Quote from: Rachel Richenda on December 26, 2016, 12:19:05 PMYou led me down a dangerous garden path about biculatimide (as well as intramuscular injections).
To further elaborate on this matter and I feel I must, I believe you are greatly over exaggerating. If you consider the following:
Expert Opin. Drug Saf. (2014) 13(11):1483-1499"Diarrhea has been reported in only 2 -- 6% of patients in Bicalutamide monotherapy studies [29-31,43,44] and only isolated cases of elevated liver enzymes were observed [67]. To date,
only one case of Bicalutamide-induced hepatic failure has been reported in the literature [68]. This hepatic failure was attributed to Bicalutamide because of the absence of other etiologic factors, the temporal relation with drug administration and the resolution of hepatitis following drug discontinuation[68]. However, the authors note that the patient was previously treated with Cyproterone and Flutamide and hypothesize that these drugs might have sensitized the patient to Bicalutamide toxicity [68]."
"Interstitial pneumonitis induced by Bicalutamide is an
extremely rare event [69]."
"the mechanism of pulmonary toxicity induction by either Nilutamide or Bicalutamide remains unclear."
Also,
https://en.wikipedia.org/wiki/Bicalutamide#Reproductive_changes"The incidence of diarrhea with bicalutamide monotherapy in the EPC trial was
comparable to placebo (6.3% vs. 6.4%, respectively).[94] In phase III studies of bicalutamide monotherapy for LAPC, the rates of diarrhea for bicalutamide and castration were 6.4% and 12.5%, respectively, the rates of constipation were 13.7% and 14.4%, respectively, and the rates of abdominal pain were 10.5% and 5.6%, respectively.[177]"
"At 5.3 years follow-up, the incidence of depression was 5.5% for bicalutamide relative to 3.0% for placebo in the EPC trial, and the incidence of asthenia (weakness or fatigue) was 10.2% for bicalutamide relative to 5.1% for placebo.[178]"
In men taking only this anti-androgen. Estrogen could well have improved or resolved this because these symptoms may be due to too little sex hormones.
"The incidence of anemia with bicalutamide as a monotherapy or with castration was about 7.4% in clinical trials.[63] A decrease of hemoglobin levels of 1–2 g/dL after approximately six months of treatment may be observed.[179]"
No difference with castration. So whether you get your gonads removed (as in SRS) or take bicalutamide, no difference.
Hot flashes and dry skin are reported. Hot flashes are remedied by estrogen while dry skin is a common feature of transwomen anyways.
"At 7.4-year follow-up, there were numerically more deaths from heart failure (1.2% vs. 0.6%; 49 vs. 25 patients) and gastrointestinal cancer (1.3% vs. 0.9%) in the bicalutamide group relative to placebo recipients, although cardiovascular morbidity was similar between the two groups and there was no consistent pattern suggestive of drug-related toxicity for bicalutamide.[17][187] In any case, although the reason for the increased overall mortality with (...) bicalutamide monotherapy has not been fully elucidated,[154] it has been said that the finding that heart failure was twice as frequent in the bicalutamide group warrants further investigation.[188] In this regard, it is notable that low testosterone levels in men have been associated in epidemiological studies with cardiovascular disease as well as with a variety of other disease states (including hypertension, hypercholesterolemia, diabetes, obesity, Alzheimer's disease, osteoporosis, and frailty).[189]
According to Iversen et al. (2006),
the increased non-prostate cancer mortality with bicalutamide monotherapy in LPC patients has also been seen with castration (via orchiectomy or GnRH analogue monotherapy) and is
likely a consequence of androgen deprivation in men rather than a specific drug toxicity of bicalutamide:[190]"
We take estrogen as opposed to these men who take none. Bio-identical estrogen has shown in studies to improve cardiovascular markers and in general, the trend in post-menopausal women towards increased cardiovascular morbidity and mortality suggests estrogen is cardioprotective. Hence, findings do not appear to pertain to us.
"the incidence of abnormal liver function tests was 3.4% for bicalutamide and 1.9% for standard care (a 1.5% difference potentially attributable to bicalutamide) at 3-year median follow-up.[17][191]
For comparison, the incidences of abnormal liver function tests are 42–62% for flutamide, 2–3% for nilutamide,[35][192] and (dose-dependently) between 9.6% and 28.2% for CPA,[193][194][195]"
To be fair, CPA doses are very high and those used in transsexual women are significantly lower. Bicalutamide doses were also high and would also not be typical of the doses used in transsexual women for the purpose of feminization and reducing masculinisation.
"In the EPC trial, bicalutamide-induced liver changes were usually
transient and rarely severe.[17] The drug was discontinued due to liver changes (manifested as hepatitis or marked increases in liver enzymes) in approximately
0.3% to 1% of patients treated with it for prostate cancer in clinical trials.[33][34]"
"The risk of liver changes with bicalutamide is considered to be
small but significant, and monitoring of liver function is recommended.[17][40]"
"
Out of millions of patient exposures,[54] a total of five cases of bicalutamide-associated hepatotoxicity or liver failure, two of which were fatal, have been reported in the medical literature as of 2016.[35][36] One of these cases occurred after only two doses of bicalutamide, and has been regarded as much more likely to have been caused by prolonged prior exposure of the patient to flutamide and CPA.[35][192][199][200][201]"
4 out of millons of patient exposures.
"Relative to flutamide (which has an estimated incidence rate of 3 in every 10,000), hepatotoxicity or liver failure is far rarer with bicalutamide and nilutamide, and bicalutamide is regarded as having the lowest risk of the three drugs.[10][199][202] For comparison, by 1996, 46 cases of severe cholestatic hepatitis associated with flutamide had been reported, with 20 of the cases resulting in death.[193] Moreover, a 2002 review reported that there were 18 reports of hepatotoxicity associated with CPA in the medical literature, with 6 of the reported cases resulting in death, and the review also cited a report of an additional 96 instances of hepatotoxicity that were attributed to CPA, 33 of which resulted in death.[193]"
"Interstitial pneumonitis with bicalutamide is said to be an
extremely rare event,[209]"
"An assessment done prior to the publication of the aforementioned study estimated the rates of pulmonary toxicity with flutamide, bicalutamide, and nilutamide as 1 case,
5 cases, and 303 cases
per million, respectively.[212]"
"In addition to interstitial pneumonitis,
a single case report of eosinophilic lung disease in association with six months of (...) bicalutamide treatment exists.[4][213] Side effects associated with the
rare potential pulmonary adverse reactions of bicalutamide may include dyspnea (difficult breathing or shortness of breath), cough, and pharyngitis (inflammation of the pharynx, resulting in sore throat).[214]"
"
A few cases of photosensitivity (hypersensitivity to ultraviolet light-induced skin redness and/or lesions) associated with bicalutamide have been reported.[215][216][217]"
"Hypersensitivity reactions (i.e., drug allergy), including angioedema and hives, have
uncommonly been reported with bicalutamide.[33]"
"A case report of male breast cancer subsequent to bicalutamide-induced gynecomastia has been published.[218] According to the authors, "this is the second confirmed case of breast cancer in association with bicalutamide-induced gynaecomastia (correspondence AstraZeneca)."[218] It is notable, however, that gynecomastia does not seem to increase the risk of breast cancer in men.[218][219] Moreover, the lifetime incidence of breast cancer in men is approximately 0.1%,[220] the average age of diagnosis of prostate cancer and male breast cancer are similar (around 70 years),[170][221] and millions of men have been treated with bicalutamide for prostate cancer,[54] all of which are potentially in support of the notion of chance co-occurrences.[218] In accordance, the authors concluded that "
causality cannot be established" and that it was "probable that the association is entirely coincidental and sporadic."[218]"
"A single oral dose of bicalutamide in humans that results in symptoms of overdose or that is considered to be life-threatening has not been established.[33][222] "
"Overdose is considered to be unlikely to be life-threatening with bicalutamide"
"
Relative to the earlier antiandrogens, bicalutamide has substantially reduced toxicity, and in contrast to them, is said to have an excellent and favorable safety profile.[61][58][62][63] For these reasons, as well as superior potency, tolerability, and pharmacokinetics, bicalutamide is preferred and has largely replaced flutamide and nilutamide in clinical practice.[66][67][68] In accordance, bicalutamide is the most widely used antiandrogen in the treatment of prostate cancer.[51][52][53] Between January 2007 and December 2009, it accounted in the U.S. for about 87.2% of NSAA prescriptions.[54]"
"The rate of nausea and vomiting appears to be lower with bicalutamide and flutamide than with nilutamide (approximately 30% incidence of nausea with nilutamide, usually rated as mild-to-moderate).[124][242] In addition, bicalutamide (and flutamide) is not associated with alcohol intolerance, visual disturbances, or a high rate of interstitial pneumonitis.[94][241] In terms of toxicity and rare reactions, as described above, bicalutamide appears to have the lowest relative risks of hepatotoxicity and interstitial pneumonitis, with respective incidences far below those of flutamide and nilutamide.[10][199][202][211] In contrast to flutamide and nilutamide, no specific complications have been linked to bicalutamide.[161]"
Compared to CPA,
"Due to the different hormonal activities of NSAAs like bicalutamide and SAAs like CPA, they possess different profiles of adverse effects.[161] CPA is regarded as having an unfavorable side effect profile,[94] and the tolerability of bicalutamide is considered to be superior.[65][202] Due to its strong antigonadotropic effects and suppression of androgen and estrogen levels, CPA is associated with severe sexual dysfunction (including loss of libido and impotence) similar to that seen with castration[94][161][171] and osteoporosis,[275] whereas such side effects occur little or not at all with NSAAs like bicalutamide.[17][161] In addition, CPA is associated with coagulation changes[271] and thrombosis (5%),[24][171] fluid retention (4%),[171] cardiovascular side effects (e.g., ischemic cardiomyopathy) (4–40%),[276][34] and adverse effects on serum lipid profiles,[94][24][161] with severe cardiovascular complications (sometimes being fatal)[161] occurring in approximately 10% of patients.[124] In contrast, bicalutamide and other NSAAs are not associated with these adverse effects.[277] Moreover, CPA has a relatively high rate of generally severe and potentially fatal hepatotoxicity (see here),[94][278] whereas the risk of hepatotoxicity is far smaller and comparatively minimal with bicalutamide (though not necessarily with other NSAAs, namely flutamide) (see here).[279][280] CPA has also been associated with high rates of depression (20–30%) and other mental side effects such as fatigue, irritability, anxiety, and suicidal thoughts in both men and women, side effects which may be related to vitamin B12 deficiency.[281][282][283][284]"
Compared to Spironolactone,
"Unlike spironolactone, bicalutamide has no antimineralocorticoid activity,[171] and for this reason, has no risk of hyperkalemia (which can, rarely/in severe cases, result in hospitalization and/or death)[288] or other antimineralocorticoid side effects such as urinary frequency, dehydration, hypotension, hyponatremia, metabolic acidosis, or decreased renal function that may occur with spironolactone treatment.[134][289][290]"
So when you say I misled you on a dangerous path and when one considers all the above, with much cited references, I must say that you are indeed greatly overestimating the risks simply because you happened to have a serious side-effect from it. Serious side-effects can also occur with other anti-androgens, a comparison was noted above. I will agree, however, that bio-identical estrogen and progesterone appear to be, on the whole, safer than taking any anti-androgen at all.
It is important to put things in perspective and not point the finger unfairly. I simply ask you to be just and objective. I consider that I have done nothing wrong and that my intentions are always good ones. My heart is in the right place and it is disappointing to note your attitude towards me.
QuoteSomeone else felt badly misled by you recently but I bit my tongue and watched them saying the same things that I have.
Have you noticed this happens very rarely? Why, you must ask yourself? And how many have appreciated my input? If I am wrong, I am wrong and I will admit it. But, in two other cases where I recall having been pointed the finger, these were not justified and this is because either the evidence in support of my claims was quite significant or that the hormone in question appears to be, on the whole, quite safe, so that suggesting it could be a part of one's regimen (if the doctor approves and is on board, of course) isn't doing anything wrong. Side-effects with almost anything that we take, anything we do, will occur. Should we avoid transitioning then? Stop going out in the world and breathe the polluted air? Stop driving, taking planes, etc? Living is a risk. So that, when I consider some drugs or hormones relatively safe, I mean to say that, on the whole, they appear to be associated with relatively few risks and that the benefit:risk ratio is quite good.
In the end, it remains...I'm not a doctor. So, you need to do the right thing, do some research of your own, consult a doctor, and be smart about it. Taking responsibility for your life and your actions is what an adult does. I believe we are all adults here. If I err, I will say so because I take responsibility for any error I make and will try not to repeat it.
Further discussion on this matter will occur privately with Rachel if she so wishes. I don't intend on pursuing this conversation in public, only privately for the benefit of others and this forum.
