Dear Dr Pate,

My name is M, a cisgender gay man, and I am married to Y, a transgender gay man. Y has currently stopped his testosterone shots after 3 years, and we are planning a pregnancy in the near future.

I came across your name in your blog, and in several posts made by transman who are in a similar position to me and my partner. I was hoping you could assist us with our major  questions, since we live in Israel, and most MD’s, OBGYN’s and other medical personnel here do not have any experience with transman fertility and pregnancy.

Since Y’s period has returned very quickly (after only one month without testosterone), our major concern at this time is on the prospect of having a healthy baby after 3 years of high-dosage testosterone treatment (250mg every 2/3 weeks). We have come across several stories of transman who got pregnant after using testosterone for some time, and there seems to be a high percentage of autistic children born that way (3/4 out of 8 stories we found, with the rest all under 3 years old – so we assume no conclusive diagnosis could be reached). In addition, we could not find any information about the effects testosterone usage has on the ova, and the chances it could cause mutations or other problems (since Y did not have a period for almost 3 years).

Do you have any information regarding these issues that we bring to our doctors for consultation? Any assistance would be appreciated, since we are currently considering giving up on the pregnancy because of that…

Thank you very much for your help 🙂

Dear M,

Thank you for your excellent questions. Congratulations also on your plans to become fathers. Being a father changes you for the better and I am so grateful to be one myself.

I have identified the the following questions from your letter:

1. What is the prospect of having a healthy baby after 3 years of high-dosage testosterone treatment?
2. Is there an increased risk of having an autistic child as a result of prior testosterone use?
3. What are the effects of testosterone on the ova (egg cells in the ovaries)? Can it cause mutations or other negative problems?

Your question about the relationship between testosterone and autism is complicated in that the diagnostic criteria has changed over time, its cause is unknown and there is no published data on transmen who father children much less those who father autistic children. That said, I have scoured the literature and will do my best to answer your questions to the limits of current scientific findings. I will do this in two ways. In “Short & Sweet” I will answer your questions as succinctly as possible and “Nitty Gritty” will probably give you more info than you care to know. All references will follow below. Thanks again for writing and good luck to you as you plan to enlarge your family.

Sincerely,

James Pate, MD
https://jamespatemd.com/

SHORT & SWEET

1. What is the prospect of having a healthy baby after 3 years of high-dosage testosterone treatment?

The most important determinants in whether or not you will have a healthy baby are the age of the ovaries, genetic predispositions, drug exposures and healthy living.

DNA is packaged into chromosomes of which humans have 46, 23 from each parent. Each chromosome has thousands of genes which form the blueprint for making and sustaining life. Unlike sperm, eggs have a long shelf life and do not get replaced when they run out. Babies with ovaries already have all the eggs their body will ever have. As they age their eggs age too and the risk for chromosomal errors continues to climb. The most common chromosome error is Down Syndrome and is a result of having an extra chromosome #21. While the risk for having a child with Down Syndrome is only 1 in 1667 for a 20 year-old, this risk rises to 1 in 385 for a 35 year-old and 1 in 106 for a 40 year-old.

We all have 2 copies of our genes. Many of us carry mutant copies that are compensated by having paired normal genes that can do all the work necessary. Individuals with 2 mutant genes will have disease, such as Tay-Sachs, cystic fibrosis or sickle cell anemia. These disorders are called recessive because you must have 2 bad genes for disease to be present. Some genes are so essential that you need to have 2 working copies to prevent disease. These disorders are called dominant because you only need 1 bad gene to have the disease. Examples of this are Huntington Disease and neurofibromatosis. The best way to find out if you have an increased risk of having a child with a genetic disease is to see a genetic counselor who will help you to review your family tree and calculate your unique risk.

Drugs including alcohol, nicotine, street drugs and pharmaceutical drugs can all impact the health of a developing baby. As much of the fetal organ formation occurs within the first 3 months of pregnancy, it is very important to stop smoking, drinking and using recreational drugs prior to becoming pregnant. You should also start taking a prenatal vitamin with extra folate (aka folic acid) and review your medications with your doctor.

Both testosterone and estrogen are present in all humans in varying amounts. They are very similar structurally and can be readily converted from one to the other by a single enzyme, aromatase. Depending on which type of testosterone you are using, it can take as long as 6 weeks for your body to get rid of it.  The major risk to a pregnancy with elevated levels of androgens like testosterone is the masculinization of a baby’s female external genitalia and brain with potential social, sexual and gender identity consequences. The effect on males appears to be blunted as male fetuses are able to compensate and maintain their total testosterone exposure within normal limits. In conclusion, testosterone should be discontinued at least 6 weeks prior to pregnancy in order to prevent its negative effects on a potentially female fetus.

2. Is there an increased risk of having an autistic child as a result of prior testosterone use?

The cause of autism remains unknown and there is no evidence to suggest that prior testosterone use increases your risk for having a child with autism. However, there have been some interesting findings that may implicate continuous exposure of elevated testosterone levels as a factor in its development.

First of all, let’s review some facts about autism. Autism is a clinical diagnosis given to a child after evaluation by a physician if s/he meets criteria however there is no blood or genetic test to confirm or refute a diagnosis. The definition of autism has changed over time and is now felt to be a part of spectrum. Current thinking is to place the typical female brain on one end of the spectrum, the typical male brain in the middle, Asperger syndrome next and autism on the other end. Thus autism can be thought of as an “extreme male brain” disorder. Evidence to support this includes the fact that autism effects 4 boys to every girl and Asperger syndrome is 8 to 1. Additionally women with congenital adrenal hyperplasia, who were exposed to elevated prenatal levels of androgens, have increased autistic traits. However, high levels of prenatal testosterone alone does NOT invariably result in autism.

3. What are the effects of testosterone on the ova (egg cells in the ovaries)? Can it cause mutations or other negative problems?

Testosterone is not known to cause mutations in egg cells. High levels of circulating androgens have been associated with polycystic ovarian syndrome (PCOS), infertility and cancers of the breast, ovary and uterus.

NITTY GRITTY

Autism spectrum disorders (ASD)

• Prevalence is 1 in 100 to 200 people.
• The typical female has a strong desire to empathize (to identify and respond appropriately to another person’s emotions and thoughts).
• The typical male has a strong desire to systemize (to analyze and construct rule-based systems).
• Individuals with ASD have a stronger desire to systemize than to empathize.

• Autism

• Impaired communication.
• Impaired reciprocal social interaction and formation of social relationships.
• Repetitive stereotyped patterns of behaviors and unusually narrow interests.
• Diagnosis is difficult to make before 18 months of age and is usually made after age 3.
• Sex ratio of 4:1 (male to female).
• Worldwide prevalence is 4 to 58.7 per 10,000.
• Between 6-10% of children with autism have a medical condition that may have led to autism. Medical conditions associated with autism are epilepsy, fragile X syndrome, tuberous sclerosis, cerebral palsy, phenylketonuria, neurofibromatosis, Down syndrome, congenital rubella and hearing and visual impairments.
• Compared to the general population, women with autism have higher rates of PCOS, male-pattern body hair growth, bisexuality or asexuality, delayed onset of menses, irregular and painful menses, severe acne, tomboyism, gender identity disorder, transsexualism and family history of cancers of the breast, ovary, uterus and prostate.

• Asperger syndrome

• Introduced as a diagnosis in 1992.
• Has normal IQ and does not have delayed language development.
• Sex ratio of 9:1 (male to female).

Prenatal testosterone

• Gestational week 6: the Sry gene on the Y chromosome initiates testicular differentiation of the fetal gonad.
• Gestational week 8: Leydig cells of the testis are capable of testosterone synthesis.
• Testosterone surges occur between weeks 8-24 of gestation (males 249 ng/dL and females 29 ng/dL) and between 0-6 months after birth (males 200 ng/dL) suggesting that these are the critical periods of hormonal influence. Testosterone surges again for males during puberty with levels 200-300 ng/dL.

• In the brain

• Affects the anatomy of the brain including the hypothalamus, limbic system and neocortex.
• Permanently inhibits the growth of certain areas of the left hemisphere and facilitates the growth of the same areas in the right hemisphere in the developing fetus.
• The human bed nucleus of the stria terminalis (BSTc) is sexually dimorphic in size and neuron number (larger in women than men). MTF individuals have BSTc comparable to cis-gendered females while FTMs compare with cis-gendered males.

• 2D:4D finger ratio

• Defined as the length of the 2nd digit (the pointer finger) divided by the length of the 4th digit (the ring finger). Measurements can be made from photocopies of the palm measuring from the proximal crease of the base of the finger to the fingertip.
• It was recognized as sexually dimorphic (lower in men than in women) as early as the year 1888 and is purported to be a maker for prenatal androgen exposure.
• Development of the bones of the hand are governed by the Hox/Homeobox genes which respond to androgens like testosterone. This process begins as early as the 9th week of gestation and becomes more marked with time. Relative finger growth may not be complete until adolescence.
• Increased androgen exposure results in elongation of the 4th digit relative to the 2nd digit and thus a lower 2D:4D ratio.
• Children with Asperger syndrome and autism have lower 2D:4D ratios than average, so thus families with lower 2D:4D ratios may have an increased risk for children with autism. However, high levels of prenatal testosterone does NOT invariably result in autism.

• Polycystic ovarian syndrome (PCOS)

• Associated with irregular or absent menstrual cycles, male-pattern body hair growth and hair loss, insulin resistance, diabetes and hypertension.
• Affects 5-10% of women and is the most common endocrine disorder among women of reproductive age.
• Animal studies have shown that prenatal exposure of excess androgens results in PCOS, insulin resistance (pre-diabetes) and hypertension.
• Testosterone levels in umbilical vein blood of female infants born to mothers with PCOS are raised to male levels. Thus PCOS pregnancies have a hyperandrogenic in-utero environment.
• FTM individuals have rates of PCOS twice as high as the general population.
• Women with autism have higher rates of PCOS than the average population.

• Congenital adrenal hyperplasia (CAH)

• A genetic disorder that causes excess adrenal androgen production and results in varying degrees of virilization of external genitalia.
• Incidence is 1 in 14,500 live births.

• In general, girls exposed to high levels of prenatal androgens show

• Male-typical childhood play including preference for boys’ toys.
• Traits of autism including low measures of empathy and need for intimacy.
• Male-typical interests as adolescents.
• Little interest in infants, marriage, motherhood, “feminine” appearance.
• Masculinization of performance in spatial orientation, visualization, targeting, personality and cognitive abilities.
• 1/3 are lesbian, bisexual or queer.
• 3-5% indicate a desire to live as males.

• In general, CAH males

• Resemble other males with respect to play patterns and interests.
• Have normal prenatal androgen levels by inhibition of androgen production from the testes.

• Complete androgen insensitivity syndrome (CAIS)

• X-linked disorder (only affects genetic males).
• Lack functional androgen receptors.
• Genetic males are phenotypically female.
• Share the same sex-typed behaviors, gender identity and sexual orientation as genetic women.
• Prevalence is 1 in 20,000 to 1 in 60,000 live genetic male births.

• Genetic males with congenital ambiguous genitalia

• May be surgically assigned to female sex at birth.
• Have more male-typical play patterns and interests than control girls.
• Girls with prenatal exposure to synthetic sex hormones
• More likely to exhibit male-typical childhood play, behavior and interests.
• More likely to report use of physical aggression in conflict situations.

Discrimination against LGBTQI parenting

• There is no evidence to suggest that LGBTQI individuals are inherently incompetent to parent nor is there evidence of harm to offspring.
• In 2006 the American Society for Reproductive Medicine (ASRM) issued an ethics advisory that urged its members to not discriminate against patients by sexual orientation.
• In 2008 the California Supreme Court found that a fertility clinic had violated the state’s anti-discrimination law by refusing to inseminate a lesbian patient.
• The American Medical Association (AMA) rejects health insurance discrimination based on gender identity and recommends that insurers cover the treatment of Gender Identity Disorder (GID).

What to expect from your providers

• Proper noun and pronoun usage (ie “dad” not “mom”, “what are your plans for feeding the baby?” not “will you breastfeed?”).
• A review of privacy issues and/or creation of a formal policies when warranted
• No information provided over the phone.
• Written medical records kept in the patient’s room.
• Aliases for patient and baby if requested.
• The public relations dept should be the media’s only contact.
• Security officer to prevent unauthorized entry or to provide escort services.
• Additional staffing if needed.
• Transfer family to another unit if desired.
• Lactation support for either parent if desired.

Possible future reproductive technologies for LGBTQI individuals

• Male pregnancy could theoretically occur if the embryo implants on the intestine as this has indeed occurred in a few women.
• Researchers have transplanted vagina-uterus-ovary units in rats however there has not been a successful similar transplant in humans.

REFERENCES

• Adams ED. If transmen can have babies, how will perinatal nursing adapt?. MCN, American Journal of Maternal Child Nursing. 35(1):26-32, 2010 Jan-Feb.
• Auyeung B. Baron-Cohen S. Ashwin E. Knickmeyer R. Taylor K. Hackett G. Fetal testosterone and autistic traits. British Journal of Psychology. 100(Pt 1):1-22, 2009 Feb.
• Auyeung B. Baron-Cohen S. Ashwin E. Knickmeyer R. Taylor K. Hackett G. Hines M. Fetal testosterone predicts sexually differentiated childhood behavior in girls and in boys. Psychological Science. 20(2):144-8, 2009 Feb.
• Baron-Cohen S. Auyeung B. Ashwin E. Knickmeyer R. Fetal testosterone and autistic traits: a response to three fascinating commentaries. British Journal of Psychology. 100(Pt 1):39-47, 2009 Feb.
• Barry JA. Kay AR. Navaratnarajah R. Iqbal S. Bamfo JE. David AL. Hines M. Hardiman PJ. Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. Journal of Obstetrics & Gynaecology. 30(5):444-6, 2010.
• Bloom MS. Houston AS. Mills JL. Molloy CA. Hediger ML. Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders. Physiology & Behavior. 100(3):221-4, 2010 Jun 1.
• Fombonne E. Epidemiology of autistic disorder and other pervasive developmental disorders. Journal of Clinical Psychiatry. 66 Suppl 10:3-8, 2005.
• Ingudomnukul E. Baron-Cohen S. Wheelwright S. Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Hormones & Behavior. 51(5):597-604, 2007 May.
• Knickmeyer R. Baron-Cohen S. Fane BA. Wheelwright S. Mathews GA. Conway GS. Brook CG. Hines M. Androgens and autistic traits: A study of individuals with congenital adrenal hyperplasia. Hormones & Behavior. 50(1):148-53, 2006 Jun.
• Knickmeyer RC. Baron-Cohen S. Fetal testosterone and sex differences. Early Human Development. 82(12):755-60, 2006 Dec.
• Knickmeyer RC. Baron-Cohen S. Fetal testosterone and sex differences in typical social development and in autism. Journal of Child Neurology. 21(10):825-45, 2006 Oct.
• Manning JT. Baron-Cohen S. Wheelwright S. Sanders G. The 2nd to 4th digit ratio and autism. Developmental Medicine & Child Neurology. 43(3):160-4, 2001 Mar.
• Manson JE. Prenatal exposure to sex steroid hormones and behavioral/cognitive outcomes. Metabolism: Clinical & Experimental. 57 Suppl 2:S16-21, 2008 Oct.
• Mouridsen SE. Rich B. Isager T. Selected testosterone-related diseases in women who have given birth to a child with infantile autism. Psychiatry & Clinical Neurosciences. 63(4):586-90, 2009 Aug.
• Murphy TF. The ethics of helping transgender men and women have children. Perspectives in Biology & Medicine. 53(1):46-60, 2009.
• Noipayak P. The ratio of 2nd and 4th digit length in autistic children. Journal of the Medical Association of Thailand. 92(8):1040-5, 2009 Aug.
• Ronald A. Happé F. Price TS. Baron-Cohen S. Plomin R. Phenotypic and genetic overlap between autistic traits at the extremes of the general population. Journal of the American Academy of Child & Adolescent Psychiatry. 45(10):1206-14, 2006 Oct.
• Rutter M. Caspi A. Moffitt TE. Using sex differences in psychopathology to study causal mechanisms: unifying issues and research strategies. Journal of Child Psychology & Psychiatry & Allied Disciplines. 44(8):1092-115, 2003 Nov.
• Vujovic S. Popovic S. Sbutega-Milosevic G. Djordjevic M. Gooren L. Transsexualism in Serbia: a twenty-year follow-up study. Journal of Sexual Medicine. 6(4):1018-23, 2009 Apr.