I'm wondering, besides PAIS, are there any other dsd's with hypogonadism and Normal levels of testosterone.  With female secondary sexual characteristics.

I have hypogonadism. My doctor has it labeled it as secondary hypogonadism. But I take testosterone to keep up my t levels.

by the way as soon as I'm able to do this, I'll get you the papers and scan them and show you what I'm talking about. if you need to see it. I see that you were talking about secondary female characteristics I think. My papers from my doctor just say "secondary hypogonadism". Honestly I don't know what it means. I just know what my gynecologists have told me about their exams on me, and what the doctors have written on the papers themselves. They haven't spoken much to me about this. All my doctors act like it's not a big deal. They just treat me as a TS individual. So I guess I'm okay with that.

Some Disorders of Sexual Development, or dsd's, have Primary Hypoginadism.

Besides, I now know I have some form of Partial Androgen Insensetiy Syndrome.

Quote from: Emily King on December 19, 2014, 10:59:54 PM
Some Disorders of Sexual Development, or dsd's, have Primary Hypoginadism.

Besides, I now know I have some form of Partial Androgen Insensetiy Syndrome.

Hi Emily,

I had to look up what dsd was. I'm not familiar with primary and secondary and what that all means. I'm not sure what my doctor meant by secondary hypogonadism for me, and since we've never discussed it I just try to make the best of things with what I have. I didn't even know what PAIS was, I had to look it up too, I knew it was a form of intersexualism, but I had forgot exactly what it was called.

are you dealing well with PAIS?

Thank you for talking to me. Maybe I can learn from you

Take care,
Alex

Prenatal exposure to synthetic hormones (estrogens and progestins) can produce DSDs and all kinds of weird endocrine problems later in life. Between 1940 and about 1980, these drugs were commonly given to pregnant women thought to be at risk of miscarriage or premature birth, in often insanely high doses. DES is the best known of these substances (and produced feminising effects on biological males), however ethinyl estradiol was quite widely used too, as well as a range of progestins. Although they're supposed to mimic a female hormone, the first generation of progestins were actually derivatives of testosterone and turned out to have quite strong androgenic effects on female fetuses. These drugs were used in millions of pregnancies, and going on what I've seen of the effects of DES, there must be a lot of people alive today who have physical and/or psychological intersex-related abnormalities as a result.

As far as the effects on male endocrine function are concerned, what seems to often happen with DES exposure is that you get below normal male T production (secondary hypogonadism), and above normal male E2. The high E2 in turn drives up SHBG levels, and the excess SHBG binds up most of the (already low) T, so free T (which is the important thing as far as biological effects are concerned) ends up well below normal. The result is that you end up with the symptoms of hypogonadism, which, when you're younger include developing a feminine body structure and possibly some female secondary sexual characteristics. As you get older, the hormone imbalance tends to get worse, so by the time you reach middle age you start developing health problems due to low testosterone. This includes psychological problems such as depression, loss of motivation, an inability to think clearly etc. That's what I think has happened in my case anyway, and looking at the blood work I've seen other hormone exposed people post, it's probably quite a common thing to happen to us. The thing is (apart from free T, which is difficult to measure and so doctors often don't look at it), nothing looks spectacularly out of range, so doctors tell the patient that their T levels are "normal", and give them a prescription for antidepressants and viagra rather than treating the low T.

Due to the fact that there are millions of biological males now approaching middle age who were exposed to DES or progestins, I think there must be a lot of that going on at the present point in time. Lab reference ranges are usually based on a random sample of patients having their blood tested, and these tend to disproportionately be sick and/or elderly people. So they're not necessarily an accurate reflection of what hormone levels should be in a healthy person.

If you look at this paper, in which testosterone in healthy males aged 20-40 was measured:
http://press.endocrine.org/doi/full/10.1210/jc.2010-3012

It says:
"In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively."

My reading of that is that "normal" (within 1 standard deviation of the mean) total T in healthy men is about 500 - 950 ng/dl, and free T 100 - 195 pg/ml. A lot of doctors are trying to tell patients with T levels well below that that their T is "normal".

If you have PAIS, your T is likely to be towards the upper end of the male range and your gonadotropins (LH and FSH) normal to high too. If you have primary hypogonadism (eg Klinefelters), T will be low while LH and FSH are high. With secondary hypogonadism, T, LH and FSH are all towards the bottom of the range. All of this only applies before you start taking hormones, once you start adding external hormones into the mix it skews the results.

Unfortunately I started ert illegally, so no blood work until nine months in.  When I was finely tested, my t level was at 145 on low dose Spiro and high dose estrogen.
My last test my t was at 65, and e at 180.

I have an unknown variant on my AR gene, so I'm not sure what is different, or what to except.

Emily, if you have PAIS, one effect of that is that you'll have a reduced sensitivity to testosterone, so (especially with your T at 65), spiro shouldn't be necessary. Has gene testing actually confirmed that you have PAIS, or is it just an explanation your doctor came up with because he couldn't find anything else? DES exposure can present in a very similar way to PAIS. If it was started early in the pregnancy it can produce very similar looking genital abnormalities to grade 3 PAIS, and other symptoms of incomplete male development (as well as making you trans!). The main difference with DES is that you're not actually insensitive to androgens, so as an adult, your body will be as effectively masculinised by testosterone as a normal male person's would be (probably that's not an experiment you would want to try though!). Also, DES exposure, if it occurred early enough to affect your genital development, is likely to have also caused retention of Mullerian duct tissue, which most commonly results in you having epididymal cysts of the testicles, but can result in partially developed female internal organs too.

If you have PAIS, then it's quite likely there will be other members on the mother's side of your extended family affected too, since it's passed through the maternal line (women are symptomless carriers, however 50 percent of their genetically male children are affected). PAIS is a relatively rare condition though, so, unless you have gene testing etc confirming it, if you were born in the DES era (i.e. prior to about 1980), I think it's a lot more likely to be DES.

I'm actually in a somewhat similar situation to you, because I started self-medicating with fertility drugs before having my first blood work done. However, my body responds in a typical male way to testosterone so I know I don't have PAIS, and my recent blood work and the fact that I'm getting good results from fertility meds are all consistent with secondary hypogonadism.

Although I have no way of knowing for sure what happened to me, my genitals are fully male, which shows that I had normal male development during the first trimester. A lot of my brain development must have occurred as male too, since, although parts of me are feminine, I don't identify as a woman, and I score as quite strongly male on most of the brain sex tests I've tried. Basically it looks like I developed as male for most of the pregnancy, apart from a period partway through where I developed as female, which has resulted in early stages of my brain's sexually dimorphic development taking place as female instead of male. No conventional cause of intersex can do that, the only thing I could find that could explain it is exposure to some kind of testosterone-disrupting chemical. There's also the fact that my life experiences are very similar to what DES sons seem to commonly go through (and late transitioning MTF trans folk in general), and I've developed a feminine body structure and other symptoms of hypogonadism, which is something that seems to very commonly happen with DES too.

I had both tests done.
I'm confirmed XY, but my gene test says I don't have any known mutations, but an unknown mutation.  My doctor says I'm PAIS.

It seems that I have a freak random accidence.  My doctor also told me to stay on Spiro, because it block the dht, or something like that.

PAIS here with the classic serum levels - high T, very high LH and FSH and a plethora of physical characteristics. Also confirmed DES exposure when mum was pregnant with me. I never had a chance.

Quote from: Wynternight on January 19, 2015, 03:15:46 AM
PAIS here with the classic serum levels - high T, very high LH and FSH and a plethora of physical characteristics. Also confirmed DES exposure when mum was pregnant with me. I never had a chance.

What did your gene test say?  Or if you didn't do the gene test, how did your doctor confirm PAIS?

Quote from: Rudy King on January 19, 2015, 03:12:52 PM
What did your gene test say?  Or if you didn't do the gene test, how did your doctor confirm PAIS?

Labs and physical presentation. I have karyotype testing ordered and waiting if I want it but she's firmly convinced it's PAIS without making me do a test that would be out of network for me here.

Since we could prove it "medically necessary", I was able to get Medicare to cover the two tests.

Quote from: Rudy King on January 19, 2015, 09:54:41 PM
Since we could prove it "medically necessary", I was able to get Medicare to cover the two tests.

I have insurance through the VA and don't qualify for Medicare. I may look into having it done elsewhere but as far as I know the big hospital here in Anchorage is out of network for me.

Quote from: Wynternight on January 19, 2015, 03:15:46 AM
PAIS here with the classic serum levels - high T, very high LH and FSH and a plethora of physical characteristics. Also confirmed DES exposure when mum was pregnant with me. I never had a chance.

PAIS is a comparatively rare condition though. If you're DES exposed, then the chances are that it's the sole source of your problems, especially since I've been told it can result in a very similar presentation to grade 3 PAIS.

Unfortunately, there aren't many studies of hormonal abnormalities in DES sons. However, I've obtained copies of 3 studies carried out in the 1970s, looking at DES sons from the Dieckmann cohort (made up of children from a study carried out in the 1950s, that showed that DES was completely ineffective at preventing miscarriages). These people were all exposed to the standard "Smith and Smith" treatment regimen, which is what most DES mothers worldwide were given. I talked about one of these 3 studies in this post a few days ago:
http://www.gendersupport.org/forums/index.php/topic,84224.msg1607617.html#msg1607617

All 3 studies show much the same thing, the main unusual finding (aside from high rates of genital abnormalities) being that the DES sons produced significantly less sperm (both the volume of ejaculate and the number of cells per ml) than the control group. In the paper I linked in that post, it says the production of sperm cells was effectively halved. One point I was trying to make in that post is that if only half as many sperm cells are being produced on average, then production of that other thing the testicles produce - testosterone - has probably been halved too. That would explain why I, and quite a lot of the people who've replied to that thread, and DES-exposed people I've chatted to on facebook etc, all tend to have eunuchoid proportions and other symptoms of below normal male T levels.

In that paper and the other two, they've compared hormone levels between the DES sons group and the control group. The DES sons have, on average, slightly lower total T and slightly higher LH and FSH than the control group, but the differences aren't very large. However, they've only measured total T, there are no measurement for free T, SHBG or estradiol (E2).

I think what happens to people like us is that our bodies try to produce a hormonal state intermediate between male and female, and that results in lowered T production and elevated E2 production (perhaps by ramping up production of the aromatase enzyme). One effect of elevated E2 is that it increases the amount of SHBG, and the excess SHBG binds up nearly all the availalable T, creating a large reservoir of inactive T and driving down free T to very low levels. The problems caused by high E2 and SHBG get talked about a lot in the hypogonadism forums I subscribe to, because it makes it look like you've got fairly decent T levels on the blood work, however nearly all of it is inactive, and the high E2 tends to further reduce the effectiveness of what little free T remains, so you continue experiencing symptoms of hypogonadism despite having what look like good T levels on paper. Free T, not total T, is the important thing when it comes to biological effects.

I've recently been talking to two DES sons, both of whom have gender dysphoria but aren't currently in a position to transition, both of whom have symptoms of hypogonadism and were refused treatment by their doctors because their T levels were "normal". One had a total T of about 500 ng/dl and the other 350ng/dl (which is actually well below normal), however the free T in both cases was very low - 60pg/ml and 71pg/ml, due to their SHBG being quite high. In neither case was their E2 measured, however one of them has quite pronounced gynecomastica, so I guess his E2 at least is well above normal male.

From a study aimed at determining what T levels should be in normal, healthy men:
http://press.endocrine.org/doi/full/10.1210/jc.2010-3012

"In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes."

I read this as saying that "normal" (within 1 standard deviation of the mean) total T in men ranges from 500 to 950 ng/dl, and free T 100 to 195 pg/ml. Both of the people I've been chatting to have free T levels that came in the bottom 2.5 percent of that study, the people with "slow walking speed, difficulty climbing stairs, frailty and diabetes". Yet they've both been refused treatment by their doctors.  I don't know what doctors are basing these decisions on, but it certainly isn't science or concerns about patient welfare.

What all this shows is that most doctors don't have the first clue when it comes to hormones. Also, that there are probably a lot of DES-exposed individuals out there who are being wrongly diagnosed with other complaints by their doctors, for problems that are actually caused by DES. Maybe you're one of them?

Ultimately it's academic: I'm transitioning and getting the hormone cocktail my body needs. My provider says PAIS but if it's solely DES there's really no way to know, I suppose.

I don't have my labs with me but I'll post my pre-HRT levels later.

Quote from: HughE on January 20, 2015, 03:21:35 PM
PAIS is a comparatively rare condition though. If you're DES exposed, then the chances are that it's the sole source of your problems, especially since I've been told it can result in a very similar presentation to grade 3 PAIS.

Unfortunately, there aren't many studies of hormonal abnormalities in DES sons. However, I've obtained copies of 3 studies carried out in the 1970s, looking at DES sons from the Dieckmann cohort (made up of children from a study carried out in the 1950s, that showed that DES was completely ineffective at preventing miscarriages). These people were all exposed to the standard "Smith and Smith" treatment regimen, which is what most DES mothers worldwide were given. I talked about one of these 3 studies in this post a few days ago:
http://www.gendersupport.org/forums/index.php/topic,84224.msg1607617.html#msg1607617

All 3 studies show much the same thing, the main unusual finding (aside from high rates of genital abnormalities) being that the DES sons produced significantly less sperm (both the volume of ejaculate and the number of cells per ml) than the control group. In the paper I linked in that post, it says the production of sperm cells was effectively halved. One point I was trying to make in that post is that if only half as many sperm cells are being produced on average, then production of that other thing the testicles produce - testosterone - has probably been halved too. That would explain why I, and quite a lot of the people who've replied to that thread, and DES-exposed people I've chatted to on facebook etc, all tend to have eunuchoid proportions and other symptoms of below normal male T levels.

In that paper and the other two, they've compared hormone levels between the DES sons group and the control group. The DES sons have, on average, slightly lower total T and slightly higher LH and FSH than the control group, but the differences aren't very large. However, they've only measured total T, there are no measurement for free T, SHBG or estradiol (E2).

I think what happens to people like us is that our bodies try to produce a hormonal state intermediate between male and female, and that results in lowered T production and elevated E2 production (perhaps by ramping up production of the aromatase enzyme). One effect of elevated E2 is that it increases the amount of SHBG, and the excess SHBG binds up nearly all the availalable T, creating a large reservoir of inactive T and driving down free T to very low levels. The problems caused by high E2 and SHBG get talked about a lot in the hypogonadism forums I subscribe to, because it makes it look like you've got fairly decent T levels on the blood work, however nearly all of it is inactive, and the high E2 tends to further reduce the effectiveness of what little free T remains, so you continue experiencing symptoms of hypogonadism despite having what look like good T levels on paper. Free T, not total T, is the important thing when it comes to biological effects.

I've recently been talking to two DES sons, both of whom have gender dysphoria but aren't currently in a position to transition, both of whom have symptoms of hypogonadism and were refused treatment by their doctors because their T levels were "normal". One had a total T of about 500 ng/dl and the other 350ng/dl (which is actually well below normal), however the free T in both cases was very low - 60pg/ml and 71pg/ml, due to their SHBG being quite high. In neither case was their E2 measured, however one of them has quite pronounced gynecomastica, so I guess his E2 at least is well above normal male.

From a study aimed at determining what T levels should be in normal, healthy men:
http://press.endocrine.org/doi/full/10.1210/jc.2010-3012

"In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes."

I read this as saying that "normal" (within 1 standard deviation of the mean) total T in men ranges from 500 to 950 ng/dl, and free T 100 to 195 pg/ml. Both of the people I've been chatting to have free T levels that came in the bottom 2.5 percent of that study, the people with "slow walking speed, difficulty climbing stairs, frailty and diabetes". Yet they've both been refused treatment by their doctors.  I don't know what doctors are basing these decisions on, but it certainly isn't science or concerns about patient welfare.

What all this shows is that most doctors don't have the first clue when it comes to hormones. Also, that there are probably a lot of DES-exposed individuals out there who are being wrongly diagnosed with other complaints by their doctors, for problems that are actually caused by DES. Maybe you're one of them?

Quote from: Wynternight on January 20, 2015, 05:41:01 PM
Ultimately it's academic: I'm transitioning and getting the hormone cocktail my body needs. My provider says PAIS but if it's solely DES there's really no way to know, I suppose.

I don't have my labs with me but I'll post my pre-HRT levels later.

I agree, from the sounds of it a lot of your prenatal development occurred as female rather than male anyway, and if you identify as a woman, then it makes perfect sense to bring your body and your hormones fully into line with your identity. I wasn't meaning to criticize your choice, more having a moan about how outrageous the whole situation is with DES and transsexuality. My thinking is that, if enough trans folk know of what happened with DES, and that there are probably other hormones still in use that are also causing transsexuality, then it'll become impossible for the pharma industry to keep it a secret any more.

Unfortunately I don't have any blood work from prior to taking hormones, but here's two sets of blood work I had done last year. In this first one,



I'd been taking my usual combination of fertility meds (clomid and HCG) and progesterone cream. Everything in that test looked OK, not just that part of the panel but everything else too.

Using a separate online calculator, my calculated value for free T is 128 pg/ml, which is just a little bit below the average for free T (141.8 pg/ml) in that study of healthy men I linked to earlier. I'd felt pretty good the day of that test, full of energy and with no aches or pains.

In this second test,


(15.2 nmol/L = 438 ng/dl)

I'd stopped taking fertility meds for 5 days. You can see how the total T has fallen by about a third, and the LH and FSH readings have basically collapsed. The FSH is flagged as being below the lower limit of the lab range (and probably the LH reading would have been too, except there would still have been some HCG in my system, which shows up as LH unless they do a special test to exclude it). That second test is basically what secondary hypogonadism looks like - LH and FSH are low, and so is total T.

Using the online calculator, my free T would have been 86 pg/ml, so it had fallen below the "normal" (100 - 195pg/ml) range for healthy men, but was still higher than what the 2 people I've been chatting to are having to put up with. I'd felt rough the day before the test and quite unwell on the morning the blood was drawn (I was actually supposed to wait a further 2 days before having it done, but by that stage had decided enough was enough, why make myself sick for a further 2 days).

Unfortunately, the doctor I saw following that second blood test (who is the senior doctor at that practice) turned out to be a total bastard. He refused to refer me on to an endocrinologist, or for a DEXA scan to assess my bone density, or for an MRI scan to see whether I have a brain injury that might explain my being hypogonadal. This is despite the fact that, apart from the blood work, I look kind of intersexed, and a physical examination would show that I have eunuchoid proportions and other symptoms of hypogonadism. I got a very strong impression that, if it had been up to him, I wouldn't have even had the tests I've had done, and I was quite lucky that I saw a junior doctor there on my first couple of visits who ordered them for me. So I'm not sure what was going on there, perhaps the practice has to bear some of the costs for those tests, or maybe he was just one of those doctors who turn eugenicist when dealing with trans and intersex folk. Either way, he's basically trying to condemn me to a slow and horrible death, and it hasn't done a lot to restore my faith in medicine. It makes me wonder how many other people like me are out there with endocrine systems damaged by drugs such as DES, whose health is now failing as a result, and are being lied to and denied treatment by their doctors.

Unfortunately for me, I go a "Planned Parenthood" type place.  So they only do basic blood work.
I finely had to go to an Endo, to get other stuff checked and about the PAIS stuff.  She basically told me, she's probably going to have to pass me off to a specialist.  Of course, I haven't heard back from her at all in nearly a month and a half.  I guess, I'm going to have to call to see if she needs more info.

I really want to find out more about my whole system, now that I know I'm Intersex.  I just wish doctors didn't suck.

hey so did anything come of this? I'm interested since this may apply to me too

And I know what you mean about doctors sucking when it comes to trans care. It seems like if they aren't trans themselves, there is A LOT of hunting we have to do to find someone that isn't going to be hands off on care and genuinely give a damn about our health. It's taken me a whole 15 years since I first learned of the word intersex to find a dr that was as interested in finding out as I've been ever since it was first suggested to me by a dr i couldn't go to...