Confusion on progesterone.

[xAmyX]

Okay, so there's something that doesn't seem to add up about progesterone treatment for transgender females. As you can see based off of what healthy natal females experience:

Normal test results

In general, normal serum progesterone test results fall in the following ranges:

    men, postmenopausal women, and women at the beginning of their menstrual cycle: 1 ng/mL or under
    women in the middle of their menstrual cycle: 5 to 20 ng/mL             <-----------
    pregnant women in their first trimester: 11.2 to 90 ng/mL
    pregnant women in their second trimester: 25.6 to 89.4 ng/mL
    pregnant women in their third trimester: 48.4 to 42.5 ng/mL

I put an arrow pointing towards the 2nd line to show what healthy biological female progesterone levels reach during the peak of their menstrual cycles. At my current dosage (which I won't say) that is the highest level (at least to my knowledge) trans women take, my results are 1.8 ng/mL.

Why the hell aren't endocrinologists not using bio-identical progesterone to closely mimic what women TRULY go through, so that we can get the full benefit of the hormone that I feel we all are missing out on. As we know, progesterone is needed for the development of the milk glands that fill the breasts in and prevent them from having a "cone" shape that estradiol treatment alone causes. Not only that, it's needed for nipple development as well.

Why do we take so little of it? Why isn't it standard to mimic natal females? Are we seen as different for some reason and should not go through what women were meant to go through?

The goal should be to reach a level of 5 through 20 ng/mL mid cycle just like any other woman, and there wouldn't be such an insane amount of trans women opting for breast augmentations. Something that is far more dangerous in my opinion, and isn't REAL. It just doesn't make sense.

I feel like 1.8 is an insult in comparison of 5-20. No wonder trans women rarely, if ever reach Tanner Stage 5.

I will certainly be bringing this up at my next appointment.

If he's uncomfortable increasing my oral dosage of progesterone to mimic those levels, I will have to ask humbly to switch me to injections then, if not that, then perhaps add trans-dermal application to compliment the oral intake, because I don't want to miss out on the full experience of being a woman in anyway I can control.

[SadieBlake]

Micronized progesterone is highly bioavailable so as far as I know there's no advantage to using an injected form and probably some disadvantage. Also oral is more effective take with food.

My P level at last test was 11ng/ml. It's a tricky thing to measure however because the half life is very short.

I'm Tanner 5 on 1.5 years of progesterone and I agree it seemed to help with a rounded shape but I can't go back and compare either.

Pm me if you want to know levels.

[xAmyX]

"The terminal half-life of progesterone in circulation is only approximately 5 minutes.[17] However, with OMP, peak concentrations of progesterone are seen about 2 to 3 hours after ingestion and the terminal half-life is extended at about 16 to 18 hours.[6] Significantly elevated serum levels of progesterone are maintained for about 12 hours and levels do not return to baseline until at least 24 hours have passed.[6] In any case, due to the relatively short terminal half-life/duration of action of OMP, it is often prescribed in divided doses of two or even three times daily.[6][119]"

That's probably what I'm going to have to do. Take it multiple times a day. I'll see what my doctor says about that. I just made an appointment. I've been taking it at bedtime, so that possibly explains the low level since the blood test was done 12 hours later. I still feel like I'll need more though to get anywhere near 11 ng/mL like you have obtained. That is actually right at the mark I want to be surprisingly.

[KayXo]

The bio-availability of micronized progesterone taken orally is quite poor, around 5% I believe but enhanced when taken with (fatty) food. Taken by injection, it needs to be done quite frequently, every 1-2 days to keep levels from significantly dropping so impractical. Transdermal creams do a poor job of transfer so that very low serum P levels are achieved. Suppositories are an option (Cyclogest).

I took a relatively high dose of oral micronized progesterone for several years with levels anywhere from 10-20 ng/dl 12 hours after last dose. My levels were certainly quite high at the peak. I took it with estradiol injected IM, also a high dose and despite very high levels of estradiol (1,000-4,000 pg/ml) and progesterone (at least 10 ng/dl, perhaps as much as 40-50 ng/dl), I had poor breast growth.

I stopped taking progesterone as I found it actually made me too lazy, unmotivated at times, have mood swings from feeling great to irritable/angry, made my skin quite dry at times, produced bloating, lower abdominal cramps and just made me look less pretty, IMO. My breasts would temporarily swell on them, for 8 hours at most then slowly go down. And also hurt. I find my areolas are actually darker now and larger on just E. I can't say if my nipples enlarged while I was on P.

[xAmyX]

I'm at tanner stage 4. 9 months oral estradiol, 9 months estradiol injections. 3 months of progesterone daily at months 6-9. 2 months cycled progesterone (14 days) at months 17 & 18 leading up to right now.

Can't say if the progesterone is the reason I'm getting such good growth, but I'm not complaining. I would love to reach Tanner Stage 5 though! Hopefully I can get there within the next 18 months which would put me at 3 years.

That was my hope since day 1. Tanner Stage 5 at 3 years. I know it's a lot to hope for, but I had my fingers crossed.

I will not get a breast augmentation no matter what.

One thing's for sure, every time I'm on a progesterone cycle, my breasts get very swelled up, sensitive to the touch, and my nipples feel like they're on fire, so it's doing something. From what I've seen, my size as it is right now is about average with a girl my weight. I weigh 127 pounds.

It just kind of freaked me out when I saw my level was only 1.8 ng/mL. The purpose of me cycling progesterone is to match a woman's cycle, which means the levels have to be right too, not just the days/timings. If I'm not mistaken, progesterone is processed through the liver, am I right? That might explain why I have such terrible levels with anything I take orally.

I had a laparoscopic cholecystectomy (gall bladder removal) done 4-5 years ago which means I have less bile to digest anything that's fat soluble. I could take it with a meal, but I doubt that would help. I'd need to order bile salts, or something of that origin. Grapefruit juice could work too. Freshly pressed, but let's be real... I'm not going to have access to 14 grapefruits every month to squeeze. Lmao! Well, I could, but seriously... I'm not that bent on getting the most out of each individual gelcap. I'd rather just up the dosage.

[SadieBlake]

I'm also not planning a BA, the only reason I'd want one is my breasts are very east-west which I think is typical for how trans women develop. I had a GF who used to complain about hers being like that because it made most bras quite uncomfortable. Now I have to agree but I don't think it's worth another procedure that might also affect sensitivity.

Your timeline isn't all that clear,. what's the cumulative time you've taken P? I read it as 5 months, 3 starting at months 6-9 and then the last two months.

I'm planning to start an experiment early next year cycling P putting the pills and  sugar placebo pills into a larger capsule that will keep me from knowing what I'm taking. My reason is that while I think P has had an effect on libido, I'd like to rule placebo effect either in or out.

Anyhow good luck with continued filling out at just shy of 2 years on hrt I'm hopeful to eventually fill out to a large B cup, right now I'm definitely B in most bras and the few A sized bras I have no longer fit well.

[josie76]

Oral (digestive) absorbtion of micronized progesterone runs around 10% up to 20% with foods. That is the amount that remains progesterone. The remaining 80-90% is absorbed as the +35 various metabolites all of which the body uses.

4- neuro-regulating hormones including allopregnanolone.
3- which lower the risk of thrombosis, directly affecting Ca2+ influx in blood platelets which opposes the Ca2+ egress caused by thrombin.
Remainder form multiple stages of hormones/steroid precursors involved in many bodily regulatory functions including blood pressure via vasodilation and controlling cholesterol types, triglycerides, and lipids.

Progesterone works with HGH and insulin like growth factor 1 and 2(I think if I remember) to allow for full lobular development in the breasts. It promotes a round full breast tissue growth.

It is common for a large flush of allopregnanolone after oral administration resulting in drowsiness and dizziness.

In the average male progesterone levels are below the 500pg/ml while in post menapausal women it runs from around 700pg to 1000pg (1ng). An average range in fertile women at ovulation is 3-7ng and luteal phase 7-20ng

In men the testes produce a small amount but it is primarily made in the HPA axes.

A particular issue with us trans women is that many of our androgen blocking meds also effect the enzyme actions needed to produce and modify progesterone into its many steroid metabolites.

For all women there is the conceptual name "estrogen dominance" where by the metabolites of progesterone are very low compared to the cellular effects of estrogens on tissue functions. No it's not a "problem" for all, but it's enough of a concern to consider it especially for us on estrogen therapy.

[KayXo]

It just kind of freaked me out when I saw my level was only 1.8 ng/mL.

Levels fluctuate, especially on oral progesterone. Blood drawn 1-4 hours after last dose could have shown much higher levels. This is why blood tests, in this particular context, aren't perfectly reliable.

The purpose of me cycling progesterone is to match a woman's cycle, which means the levels have to be right too, not just the days/timings.

A ciswoman's progesterone levels rise in the second part of the menstrual cycle to prepare for pregnancy and traditionally, women usually became pregnant so that today, going through a cycle of ups and downs, again and again, isn't natural. It's believed that perhaps this is the reason breast cancer has risen in women, too many cycles.

The right level for you would be impossible to gauge in advance. A ciswoman's sensitivity to progesterone might differ markedly from yours because of her hormonal environment in-utero, genetics (even variation exists among ciswomen), other hormones present (estrogen increases sensitivity to progesterone so if your E is higher, you might need less P) and during puberty, a girl's body might be more sensitive (i.e. due to growth hormones, telomere length, etc.), etc. This is why, in certain instances, I believe mimicking ciswomen is perhaps not the right approach. Just my 2 cents. P.S. I'm not a doctor.

If I'm not mistaken, progesterone is processed through the liver, am I right? That might explain why I have such terrible levels with anything I take orally.

Some is lost and metabolized in the digestive tract and also liver.

I had a laparoscopic cholecystectomy (gall bladder removal) done 4-5 years ago which means I have less bile to digest anything that's fat soluble. I could take it with a meal, but I doubt that would help. I'd need to order bile salts, or something of that origin.

I also had my gallbladder removed and despite this, I digest fats quite well and eat high fat, the body adapts. I took progesterone with my meal, every time and it made a significant difference! Taking bile salts gave me stomach cramps and was a terrible idea, in my case.

Grapefruit juice could work too. Freshly pressed, but let's be real... I'm not going to have access to 14 grapefruits every month to squeeze. Lmao! Well, I could, but seriously... I'm not that bent on getting the most out of each individual gelcap.

I ate grapefruit every day but I don't think it made such a difference...or perhaps it did, who knows?!

while I think P has had an effect on libido, I'd like to rule placebo effect either in or out.

I am 100% certain P had an effect on my libido and I believe it did because it relaxed me as taking alcohol has the same effect.

For all women there is the conceptual name "estrogen dominance" where by the metabolites of progesterone are very low compared to the cellular effects of estrogens on tissue functions. No it's not a "problem" for all, but it's enough of a concern to consider it especially for us on estrogen therapy.

As far as the studies go, it seems the only risk might be uterine/endometrial cancer. We don't have a uterus.

[xAmyX]

One of the main issues with cancer is that it's mostly caused by ionizing radiation. Since technology has been developed, our exposure to this type of radiation has increased dramatically. From X-Rays, to CT scans, and the worst of them all, that's right Mammograms. CT Scans use significantly more radiation than X-Rays, and Mammograms use significantly more radiation than CT Scans, and since many natal females get Mammograms regularly, they're essentially cooking the cells within their breasts immensely. Causing mutations, and damage to the genetic structure of the RNA.

Cancer is often the result.

Good thing trans woman do not subject our breasts to this torture anywhere near as often.

There are other factors that can speed up the growth of cancer, but it has to come from somewhere, and ionizing radiation is the biggest culprit.

[KayXo]

One of the main issues with cancer is that it's mostly caused by ionizing radiation. Since technology has been developed, our exposure to this type of radiation has increased dramatically. From X-Rays, to CT scans, and the worst of them all, that's right Mammograms. CT Scans use significantly more radiation than X-Rays, and Mammograms use significantly more radiation than CT Scans, and since many natal females get Mammograms regularly, they're essentially cooking the cells within their breasts immensely. Causing mutations, and damage to the genetic structure of the RNA.

Cancer is often the result.

Good thing trans woman do not subject our breasts to this torture anywhere near as often.

There are other factors that can speed up the growth of cancer, but it has to come from somewhere, and ionizing radiation is the biggest culprit.

I tend to agree with this and this is why I have no intention to ever get a mammogram, especially considering studies so far have concluded the risk in breast cancer does not increase in transwomen due to HRT.

[xAmyX]

It's not entirely useless. For example, the cancer can come from another source, and the Mammogram could then pinpoint that and allow the person to react accordingly at an earlier timeline in it's progression. That could certainly be a life saving situation. The main concern though is if you do not have cancer, you're increasing your chance of getting it, so it's a double edged sword. Should you, or shouldn't you? I would start with breast exams. Most doctors are qualified to feel around and check for any unusual changes.

Many of the hormones women take are synthetic. They're not bio-identical. Not only is that not healthy, it can certainly cause unusual growth spurts. The body naturally reverses cancer at it's benign stage successfully, but if you throw high & unusual levels of growth at it, your natural defenses may not be able to keep up.

[KayXo]

I would start with breast exams. Most doctors are qualified to feel around and check for any unusual changes.

Agree.

Many of the hormones women take are synthetic. They're not bio-identical.

At menopause (or after a total hysterectomy), most women now take bio-identicals. By the way, bio-identicals are also synthetic insofar as they are produced in the lab from plants while Premarin is natural because it's extracted directly from the urine of pregnant mares. Important precision, I think.

Not only is that not healthy, it can certainly cause unusual growth spurts. The body naturally reverses cancer at it's benign stage successfully, but if you throw high & unusual levels of growth at it, your natural defenses may not be able to keep up.

Premarin alone in a large randomized controlled trial (WHI) was found not to increase breast cancer risk and actually reduce the risk, over time, significantly. Other studies found birth control pills use did not increase risk, one study even found with higher dose pills, risk was lower and finally some studies even found no change with progestins such as Provera so whether bio-identical vs not makes a difference in the risk of cancer is debatable especially considering transwomen were prescribed non bio-identicals (sometimes, at very high doses) for several decades with very few cancers reported in the literature.

High doses of estrogens, bio-identical or not, have been used since the 1960's in animals and humans to treat advanced breast cancer with just as much effectiveness as anti-estrogens. Also,  it's been found that the more pregnancies (when estrogen and progesterone are VERY high) a woman has, the lower her risk of cancer.

Food for thought...

[xAmyX]

In recent years, a large number of studies have focused on breast cancer risk in women under age 45. Meirik and colleagues (1986) published the first report suggesting a dose-response relationship with duration of oral contraceptive use among young women: for use of 8 to 11 years, an RR of 1.4 was found; for 12 or more years of use, a 2.2-fold excess risk of breast cancer was found. Paul and colleagues (1986) reported an RR of 4.6 for use of 10 or more years among women aged 25–34. McPherson and coworkers (1987) found an increased RR of 1.8 for use exceeding 11 years among a group of British women through age 45. The fact that U.K. prescription patterns were about five years ahead of those in the United States has been offered as a possible explanation for the earlier emergence of positive studies from the United Kingdom.

A hospital-based case-control study conducted in the northeastern United States (Miller et al., 1989) among women under age 45 ob served a twofold excess risk for oral contraceptive use of five to nine years' duration and a fourfold excess risk for use of 10 or more years. Questions have been raised about Miller's findings because of concern about the appropriateness of the hospitalized control group and because there appears to be a lower proportion of exposed controls than would be expected from national data. A well-conducted study in the United Kingdom (U.K. National Case-Control Study Group, 1989) among women under age 36 recently reported a significant dose-response pattern for duration of use. Oral contraceptive use of 49 to 96 months was associated with a 1.4-fold excess risk, and use exceeding 96 months was associated with a 1.7-fold excess breast cancer risk. This case-control study was one of the few that was able to validate the self-reported data on oral contraceptive use so as to rule out the often-raised criticism of recall bias.

Conflicting observations have been recorded among the three large prospective cohort studies. The largest, the Nurses Health study in the United States (Romieu et al., 1989), found no increase in risk for any duration of use (or for any other aspect of oral contraceptive use except current use). Current use of oral contraceptives was associated with an overall adjusted RR of 1.5. This excess risk was confined to women between ages 40 and 50. Tumors in current users were reported to be larger and to have more lymph node involvement at the time of diagnosis than were tumors in women not currently using oral contraceptives. The Oxford cohort in the United Kingdom has seen no evidence of increased risk related to oral contraceptive use (Vessey et al., 1989). However, the Royal College of General Practitioners cohort in the United Kingdom reported excess breast cancer risk for longer durations of oral contraceptive use, although there was no consistent dose-response pattern (Kay and Hannaford, 1988). In this cohort, there were inconsistent, mildly elevated risks for duration of use among women of all ages. In two subgroups, women ages 30 to 34 and women who were parity 1, much higher risks were seen—as high as a 10-fold excess risk for use of 10 or more years. Both of the cohorts formed in the United Kingdom began recruitment in 1968 and excluded women not involved in a married or living as married relationship (Kay and Hannaford, 1988; Vessey et al., 1989). The Nurses' Health study recruited women aged 30–55 in 1976 (Romieu et al., 1989). All three of these cohorts may have been initiated too early to include many women born recently enough to have had the opportunity to use oral contraceptives at a young age or for a long duration.

https://www.ncbi.nlm.nih.gov/books/NBK234348/

[xAmyX]

Norethindrone was the first progestin, a synthetic version of a natural steroid hormone, progesterone. A few birth control pills contain only a progestin, while the rest combine a progestin and an estrogen analogue. In the more than 60 years since Djerassi's landmark synthesis, drug makers have experimented with different formulations of oral contraceptives, including introducing new types of progestins and varying levels of estrogen. Their goal has been to maintain the Pill's effectiveness, while reducing undesirable side effects.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827491/