Is there a useful window for progesterone?

[kelly_aus]

What you provided was anecdotal evidence, nothing more. I have experience and education on the subject, and based on what I've read, well.. I could point out a number of things, but you clearly have your opinion and it's clear nothing I say will dissuade you, that's fine.

It amuses me that people get so worked up about the use of progesterone.

[KayXo]

Known side effects of progesterone include:  dizziness, drowsiness, sleepiness, and fatigue, and can, via oral administration, also cause depression and anxiety.

About that last effect, I think perhaps the drop in progesterone levels can trigger depression and anxiety because especially orally, progesterone gets extensively metabolized to neurosteroids (allopregnanolone, pregnanolone) which have long known to have anti-depressant and anxiolytic effects because they are GABA agonists. Orally, these neurosteroids tend to quickly drop after peaking so would lead to depression and anxiety.

I've personally taken high doses of progesterone for years and I can attest to feeling euphoric and amazing the first few hours and then, there is a drop. If levels remained more constant, it would be different and this is why I don't think progesterone, per say, can result in depression and anxiety.

Can you say with any certainty that the growth wouldn't have happened without progesterone? The trans community id full of anecdotes like this - even without any real proof.

It's well established that progesterone stimulates lobulo-alveolar structures inside the breast. Whether that adds much to breast volume or not is debatable.

I know, for a fact, that when progesterone hits me (I know because I suddenly feel "high", calm, happy), my boobs also suddenly become larger, tender and they start to hurt. There is no doubt in my mind. BUT, that effect will only last a few hours, at most 10 hours after which all that tends to subside. I now suspect it may be mostly water retention because the effect is so quick but over time, I've noticed glands forming on the periphery of my breasts and I suspect this is due to progesterone.

we agreed that it would be of little benefit.

I think it may depend on the person, perhaps. We need studies in transwomen to better gauge its role (not only for breast development) and whether, it can be indeed useful for some or all of us. In the meantime, we have several girls trying it with some liking it and others, not so much or finding no benefit. So be it.

I found it made my skin and hair nicer, softer and more "glowy". It increased my libido, the amount of fluid secreted during arousal and made things better sexually speaking. I will admit to having more mood swings on it (potential explanation provided above), from being super sweet and "zen" to being super irritable and quite aggressive, at times. My breasts have actually grown more since reducing progesterone (hard mass underneath the areola) and that is not necessarily surprising as it is somewhat anti-estrogenic. I also feel less bloated. Lastly, I'm getting more attention from the guys which I don't mind. 

J Sex Med. 2014 May;11(5):1240-7.

"Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions."

Why such research has not yet been pursued, I don't know. 

[LizK]

I know, for a fact, that when progesterone hits me (I know because I suddenly feel "high", calm, happy), my boobs also suddenly become larger, tender and they start to hurt. There is no doubt in my mind. BUT, that effect will only last a few hours, at most 10 hours after which all that tends to subside. I now suspect it may be mostly water retention because the effect is so quick but over time, I've noticed glands forming on the periphery of my breasts and I suspect this is due to progesterone.

This is pretty much what my Dr said when I broached the subject with her. Her comment was yes you may get some growth but it is fluid and will go away anyway. Your experience seems to bare this out.

[AshleyP]

This is pretty much what my Dr said when I broached the subject with her. Her comment was yes you may get some growth but it is fluid and will go away anyway. Your experience seems to bare this out.

When I got a prescription for MPA, I did a lot of googling on the side effects. Most of the feedback came from older cis females, but there were scores of comments along the lines of, "I can't believe how much it made my breasts swell."

Sadly, I'm afraid that the "growth" that I've had is just swelling since it happened over such a short period. As I mentioned in another thread, I'm afraid the girls may just deflate one day. otoh, it's better to have tried and failed than to have never grown breasts at all.

All the best,
--Ashley 

[josie76]

Not having progesterone in the body leads to a condition called estrogen dominance. Basically progesterone performs a balancing function to some of estrogen's less helpful effects.

At least in the bio-identical form

Estrogen can:

interfere with Thyroid functioning - increased numbers women have hypothyroidism. Progesterone: blocks this effect
Can impair blood sugar control - progesterone stabilizes this
Can increase risk of blood clots - progesterone normalizes clotting
increased risk breast cancer - progesterone lowers risk
can reduce cell oxygen levels - progesterone balances oxygen levels
salt and fluid retention - progesterone natural diaretic
linked to autoimmune triggering - progesterone helps prevent autoimmune triggering
can cause depression and anxiety - progesterone can reduce depression and anxiety
progesterone can increase activity of estrogen recptors



However the opposite can be true. When progesterone's effects out weigh estrogen's the Progesterone can cause:
depression and anxiety
sleepiness
digestive issues
headaches

For me the interaction of progesterone and keeping the thyroid working right is pretty important.
Since starting MPA I have been hungry all the time. I think my salt needs went up. But my finger nails now take alot to break where on just estradiol bumping them would chip one.

[KayXo]

Not having progesterone in the body leads to a condition called estrogen dominance. Basically progesterone performs a balancing function to some of estrogen's less helpful effects.

Conjecture and not substantiated by studies. We need to be careful and not just blindly accept assertions from even professionals. I've spent countless hours browsing through actual studies and the evidence is seriously lacking.

Estrogen can:

interfere with Thyroid functioning - increased numbers women have hypothyroidism.

I have very high levels of E2 (1,000-4,000 pg/ml), disproportionate to the lower levels of P in my blood (10-20 ng/dl), and yet since the 3 years, I've been like this, absolutely no thyroid problems. Increased numbers may have hypothyroidism but to establish causality is impossible. There are several variables involved and we just don't know what causes what.

Can impair blood sugar control progesterone stabilizes this

Actually, several studies, for instance, using pellets of E in women, have found a reduced fasting insulin level and increased insulin sensitivity while progesterone may have the opposite effect and increase glucose intolerance, thereby increasing insulin output and weight gain.

Can increase risk of blood clots - progesterone normalizes clotting

Estradiol that is bio-identical and that is taken non-orally has a negligible impact on coagulation because a much smaller amount circulates through the portal vein and a much higher amount circulates in the blood and through various tissues. Progesterone appears to have NO effect on coagulation.

In one study in men with advanced prostate cancer and increased tendency to clot, the administration of E2 taken transdermally in high levels normalized certain clotting parameters. Authors concluded estradiol might protect against the risk of thrombosis.

increased risk breast cancer - progesterone lowers risk

In two large randomized trials involved ciswomen, estrogen alone significantly reduced the risk of breast cancer. High doses of estrogens are also sometimes used in women with advanced breast cancer with some degree of success, comparable to anti-estrogens such as tamoxifen.

Transwomen, mostly taking E and having taken very high doses for several decades rarely get breast cancer. The risk does not increase. P is only occasionally prescribed to transwomen and very rarely, bio-identical progesterone.

E, in women with previous breast cancer, has shown NOT to increase the risk of breast cancer.

Progesterone has, so far, shown not to increase nor to decrease the risk of breast cancer. The effect is neutral.

salt and fluid retention - progesterone natural diaretic

Interestingly, estrogen has shown in some studies to have a diuretic effect, similar to progesterone through several different mechanisms, for instance, increasing urodilatin and attenuating vasopressin action and even decrease aldosterone levels.

Progesterone, taken orally, may significantly elevate deoxycorticosterone levels such that the anti-diuretic may be annulled. Many women report an increase in fluid retention upon taking progesterone.

Not that clear cut.

can cause depression and anxiety - progesterone can reduce depression and anxiety

MANY studies have shown estrogen can actually alleviate depression and anxiety in women with post-partum depression and in some peri- or post-menopausal women. Not always but sometimes. But I have yet to come across a study in women where estrogen increases depression scores. Some studies have noted an increase in anxiety with estrogen.

Progesterone appears to have an anti-depressant and anxiolytic effect in some while the opposite seems true in others. It depends.

progesterone can increase activity of estrogen recptors

False. Progesterone downregulates and decreases estrogen sensitivity.

https://www.ncbi.nlm.nih.gov/pubmed/3297211

"Progesterone may also have an antagonistic activity against estradiol, mediated through a decrease in the replenishment of the estrogen receptor, and also through increased 17 beta-hydroxysteroid dehydrogenase which leads to accelerated metabolism of estradiol to estrone in the target organ."

Some studies have observed decreased breast proliferation with progesterone and increased growth with estrogen alone.

However the opposite can be true. When progesterone's effects out weigh estrogen's the Progesterone can cause:
depression and anxiety
sleepiness
digestive issues
headaches

I tend to agree with this.

Since starting MPA I have been hungry all the time. I think my salt needs went up. But my finger nails now take alot to break where on just estradiol bumping them would chip one.

MPA or medroxyprogesterone acetate is NOT progesterone and although sharing a common progestogenic effect, they also have very dissimilar effects on the body as they bind and trigger other receptors in the body in ways that are quite different which would account for why:

MPA, but not progesterone, increases the risk of breast cancer
MPA, but not progesterone, increases the risk of blood clots
MPA, but not progesterone, triggers androgen receptors and may result in androgenic symptoms
MPA, but not progesterone, tends to oppose estradiol's beneficial effects on blood vessels and lipids
MPA, and less often, progesterone leads to depression/anxiety and sometimes suicidal ideation

You change a molecule, ever so slightly and you can get quite differing effects. Sadly, several doctors treating us don't make that distinction.

[josie76]

I've seen some of the same opposing studies leaving the subject pretty wide open. I just posted what is more available information put out there. I know someone with hypothyroidism and her hormones are all out of sorts. I've seen the studies that say one causes the other then the opposite. Likely they interrelate with either issue making the other worse.

I know MPA is not actual progesterone and it has a number of undesirable potential side effects. I have read that human progesterone does not cause many such side effects. As to clotting, yes I know some studies show little risk with bioidentical E and certain delivery methods reduce it further. E on it's own does have an effect on the blood clotting factor. Nothing like the synthetic estrogen like chemicals do.

For me MPA has been fine. I actually feel better with it than E alone. It has sort of stabilized my moods. I take a single dose every night and do not cycle it.

[Pisces228]

I started micronized progesterone at 9 months.  I take it daily and have noticed my breasts are much heavier and look like small boobs, not traffic comes.  They are firm when squeezed and very sensitive.  I find my mood is more stable and I sleep better. 

[RobynD]

I'm not sure how to actually cycle progesterone (prometrium) it that is a thing or if it will matter in any way, but i will do more research.

[Pisces228]

I'm not sure how to actually cycle progesterone (prometrium) it that is a thing or if it will matter in any way, but i will do more research.

I would like to learn more about cycling as well to see if it makes a difference.  I have heard two weeks on and then two weeks off, or just ten days out of the month.  Also, would you have to increase your dose on cycle days if you aren't taking it daily?  I shall research as well.

[Dena]

The old cycling I used was estrogen days 1-21 and provera days 16-21. That would pretty well mimic a women's hormone cycle but doctors may have changed the interval because blood tests can now determine how well the body tracks the dosage. The first time on HRT, my hormones were only tested once and that was to measure testosterone for diagnostic reasons long before I started HRT.

[AshleyP]

The old cycling I used was estrogen days 1-21 and provera days 16-21. That would pretty well mimic a women's hormone cycle but doctors may have changed the interval because blood tests can now determine how well the body tracks the dosage. The first time on HRT, my hormones were only tested once and that was to measure testosterone for diagnostic reasons long before I started HRT.

Does that mean that you didn't take anything on days 22-28?

All the best,
--AshleyP

[Dena]

Does that mean that you didn't take anything on days 22-28?

All the best,
--AshleyP

Or days 22-31 depending on the month. The idea at the time was just like a genetic woman, it would give the body a rest from hormones. It never bothered me but if you are sensitive to hormone swings, you could possibly feel the effect of cycling. Now I am only on estradiol and it's a pill a day.

[KayXo]

Some authors and researchers are now suspecting and raising the possibility that one of the reasons for the increased incidence of breast cancer amongst ciswomen is due to the increase in the number of menstrual cycles during their lifetime, due to increased cycles of cell proliferation and apoptosis and increased risk of DNA mutations. Traditionally, women spent less time menstruating and more time being pregnant and nursing.

Such cycling might also result in mood swings and PMS. No study has ever shown a benefit associated with cycling vs continuous intake.

[LexiDreamer]

The old cycling I used was estrogen days 1-21 and provera days 16-21. That would pretty well mimic a women's hormone cycle but doctors may have changed the interval because blood tests can now determine how well the body tracks the dosage. The first time on HRT, my hormones were only tested once and that was to measure testosterone for diagnostic reasons long before I started HRT.

Most people who try to mimic cis-women cycles seem to forget what the main effect of the cycle is for. The cycling is to trigger the release of an egg from the fallopian tubes, and to build up and shed the endometrial lining of the uterus.

If you don't have a uterus or fallopian tubes, what's the point of mimicing the cycles?

Once all of a cis-woman's eggs have been released, the cycling ceases. It's called menopause.

Unfortunately, most MtF transwomen are not bio-identical to cis-women, therefore many things that apply to them don't apply to us. It's a shame most doctors blindly ignore that.

[KayXo]

To elaborate on the above, cycling on and off again for as many times as women do today is just not natural. Progesterone (and estrogen) increases during the second phase to prepare the woman for pregnancy, get the endometrium ready to receive a fetus and nourish it for 9 months. Of course, it exerts many other essential functions that help maintain pregnancy. All those changes are in anticipation of what's to come if the egg is fertilized. In the past, women didn't have the option of birth control and often did end up being pregnant, with much less time being spent in and out of cycles every month or so.

[Cindy]

The latest guidelines were published recently

Endocrine Treatment of Gender-Dysphoric/ Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline
Wylie C. Hembree,1 Peggy T. Cohen-Kettenis,2 Louis Gooren,3 Sabine E. Hannema,4 Walter J. Meyer,5 M. Hassan Murad,6 Stephen M. Rosenthal,7 Joshua D. Safer,8 Vin Tangpricha,9 and Guy G. T'Sjoen,10
J Clin Endocrinol Metab, November 2017, 102(11):1–35

To quote

"Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in transgender females is extremely sparse and based on the low quality of evidence. Current evidence does not indicate that progestogens enhance breast development in transgender females, nor does evidence prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions. "

Unquote (I have removed reference numbers from the quote for clarity).

Basically - no one knows.

[KayXo]

In my mind, there is no doubt that progesterone makes breasts fuller, more swollen and enlarges both the areola and nipple. This is, in part, why breasts in pregnant women typically become so much wider and bigger. It's also been shown that certain structures depend on progesterone to form such as lobules and alveoli. As long as you take progesterone (or another progestogen), the breasts will continue to look fuller. Same with estrogen, stop it, and the breasts will begin to atrophy to a certain degree.

I know all this from personal experience and from having read hundreds of testimonies from other women throughout the years. Every time I take a progestogen, whether it be cyproterone acetate (a progestogen/anti-androgen used in a large number of transsexual women since the 1980's) or progesterone, my breasts become larger, more so if the estrogen I am taking is already having a significant effect on my breasts.

BUT, with taking progesterone orally, the problem is that it is metabolized in such a way that lots of other metabolites are also produced and can make one feel quite tired. Also, levels tend to fluctuate too much with levels dropping quite quickly. There are also undesirables with taking progesterone in general like gaining too much weight, abdominal bloating, increase in cellulite, feeling tired/lazy, anti-estrogenic effects, etc. At times though, I felt quite good on progesterone, relaxed and in a good mood, my hair and skin seemed shinier/softer, my libido increased and I even felt more motivated to do things.

I recently quit progesterone because I'd rather have smaller breasts and look thinner with less cellulite than have large breasts, look "pregnant" and feel "lazy" most of the time. The undesirables, for me, seemed to outweigh the positives but the line between bad and good was thin and this is why it took me so long to decide. I substituted progesterone for a little testosterone, continue to take estrogen and so far, feel better on that combo. My body shape is improving, I have more energy but my boobs are smaller.

To each to decide what is more suitable for them in accordance with their doctor.

We know how progestogens affect the breast from several clinical studies in animals and humans (including transsexual women on cyproterone acetate) but in order to put this to rest once and for all, we need large randomized controlled trials in transwomen with some taking progesterone (through different routes), dydrogesterone and/or hydroxyprogesterone caproate and some taking nothing. Then, after 1 year or so, make comparisons not only between the different groups and but also compare the situation pre-progestogen vs post-progestogen. Until such studies aren't conducted, the debate will rage on and reports will remain anecdotal.

But, like I said, there is absolutely no doubt in my mind that progestogens do increase breast size and will maintain this as long as they are taken and, for some, that is fine and presents no problems or health risks.

[Cindy]

I agree with you and with the report from people far more learned than I in the area.

There is no scientific proof.

[judithlynn]

Yes for me I am only just starting month two and am already seeing positive benefits from the daily dose taken each night before I go to bed.

My pharmacist has recommended 3 months continuous them moving to 3 weeks Oestrogen only and 1 week Oestrogen & Prometrium.
Judith