hypogonadism Archives - Hormones Matter

Hormone Treatment During Pregnancy and Gender Variance in Later Life

Published on November 3, 2021

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For as long as I can remember, I’ve always had an unusual partially feminine gender identity, but until recently I never consciously acknowledged it. Then, a couple of years ago I realised that, although at a conscious level I identify as male, my body language, my pattern of arousal and orgasm, and my instinctive social behaviour are all very much more like what you’d typically see in a woman rather than a man. In addition, I appear to be suffering from secondary hypogonadism (i.e. my brain regions that control hormones aren’t working correctly), and I have a “eunuchoid” body structure, which indicates that my testosterone production has been below normal all my life.

Is Being Transgendered Just One of Those Things?

Although it never became my career, as a student I excelled at both chemistry and biology, and I’ve retained an amateur interest in the sciences ever since. Most people seem to assume that being transgendered is “just one of those things”, but I resolved to use that background in science to try and figure out whether there was an actual physical explanation for it. Accordingly, I tried to discover as much as I could about sexual development in the unborn child, and the kinds of things that can go wrong with that process.

Sexual Blueprints

Our sex-determining chromosome, the Y chromosome, is far smaller than any of our other chromosome and only has a few dozen functional genes on it. Basically all the Y chromosome does is to tell your undifferentiated gonads to turn into testicles (without it they’ll turn into ovaries instead). All of the genetic blueprints for actually building a male or female body are located elsewhere in your genome, so everyone has the full set of instructions for both sexes.

By default the “female” instructions are what get followed during fetal development, but if there’s testosterone present, the “male” instructions will be followed instead. Ordinarily this system works quite well, and you’ll develop as one sex throughout the pregnancy (which one depending on whether you have testicles churning out testosterone or not).

An Endocrine Disruptor

What appears to have happened in my case is that the pregnancy was no different from that of any other male baby, except that partway through the second trimester, something catastrophic happened that severely disrupted my endocrine system, so that for a few weeks I wasn’t producing any testosterone. Following that, my endocrine system recovered and everything went back to normal for the remainder of the pregnancy. The result is that I was built using the instructions for male development for most of the pregnancy, but during the time I wasn’t producing any testosterone, the instructions for female development were followed instead. That seems to have happened after all my physical development had completed, but very early in the process of wiring up my brain’s permanent structure (all the things that are affected seem to be associated with evolutionarily ancient parts of the brain, which points to the period of female development having happened early on in the process of wiring up my brain).

Based on when genital development takes place and when the process of building the permanent structure of the brain begins, I was able to work out that whatever it was must have happened somewhere around 16 or 17 weeks after conception, at or very soon after the time my mother would have first felt me moving inside her. Knowing what she was like when I was younger, my immediate thought was that she must have had a depressive episode, decided that she couldn’t cope with another child so soon after the first, and taken an overdose of something in an attempt to bring on a miscarriage.

A DIY Abortion That Didn’t Take

A bit of snooping on maternity forums soon revealed that the first thing most unhappily pregnant women contemplating a DIY abortion seem to think of is an overdose of contraceptive pills. I was able to subsequently confirm that my parents were using birth control pills for contraception at the time – the high dosage first generation ones. There was also something otherwise completely inexplicable that happened later in my childhood, which makes me think she must have been hiding a guilty secret along those lines.

My mother passed away in 2010, and in a way I’m glad that happened before I discovered any of this, because I would have been angry with her and she didn’t deserve that. She did her best to be a good mother to me and to all her other children, and I don’t hold her responsible in any way for what happened. I can’t blame my father either. He lost 3 brothers during his childhood and then his first wife died on their honeymoon, so I can understand why he became so obsessed with the idea of having a large family.

Brain Sexual Identity and DES

One further thing that made me think an exposure to artificial female hormones is the cause of my conditions was reading in the book “Brain Sex” about a pattern of behaviour commonly shown by teenage boys whose mothers were given treatment with a drug called diethylstilbestrol or DES in an attempt to prevent miscarriage . The boys in the study were typically very shy, socially withdrawn, had low self esteem, were regarded as sissies, bullied, ostracised by their peers, with no ability to fight back when attacked and no interest in sport. The authors of the book described it as “feminized behaviour”, and my teenage years matched it so closely it could have come straight out of my school report!

The main hormonal component of the contraceptive pills my parents were using is norethisterone acetate, a progestin, whereas DES is an estrogen. What estrogens and progestins both have in common is that they are female hormone derivatives, and are basically completely incompatible with masculinity. Both types of hormone have the ability to disrupt testicular hormone production at quite modest doses, well below those commonly used for medical treatment for women.

DES was for many years used to chemically castrate men suffering from hormone-sensitive prostate cancer, while progestins are commonly used for chemical castration of sex offenders and transsexuals. If they also suppress testosterone in a male fetus, then any use of them during a pregnancy of a male child carries a risk of creating a baby who developed as the wrong sex for part of the pregnancy. This is what I think happened to me, and to the DES sons.

For nearly two years I’ve been trying to find out as much as I can about DES sons, reading their personal accounts of how they’ve been affected and chatting with them online. Among the ones I’ve had contact with or whose life stories I’ve read, there seems to be a very high incidence of both intersex-related genital abnormalities and gender dysphoria. As a group they seem to commonly experience many of the same problems I have (a genital abnormality, feminized behaviour as a teenager, low testosterone and problems with hormones, gender variance). The key difference is that on the whole they seem to be far more psychologically female than I am (which is exactly what you’d expect, considering that their exposure was for a much larger part of the pregnancy than mine). I think it’s quite likely that for most of them, their testosterone production was completely suppressed and they were developing as female throughout the time their mothers were on the drug!

DES and all other estrogens were withdrawn from use in pregnancy 30 years ago, however, treatments for prevention of miscarriage, based on progestins rather than estrogens, continue to be used to the present day. One of these involves a progestin called hydroxyprogesterone caproate, given as a weekly intramuscular injection of either 250mg or 500mg, starting 16 weeks into the pregnancy – just around the time I think my hormone exposure occurred. The difference is that this treatment continues to be administered for the remainder of the pregnancy. If this drug does suppress testosterone production in a male fetus, then it’s hard to imagine a treatment better suited to creating as baby with a male body but a female brain! I’m fairly sure that if you gave an adult man 250mg per week of this drug, his testosterone production would be seriously impaired. Why wouldn’t the same happen to a male fetus?

Females Affected Too

In this article, I’ve only been looking at the effects of artificial sex hormones on a male fetus, however it’s likely that, under the right circumstances, a female fetus could be affected too. This could happen if the external hormone mimics the action of testosterone (e.g.progestin induced virilization), or if it disrupts endogenous hormone production in a way that causes excessive androgens to be produced (hyperandrogenism).

Postscript: This article was published previously September 2013.

Hypogonadotropic Hypogonadism, a GnRH Pump, and Craniocervical Instability

by JLP

Published on June 21, 2021

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Early Hormone Issues

In my mid 20’s, as a married woman I wanted to become pregnant. I went off birth control pills and discovered, once off birth control, I did not have periods. It became clear I would have trouble conceiving. It was initially thought maybe I had PCOS since I was a bit overweight. Progesterone challenge yielded scant to no vaginal bleeding. I ultimately ended up at Mass General in Boston for a clinic trial using pulsatile GnRH for anovulatory infertility.

As a part of the trial, my LH levels were measured multiple times an hour for over 10 hours. The testing revealed that my LH was flat lined. I was a candidate for the GnRH pump. Once one became available, I flew back to Boston. An ultrasound of my uterus revealed a prepubescent sized uterus and the GnRH pump was inserted. Within a week, I was pregnant. I was told I had hypogonadotropic hypogonadism. Labs were also performed on my two sisters and my mom. It was determined that my condition was a result of a head injury that I received in a motor vehicle collision in 1995, at the age of 16.

I felt phenomenal when pregnant, what I feel like ‘normal people’ feel like all the time. I had a good amount of energy and mental clarity. The pregnancy was uneventful. Postpartum, I developed severe vaginal dryness and atrophy of the tissues. I had diffuse muscle and joint pain, numbness particularly in my hands and a lot of achiness. Within a few months, I was having difficulty climbing stairs. My legs would shake. I eventually found myself at a functional medicine doctor. All of my hormone levels were low. FSH, LH were always low. In addition, I had low progesterone, nonexistent estradiol and testosterone levels. IGF-1 was 11, the lowest he had ever seen. I started Semorelin 0.3 subcutaneous nightly, along with estrogen, testosterone and progesterone, and thyroid replacement. Over time, I began to feel more ‘normal’.

Craniocervical Problems

As a young person, I always recall having lower amounts of energy than others around me, required more sleep and poor exercise tolerance. Interestingly I have never been able to blow dry my hair or hold my arms above my head for any period of time due to fatiguing of my arms.

In December of 2019 through March 2020, I developed tightness of the right side of my body which developed into difficulties with balance, and right sided weakness, dysphonia, dysphagia with liquids, shortness of breath, and urinary incontinence. An area was found on my cervical spinal cord and it was felt to be the beginnings of MS. I was admitted for IV steroids without significant change. I strongly felt my symptoms were positionally worse when I slept prone with my neck extended. An initial neurologist, I saw felt I had cervical stenosis and when the neck extended I was pinching my cord due to lack of space in cervical canal. After progressive worsening for 2-3 months, I underwent C4-7 fusion for cervical myelopathy and my symptoms improved dramatically but began to return 6-8 weeks after surgery albeit not as severe. By the fall of 2020, I was experiencing worsening fatigability, shortness of breath and voice fatigue worse after being upright for a period of time I would have to lay down between seeing clients. If I wasn’t working for myself I would’ve had to stop working. Symptoms stabilized a bit once I returned to wearing a hard cervical collar nightly.

In January of 2021, I saw a specialist in craniocervical instability. He reviewed my flexion/extension MRI images and felt C3-4 was a problem, he called it a rotary disc herniation and a slight Chiari malformation. I returned to my surgeon, who on March 6, 2021 performed C3-4 fusion and revised C4-5 and C5-6 due to lack of subarachnoid space or residual stenosis. Post-surgery, I could finally lift my arms above my head, my balance was restored and my reflexes returned to normal. I felt like I finally had my life back. I followed a low inflammation diet because he had told my mom there was a lot of scar tissue. My right leg was not tight or heavy when I woke up in the morning. No numbness to my hands. The deformity I had developed in my right hand had resolved. Unfortunately, just over 8 weeks after surgery some of symptoms began to return. I am back to wearing a cervical collar every night, provided I do this, my balance is better. I still occasionally have muscle fasciculations in quads and glutes. Hyperreflexia and Hoffman’s sign had returned.

Heart Rhythm Irregularities, Hypermobility Disorder, and Vitamin Deficiencies

Incidentally found on pre op electrocardiogram was an interventricular cardiac conduction delay. I was cleared for my second cervical fusion by cardiology. This had developed between March 2020 and March 2021.

During my work up the doctor diagnosed me with hypermobility spectrum disorder and ordered a micronutrient test which was telling. Over the years, every vitamin I have been tested for has been low. So I have taken a multivitamin, B12 and vitamin D for years, but it doesn’t appear that supplementation has helped. Intrinsic factor was high normal at 17. The micronutrient tests showed abnormally low vitamin K1, K2, zinc, iron, and selenium as well as low serine and asparagine. While many of the vitamins tested within the reference ranges, most were at lower end and below average.

I have an identical twin sister and she has helped me along this journey. Given our family history she worries about her own health and our future. She found the Hormones Matter website and began investigating thiamine issues and I began investigating mitochondrial deficiencies.

I uploaded my Ancestry DNA data to Genetic Genie and found homozygous pattern for mitochondrial disease Allele GG

Gene: MT-ND4
Variant: m.11467A>G
rsID: rs2853493

Livewello results for mitochondrial dysfunction revealed three sets of homozygous SNPs.

Rs1142530. TT
Rs 11666067. AA
Rs 1051266. CC

Results of Mitoswab testing: citrate synthase 15.58 (128%); RC I 4.8 (71%); RC IV 0.585 (189%); RC II 0.218 (113%); RC II + III 0.041 (45%).

I have an appointment pending at Children’s Hospital of Philadelphia for October for their Mitochondrial Medicine Clinic.

Diet and Supplements

I am currently on Thorne multivitamin elite, allithiamine – 50mg two daily, one carnitine 500mg two times per day. Coq10 2 times a day, Thorne 3-k complete one per day.

My diet is good and always has been. I eat more fruits than vegetables; more lean meat than not, rarely if ever a soda. I have a sweet tooth and eat some carbs, but keep it under control. Alcohol max of 3-5 drinks per week.

Weight has always been an issue. I am currently 210lbs at 5’8”. My energy level is low and I feel the need to nap daily.

Family History

Maternal grandmother developed ALS at 72 and died the same year she was diagnosed.
Dad died at 52, insulin dependent diabetes mellitus, depression, headaches, enlarged heart.
Paternal uncle died at 53, non-insulin dependent diabetes mellitus. He had poor health his entire life.
Paternal aunt died at 60 after greater than 10 year battle with Parkinson’s disease.
Paternal aunt died at 70 after ten year battle with immobility and memory loss, Alzheimer’s with ataxia. She also had IDDM, as did all three of her children by the age 12.
Niece and nephew have a MODY 2 genetic defect, which is a form of maturity onset diabetes of the young causing elevated HbA1c.
My eldest sister age 44, has always suffered with severe headaches, severe insomnia (melatonin level 0), hip and back issues. Multiple back surgeries and hip replacement at 39. She started on good multivitamin and saw significant improvement in muscle pain.
Twin sister has easy fatigability, shortness of breath, headaches and jaw pain. Noticed improvement with Thorne’s multivitamin elite, Neurochondria, and magnesium.

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