Tuesday, 24 October 2006

Yet Another Data Point

Another blood test, the last before my Op.

Oestrodiol level a new high, 301 pMol/L. Of course a normal Human being would have at least 600, but I'll take whatever I can get. Still the highest on record.

If the hypothesis about my condition is correct, we could reasonably expect levels to slowly increase as the receptors in the cells get "turned over:, and saturated with post-pubescent levels of hormones.

The progression since starting 8mg of Progynova, tests every 3 months, is 179, 241, 301. Vs a pre-HRT level of about 195.

Still not proven, but the hypothesis has made its first prediction, and come up trumps.

Meanwhile I'm recovering from jaw surgery on Monday, the wisdom tooth had J-curve roots. The extraction didn't hurt despite me having only local anaesthetic, though the bone saw wasn't a pleasant experience. Today, I've just come back from my usual day-trip every 3 months to see Professor Steinbeck, my endocrinologist. All the blood tests - apart from the weird hormonal results - are now slap-bang in the middle of the normal range, so I'm cleared for surgery by him. Next stop, my GP to get BP and cardiac functions checked, and I'll be set to go.

The last bit of medical preparation before the op.

5 comments:

Lloyd Flack said...

Zoe,

Just what is the hypothesis for the cause of the sex reversal. You've mentioned the interaction of two mutations and the Liptor. Now presumably one of the mutations is the one that someone suggested here. What was the other and how did they interact?

Zoe Brain said...

As far as I can understand it: the first is an as-yet unamed syndrome first identified in a paper I quoted. Basically, it causes high levels of LDL cholesterol. It appears that the cell membranes in the glands are impermeable to serum LDL cholesterol. As LDL cholesterol is the basic building block for all manner of hormones, this means that the glandular cells have to rely on "local production". Hormones are produced, but at lower levels than normal.

In a male with Leydig cells affected by this, both oestrogen and testosterone production would be affected, as would DHT. Puberty would be partial, unless the oestrogen was "soaked up" by fat cells. The patient would tend not to have male-pattern baldness, and signs of an incomplete puberty, such as short legs, un-masculinised skull, mild to moderate hypogonadism etc. Basically, similar symptoms to Kleinfelters syndrome, where the patient is genetically 47xxy rather than 46xy.

If a statin is administered to such a person, due to the high levels of LDL in the blood compared to HDL (the liver's producing it, but it's not being consumed at normal rates), then as the paper shows, sexual dysfunction due to complete cessation of testosterone and oestrogen production results. Statins preferentially affect glandular LDL production, so by the time total serum LDL levels drop to a safe level, the body has a very low level of sex hormones indeed. But there's no feminisation, as there's no oestrodiol either, the person is neutered, not feminised.

As the hormonal receptors in the body are not in a constantly near-saturated state, administration of extra testosterone or oestrogen will be "soaked up" and not appear in serum levels. At least until either the receptors are saturated, or turned-over, which I believe happens every 3 years. Thus if external hormones sufficient for a +600 pMol/L steady-state concentration were administered, the serum values would increase from a base level by about 50-60 pMol/L every 3 months.

My values at 3, 6, and 9 months were 179, 241, and 301. Only three data points, but otherwise medically inexplicable, any normal human would have at least 600.

That's one.

The second is a form of familial non-neoplasmic Cushing's syndrome, hypercortisolism. The adrenal glands are over-stimulated to produce cortisol, which means (amongst other things) that the patient bruises easily, and has a strong tendency to gain weight even when on a 1500 cal/day or less diet. In a male patient, puberty is more complete, as the naturally produced oestrodiol is sequestrated in additional fat. The adrenal glands in such a person would be slightly hypetrophied (enlarged).

If a statin is administered to such a patient, the cortisol production would drop dramatically, leading to very dramatic weight loss. This would cause a huge bolus of oestrogen to enter the bloodstream, but as the cellular receptors would normally be at near saturation, only minor feminisation would result, and the excess oestrogen would be excreted.

That's two.

Put the two together, and in a male patient not administered a statin, puberty would be more complete (but still with some signs of incompleteness), as the oestrodiol is absorbed, but again, they would bruise easily and be overweight regardless of diet or exercise, and have dangerously high LDL levels. Plus hypertrophied adrenal glands.

Now add a statin and you get a chain reaction.

First, testosterone, cortisol and oestrogen production ceases. There would be massive weight loss, and total loss of male sexual function, instant sterility. Then the huge bolus of oestrogen hits cellular receptors that are not nearly-saturated, and is absorbed at a rate only usually seen in precocious female puberty.

With such a catastrophic change, it is likely that feedback mechanisms would cause hormonal instability. A sinusoidal PMT-Menopause cycle, probably with a 4-week period. If the patient is lucky, the variation would be quickly damped. If unlucky, the system would go Chaotic or the variation be forced, leading to insanity from neurological changes and probably metabolic shutdown and death.

The optimal treatment in all such cases of metabolic and hormonal instability (however caused) is a large dose of anti-androgens and an escalating dose of oestrogens, as there is no anti-oestrogen available. Otherwise, for a male, a large dose and continuing dose of testosterone, and an oestrogen antagonist (too bad none exists). The aim is to CTRL-ALT-DEL the system and reset it into a known, safe state. A male would get a significant degree of feminisation, but with surgery and hormone therapy after things had settled down, might be able to recover, though it's likely fertility would be hopelessly compromised.

The Leydig cell anomaly could be reasonably expected to cause under-masculinisation during foetal development, so chances of Harry Benjamin's Syndrome (HBS) are increased, possibly to the 1 in 5 level found when DES is administered to the mother in the first trimester. Odds are further increased if the patient had a brother born immediately before, as there may be some anti-androgens in the mother's system from that.

For a genetically male patient with HBS, the "instant female puberty" from this would be something of a Godsend, and continued feminisation and transition would be the optimal therapy.

This hypothesis may or may not be correct: but it fits all the facts, I have all the symptoms, and many of the facts and figures are otherwise inexplicable.

It would be useful from a scientific viewpoint to delay SRS for 6 months, and see if the expected serum oestrodiol levels at 12 and 15 months would be circa 300 and circa 360 respectively.

If so, Science can go take a running jump. Given the total shutdown of testicular function, removal of them shouldn't affect the results, though it's another unshackled variable. As the testes are now semi-permanently retracted, there is a growing risk of testicular cancer due to thermal stress, so from an ethical viewpoint, continuation would be undesirable.

That's Zoe the Scientist speaking. Zoe the woman wants her sentence to be ended as soon as possible. It would be nice to look approximately normal after so very many years. Given the seven kinds of hormonal hell I endured in those first three months, I think I deserve it.

Jackie_TS said...

Hi, I'm very interested in all of this and would like some background if it available. I'm a 56 yro male that about 2 years ago started getting symptoms very similar to female puberty, but at a sligthly slower rate than normal. Increased emotionalism, periodic moodiness, breast development (currently B cup), and about 6 months ago period type symptoms. All without any hormones, creames, etc. on my part, the body just started doing this on its own. I've been diagnosed as GID and transexual as I alway felt I should have been female, and have cross dressed to feel complete and at peace all my life. For over 2 years I've been going out female 4-5 nights a week. Tests have revealed possible intersexed, but everyhting so far comes back ambiguious or inconclusive. Chromosome tests can back with 1 test showing male only chromosomes, and a second test showing both male and female chromosomes as present. Ultrasound found no conclusive uterus, but extra tissue, tubes, and an extra collection area, with a recommendation for MRI for a better identification of the extra stuff. But all that takes time and i just can't wait around forever, so last week I started hormones, but am still looking for answers as to why I just suddenly started all these female puberty like characteristics without any hormonal trigger that I'm aware of.
Jackie

Zoe Brain said...

Jackie, please contact me via e-mail.

mailto:aebrain@webone.com.au

But in the meantime, know that you're not alone. From the sounds of it, you're #8 that has been identified so far.

Please have a look at what happened to me in the first year, over at my post annus mirabilis.

I appear to hold the record for swiftness of change, most other cases have taken 2-3 years, and have a different etiology.

I suggest that you also contact Kathy Noble, via Changeling Aspects, as she is one of our little group too, though the cause of her impromptu feminisation was a hormonal imbalance.

I'd also recommend you get that MRI imaging done. You see, any vestigial tissue (assuming you have mixed gonadal digenesis) may be a cancer risk. You really need to find out as much data as you can about your condition, apart from the Transition aspects.

If you do have such tissue, you may be classified as Intersex, and thus with GIDNOS rather than GID under the DSM IV. Sorry about the alphabet-soup, but the psychs made me do it. This may affect your treatment regime, smoothing the way in some areas.

Please contact me privately on this. I can also very highly recommend a support site called Beginning Life. You don't have to do this alone, help from people who understand is available. Not just emotional support either, practical information about hormones and surgical therapy, if it comes to that. Who to see, what to do, how to change your name legally, facial hair clearance, the works.

Welcome, and just by you posting your comment, you've made years of blogging worthwhile. Thanks! Hugs too, Zoe

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