Thinking About Starting Testosterone for XXY/XXYY/XXXY
Presentation slides from the 2017 AXYS Family Conference presentation:
Thinking About Starting Testosterone for XXY/XXYY/XXXY (PDF)
Presented by Shanlee Davis, MD, MSCS
The Challenges of Klinefelter’s
“The Klinefelter Syndrome: Current Management and Research Challenges”—From the scientific journal, Andrology, this article summarizes the concluding “Round Table Discussion” of the 2nd International Workshop on the Klinefelter Syndrome in Munster, Germany, March, 2016. Topics include syndrome characteristics, centers of competence for diagnosis and treatment, counseling, support groups, early screening, fertility, testosterone treatment, and basic research. Click here.
See also: “Speaker Abstracts from the 2nd International Workshop on Klinefelter Syndrome March 2016 Münster, Germany.”
Mortality in Patients with Klinefelter Syndrome in Britain: A Cohort Study
Article Title: Mortality in Patients with Klinefelter Syndrome in Britain: A Cohort Study
Authors: Anthony Swerdlow, Craig Higgins, Minouk Schoemaker, Alan Wright, and Patricia Jacobs
Date of Publication: December 1, 2005
“Patients diagnosed with Klinefelter syndrome have raised mortality from several specific causes. This may reflect hormonal and genetic mechanisms.”
An Extra X or Y Chromosome: Contrasting the Cognitive and Motor Phenotypes in Childhood in Boys with 47,XYY Syndrome or 47,XXY Klinefelter Syndrome
Article Title: An extra X or Y chromosome: contrasting the cognitive and motor phenotypes in childhood in boys with 47,XYY syndrome or 47,XXY Klinefelter syndrome
Authors: Judith L. Ross, Martha P.D. Zeger, Harvey Kushner, Andrew R. Zinn, and David P. Roeltgen
Date of Publication: 2009
“The results from these large XYY and KS cohorts have important neurocognitive and educational implications. From the neurocognitive standpoint, the presenting findings afford an opportunity to gain insights into brain development in boys with XYY and those with KS. From the educational standpoint, it is critical that boys with XYY or KS receive appropriate educational interventions that target their specific learning challenges. These findings also provide important information for counseling clinicians and families about these disorders.”
Neurocognitive research on 47,XXY
Title: Neurobehavioral and Psychosocial Issues in Klinefelter Syndrome
Authors: Daniel H. Geschwind and Elisabeth Dykens
Date of Publication: 2004
This is one of the “gold standard” research articles on 47,XXY neurocognitive implications. It contains pretty intense medical terminology but it would be recognized as excellent resource/reference material by physicians, educators, the courts, etc. It should help parents and others understand there are absolutely biological issues involved with potential problem behaviors that may be happening with someone that is 47,XXY.
Comparing 47,XXY and 47,XYY boys
Title: An extra X or Y chromosome: contrasting the cognitive and motor phenotypes in childhood in boys with 47,XYY syndrome or 47,XXY Klinefelter syndrome
Authors: Judith L. Ross, Martha P.D. Zeger, Harvey Kushner, Andrew R. Zinn, and David P. Roeltgen
Date of Publication: December 2009
A research article on comparing the similarities and differences in boys with 47,XXY and 47,XYY from a neurocognitive testing standpoint.
Complexities of Hypogonadism
Article Title: Complexities of Hypogonadism
Author: Dr. Poochellam Muthalagu
Date of Publication: June 30, 2011
Dr. Poochellam Muthalagu looks at the primary and secondary reasons for hypogonadism and examines the different treatments available in this country.
Male hypogonadism is a clinical syndrome defined by low testosterone levels associated with sexual dysfunction, particularly diminished libido, mood disturbances, reduced lean body mass and increased adipose tissue mass.
A wide range of effective and well-tolerated treatment options exist. These include testosterone (T) gels and T patches. There is also a mucoadhesive sustained-release buccal tablet, but this is not available in Ireland. Intramuscular testosterone injections and subcutaneous depot implants (T pellets) are still the standard therapy.
Testosterone replacement therapy (TRT) can be individualised to enhance patient health and wellbeing. Screening and ongoing monitoring are necessary to ensure both the efficacy and safety of TRT, particularly prostate safety. Investigational agents, including selective androgen receptor modulators, may offer new pharmacodynamic and/or pharmacokinetic properties that enhance outcomes of TRT.
Male hypogonadism is defined as the failure of the testes to produce androgen, sperm or both. Although the disorder is exceedingly common, its exact prevalence is uncertain.
Testosterone production declines with advancing age; some 20 per cent of men older than 60 years and 30-40 per cent of men older than 80 years have serum testosterone levels that would be subnormal in their younger adult male counterparts.
This apparent physiologic decline in circulating androgen levels is compounded in frequency by permanent disorders of the hypothalamic-pituitary-gonadal axis. These include the transient deficiency states associated with acute stressful illnesses, such as surgery and myocardial infarction, and the more chronic deficiency states associated with wasting illnesses, such as cancer and acquired immunodeficiency syndrome (AIDS).
Klinefelter Syndrome and Other Sex Chromosomal Aneuploidies
Article Title: Klinefelter syndrome and other sex chromosomal aneuploidies
Author: Jeannie Visootsak and John M. Graham Jr.
Date of Publication: October 24, 2006
The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY) to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH). The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15–16 points, with language most affected, particularly expressive language skills.
Bone Density
We rarely use Wikipedia as a resource, but this overview on bone density is quite well done. As with any medical issue or question, please consult your physician. The Wikipedia entry is a general discussion of the topic. It is not specifically related to X and Y Chromosome Variations. For individuals who are 47,XXY, untreated hypogonadism can lead to osteoporosis and osteopenia. Most benefit from testosterone replacement therapy (TRT). Those who identify as intersex or choose not to use TRT should seek competent medical help for alternative methods to preserve bone density.
Gender Considerations with 47,XXY
Authors: A.S. Herlihy, L. Gillam
Date of Publication: March 2011
www.ncbi.nlm.nih.gov/pubmed/21453406
International Journal of Andrology ｪ 2011 European Academy of Andrology, 1–2
A common genetic condition affecting males, Klinefelter syndrome (KS), is often described as ‘The Forgotten Syndrome’.Although the prevalence of KS has been estimated to be as high as 1 in 450 (Herlihy et al., in press.), between 50 and 70% of males are never diagnosed (Bojesen et al.,2003). Klinefelter et al., 1942 first described KS as a syndrome in males, characterized by tall stature with eunuchoidal body proportions, gynaecomastia, small testes,hypogonadism, azoospermia and increased FSH levels(Klinefelter et al., 1942). The cause of this syndrome was identified 17 years later as an additional X chromosome in males, resulting in a 47, XXY karyotype (Jacobs & Strong,1959). Since then, there have been many advances in research concerning the biomedical aspects of KS, in addition to the cognitive and neuropsychological features,providing a greater understanding of the variety of behavioural, learning and psychological difficulties that may be present (Bojesen & Gravholt, 2007).