Quote from: Pipes on January 30, 2016, 11:25:57 PM
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Endocrinologist Response:
Based on the Endocrine Society guidelines we do not use progesterone replacement in the trans population (there are no patients I am aware of here who are taking it). This is largely due to the lack of evidence for improved outcomes
Am J Surg Pathol. 2000 Jan;24(1):74-80.Short-term and long-term histologic effects of castration and
estrogen treatment on breast tissue of 14 male-to-female transsexuals
in comparison with two chemically castrated men."(...) Hence, combined progestative antiandrogens and estrogens are
necessary for genetically male breast tissue to mimic the natural
histology of the female breast."
"(...)Hence, Orentreich and Durr9 appropriately concluded from their
theoretical studies that estrogen alone or combined with orchidectomy
may not always induce acinar formation in the male mammary gland.
These authors thought that it could not be determined whether
estrogen, orchidectomy, and progesterone together always produce
lobules and acini, but they inferred that some castrated male-to-
female transsexuals who had received estrogens and progestins for prolonged
periods have breast tissue that histologically simulates
that of the female, that is, with acinar and lobular formation.
9 Our study now shows their hypothesis in general to be correct, but
it does not take an orchidectomy for the acinar and lobular formation
to occur, and moreover, such formation seems to decrease when
progestative antiandrogen treatment is stopped after surgical
castration.
Our findings in patient F indicate that prolonged and
regular intake of proper doses of progestins and estrogens
is needed for the full development and maintenance
of the female histology.""(...)progestative drugs are known to stimulate
the formation of acini and lobules in females.7 "
J Sex Med. 2014 May;11(5):1240-7.
Clinical review: Breast development in trans women receiving cross-sex hormones."Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is
extremely sparse and based on low quality of evidence. 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."
Journal of the Gay and Lesbian Medical Association, Vol. 4, No. 4, 2000"The use of progesterone to augment breast development
is controversial in physicians treating MTF transsexuals."
"Although some physicians working with transgendered patients do not
prescribe progesterone, others argue feminization involve the actions of
both estrogen and progesterone (31)."
"Progesterone is important for breast development (24)."
"Micronized progesterone (Prometrium) is advantageous because it has
a more favorable side effect profile (anxiety and irritability)"
Endocrine therapy of transsexualism and potential
complications of long-term treatment.
Archives of Sexual Behavior. Date: 04-05/1998"the addition of a progestin is indicated initially or several months following
onset of estrogen therapy which may have an additional effect on breast enhancement."
Steroids. 2004 Mar;69(3):145-59."The importance of the sex steroid hormones 17beta-estradiol
and progesterone for normal development of the mammary gland was
recognized several decades ago and has been unequivocally confirmed
since."
Volume 18a of Elsevier's New Comprehensive
Biochemistry, Titled 'Hormones and Their Actions, Part I', Published 1988. "Progesterone also acts synergistically with estrogen in the normal
development of the breast. Estrogen stimulates cell mitosis and growth
of the ductal system, while lobular development and differentiation is
dependent on progesterone. When estrogen is administered in the absence
of progesterone, the tubular system proliferates and the ducts dilate
resulting in the formation of cysts and fibroses. These changes are
comparable to those observed in fibrocystic disease and are suppressed
by progestins, so that normal breast development requires that estrogen
and progesterone be administered together.[2-4]"
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. 2014 Jan 6."Results of this small, double-blind, placebo-controlled, cross-over study showed that the use of orally administered natural progesterone caused a significant reduction in BP in individuals with mild to moderate HTN who were not using any other antihypertensive medications."
Psychoneuroendocrinology. 2008 Sep;33( 8 ):1124-31."In summary progesterone demonstrated a distinct sleep promoting effect by reduction of time of wake without impairing cognitive functions during daytime. As possible mechanisms of progesterone a GABA-agonistic effect and the regulation of gene expression via the progesterone receptor are discussed. Progesterone might be useful in the treatment of sleep disturbances of postmenopausal women."
J Womens Health Gend Based Med. 2000 May;9(4):381-7"When compared with the MPA-containing
regimen,
women using micronized progesterone-containing HRT
experienced significant improvement in vasomotor symptoms, somatic
complaints, and anxiety and depressive symptoms."
Maturitas. 2015 Mar 9."In a cross-sectional study of 176 women who had previously switched from HT containing MPA to HT containing micronized progesterone, 71% had switched because of the better side effect profile, 35% because they believed the long-term risks would be fewer, and 23% because of intolerance to MPA [21]. When evaluated at 1 to 6 months after switching, the women experienced significantly better quality of life, including less depression and anxiety, than with MPA (both P < 0.001) [21]. Patient satisfaction questionnaires also indicated that women preferred micronized progesterone over their previous regimen for better symptom control and fewer adverse effects (P < 0.001) [21]. In the study by Ryan and Rosner of CEE with either progesterone or MPA, results on the Women's Health Questionnaire showed a significant group-by-visit interaction indicating better quality of life in the progesterone group in the cognitive difficulties domain (P = 0.015) [19]."
"Sleep was significantly improved after 6 months of CEE plus micronized progesterone but not with CEE plus MPA in a randomized study of 21 postmenopausal women tested in a sleep laboratory [22]. Specifically, the progesterone group (but not MPA) had significant improvements in sleep efficiency due to decreases in time spent awake"
"Progesterone stimulated nitric oxide synthesis and inhibited adhesion of platelets to endothelial cells in rat endothelial cell cultures"
Geburtshilfe Frauenheilkd. 1991 Apr;51(4):257-61."Because of the influence of estrane on lipids, one often advises against a replacement therapy with progestogens in hysterectomised women. With increasing knowledge of encountered extragenital functions of sexual steroids, the latter is questionable, if natural progesterone is given, which is (said to be) lipid-neutral, performing the function of the progestogens, which is quite more than reproduction only, more efficiently than estrane or gonane. Due to the competitive blocking of aldosterone the effect of progesterone is sodium-diuretic and diuretic, being as important as the therapy of climacteric complaints, as well as the consequence, which is the result of the physiological connection between progesterone and encephalics. Moreover, the effect of the progestogens is to tonicise the vascular system and is linked to a number of intestinal hormones in order to adjust their function. Therefore,
progesterone seems to perform a great variety of extragenital functions. Menopausal women should not be deprived of the benefits of these functions within the framework of a replacement therapy."
Quoteand more importantly because of the risk of adverse events with combined hormone therapy. Much of this data came from a large study called the Womens Health Initiative, which was actually stopped early due to increased breast cancer, pulmonary embolism, and cardiovascular disease in the female patients taking estrogen+progesterone compared to those taking estrogen alone.
Your doctor ignores the differences between the progestogen used in this study, medroxyprogesterone acetate (MPA) and bio-identical micronized progesterone which was not used in this study.
Climacteric. 2013 Aug;16 Suppl 1:69-78."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."
Maturitas 46S1 (2003) S7–S16"Basically all progestins do have only one effect in common, the progestogenic effect on the estrogen-primed endometrium of the rabbit, but there are large differences between progestins in the multitude of other biological effects elicited."
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."
Int J Cancer. 2005 Apr 10;114(3):448-54."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. The increase in risk reached
significance when estrogens were combined with synthetic progestins
and was significantly greater than when combined with
micronized progesterone."
J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108."Controlled studies and most observational studies published over
the last 5 years suggest that the addition of synthetic progestins
to estrogen in hormone replacement therapy (HRT), particularly in
continuous-combined regimen, increases the breast cancer (BC) risk
compared to estrogen alone. By contrast, 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."
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."
Clin Ther. 1999 Jan;21(1):41-60; discussion 1-2."The results of published clinical studies show minimal or no changes in lipid profile, blood pressure, or carbohydrate metabolism during treatment with oral micronized progesterone.28 This safety profile contrasts with the reported negative effects of some synthetic progestins, including adverse effects on lipid metabolism and glucose tolerance. Several studies, including the 3-year prospective PEP1 study, 4, 28 have shown that oral micronized progesterone significantly improves metabolic tolerance compared with such progestins as MPA.52,54,58"
"Only minor adverse events have been reported in association with oral micronized progesterone therapy in clinical trials. Dizziness and sleepiness are the primary adverse reactions reported.33 However, these side effects can be suppressed by administering micronized progesterone once daily at bedtime. 29 Oral micronized progesterone is therefore an effective and well-tolerated form of progestogen replacement in premenopausal and postmenopausal women."
Experimental and Clinical Psychopharmacology 2007, Vol. 15, No. 5, 427–444"It is important to note that although progesterone and synthetic progestins are used for similar purposes, these may not exert similar modulatory effects on target organs, and each progestin molecule may have specific effects on neuroendocrine action (Bernardi et al., 2006). For example, a commonly used progestin, MPA, was shown to induce more negative somatic effects"
"MPA and natural progesterone also were found to differ with respect to molecular signaling in human endothelial cells, suggesting that there may be differential cardiovascular effects"
J Hypertens. 2003 Jun;21(6):1145-9."We conclude that progesterone given without oestrogen does not adversely affect vascular function in postmenopausal women"
PLoS One. 2014 Jan 21;9(1)"Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, bloodpressure, 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)."
Climacteric. 2013 Aug;16 Suppl 1:69-78."Natural progesterone and some of its derivatives, as
well as the non-ethinylated drospirenone and dienogest, do
not exert any androgenic effect and have no negative effect
on the lipids or on the endothelial cells 1,70 ."
"it appears that transdermal
estradiol alone or combined with natural progesterone
does not increase thrombotic risk."
"In experiments conducted in ovariectomized female monkeys
fed a highly atherogenic diet, estrogens preserved normal
endothelial-dependent dilator responses of coronary arteries
to acetylcholine, and progesterone did not alter this
cardioprotective mechanism. While MPA diminished the
endothelium-dependent vasodilation 68"
"Estradiol has been shown to trigger the expression of the
endothelial nitric oxide synthase (eNOS) gene and increase the
release of nitric oxide, causing relaxation of the vascular
smooth muscle cells."
"Progesterone or drospirenone did not interfere with the induction or activation
of eNOS by estradiol, while MPA did."
Hum Reprod. 1999 Mar;14(3):606-10."Natural progesterone is devoid of any androgenic activity that might compromise lipoprotein metabolism or induce teratogenicity. Moreover, it probably has a direct beneficial effect on blood vessels."
Lipids Health Dis. 2012 Oct 9;11:133."Cyclic, short term exposure to vaginal micronized progesterone did not alter the metabolic and cardiovascular effects of non-oral E2 in early, apparently healthy, postmenopausal women."
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."
"there was no significant change in APC sensitivity among women who used transdermal estrogens combined with micronized progesterone compared with nonusers."
Gynecol Endocrinol. 1993 Jun;7(2):111-4."Levels of lipoprotein A and liver enzymes did not change. It is concluded that micronized natural progesterone is an attractive means of progesterone supplementation in postmenopausal hormone replacement therapy without any liver-related side-effects."
Gynecol Endocrinol. 1996 Feb;10(1):41-7.
Clinical evaluation of near-continuous oral micronized progesterone therapy in estrogenized postmenopausal women."No significant changes were observed in blood glucose or liver enzymes."
Contraception. 1987 Oct;36(4):373-402.
Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications--a review."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"
http://www.merck.ca/assets/en/pdf/products/Prometrium-PM_E.pdf"OVERDOSAGE
Symptoms
The toxicity of progesterone is very low."
Experimental and Clinical Psychopharmacology
2007, Vol. 15, No. 5, 427–444
Progesterone: Review of Safety for Clinical Studies"Progesterone has been shown to be safe and effective for many clinical applications. The therapeutic effects of progesterone and its neuroactive metabolites reflect interactions with serotonin, dopamine, Nmethyl- D-aspartate, beta-endorphin, and sigma receptors (Pluchino et al., 2006; Schumacher et al., 2007)."
Steroids. 2003 Nov;68(10-13):831-6."Particularly, the Postmenopausal Estrogen/Progestin Intervention (PEPI) trial clearly showed the different impact of sequential micronized progesterone or medroxyprogesterone acetate (MPA) on estrogen therapy
(ET) with CEE. Indeed, while all women had increases in HDL-C and reductions in LDL-C while on estrogens, the addition of MPA was associated with a partial reversal of the positive effect on HDL-C (not on LDL-C),
that was not obtained with micronized progesterone [5]."
"Indeed, by using Cynomolgus monkeys, Adams' group in North Carolina has been able to show consistently that 17β-estradiol modulates coronary arteries dilatation in estrogen-deprived animals [17]. Co-administration of natural progesterone did not alter the effect of estrogen. However, in the same model, the addition of cyclic or continuous MPA inhibited the vasodilatory effect of estrogen responses by 50% [18]. These data have been confirmed by other groups, showing that progesterone plus estradiol protects, but MPA plus estradiol does not, against coronary artery vasospasm[19], thus highlighting the difference between natural progesterone and MPA."
"Recent work looking at the additional effects of natural progesterone or MPA on coronary blood flow and myocardial ischemia in postmenopausal women shows that progesterone has synergistic vasodilatory effects when added to estrogens [26]. In contrast, MPA does not share this action, therefore indicating that, on this particular target, all progestins are not the same [26]."
J Am Coll Cardiol. 2000 Dec;36(7):2154-9."Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration."
Drugs Aging 2004; 21 (13): 865-883 "In monkeys, neither natural progesterone nor nomegestrol
acetate inhibits the beneficial effect of estrogen on the coronary artery dilator response. However, when medroxyprogesterone acetate was combined with estrogen, the positive response was inhibited by 50%.[69,70]"
Trends in Endocrinology & Metabolism
Volume 11, Issue 2, 1 March 2000, Pages 69–71"Curiously, addition of the synthetic progestin, medroxyprogesterone, blocked the modulating effects of oestrogen on serotonin activity, while natural progesterone did not."
Just browsing through forums, you will also come across many transgendered women (including myself) noticing positive improvements in their feminization and health on bio-identical progesterone so IT IS prescribed to us and some women report positive effects. These, of course, are anecdotal.
You should perhaps see a doctor who is more informed on the subject matter or show them these papers, explaining the differences. I hope your doctor will be humble and open enough to see that he was mistaken.
