Explaining Partial Androgen Insensitivity

I took a writing hiatus due to experiencing an ongoing medical crisis. I am still sorting out how to live with my new diagnosis, which sadly interferes with my ability to write, to think, to sleep, to laugh and to live how I want to live my life. My diagnosis doesn’t just affect me; it affects my partner Dutch, my entire family, my friends and my pets and my ability to perform at my bill-paying day job.

I am not back to being 100 percent myself yet. This is my first blog post in nearly two months. I am considering this to be a small win in my battle back to health and wellness.

 

A friend told me about a young colleague undergoing gender reassignment surgery. This was not an act of malice or of gossip. It was simply my friend, who is of an older generation, wanting to better understand the situation. We now talk about gender reassignment surgery in the news and at the coffee maker at work where previously this was a taboo topic that wasn’t discussed openly.

My friend’s colleague was diagnosed during his youth with partial androgen insensitivity syndrome (PAIS). Androgen insensitivity is a condition that affects sexual development before birth and during puberty.

People with androgen insensitivity conditions are genetically male, with one X chromosome and one Y chromosome in each cell, yet their bodies are unable to respond properly to male sex hormones, or androgens, which includes testosterone and dehydroepiandroesterone or DHEA. As a result, the person has some or all of the physical traits of a female with the genetic makeup of a male.

The inability to respond properly to androgens is due to a change or mutation in the androgen receptor (AR) gene, which is the gene that allows cells to respond to androgens that direct sexual development in males and that regulate hair growth and sex drive in both males and females.

The AR gene mutation affects the development of the reproductive and genital organs of fetuses who have the mutation. During the first ten weeks of pregnancy, the external anatomy of male and female embryos appear to be identical. The presence or absence of the male sex hormone testosterone determines if an embryo will develop male or female genitalia.

In PAIS, an embryo will have ambiguous genitalia, meaning the development of the external genitalia will be intermediate between male and female. In other words, the physical outside genitals may not look “normal.” The clitoris will either be large or the penis will be small.

Having ambiguous genitalia is considered to be a form of male pseudohermaphroditism, in which the baby is born with testes and possesses both male and female sex characteristics. People born with PAIS may be raised as physical males or as physical females and can have either a male or female gender identity. The gender the child is physically raised as may not match the child’s chosen gender identity, especially after puberty. This is why some adult males with PAIS undergo gender reassignment surgery in order to live as physical females.

The symptoms of PAIS vary depending upon severity of the disorder. In the least severe cases, infertility results from the hardening of the tubules in the testes or from lack of viable sperm present in semen. The use of replacement testosterone may be used in males with PAIS to help reduce the side effects of their disorder.

Symptoms in more severe cases of PAIS include hypospadias, in which the opening of the penis is on the underside rather than the tip and that requires surgical correction in order to restore proper urine flow; hypogonadism, which is failure of the testes or ovaries to function properly; and gynecomastia (commonly called “man boobs”), which is when male breast tissue swells due to a hormone imbalance and looks more like developed female breasts in appearance.

Other symptoms of PAIS include testes that do not descend, and which, if not surgically removed, can lead to cancer later in life; a decrease in the functioning of the cells in the testes that produce androgens; possible sexual impotence; little to no facial and/or chest hair; and a high-pitched voice.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for individuals. Humans normally have 46 chromosomes, with pairs numbered 1 through 22 while the sex chromosomes are labeled X and Y. Each chromosome has a short arm, designed as “p” and a long arm, designed as “q.” Chromosomes are then sub-divided into numbered bands. This breakdown helps researchers locate genetic abnormalities using a standardized system, much like we locate books in libraries using the standardized Dewey decimal system.

Genetically, PAIS is inherited as an X-liked, recessive trait. The gene causing the mutation is located at Xq11-q12, which means the mutation is found in the X sex chromosome, along the long q arm, between bands 11 and 12.

Males are affected more frequently by X-linked recessive disorders than females. Multiple males in the same family can be affected by X-linked disorders.

In genetic males (who only have one X chromosome), one altered copy of the gene in each cell is sufficient to cause the AR gene mutation. In genetic females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause androgen sensitivity disorders. The majority of androgen sensitivity disorders are inherited from mothers who carry the AR mutation gene on one of their two X chromosomes. The remaining cases result from a new mutation that occurs either in the mother’s egg cell prior to fertilization or during early fetal development.

A male with an X-linked chromosome disorder cannot pass the disorder on to his male offspring because the Y chromosome is genetically passed from fathers to sons. The disease lies within the X chromosome, which the affected male passes genetically only to his female offspring. Daughters of men with X-linked chromosome disorders are carriers of the disorder.

As female carriers of an X-linked chromosome disorder, a woman who becomes pregnant faces a 25 percent chance with each pregnancy of having a daughter who is a carrier of the disorder, a 25 percent change of having a daughter who is a non-carrier, a 25 percent chance of having a son affected by the X-linked disorder and a 25 percent chance of having an unaffected son.

Androgen insensitivity disorders are rare, affecting an estimated 2 to 5 per 100,000 people who are genetically male, according to the United States National Library of Medicine.

Psychological and genetic counseling for parents of infants and young children diagnosed with androgen disorders is important in the care of the child. Counselors can assist the parents in how to tell the child about his or her genetic disorder and can help the child better understand the disorder before, during and after puberty.

It is important when we encounter someone undergoing gender reassignment to be respectful of their decision, no matter the reason, and to not be prying or judgmental. When someone wants to be open about their sexual reassignment experience, listen to him or her with an open mind. We can learn from one another just as much as we can learn from a blog or a book.

XOXO,

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