Dr. Karen Tordjman, a senior lecturer at Tel Aviv University's Sackler Faculty of Medicine didn't have an immediate diagnosis for the under-masculinized young man who walked into her office. A 25-year-old university student who had served in an elite commando unit in the Israeli navy, he was handsome in a fashion-model kind of way: rail thin, with a smooth face and delicate, feminine features. Closer inspection revealed no body hair other than sparse patches in his armpits and groin. His genitals were small and heavily scarred.
The young man had reluctantly agreed to visit the medical clinic at the insistence of his girlfriend, who wanted an explanation for his condition. He couldn't have known he was initiating a years-long medical journey that would lead Dr. Tordjman and a team of physicians to discover a new genetic mutation, bolster the case for a counterintuitive medical treatment, and push the limits of male fertility. "We offered treatment not for his future reproductive capabilities but for his appearance," says Dr. Tordjman. "We didn't guarantee him anything, but we said we'd try."
Her research, published in the journal Andrologia in June, will allow future genetic screening for the mutation.
Uncharted waters
Dr. Tordjman and her colleague Dr. Amnon Botchan, also a Sackler lecturer, began by obtaining the patient's medical records. The records showed that two of his uncles had been diagnosed with androgen receptor insensitivity—a rare condition that results in the body under-responding to the androgen hormones that drive male sexual development. Usually caused by a mutation in the androgen receptor gene, the condition impairs the development of male genitalia in the womb and of secondary male sexual characteristics during puberty.
In cases of complete androgen insensitivity, no male sexual development takes place. The result is men who look like women on the outside but have testes rather than female genitalia inside their bodies. Such cases are often diagnosed only during puberty, when the individuals develop breasts and other female sexual characteristics but do not start menstruating. In cases of partial androgen insensitivity, which range from mild to severe, the individuals are born with ambiguous genitalia. If doctors determine that surgically creating male genitalia is infeasible, they tend to assign the female gender.
Dr. Tordjman's patient, who reported a consistent heterosexual orientation, had not had sex reassignment surgery or been given androgen treatments to try to enhance his sexual development at birth. But he had been diagnosed with the same condition as his uncles and undergone operations to correct genital malformations at age three and to remove breast tissue during puberty. Genetic testing, performed with the help of French researchers Dr. Serge Lumbroso and Prof. Charles Sultan, confirmed that he had a mutation of his androgen receptor gene—one that had not previously been reported.
A family affair
Hoping to masculinize the patient per his wishes, Dr. Tordjman started him on high-dose testosterone therapy. Theoretically, this type of therapy makes little sense for patients with androgen receptor insensitivity, because their bodies create plenty of testosterone—it's just that they are unable to put it to use. But Tordjman had read about a case in which the therapy had worked and decided to give it a try.
After several months of weekly injections, the patient appeared dramatically more masculine. He gained 18 pounds—mostly of muscle—and grew hair on his face and body, leading him to shave for the first time in his life. His voice, which had always been high-pitched, did not change. (The voice, says Tordjman, is stubbornly resistant to hormone therapy.) The treatments continued for four years, during which the patient and his girlfriend got married and eventually began talking about having a baby.
Infertility in men with androgen receptor insensitivity is nearly universal, even in mild cases; and no one with a case as severe as the patient's was known to have successfully fathered a child. But having seen a significant improvement in his sperm count, Tordjman took another long shot and referred the couple for fertility treatment. When Tordjman next saw the patient several years later, he was pushing a baby girl into her office in a stroller.
Children have a 50-percent chance of inheriting a mutation for androgen receptor insensitivity from a parent. While fathers have typically been left out of the equation given the male sterility associated with the condition, this case will force a rethinking of that dogma and encourage the use of testosterone and fertility treatments in men with the condition, says Tordjman.
"My suggestion is in any case like this with partial androgen insensitivity, even if you don't know where in the androgen receptor gene the mutation lies, testosterone treatment is worth trying," she says.
Explore further: Study finds genetic mutation in castration-resistant prostate cancer
Medical Xpress on facebook
Related Stories
Androgen suppression
Mar 27, 2012
Androgen suppression – the inhibition of testosterone and other male hormones – is a routine therapy for prostate cancer. Unfortunately, it can dramatically reduce the quality of patients' sex lives and, more importantly, ...
Study finds genetic mutation in castration-resistant prostate cancer
Aug 29, 2013
The mutation occurs in the androgen-synthesizing enzyme 3βHSD1 in castration-resistant prostate cancer (CRPC), according to research published online today in Cell. This mutation enables the tumor to make its own supply ...
Researchers identify novel class of drugs for prostate cancers
May 28, 2013
A new study on prostate cancer describes a novel class of drugs developed by UT Southwestern Medical Center researchers that interrupts critical signaling needed for prostate cancer cells to grow.
Targeting aggressive prostate cancer
Aug 14, 2013
A team of researchers from UC Davis, UC San Diego and other institutions has identified a key mechanism behind aggressive prostate cancer. Published on August 14, 2013 in Nature, the study shows that two long non-coding RNAs ( ...
Noninvasive assay monitored treatment response in patients with metastatic prostate cancer
Oct 23, 2012
Deciding the ideal treatment for patients with metastatic prostate cancer that stops responding to initial therapy could be guided by certain analyses of cancer cells isolated from the patients' blood, according to data published ...
Recommended for you
CDC shutdown: Mayo Clinic expert explains what it means for this flu season—and the next
40 minutes ago
Flu season is under way, but how many Americans have been hit so far, how badly, and which influenza bugs are to blame is unclear. That information is important to prevent and manage outbreaks, and it is crucial for creation ...
USDA: Poultry plants linked to outbreak stay open
4 hours ago
The Agriculture Department says three California poultry processing facilities linked to a salmonella outbreak in raw chicken can stay open, for now.
Urine biomarkers reveal mitochondrial dysfunction in diabetic kidney disease
15 hours ago
Researchers at the University of California, San Diego School of Medicine have identified 13 metabolites – small molecules produced by cellular metabolism – that are significantly different in patients ...
Antibiotic resistance ups Salmonella hospitalizations
16 hours ago
(HealthDay)—Because of antibiotic resistance, 42 percent of patients stricken with Salmonella tied to a California chicken farm have required hospitalization, the U.S. Centers for Disease Control and Pr ...
Security Council urges UN to combat Haiti cholera
17 hours ago
The Security Council urged the United Nations on Thursday to keep up efforts to combat cholera in Haiti in a resolution extending the mandate of the peacekeeping force whose soldiers have been widely blamed for starting the ...
New hepatitis C drug shows potential in phase 2 trials
21 hours ago
The addition of danoprevir to the current treatment regimen for patients with hepatitis C leads to high rates of remission, according to a new article in Gastroenterology, the official journal of the American Gastroenterological Associ ...
User comments
© Medical Xpress 2011-2013, Phys.org network
Dr. Karen Tordjman, a senior lecturer at Tel Aviv University's Sackler Faculty of Medicine didn't have an immediate diagnosis for the under-masculinized young man who walked into her office. A 25-year-old university student who had served in an elite commando unit in the Israeli navy, he was handsome in a fashion-model kind of way: rail thin, with a smooth face and delicate, feminine features. Closer inspection revealed no body hair other than sparse patches in his armpits and groin. His genitals were small and heavily scarred.
The young man had reluctantly agreed to visit the medical clinic at the insistence of his girlfriend, who wanted an explanation for his condition. He couldn't have known he was initiating a years-long medical journey that would lead Dr. Tordjman and a team of physicians to discover a new genetic mutation, bolster the case for a counterintuitive medical treatment, and push the limits of male fertility. "We offered treatment not for his future reproductive capabilities but for his appearance," says Dr. Tordjman. "We didn't guarantee him anything, but we said we'd try."
Her research, published in the journal Andrologia in June, will allow future genetic screening for the mutation.
Uncharted waters
Dr. Tordjman and her colleague Dr. Amnon Botchan, also a Sackler lecturer, began by obtaining the patient's medical records. The records showed that two of his uncles had been diagnosed with androgen receptor insensitivity—a rare condition that results in the body under-responding to the androgen hormones that drive male sexual development. Usually caused by a mutation in the androgen receptor gene, the condition impairs the development of male genitalia in the womb and of secondary male sexual characteristics during puberty.
In cases of complete androgen insensitivity, no male sexual development takes place. The result is men who look like women on the outside but have testes rather than female genitalia inside their bodies. Such cases are often diagnosed only during puberty, when the individuals develop breasts and other female sexual characteristics but do not start menstruating. In cases of partial androgen insensitivity, which range from mild to severe, the individuals are born with ambiguous genitalia. If doctors determine that surgically creating male genitalia is infeasible, they tend to assign the female gender.
Dr. Tordjman's patient, who reported a consistent heterosexual orientation, had not had sex reassignment surgery or been given androgen treatments to try to enhance his sexual development at birth. But he had been diagnosed with the same condition as his uncles and undergone operations to correct genital malformations at age three and to remove breast tissue during puberty. Genetic testing, performed with the help of French researchers Dr. Serge Lumbroso and Prof. Charles Sultan, confirmed that he had a mutation of his androgen receptor gene—one that had not previously been reported.
A family affair
Hoping to masculinize the patient per his wishes, Dr. Tordjman started him on high-dose testosterone therapy. Theoretically, this type of therapy makes little sense for patients with androgen receptor insensitivity, because their bodies create plenty of testosterone—it's just that they are unable to put it to use. But Tordjman had read about a case in which the therapy had worked and decided to give it a try.
After several months of weekly injections, the patient appeared dramatically more masculine. He gained 18 pounds—mostly of muscle—and grew hair on his face and body, leading him to shave for the first time in his life. His voice, which had always been high-pitched, did not change. (The voice, says Tordjman, is stubbornly resistant to hormone therapy.) The treatments continued for four years, during which the patient and his girlfriend got married and eventually began talking about having a baby.
Infertility in men with androgen receptor insensitivity is nearly universal, even in mild cases; and no one with a case as severe as the patient's was known to have successfully fathered a child. But having seen a significant improvement in his sperm count, Tordjman took another long shot and referred the couple for fertility treatment. When Tordjman next saw the patient several years later, he was pushing a baby girl into her office in a stroller.
Children have a 50-percent chance of inheriting a mutation for androgen receptor insensitivity from a parent. While fathers have typically been left out of the equation given the male sterility associated with the condition, this case will force a rethinking of that dogma and encourage the use of testosterone and fertility treatments in men with the condition, says Tordjman.
"My suggestion is in any case like this with partial androgen insensitivity, even if you don't know where in the androgen receptor gene the mutation lies, testosterone treatment is worth trying," she says.
Explore further: Study finds genetic mutation in castration-resistant prostate cancer
Medical Xpress on facebook
Related Stories
Androgen suppression
Mar 27, 2012
Androgen suppression – the inhibition of testosterone and other male hormones – is a routine therapy for prostate cancer. Unfortunately, it can dramatically reduce the quality of patients' sex lives and, more importantly, ...
Study finds genetic mutation in castration-resistant prostate cancer
Aug 29, 2013
The mutation occurs in the androgen-synthesizing enzyme 3βHSD1 in castration-resistant prostate cancer (CRPC), according to research published online today in Cell. This mutation enables the tumor to make its own supply ...
Researchers identify novel class of drugs for prostate cancers
May 28, 2013
A new study on prostate cancer describes a novel class of drugs developed by UT Southwestern Medical Center researchers that interrupts critical signaling needed for prostate cancer cells to grow.
Targeting aggressive prostate cancer
Aug 14, 2013
A team of researchers from UC Davis, UC San Diego and other institutions has identified a key mechanism behind aggressive prostate cancer. Published on August 14, 2013 in Nature, the study shows that two long non-coding RNAs ( ...
Noninvasive assay monitored treatment response in patients with metastatic prostate cancer
Oct 23, 2012
Deciding the ideal treatment for patients with metastatic prostate cancer that stops responding to initial therapy could be guided by certain analyses of cancer cells isolated from the patients' blood, according to data published ...
Recommended for you
CDC shutdown: Mayo Clinic expert explains what it means for this flu season—and the next
40 minutes ago
Flu season is under way, but how many Americans have been hit so far, how badly, and which influenza bugs are to blame is unclear. That information is important to prevent and manage outbreaks, and it is crucial for creation ...
USDA: Poultry plants linked to outbreak stay open
4 hours ago
The Agriculture Department says three California poultry processing facilities linked to a salmonella outbreak in raw chicken can stay open, for now.
Urine biomarkers reveal mitochondrial dysfunction in diabetic kidney disease
15 hours ago
Researchers at the University of California, San Diego School of Medicine have identified 13 metabolites – small molecules produced by cellular metabolism – that are significantly different in patients ...
Antibiotic resistance ups Salmonella hospitalizations
16 hours ago
(HealthDay)—Because of antibiotic resistance, 42 percent of patients stricken with Salmonella tied to a California chicken farm have required hospitalization, the U.S. Centers for Disease Control and Pr ...
Security Council urges UN to combat Haiti cholera
17 hours ago
The Security Council urged the United Nations on Thursday to keep up efforts to combat cholera in Haiti in a resolution extending the mandate of the peacekeeping force whose soldiers have been widely blamed for starting the ...
New hepatitis C drug shows potential in phase 2 trials
21 hours ago
The addition of danoprevir to the current treatment regimen for patients with hepatitis C leads to high rates of remission, according to a new article in Gastroenterology, the official journal of the American Gastroenterological Associ ...
User comments
© Medical Xpress 2011-2013, Phys.org network
0 comments:
Post a Comment