Quote from: Pipes on February 04, 2016, 04:12:51 PM
Here is the reply I just got from my VA endo.

"You are correct to point out that the Womens Health Initiative studied medroxyprogesterone, not micronized progesterone. However there have not been any large scale studies specifically with progesterone so the best we can say is the effect on things like breast cancer and blood clots is unclear.

Your endo is once again wrong and probably ignores/is unaware of all the studies done to date on progesterone. I have provided some of them, here in this thread...have you shown these studies to your endo? I have a whole document with plenty of science to support the notion that micronized progesterone neither increases breast cancer, nor clotting. I can PM you this document, if you wish. In the meantime, here are some you can send to your doctor

Int J Cancer. 2005 Apr 10;114(3):448-54.

"We assessed the risk of breast cancer
associated with HRT use in 54,548 postmenopausal women who had never
taken any HRT 1 year before entering the E3N-EPIC cohort study (mean
age at inclusion: 52.8 years); 948 primary invasive breast cancers
were diagnosed during follow-up (mean duration: 5.8 years). Data
were analyzed using multivariate Cox proportional hazards models. In
this cohort where the mean duration of HRT use was 2.8 years, an
increased risk in HRT users compared to nonusers was found (relative
risk (RR) 1.2 [95% confidence interval 1.1-1.4]). The RR was 1.1
[0.8-1.6] for estrogens used alone and 1.3 [1.1-1.5] when used in
combination with oral progestogens. The risk was significantly
greater (p <0.001) with HRT containing synthetic progestins than
with HRT containing micronized progesterone, the RRs being 1.4 [1.2-
1.7] and 0.9 [0.7-1.2], respectively."

"(...)Our study shows an increased risk of breast cancer associated
with HRT use. It indicates that the association between HRT use
and breast cancer risk most likely varies according to the type of
progestogen used. There was no or little increase in risk with
estrogens used alone or combined with micronized progesterone,
at least when used for short periods."

PLoS One. 2013 Nov 1;8(11)

"This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer"

Climacteric. 2013 Aug;16 Suppl 1:69-78.

"The French E3N cohort study found that the association of estrogen – progestin combinations with breast cancer risk varied significantly according to the type of progestin: the relative risk was 1.00 (95% CI 0.83 – 1.22) for estrogen –progesterone"

Breast Cancer Res Treat. 2014 Jun;145(2):535-43.

"Among short-term users, only those currently using estrogens associated with a progestagen other than progesterone/dydrogesterone had a significantly elevated breast cancer risk (HR 1.70, 95 % CI 1.50-1.91, compared with never users)."

Breast Cancer Res Treat. 2008 Jan;107(1):103-11.

"The association of estrogen-progestagen combinations with breast cancer risk varied significantly according to the type of progestagen: the relative risk was 1.00 (0.83-1.22) for estrogen-progesterone"

"These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone"

Arch Gynecol Obstet. 2014 Aug;290(2):207-9.

"The authors concluded that: (1) ET and EPT containing natural progesterone did not increase BC risk "

"Compared with MHT never use, BC risk was increased with MHT containing "other" progestogens (adjusted RR 1.69; 95 % CI 1.50–1.91) but not with those containing progesterone (adjusted RR 1.00; 95 % CI 0.83–1.22)"

"All these findings taken together suggest a more favourable effect for micronized progesterone and dydrogesterone on postmenopausal mammary gland. »

J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.

"a recent study suggests that the addition of natural progesterone in cyclic regimens does not affect BC risk. This finding is consistent with in vivo data suggesting that progesterone does not have a detrimental effect on breast tissue."

Climacteric. 2013 Aug;16 Suppl 1:44-53.

"Natural, 'body-identical' progesterone, devoid of any androgenic as well as glucocorticoid activities but being slightly hypotensive due to its antimineralocorticoid activity, appears to be the optimal progestogen in terms of cardiovascular effects, blood pressure, VTE, probably stroke and even breast cancer »

Climacteric. 2012 Apr;15 Suppl 1:3-10.

"Unlike some progestogens, progesterone is also not associated with an increased risk of VTE, or with an increased risk of breast cancer."

Climacteric. 2003 Dec;6(4):293-301.

"In both peripheral and cerebral vasculature,
synthetic progestins caused endothelial disruption, accumulation of
monocytes in the vessel wall, platelet activation and clot
formation, which are early events in atherosclerosis, inflammation
and thrombosis. Natural progesterone or estrogens did not show such
toxicity."

Maturitas. 2015 Mar 9.

"When taken with oral or transdermal estrogens, no significant association of venous thromboembolism (VTE) with concomitant micronized progesterone"

"Similar results had been previously reported for the ESTHER study in which micronized progesterone and pregnane derivatives did not increase risk for VTE"

Maturitas. 2011 Dec;70(4):354-60.

"With respect to the different pharmacological classes of progestogens, there is evidence for a deleterious effect of medroxyprogesterone acetate on VTE risk. In addition, observational studies showed that norpregnane derivatives were significantly associated with an increased VTE risk whereas micronized progesterone could be safe with respect to thrombotic risk."

Circulation. 2007 Feb 20;115(7):840-5.

"In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk."

Climacteric. 2012 Apr;15 Suppl 1:11-7

"Micronized progesterone has also been shown not to increase the risk of venous thromboembolism and further reduced the incidence of new-onset diabetes when combined with transdermal estrogen. Micronized progesterone has a neutral effect on the vasculature, including a neutral or beneficial effect on blood pressure"

Menopause. 2010 Nov-Dec;17(6):1122-7

"recent data have shown that norpregnane derivatives but not micronized progesterone increase venous thromboembolism risk among transdermal estrogens users."

"These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone"

Climacteric. 2013 Aug;16 Suppl 1:44-53.

"The crucial point is that, in the studies where the effect of micronized progesterone, irrespective of the route of estradiol administration, could be evaluated (since it is used in significant amounts almost only in France), micronized progesterone strictly did not modify the VTE risk (OR 0.7; 95% CI 0.3–4.9 in the ESTHER study45; OR 0.9; 95% CI 0.6–1.15 in the E3N study32)."

Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:243

"Progesterone clearly inhibited tumor necrosis factor-–activated expression of VCAM-1
protein and its mRNA in HUVECs."

"Electrophoretic mobility shift assays demonstrated that
progesterone, but not MPA, inhibited DNA binding of the
transcription nuclear factor-B, which is critical for the inducible
expression of VCAM-1. Because the expression of VCAM-1 is one of the
earliest events that occurs in the atherogenic process, this
adhesion molecule might be a target molecule for progesterone on
vascular walls."

Climacteric. 2013 Aug;16 Suppl 1:69-78.

"it appears that transdermal
estradiol alone or combined with natural progesterone
does not increase thrombotic risk."

"none of the recent statements addressed the
difference between MPA and progesterone, even though the
differences in action between the two molecules have been
demonstrated in receptor interaction and transactivation 1,16
and in vivo , in vessels 79 , brain 80 , and heart 81 . It would be
unfortunate if this confusion between the molecules deprives
menopausal women of the well-known effects and benefits of
progesterone. »

Contraception. 1987 Oct;36(4):373-402.

"No side effects have been reported as far as lipids profile, coagulation factors and blood pressure are concerned. Therefore oral micronized progesterone appears suitable for hormonal replacement therapy in various areas, essentially postmenopause therapy, premenstrual syndrome, correction of irregular cycles and pregnancy maintenance."

PLoS One. 2014 Jan 21;9(1)

"Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change).»

I have been on a moderate-high dose of oral micronized progesterone for almost 2 yrs. My clotting factors came back normal.

In clinical trials and randomized controlled trials evaluating micronized progesterone, mentioned in Prometrium's product monograph, not one single case of thrombosis or altered coagulation factors is mentioned. Neither is any case of breast cancer or cardiovascular incidence. All side-effects more commonly associated with progesterone were minor and benign. Rare cases of fetal death and hepatoxicity have also been reported when progesterone was prescribed to pregnant women during the second and third trimesters but causality was NOT established.

Add to that the fact that breast cancer risk is extremely low among transgender women (10 cases reported since 1968) despite decades of prescribing them high doses progestogens (medroxyprogesterone acetate and cyproterone acetate).

Journal of Clinical & Translational Endocrinology 2 (2015) 55-60

"Although studies are small, overall cancer incidence in transgender men and transgender women to-date has not been found to be different than their respective male and female controls [5]. There are no reports of change in breast cancer specific risk among transgender individuals on estrogen compared to secular trends of male breast cancer incidence. Rates are lower relative to secular trends of female breast cancer rates."

"Additionally, there are ten case reports of breast cancer development among MTF individuals on estrogen since 1968"

J Sex Med.2013Dec;10(12):3129-34.

"We researched the occurrence of breast cancer among transsexual persons 18-80 years with an exposure to cross-sex hormones between 5 to >30 years. Our study included 2,307 male-to-female (MtF) transsexual persons undergoing androgen deprivation and estrogen administration (52,370 person-years of exposure)"

"Among MtF individuals one case was encountered, as well as a probable but not proven second case."

"The number of people studied and duration of hormone exposure are limited but it would appear that cross-sex hormone administration does not increase the risk of breast cancer development, in either MtF or FtM transsexual individuals. Breast carcinoma incidences in both groups are comparable to male breast cancers. Cross-sex hormone treatment of transsexual subjects does not seem to be associated with an increased risk of malignant breast development."

Makes you wonder why some of us are asked by our doctors to undergo mammographic exams when men who aren't on HRT are never asked to do so  and our risk of getting a breast cancer risk is equivalent to theirs. 

...Also

Pregnant women have very high levels of progesterone, up to 200 ng/ml +

- http://www.ilexmedical.com/files/PDF/Progesterone_ARC.pdf (page 2)

"If conception occurs, the levels of progesterone are maintained at mid-luteal
levels by the corpus luteum until about week six. At that time, the placenta
becomes the main source of progesterone and levels rise from approximately
10-50 ng/mL in the first trimester to 50-280 ng/mL in the third trimester.1,12,13"

- Neuropsychobiology. 2014;69(3):147-53.

"The mean age of the women was 30.7 ± 4.5 years and 55
(57.3%) were nulliparous (pregnant with their first child).
The assessments were made in gestational week 38.2 ± 0.6
and the median number of days until parturition was 13.5
days (range 1–32 days)."

In 95 women. Late pregnancy.

Average Progesterone levels:
683 nmol/L (+/- 229), 454 – 912 nmol/L
215 ng/ml (+/- 72), 143 – 287 ng/ml

and yet...

J Pharm Pract. 2014 Apr 17;27(3):243-252.

"Pregnancy is associated with an increased risk of venous thromboembolism (VTE), with a reported incidence ranging from 0.49 to 2 events per 1000 deliveries"

Risk of VTE is at 0.05-0.2 %.

Ann Intern Med. 2005 Nov 15;143(10):697-706.

« The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to 5.22;P < 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100,000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs. 95.8 per 100,000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100,000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100,000). "

Hence, most cases of DVT and PE, already quite low, are present post-partum, not during pregnancy. DESPITE HIGH LEVELS OF PROGESTERONE and...

http://ww5.komen.org/BreastCancer/NotHavingChildrenorHavingFirstAfterAge35.html

"In general, the more childbirths a woman has had the lower her risk of breast cancer [7-12]. After the first child, each childbirth lowers risk.

Women whose childbirths are spaced close together may get more benefit than women whose childbirths are spaced far apart [7]."

"Women who never give birth have a slightly higher risk of breast cancer compared to women who have had more than one birth [7]."

http://parade.com/37175/parade/why-do-nuns-have-a-high-rate-of-breast-cancer/

"The more children a woman has, and the longer she breastfeeds them, the lower her risk of developing breast cancer.  Before the Industrial Revolution, when women had many more children than they now do, breast cancer was relatively uncommon.  It is now calculated that Western women could reduce their breast cancer risk by nearly 60% if they returned to the pre-industrial levels of fertility and breastfeeding. For each child a woman has, the risk of breast cancer decreases by 7%"

To summarize, pregnancy (a time when progesterone levels are at a high) is associated with a very low rate of thrombosis complications (most of these cases taking place after pregnancy, when progesterone levels drop) and is associated with a lower incidence of breast cancer risk.

Notice how your endo changed his stance on progesterone, originally asserting that progesterone had adverse health risks because of the WHI study and now stating that its health risks are, at the very least, unclear.

Most recent reply from VA endo:
(5 months later, we are still discussing...)

I heard back from pharmacy and micronized progesterone is not available through the VA. We could potentially obtain approval for medroxyprogesterone. The pharmacist quoted the following, which is similar to our prior discussions:

"Progestins have been used in some cross-sex hormone regimens, but their
use is controversial and more recently not routinely recommended. Though
expected to improve breast growth and development, the benefits of
progestins added to cross-sex hormone therapy have not been clearly
demonstrated. Considering the uncertain benefit along with the potential
risks of progestin addition (e.g., depression, weight gain, lipid changes,
cardiovascular risk, and questionable cancer risk), progestins are not
routinely recommended.  A situation where a progestin may be considered
may be in a patient that has reached maximal estrogen doses or is
intolerant of estrogen-based regimen and who is not a candidate for other
androgen-suppressive therapy."

So our options, from the VA, are the following:
1. Since your breast size continues to improve, we can wait until maximal benefit has been reached with estrogen and then consider progesterone treatment (which may not be needed, depending on the maximum obtainable size relative to your mother). This is the approach most providers who work with transgender patients (and who have experience with progesterone) recommend.

2. Or, alternatively, we can consider medroxyprogesterone sooner if you feel you would like to pursue it despite the potential risks.

Quote from: Pipes on July 11, 2016, 11:38:29 AM
Most recent reply from VA endo:
(5 months later, we are still discussing...)

I heard back from pharmacy and micronized progesterone is not available through the VA. We could potentially obtain approval for medroxyprogesterone. The pharmacist quoted the following, which is similar to our prior discussions:

"Progestins have been used in some cross-sex hormone regimens, but their
use is controversial and more recently not routinely recommended. Though
expected to improve breast growth and development, the benefits of
progestins added to cross-sex hormone therapy have not been clearly
demonstrated. Considering the uncertain benefit along with the potential
risks of progestin addition (e.g., depression, weight gain, lipid changes,
cardiovascular risk, and questionable cancer risk), progestins are not
routinely recommended.  A situation where a progestin may be considered
may be in a patient that has reached maximal estrogen doses or is
intolerant of estrogen-based regimen and who is not a candidate for other
androgen-suppressive therapy."

So our options, from the VA, are the following:
1. Since your breast size continues to improve, we can wait until maximal benefit has been reached with estrogen and then consider progesterone treatment (which may not be needed, depending on the maximum obtainable size relative to your mother). This is the approach most providers who work with transgender patients (and who have experience with progesterone) recommend.

2. Or, alternatively, we can consider medroxyprogesterone sooner if you feel you would like to pursue it despite the potential risks.

My non VA doc said the same thing. Rewards have not been proven to outweigh the risks.


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Quote from: allisonsteph on July 13, 2016, 03:03:23 PM
My non VA doc said the same thing. Rewards have not been proven to outweigh the risks.


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VA Is now claiming they have no access to micronized progesterone and can only prescribe me medroxyprogesterone...

They are advising against it but not refusing...

/scared

Quote from: Pipes on July 20, 2016, 12:56:38 AM
VA Is now claiming they have no access to micronized progesterone and can only prescribe me medroxyprogesterone...

They are advising against it but not refusing...

/scared

I have been taking medroxyprogesterone since the end of last year. I mostly wanted it to see if it did effect my breast growth in the next year before deciding on whether to get implants or not. It also helps with anxiety, and can help you fall asleep at night, which are major bonuses for me considering my anxiety issues and insomnia. So far I really like the benefits I have received, and I'm still monitoring my blood and vitals every three months with my prescribing physician. As long as you're careful and pay attention to any changes you experience, you should be fine too.

The trouble with a lot of the bad data attached to progesterone in either form, is that most studies are only done with HRT in women going through menopause. Trans people are generally not invited to these studies, so it's hard to predict how the drugs will effect trans bodies.

It's similar to how medical studies used to only be performed on men, until people finally realized that some drugs affect female bodied people differently. The medical industry is still predominantly cis and sexist, despite the slow progress it's making.


     Hugs,
- Katie
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Thank you for all the great references.

It took a year to finally convince my endo to allow me to try generic progesterone added to my estradiol.  My next blood draw and appointment will be this coming October.

I have been on the progesterone since May; I am not definitive, but I sense improvements.

     -  I weighed 115 kg at the beginning of the year.  I am now down to 90 kg.  My breast size reduced from D to C due to weight loss.  My breast size has returned to D since starting progesterone.

     -  I had patches of extremely dry skin on my face.  Those dry patches are moderated.

     -  My fingernails were continually brittle, chipping, flaking, cracking.  That has greatly diminished.

     -  I experienced several episodes when my hair came out profusely when I combed it.  I showed a sample of hair loss from one day to my endo; I have experienced few episodes of such hair loss, my hair seems much better and not as thinned as before.

I told my doctor that I would not continue if there was trouble but want to continue as long as there are no negative effects.  I suppose the October blood draw will determine what effects progesterone is having upon my system.

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