About this study, one interesting statement is this:
"Gooren et al. (2008), reported no increase in VTE among 2236 male-to-female (MTF) transgender individuals on HT from 1975 to 2006 compared with controls, with the exception of those who used ethinyl estradiol, for which there was a 6–8% incidence [4]."
This would confirm my earlier statement.
Also...
"Additionally, while Wierckx et al. (2013) observed 5% of 214 MTF individuals to have a VTE within the first three years of estrogen therapy, 10 out of 11 of these women had at least one VTE risk factor such as smoking, immobilization due to gender confirmation surgery, or a hypercoaguable disorder [5]."
HRT consisted of
- cyproterone acetate (n=2)
- oral EV + CPA (n=2)
- oral EV only (n=1)
- transdermal estradiol (n=3)
- ethinyl estradiol (n=1)
- conjugated equine estrogens (n=1)
- unknown (n=1)
So, 4 out of the 11 only took bio-identical estradiol and nothing else. But, out of those 11,
- 7 smoked
- 3 were immobilized due to surgery
- 1 had a clotting disorder
In reviewing all cases of DVT/pulmonary embolism and cardiovascular complications in this study, the first thing one notices is that smoking is quite prevalent, 14 of 19 being smokers or former smokers (n=1). 11 out of 19 ppl were 50 yrs of age or older. 6 out of 8 ppl with cardiovascular problems were 50 yrs of age or older.
The smoking frequency or presence/absence is not noted in the control groups so we have no way of knowing whether transsexual women smoked more, as much, or less than the control groups. This is unfortunate as this would have elucidated the role of HRT in the etiology of DVT/CVD more clearly.
One must not also ignore the fact that some transsexual women supplement by taking more estrogen illegally (self-medicating) after realizing that the doses prescribed are too low and aren't producing satisfactory results. The type of estrogen and dose may be adversely affecting their health. This not factored in so who knows? And are they reporting accurately and honestly what they are taking?
Cancer was also not more prevalent among transsexual women. Ten transpersons (9 women, 1 man) died. 6 because of suicide which seems quite prevalent among our population, sadly. 2 from CVD, 1 from cancer and 1 unknown.
They state in the discussion section
"The incidence of venous thrombosis and/or pulmonary embolism in this study (5.1%) was lower than that reported by Van Kesteren et al. (7), who showed that 6.4% of their sample experienced this during hormone treatment. The use of high-dose oral ethinyl estradiol (*μg OD) may explain the higher incidence in the latter study, as the type and route of administration of this estrogen are known to affect the coagulation system negatively (5, 17, 18). However, Ott et al. (19) did not observe any venous thrombosis and/or pulmonary embolism incidents during their follow-up study of 162 trans women (mean age 36 years) who received transdermal 17β-estradiol therapy for an average of 4.4 years. This may be a safer type of estrogen and route of administration, although 37% of the trans women who experienced venous thromboses in our sample received transdermal 17β-estradiol therapy. The older age of the participants and the longer follow-up period in the present study may also contribute to the higher incidence of these events."
How about maybe those women on transdermal having a venous thrombosis experienced this because of their smoking (or immobilization due to surgery or genetic predisposition) or because they didn't reliably report what they really took as a result of supplementing outside or were assumed to follow protocol when they really didn't because they found the doses too conservative and not enough to produce results. These are all important factors to consider.
"the majority of trans women who experienced myocardial infarction or CVD were aged over 50 years, had one or more cardiovascular risk factors (mainly smoking), and had undergone cross-sex hormone therapy for a short duration."
"We discovered that both trans men and women had a higher prevalence of type 2 diabetes than the control men and women, with
almost all diagnoses being made before starting hormone therapy in trans women."
In an earlier study by Wierckx
http://www.ncbi.nlm.nih.gov/pubmed/22906135 (no control group)
of those transsexual women who had a thromboembolic event and cardiovascular problems (n=6), it is interesting to note that of those women
- 5 were smokers or former smokers with years of smoking ranging from 18-45.
- all but one (or two, the second not specifying which type of estrogen) were on estrogens that were NOT bio-identical AND cyproterone acetate (n=2)
It is also stated
"a quarter of the transsexual women had osteoporosis at the lumbar spine and radius."
which strongly suggests the estrogen doses prescribed were too low, increasing the likelihood that transsexual women supplement outside their protocol due to unsatisfactory results. Doctors don't realize they are harming their patients by underprescribing because for one, they are increasing health risks due to insufficient sex hormones in the body AND because they are giving women more incentive to source estrogen from outside sources which might increase risks. Underprescribing also increases likelihood that feminization will be less than optimal and that FFS will be resorted to, with all the risks associated with this type of surgery.
Furthermore, it is stated in the original study that
"Venous thrombosis events (VTE) were reported in MTF individuals as early as 1976, when a 29-year old transgender woman with no history or risk factors for VTE presented with pulmonary embolism after beginning estrogen therapy of diethylstilbestrol (DES) [7]. A 1978 paper also observed an occlusion of the middle cerebral artery during estrogen therapy in a transgender woman, where the patient was reported using mestranol, a 3-methyl ether of ethinyl estradiol [8]."
In both cases, the estrogen taken is not bio-identical.
"Wilson et al. (2009) also observed increases in inflammatory markers (cytokine IL-6, IL-1 and IL-8, clotting factors FV11 and FVIX and superoxide dismutase) consistent with this hypothesis for MTF individuals taking oral estrogen, but not for those taking transdermal estrogen [14]."
In this study, those taking oral estrogen were taking Premarin (moderate dose). NOT bio-identical estradiol.
On a positive note
"While some guidelines for transgender medical care express concerns for elevated cancer risk with certain hormone regimes, current data suggest that the risk of cancer may not rise."
"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."
"A comprehensive study among the medical records of 2306 orchidectomized MTF individuals reported an overall rare but possible incidence of prostate cancer of 0.04%"
"Additionally, there are ten case reports of breast cancer development among MTF individuals on estrogen since 1968"
This is VERY low.
"The three largest studies to date on mortality and transgender hormone therapy suggest no direct increased risk in mortality." Although suicide seems to be more prevalent among this population.
"Roberts et al. (2013) (n = 55) reported elevated median triglyceride levels of 120 mg/dL among MTF adults compared to both male (80 mg/dL median) and female (60 mg/dL median) control groups, with the range of participant values spanning from 34.2 to 242.6 mg/dL [46]. Cholesterol (LDL) levels among MTF individuals resembled female controls."
We don't have any information about their HRT.
"Roberts et al. (2013) reported that for MTF adults on estrogen therapy the values of hemoglobin and hematocrit were similar to female controls [48]."
"In Roberts et al, 2013 among MTF individuals, alkaline phosphatase, potassium and creatinine values resembled male controls [48]."
"Roberts et al. (2013) reported no difference in blood urea nitrogen values"
"Yahyaoui et al. (2008) found that fractional excreted of uric acids (FEUC) levels increased among 22 MTF individuals"
Of those 22, 18 took conjugated equine estrogens.
"Most studies on glycemic control in transgender individuals on HT report increased insulin resistance and fasting glucose."
Whether these are caused by cyproterone acetate, non bio-identical estradiol, smoking or bad eating habits in transsexual women, who knows? In all these studies, most women had been on estrogen that wasn't bio-identical.
"Studies with the greatest statistical power show increased rates of osteopenia in transgender women on HT, however these may be limited by including participants who used anti-androgens for one year before starting estrogen therapy."
What did I say about only taking anti-androgens? And underprescribing?
"There are reports of enlarged pituitary glands among MTF individuals on HT [60], as well as six case reports of prolactinoma [61], [62], [63] and [64]. Prolactin levels have also been reported to be elevated among MTF individuals during long-term HT [60]."
All these cases included estrogen that wasn't bio-identical and/or cyproterone acetate which both stimulate prolactin to a significant degree and abnormally. One case involved extremely HIGH doses of injectable estrogen, unheard of, combined with EE and CPA.
"There are two case reports of systemic lupus erythematosus occurring in MTF individuals with no prior history of autoimmunity deficits; one case presented with SLE 1 year after starting estrogen injections, and another after 20 years on HT [68] and [69]."
In the case of estrogen injections,
"He had been taking "hormone shots" to induce feminization for at least 1 year prior to admission. He was evasive about the injections, and declined to give information on how he acquired them, and the brand and formulation used. He had developed obvious feminine features, including a higher pitched voice and gynecomastia."
Vague information and researcher bias and ignorance as they call the woman a "he" and reported higher pitch due to HRT which cannot happen. LOL.
In the second case, where HT was taken for 20 yrs, the hormone was Premarin (moderate dose).
"Hypercoaguable risk factors, including the use of a thrombogenic estrogen, ethinyl estradiol, have been associated with many of the cases of reported VTE, and as such the risk of these adverse events may continue to decline as the usage of this drug diminishes [3]."
"The Standards of Care (SOC) released by the World Professional Association for Transgender Health (WPATH) report that the greatest risk factor of MTF HT to be VTE and increased triglycerides, which is supported by this literature review [70]."
VTE should be an non-issue if all TS women were given bio-identical estradiol (oral and non-oral), without exception. I think we would then find no difference between this population and the general population IF the factor of smoking is controlled for (same in both populations).
Triglycerides, I suspect, could be caused by cyproterone acetate as well as non bio-identical estrogen. If CPA was discontinued as a treatment and substituted instead with either a GnRh analogue or just estrogen, I think this would greatly improve things.
To conclude, this study does not really fully address health risks with bio-identical estradiol only, without CPA, without estrogens such as ethinyl estradiol and conjugated equine estrogens.
There are only four cases where VTE was associated with the use of bio-identical estradiol but other factors such as smoking, age, clotting predisposition and immobility were present and as such, we cannot conclude with certainty that bio-estradiol CAUSED VTE/DVT. There is also the issue of supplementation that cannot be verified.
Interestingly, there are two studies from Germany (1998 and 2005) where all except 2 out of 103 took bio-identical estradiol (orally and non-orally), where doses on average were not conservative, sometimes combined with cyproterone acetate or GrNh analogue. There was only one case of DVT due to a genetic predisposition (mutation) and one case where clotting factors were abnormal but we don't know what type of estrogen was used and if CPA was taken.
I intend to reread several times this study and other related studies to really get a clear picture of it all.
