nS9kB1-nTc5iy-nDDUYf-o8Dujj-dZrRbo-yQcADM-nM4fy9-4BYXRj-dieVW6-oowrrL-rwZo4C-eeZ2WB-bvxDXq-dyu3pu-vcFhob-5pqov9-qebnFQ-fzysmy-8ZRGME-mEN11z-aLKn6M-bJsqVH-nBBh4w-omZoFq-nBBgMu-ivf5Mn-o5GPdY-Fg2yY-cwU2o7-o5GNXq-ooXhPB-7BJjf8-GTqKj-okaA4u-4sCW6q-omV8e8-ooXoQp-ooXqQM-o5HRcc-nJGuCU-nS9z4Q-4CH7rh">Erika/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>The Children’s Cancer Institute in Sydney <a href="http://www.smh.com.au/national/health/australianfirst-program-aims-to-eliminate-childhood-cancer-deaths-20150901-gjcqkt.html">recently launched</a> an ambitious program. From early next year, scientists will analyse the unique cancer cells of 12 children diagnosed with the most aggressive forms of the disease to find the best treatment for each child. </p>
<p>By 2020, they aim to have these individualised treatment options available to all children diagnosed with cancers that have a less than 30% survival rate. This way of tailoring treatment to each person is known as personalised medicine, and advances in DNA sequencing have paved the way for a new era in cancer management. </p>
<h2>Tailoring treatments</h2>
<p>The modern use of the term “personalised medicine” is based on the idea that by understanding the specific molecular code of a person’s disease, and particularly its genetic makeup, we can more accurately tailor treatment to them. This approach is also referred to as precision medicine.</p>
<p>Cancer is fundamentally a disease of altered genomics – genetic material making up the structure of cells. Because these alterations are different in each person, every tumour is programmed differently with genes made up of varying sequences of DNA. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99135/original/image-20151021-15424-1sn93sn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Cancer cells are programmed with a unique code.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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</figure>
<p>This is why not everyone will respond the same way to a given treatment. Determining the DNA sequence that makes up the genome of each tumour (genomic sequencing) helps doctors understand how the tumour may be effectively targeted.</p>
<p>Traditionally, identifying effective cancer treatments relied on large clinical trials involving thousands of patients. This approach successfully identifies drugs effective for general cancer features, but these may miss the unique Achilles heel in some people’s cancers.</p>
<p>Because personalised medicine is customised treatment for individuals, clinical trial designs are moving from population-based to <a href="http://www.nature.com/news/personalized-medicine-time-for-one-person-trials-1.17411">one-person trials</a>. Here, a person with a specific genomic makeup is given targeted therapies and the responses are tracked over time. </p>
<h2>Genomic framework</h2>
<p>While the Sydney children’s program has been described as the first of its kind in Australia, the concept of personalised medicine is not new. Cancer doctors have always managed each person’s cancer by using all the available information about the tumour and other pre-existing medical conditions. </p>
<p>But there are important differences in the development of personalised medicine today. </p>
<p>Breast cancer treatment is one example. For the last 40 years, a large factor dictating the clinician’s choice for breast cancer therapy was the <a href="http://www.biomedcentral.com/content/pdf/s12916-015-0369-5.pdf">presence or absence of oestrogen receptors</a> in the tumour. Oestrogen receptors receive signals from the hormone oestrogen, which then generates a reaction. Without them, oestrogen wouldn’t have any affect. </p>
<p>If a woman’s tumour didn’t have these receptors, then doctors wouldn’t give them drugs that affected oestrogen as there would be no point. </p>
<p>But now it has become apparent that having oestrogen receptors is not the only criteria for the use of these drugs, as not all women who have oestrogen receptors will benefit from them.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99138/original/image-20151021-15440-tfxxk8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A personalised approach to treatment can prevent having to undergo a therapy that isn’t working.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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</figure>
<p>So researchers have gone deeper to see that this is due to the <a href="http://www.biomedcentral.com/content/pdf/s12916-015-0369-5.pdf">different way oestrogen receptors function</a> in cancer cells. </p>
<p>Understanding the genomic framework of the tumour can determine this function and thus predict the types of women who, despite having the receptor, would likely not benefit from such hormonal therapy.</p>
<h2>Different classifications</h2>
<p>This understanding of a tumour’s genomic makeup has also led scientists to expand the way cancer is classified. Where previously we categorised cancers by their organ of origin (breast, pancreas etc), findings like the above mean we can now also use a genomic definition. </p>
<p>This has positive implications for optimising cancer treatment.</p>
<p>For instance, one of the most aggressive forms of breast cancer is HER2-positive cancer (human epidermal growth factor receptor 2). The subtype accounts for about 15% of breast cancers, and occurs when the tumour has extra copies of the HER2 receptor gene that promotes cancer cell growth.</p>
<p>Drugs targeting the HER2 protein have shown <a href="http://canceraustralia.gov.au/publications-and-resources/cancer-australia-publications/recommendations-use-trastuzumab-herceptin%C2%AE-treatment-her2-positive-breast-cancer">dramatic success in improving outcomes</a> for people with this subtype. They have become standard treatment.</p>
<p>But it has <a href="http://www.ncbi.nlm.nih.gov/pubmed/25896973">recently been discovered</a> that excessive HER2 is also present in about 8% of gastric cancers and 3% of pancreatic cancers. This means a therapy successful in one location has the potential to work in another, because the tumour types are similar.</p>
<p>Clinical <a href="http://www.garvan.org.au/news-events/news/potential-treatment-for-a-specific-kind-of-pancreatic-cancer">trials are currently assessing</a> whether HER2-targeted drugs can then also be effective against these pancreatic tumour types. </p>
<h2>Cost and benefit</h2>
<p>Most major cancer hospitals in Australia have trials investigating personalised medicine at some level. But genomic analyses aren’t widely performed on an individual patient basis.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99139/original/image-20151021-15414-1ney30d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Understanding a tumour’s genome can dramatically improve outcomes.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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</figure>
<p>It is likely examining each tumour in this way will become routine treatment in the near future. There are already international providers who will (for a fee) sequence tumours and suggest treatments based on this information.</p>
<p>For instance, the <a href="http://www.mycancerisunique.com">Foundation Medicine test</a> profiles some 400 known cancer driver genes and can be purchased for $US5,800 (approximately $A8,000). This type of test is not routine in Australia, but internet-savvy patients who have the financial means can arrange to have their tumour analysed with the help of their doctor.</p>
<p>Further to that cost of sequencing is the actual treatment, which may sometimes be an expensive drug not listed on the Australian Pharmaceutical Benefits Scheme for this particular use.</p>
<p>But there are advantages to the personalised approach that transcend cost. </p>
<p>Besides the potential of finding the right treatment, it can lead to stopping a therapy that isn’t working. Or result in a therapy not being undertaken at all; therapies that in many cases are themselves expensive and often have the added burden of side effects.</p><img src="https://counter.theconversation.com/content/47349/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Elizabeth Williams receives funding from Movember Foundation and the Prostate Cancer Foundation of Australia through a Movember Revolutionary Team Award.</span></em></p><p class="fine-print"><em><span>Rik Thompson receives funding from the National Breast Cancer Foundation, the NHMRC and Princess Alexander Hospital Foundation</span></em></p>Personalised medicine is based on the idea that by understanding the specific molecular code of a person’s disease, and particularly its genetic makeup, we can more accurately tailor treatment.Elizabeth Williams, Associate Professor, School of Biomedical Sciences, Queensland University of TechnologyRik Thompson, Professor of Breast Cancer Research, Institute of Health and Biomedical Innovation and School of Biomedical Sciences,, Queensland University of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/316872014-09-17T20:29:00Z2014-09-17T20:29:00ZHere’s what you need to know about testosterone<figure><img src="https://images.theconversation.com/files/59248/original/pyf7g9dm-1410929922.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Testosterone is important for the physical changes that happen during male puberty, and features typical of adult men, such as facial and body hair.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/dave77459/3291249702">Dave 77459/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p>Testosterone is blamed for violence in males, implicated in sport scandals, linked to sexual prowess, desired by gym devotees, and promoted as a tonic for ageing. But how many of us really understand what testosterone is, what it does, and why it’s important?</p>
<p>Testosterone levels are about ten times higher in men than women. While it does have important functions in women, its role is quite different so this article will focus on testosterone in men.</p>
<h2>Testosterone and development</h2>
<p>Testosterone is the most important male sex hormone (androgen); it’s needed for normal reproductive and sexual function. Hormones are chemical messengers made by glands and carried in the blood to act on various organs.</p>
<p>This particular hormone is important for the physical changes that happen during male puberty, such as development of the penis and testes, and for features typical of adult men, such as facial and body hair. Testosterone also acts on cells in the testes to make sperm.</p>
<p>It’s important for overall good health; testosterone helps the growth of bones and muscles, and it affects mood, libido (sex drive), and certain aspects of mental ability.</p>
<p>The hormone is present in the body from the early stages of fetal life to old age. At the earliest stage of development, it helps the fetus develop both a male body and a “male brain” (there are gender differences, or “sexual dimorphism” in the human brain).</p>
<p>Levels are highest between the ages of 20 and 30. As men age, testosterone levels fall by about 1% to 2% every year, although <a href="http://dx.doi.org/10.1210/jc.2012-3842">recent research suggests</a> this may not be true of all men as they age. It seems a large part of the drop in testosterone levels in older men is <a href="http://dx.doi.org/10.3109/10408363.2012.725461">due to chronic conditions</a>, such as obesity and diabetes. </p>
<p>If men remain very healthy into old age, their testosterone levels may stay the same as when they were younger.</p>
<h2>Too little and too much</h2>
<p>Low testosterone is usually caused by a genetic disorder (such as Klinefelter’s syndrome, the commonest chromosomal disorder in males that leads to poor testicular function) or damage to the testes or, in rare cases, a lack of certain complementary hormones made by the brain.</p>
<p>It’s thought that about one in 200 men under 60 years of age and about one in 10 older men may have low testosterone levels, but exact numbers are not known.</p>
<p>Low testosterone levels have a variety of effects at different ages. In young boys and teenagers, it means the testes and penis don’t grow properly and there’s poor development of muscles and facial and pubic hair. Boys with low levels of the hormone may be taller than their peers and their voice may not deepen.</p>
<p>In adults, low energy levels, mood swings, irritability, poor concentration, reduced muscle strength and changes in body fat distribution, and low sex drive may result from low testosterone. But that’s not to say that low levels of the hormone is the only possible cause of these symptoms. </p>
<p><a href="http://search.informit.com.au/documentSummary;dn=377696995207869;res=IELHEA">Research suggests</a> that men with low testosterone may have a higher risk of chronic conditions, such as stroke and heart disease. Older men with low testosterone also have thinning bones and that puts them at risk of fractures.</p>
<p>Too much testosterone can cause problems too. Although people <a href="http://dx.doi.org/10.1016/S0031-9384(02)00647-9">link the hormone with aggression</a>, this hasn’t held up under scrutiny. Rather, <a href="http://dx.doi.org/10.1016/j.neubiorev.2004.12.007">research has shown</a> testosterone levels are associated with quite different traits, such as care-giving and empathy.</p>
<h2>Supplementing needlessly</h2>
<p>Longevity is highest for those men with testosterone levels in the mid-range – not too high or too low – and <a href="http://dx.doi.org/10.1210/jc.2013-3272">recent research</a> supports the idea that too much or too little testosterone is best avoided. </p>
<p>For men with a clinical diagnosis of low levels, testosterone therapy can bring the amount of the hormone in their blood back to normal and restore and maintain good health. In boys, it can restore sexual development. </p>
<p>But in men with normal testosterone levels, taking supplements of the hormone is not appropriate and can cause problems. Taking testosterone can lead to a reduction in the size of the testes, and it can slow or stop sperm being made. And it can take many months to go back to normal once the man stops taking testosterone.</p>
<p>There is some controversy around studies suggesting that older men taking testosterone have an increased risk of cardiovascular disease but the jury is still out. What we do know is that <a href="http://theconversation.com/testosterone-supplements-why-the-fuss-26151">there’s no good evidence</a> for the much-publicised “benefits” of testosterone supplements in old age, except for men with clinically diagnosed low testosterone.</p><img src="https://counter.theconversation.com/content/31687/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Professor Robert McLachlan is the Director of Andrology Australia (The Australian Centre of Excellence in Male Reproductive Health). He has a strong track record of clinical research into male contraception, androgen physiology and male infertility. His research program has been supported by continuous NHMRC funding for the past 25 years. Professor McLachlan is a Scientific Advisor to Eli Lilly.</span></em></p>Testosterone is blamed for violence in males, implicated in sport scandals, linked to sexual prowess, desired by gym devotees, and promoted as a tonic for ageing. But how many of us really understand what…Rob McLachlan, Head, Clinical Andrology, Hudson InstituteLicensed as Creative Commons – attribution, no derivatives.