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Gene variants provide insight into brain, body incongruence in trans people

About 0.5 to 1.4% of individuals born male and 0.2 to 0.3 % of individuals born female meet criteria for gender dysphoria. Identical twins are more likely than fraternal twins to both report gender dysphoria.



Some of the first biological evidence of the incongruence transgender individuals experience, because their brain indicates they are one sex and their body another, may have been found in estrogen receptor pathways in the brain of 30 transgender individuals.

“Twenty-one variants in 19 genes have been found in estrogen signaling pathways of the brain critical to establishing whether the brain is masculine or feminine,” says Dr. J. Graham Theisen, obstetrician/gynecologist and National Institutes of Health Women’s Reproductive Health Research Scholar at the Medical College of Georgia at Augusta University.

Basically — and perhaps counterintuitively — these genes are primarily involved in estrogen’s critical sprinkling of the brain right before or after birth, which is essential to masculinization of the brain.

Variants investigators identified may mean that in natal males (people whose birth sex is male) this critical estrogen exposure doesn’t happen or the pathway is altered so the brain does not get masculinized. In natal females, it may mean that estrogen exposure happens when it normally wouldn’t, leading to masculinization.

Both could result in an incongruence between a person’s internal gender and their external sex. The negative emotional experience associated with this incongruence is called gender dysphoria.

“They are experiencing dysphoria because the gender they feel on the inside does not match their external sex,” Theisen says. “Once someone has a male or female brain, they have it and you are not going to change it. The goal of treatments like hormone therapy and surgery is to help their body more closely match where their brain already is.”

“It doesn’t matter which sex organs you have, it’s whether estrogen, or androgen, which is converted to estrogen in the brain, masculinizes the brain during this critical period,” says Dr. Lawrence C. Layman, chief of the MCG Section of Reproductive Endocrinology, Infertility and Genetics in the Department of Obstetrics and Gynecology. “We have found variants in genes that are important in some of these different areas of the brain.”

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These brain pathways are involved in regions of the brain where the number of neurons and how connected the neurons are typically differ between males and females.

They note that while this “critical period” for masculinizing the brain may seem late, brain development actually continues well after birth and these key pathways and receptors already need to be established when estrogen arrives.

While it’s too early to definitively say the gene variants in these pathways result in the brain-body incongruence called gender dysphoria, it is “interesting” that they are in pathways of hormone involvement in the brain and whether it gets exposed to estrogen or not, says Layman.

He and Theisen are co-corresponding authors of the study in the journal Scientific Reports.

“This is the first study to lay out this framework of sex-specific development as a means to better understand gender identity,” Theisen says. “We are saying that looking into these pathways is the approach we are going to be taking in the years ahead to explore the genetic contribution to gender dysphoria in humans.”

In fact, they already are exploring the pathways further and in a larger number of transgender individuals.

For this study, they looked at the DNA of 13 transgender males, individuals born female and transitioning to male, and 17 transgender females, born male and transitioning to female. The extensive whole exome analysis, which sequences all the protein-coding regions of a gene (protein expression determines gene and cell function) was performed at the Yale Center for Genome Analysis. The analysis was confirmed by Sanger sequencing, another method used for detecting gene variants.

The variants they found were not present in a group of 88 control exome studies in nontransgender individuals also done at Yale. They also were rare or absent in large control DNA databases.

Reproductive endocrinologist/geneticist Layman says his experience with taking care of transgender patients for about 20 years, made him think there was a biological basis. “We certainly think that for the majority of people who are experiencing gender dysphoria there is a biologic component,” says Theisen. “We want to understand what the genetic component of gender identity is.”

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While genetics have been suggested as a factor in gender dysphoria, proposed candidate genes to date have not been verified, the investigators say. Most gene or gene variants previously explored have been associated with receptors for androgens, hormones more traditionally thought to play a role in male traits but, like estrogen in males, also are present in females.

MCG investigators and their colleagues decided instead to take what little is known about sex-specific brain development — that estrogen bath needed in early life to ensure masculinization of the brain– to hone in on potential sites for relevant genetic variances. Extensive DNA testing initially revealed more than 120,000 variants, 21 of which were associated with these estrogen-associated pathways in the brain.

Animal studies have helped identify four areas of the brain with pathways leading to development of a male or female brain, and the investigators focused on those likely also present in humans. Laboratory studies have indicated that disrupting these brain pathways in males and females during this critical period results in cross sex behavior, like female rodents mounting and thrusting and males taking on a more traditional female posture when mating. These cross sex behaviors, which also have been documented in non-human primates, emerge during the natural sex hormone surge of puberty.

While sex specific brain development has not been thoroughly evaluated in humans, as with animals, the effects typically play out most at the time of puberty, a time when sex hormones naturally surge, when the general awareness of our sexuality really begins to awaken and when the complex state of gender dysphoria may become easier for adolescents to articulate, the investigators say. Layman notes that many individuals will report experiencing gender incongruent feelings as early as age 5.

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Theisen notes that we all are full of genetic variants, including ones that give us blue eyes versus brown or green, and the majority do not cause disease rather help make us individuals. “I think gender is as unique and as varied as every other trait that we have,” Theisen says.

The investigators suggest modification of the current system for classifying variants that would not imply that a variant means pathogenic, or disease causing.

Last year, the World Health Organization said that gender incongruence is not a mental health disorder and six years before that The Diagnostic and Statistical Manual of Mental Disorders, replaced gender identity disorder with general dysphoria.

About 0.5 to 1.4% of individuals born male and 0.2 to 0.3 % of individuals born female meet criteria for gender dysphoria. Identical twins are more likely than fraternal twins to both report gender dysphoria.

Gender affirming therapies, like hormone therapies and surgeries along with mental health evaluation and support, help these individuals better align their bodies and brains, the physician-scientists say.

Transgender individuals experience increased rates of discrimination, sexual violence and are at increased risk of depression, substance abuse and attempted suicide. About 26% report use of alcohol or other drugs to help cope; 19% have been denied medical care by a physician or other provider, some report verbal harassment in a medical environment and insurance companies do not consistently cover the cost of gender affirming hormone or surgical therapies.

A problem, the investigators say, is an overall lack of understanding of the biologic basis of gender dysphoria.

While their study of 30 individuals — they now have data on more than 30 others — appears to be the largest to date, the sample size prompted them to classify the published findings as preliminary.


PNP should stop all forms of profiling – Sen. Binay

Sen. Nancy Binay urged the Philippine National Police (PNP) to end all kinds of profiling that target specific individuals or groups based on appearance, political beliefs, religion, ethnicity, gender identity or sexual orientation.



Screencap from the Twitter page of Sen. Nancy Binay

Philippine Sen. Nancy Binay urged the Philippine National Police (PNP) to end all kinds of profiling that target specific individuals or groups based on appearance, political beliefs, religion, ethnicity, gender identity or sexual orientation.

Binay issued the call for a “standing policy banning operations with a gender or political bias” after a transgender woman claimed she was “profiled” by Makati cops under “Oplan X-Men.”

For Binay, police profiling “borders on grave abuse”, particularly since even innocent law-abiding citizens have been wrongly arrested or accused of crimes.

In a statement, Binay said: “Pipilitin kang sumama sa presinto at kukunin ang personal na impormasyon mo na wala namang malinaw o legal na dahilan. Bakit, may kaso ba? May complaint ba? May krimen bang nagawa? Warrantless arrest ba ito? (Cops force you to come to their police station and get your personal information without clear and legal reasons. Why? Do you have a case? Is there a complaint? Did you commit a crime? Is this a warrantless arrest?)”

Binay questioned gender profiling, red- or prostitute-tagging and the propriety of arresting people on the basis of observed characteristics or behavior.

For Binay, “dahil sa mali-maling profiling, people’s rights have been trampled. Sana huwag nang pamarisan pa ang pangyayaring ito ng ibang local police (because of wrong profiling, people’s rights have been trampled. I hope other local police don’t follow suit).”

Binay added that “police should be accountable for abusive practices.”

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The senator is urging to the PNP and other law enforcement agencies to have a “clear and enforceable policy” ending bigotry, particularly institutionalized homophobia and transphobia, in their organizations. She suggested that cops undergo gender awareness and sensitivity training to avoid further malicious and unsubstantiated arrests.

Earlier, Makati City police chief Rogelio Simon said that profiling operations are not wrong per se; but because of the ruckus created by Operation X-Men, the two cops involved in an incident wherein a transgender woman was wrongfully almost forced to be profiled were fired.

As per an report, too, National Capital Region Police Office (NCRPO) chief Maj. Gen. Debold Sinas said that the agency will continue its profiling operations as this was the directive of the PNP chief.

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Same-sex wedding held in British Embassy Manila

British Ambassador Daniel Pruce officiated a same-sex wedding in the British embassy in Manila, marking not only Valentine’s Day but the 87th same-sex marriage conducted in the premises.



Screencap from the British Embassy Manila FB page


British Ambassador Daniel Pruce officiated a same-sex wedding in the British embassy in Manila, marking not only Valentine’s Day but the 87th same-sex marriage conducted in the premises.

In a Facebook post, British Embassy Manila claimed: “Love is in the air! Congratulations to Mark and Richard who were married by Ambassador Daniel Pruce on #ValentinesDay. We wish you a lifetime of love and happiness.”

It is worth noting that while same-sex marriage is not outright banned by the Philippine Constitution, the country’s Family Code limits marriage as a sacrament between one man and one woman.

However, foreign embassies are given extraterritorial privileges under the Geneva Convention. These include immunity from intrusion, damage and disturbance by the host countries.

Same-sex marriage was legalized in Great Britain in 2014; and so the embassy said the UK “continues to champion the rights and equal treatment of all regardless of gender.”

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Makati City police now – apparently – profiling members of LGBTQIA community

The practice of profiling members of the LGBTQIA community is – apparently – actually already part of the implemented practices of Makati City’s police via its “Operation X-Men.”



Screencap from Makati City police's SCADS

On February 14, transgender woman Anne Pelos was walking along Makati Ave. in Makati City, when she was stopped by a police officer who wanted her to go with him to the police station. Asked why, Pelos was told Makati police was instructed to to bring in transgender people (in this case in particular, transgender women) “for profiling.”

Though Pelos – who works in the business process outsourcing (BPO) industry – was able to walk away from the traumatizing incident with her friends documenting/recording what transpired, the practice of profiling members of the LGBTQIA community is – apparently – actually already part of the implemented practices of Makati City’s police via its “Operation X-Men.”

In January, in an earlier post in Facebook, Makati police’s Station Community Affairs and Development Section (SCADS) stated that “Oplan X-Men is an intensified operation that aims to rescue ladyboys (sic) from exploitation and human trafficking in ill-repute areas.”

On January 22, at 11:52 PM, for that matter, the city’s police “invited” 67 individuals to the Makati City Police Station, with those invited coming from “illegal settlers inside Manila South Cemetery” and as a result of “Oplan X-Men at Burgos, Poblacion, Makati City.”

As reported, the rounding up of people was “conducted through the combined efforts of Station Operations, Women’s Desk, Station Intelligence and Station and Drug Enforcement Unit.”

According to the Commission on Human Rights (CHR), which has started investigating “Oplan X-Men”, the CHR recognizes incidents in which the police may “invite” individuals to their headquarters. However, “the public should exercise caution, as these may be used to effect warrantless arrests,” CHR spokesperson Jacqueline de Guia was quoted as saying by

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De Guia added that “this recent incident further highlights the violence and harassment experienced every day by the LGBTQI community because of their sexual orientation and gender identity (and expression).”

On her Facebook recollection of the incident, Pelos surmised that she was targeted because of what she was wearing (i.e. a white tube dress, which may be stereotypically associated with what sex workers in the area also wear).

But Pelos said that “I have an honest and decent job…” adding that “you should not just judge all trans people and drag them to the police precinct.”

On February 17, following the ruckus caused by the profiling, the two cops (Patrolman Timmy Paez and Police Corporal Juliel Atal) who invited Pelos to their headquarters after accosting her as she was walking home along Makati Avenue were supposedly fired.

Also, surprisingly, even after SCAD’s earlier mention of the same, Makati City police chief Rogelio Simon also told news outlet Rappler that Oplan X-Men was not a part of any police activity in Makati.

This is not the first ill-conceived attempt to profile members of the LGBTQIA community.

In 2017, former Quezon City mayor Herbert Bautista issued a memorandum to task the heads of the local government unit’s various offices to profile “all employees who belong to the (LGBTQIA community)… regardless of the employment agreement.”

Incidentally, Nazi Germany also profiled members of the LGBTQIA community; and under the Third Reich, it is estimated that approximately 100,000 men were arrested for homosexuality, of which around 5,000-15,000 were sent to concentration camps.

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For CHR’s De Guia, the incident stresses “the need to pass the SOGIE Equality Bill to penalize all forms of discrimination.”

The proposed bill that eyes to protect the human rights of members of the LGBTQIA community continues to languish in Congress after two decades.

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Women in leadership positions face more sexual harassment

Power in the workplace does not stop women’s exposure to sexual harassment. On the contrary, women with supervisory positions are harassed more than women employees.



Photo by Isabella Mariana from

Power in the workplace does not stop women’s exposure to sexual harassment. On the contrary, women with supervisory positions are harassed more than women employees. These are the results from a new study from the Swedish Institute for Social Research at Stockholm University, which examined the conditions in Sweden, USA and Japan.

Written by Folke, O., Rickne, J., Tanaka, S., & Tateishi, Y., Sexual Harassment of Women Leaders appeared in Daedalus.

By analyzing the responses from three surveys, researchers at the Swedish Institute for Social Research, SOFI, at Stockholm University, together with fellow American and Japanese researchers, have studied the prevalence of sexual harassment across the organizational hierarchy. The study shows that women with supervisory positions experienced between 30 and 100 per cent more sexual harassment than other women employees. This was true across the United States, Japan, and Sweden, three countries with different gender norms and levels of gender equality in the labour market. Comparing levels of leadership, exposure to harassment was greatest at lower levels of leadership, but remained substantial and similar to the level of harassment for the highest positions.

“When we first started to study sexual harassment, we expected a higher exposure for women with less power in the workplace. Instead we found the contrary. When you think about it, there are logical explanations: a supervisor is exposed to new groups of potential perpetrators. She can be harassed both from her subordinates and from higher-level management within the company. More harassment from these two groups is also what we saw when we asked the women who had harassed them,” says Johanna Rickne, Professor of Economics at SOFI.

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In all three countries, women with supervisory positions were subject to more harassment when their subordinates consisted of mostly men.

“Sexual harassment means that women’s career advancement comes at a higher cost than men’s, especially in male-dominated industries and firms. Additional survey data from the United States and Japan showed that harassment of supervisors was not only more common than for employees, but was also followed by more negative professional and social consequences. This included getting a reputation of being a ‘trouble maker’ and missing out on promotions or training,” says Olle Folke, affiliated researcher at SOFI and associate professor at Uppsala University.

The study addressed the risk of measurement error from different awareness of sexual harassment among supervisors and employees. Questions on whether or not particular behaviours should, or should not, be defined as harassment showed similar answers in the two groups. This makes it unlikely that the results derive from different perceptions of work interactions, rather than different treatment in those interactions.

The study used two different measurement tools. The surveys in the United States and Japan included the Sexual Experiences Questionnaire, a survey instrument with a list of behaviours, developed for studies in the US military. All three countries were also surveyed with subjective questions about whether the person had been exposed to sexual harassment. The time span for all questions was the previous 12 months.

The Swedish results come from five waves of the Swedish Work Environment Survey, a nationally representative dataset collected biannually by Statistics Sweden (1999, 2001, 2003, 2005, and 2007) and with a total of 23,994 female respondents. In the United States and Japan, the research team collected new survey material during 2019. The US sample included 1,573 employed female citizens, whereof 62 per cent had supervisory positions, while the Japanese sample included 1,573 respondents, of which 17 per cent of the women were in supervisory positions. Apart from questions about sexual harassments, respondents were asked about perpetrators, how they reacted to the harassment, and what social and professional consequences followed the victimization.

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Transfer of Pemberton to Bilibid sought after VFA termination

The killer of transgender woman Jennifer Laude, US serviceman Joseph Scott Pemberton, should be transferred to the New Bilibid Prison following the termination of the Philippines’ Visiting Forces Agreement (VFA) with the US.



Stop the special treatment.

The killer of transgender woman Jennifer Laude, US serviceman Joseph Scott Pemberton, should be transferred to the New Bilibid Prison following the termination of the Philippines’ Visiting Forces Agreement (VFA) with the US.

This is the call made by Atty. Harry Roque, who served as the legal counsel of the Laude family, at CNN Philippines’ The Source.

“I hope after the six month period, and the VFA has finally been terminated, that he will be finally moved to Muntinlupa where he belongs — together with the Ampatuans and other killers,” Roque was quoted as saying.

Pemberton was sentenced to six to 12 years in prison after he was found guilty in the 2014 murder of Laude, who was found lifeless in an Olongapo City motel room after a night out with Pemberton in October of that year. With her neck blackened with strangulation marks, Laude was found with her head rammed into a toilet.

To date, the American soldier is detained at the custodial center in Camp Aguinaldo, Quezon City. And for Roque, even if this is pursuant to provisions of the 1998 military deal, this is a copout since the space is a “golden cage”.

Now with the notice of VFA termination on the table, Roque said Pemberton’s move to the state penitentiary should now be pursued.

“The only reason why he’s being kept in that golden cage is because of the VFA. Without the VFA, he should be treated like all other prisoners, convicted felons, and sent to Muntinlupa,” Roque said.

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According to Ms Kate Montecarlo Cordova or the Association of Transgender People in the Philippines (ATP), “it does not bother me if he will be transferred to Bilibid after the cancellation of VFA if that is the right thing to do. Doing what is the right thing through legal means is upholding justice and righteousness. It is serving what is due both to the victim and to the perpetrator.”

And in a statement provided to Outrage Magazine, Toni Gee Fernandez of the Mujer LGBT Organization, Inc. in Zamboanga in Mindanao said that they “commend… our national government for taking on the courage and strong political will to make a stand in terminating the VFA.”

But “this historic decision by the government gives rise to two very crucial questions (also affecting) the LGBTQIA community”: 1) Due to the termination, can the Philippines… finally exercise jurisdiction over any and all US military personnel for crimes committed within our territory? 2) If so, does this mean that Pemberton, the US military personnel convicted for the brutal murder of Jennifer Laude in 2014, be finally moved to the New Bilibid Prison in Muntinlupa City to continue serving the remainder of his sentence?

For Mujer LGBT Organization, Inc.: “It is high time that we let our laws take over those who deserve to be punished for what they did to our countrymen.”

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Religious, moral beliefs may exacerbate concerns about porn addiction

Moral or religious beliefs may lead some people to believe they are addicted to pornography even when their porn use is low or average.



Photo by Artem Labunsky from

Moral or religious beliefs may lead some people to believe they are addicted to pornography even when their porn use is low or average, according to new research published by the American Psychological Association.

“Self-reported addiction to pornography is probably deeply intertwined with religious and moral beliefs for some people,” said lead researcher Joshua B. Grubbs, PhD, an assistant professor of psychology at Bowling Green State University. “When people morally disapprove of pornography but still use it anyway, they are more likely to report that pornography is interfering with their lives.”

In two studies with more than 3,500 participants, the researchers found that moral or religious beliefs may be a central contributing factor to distress over porn use. Such a view may complicate an accurate diagnosis of compulsive sexual behavior disorder (CSBD), which includes porn addiction and detrimental sexual behaviors such as patronizing prostitutes. The research was published online in the Journal of Abnormal Psychology.

“Moral Incongruence and Compulsive Sexual Behavior: Results From Cross-Sectional Interactions and Parallel Growth Curve Analyses” was done by Joshua B. Grubbs, PhD, Bowling Green State University; Samuel L. Perry, University of Oklahoma-Norman; Shane W. Kraus, PhD, University of Nevada-Las Vegas; Karol Lewczuk, PhD, Cardinal Stefan Wyszynski University; and Mateusz Gola, PhD, University of California-San Diego and Polish Academy of Sciences

In one experiment, 2,200 online participants who were selected to be representative of the U.S. population, along with 467 undergraduate students from Bowling Green State University, were surveyed about their porn use and their religious and moral beliefs. People who viewed pornography and believed pornography is morally wrong were more likely to report that they were addicted to porn than those who didn’t find porn use to be morally objectionable. Participants who reported they were religious or who regularly attended religious services were more likely to believe they were addicted to porn, even if their porn use was the same as less religious participants who didn’t believe their porn use was a problem.

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In another online experiment, 850 U.S. adults who used porn were surveyed about their porn use and religious beliefs and then were invited to complete follow-up surveys every four months for a year. The findings were similar, with more religious participants reporting an addiction to pornography. These feelings tracked together over time: Increases in feelings of moral disapproval of pornography corresponded to increases in feelings of addiction to pornography.

“We are not suggesting that people need to change their moral or religious beliefs, but it’s not helpful for someone with a low or normal amount of porn use to be convinced that they have an addiction because they feel bad about it,” Grubbs said. “However, if someone wants to reduce their porn use because it causes distress, then therapists should work with them in a non-judgmental way that doesn’t induce shame.”

CSBD has been controversial due to conflicting research on whether it is a distinct mental illness. CSBD is not included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychiatric Association in 2013. In 2018, the World Health Organization included CSBD in the 11th edition of the International Classification of Diseases, a commonly used worldwide standard reference for health conditions and mental illnesses. In the International Classification of Diseases, CSBD is categorized as an impulse control disorder, which includes “a persistent pattern of failure to control intense, repetitive sexual impulses or urges resulting in repetitive sexual behavior.”

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Grubbs said he supports a diagnosis for CSBD as a distinct mental illness, but mental health professionals must ensure their own biases don’t lead to inaccurate diagnoses. Previous research has shown that therapists are less likely to diagnose LGBTQ people with CSBD, while religious therapists are more likely to view porn use as addictive and evidence of a mental illness.

Some people seeking treatment for CSBD may not meet the diagnostic criteria even if they are distressed about their porn use, Grubbs said. Clinicians will need to find objective measures, not just the subjective feelings of clients, to diagnose CSBD, such as failed attempts to stop using porn or impairment in job or family duties caused by porn use.

“This diagnosis enables access to care for people who need treatment,” Grubbs said. “Just like cultural sensitivity is needed for any diagnosis, CSBD will require that clinicians and therapists be aware of and sensitive to the unique aspects of themselves and their clients that might influence how symptoms should be addressed.”

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