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May 18 17 12:18 PM

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--- Because I was taking Finasteride (antiandrogen) and experienced atrial fibulation (cardio arhythmia). Deep wading here, but seemingly essential. My docs won't prescribe antiandrogens for me.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516188/

 Cardiovascular effects of hormone therapy for prostate cancer

Jason F Lester1 and Malcolm D Mason1,
2Author information ► Copyright and License information ►Go to:

Abstract
Androgen deprivation therapy (ADT) has been the mainstay of treatment for advanced prostate cancer for decades, and has been shown to control disease and improve symptoms. In addition, for men with high-risk localized or locally advanced prostate cancer, short-course ADT in combination with radiotherapy improves survival. There is evidence that ADT increases cardiovascular risk, particularly in men with preexisting cardiovascular disease. This increased risk may apply even with short-course ADT. In an individual patient, the benefits of ADT should be balanced against the risk, and patients who require ADT should have risk factors for cardiovascular disease optimized. There is some evidence to suggest that more contemporary methods of delivering ADT may reduce cardiovascular risk.Keywords: androgen deprivation therapy, testosterone, cardiovascular risk, hypercoagulability, prostate cancer patients, dihydrotestosterone, androgen receptorGo to:Basic physiologyOne of the key drivers of prostate cancer is the androgen testosterone. The production of testosterone primarily occurs in the testes, and this process is regulated by luteinizing hormone (LH) produced by the anterior pituitary gland. In turn, the production of LH is regulated by gonadotropin-releasing hormone (GnRH) (also called luteinizing hormone-releasing hormone [LHRH]), produced by the hypothalamus. Testosterone acts as a “negative feedback” to maintain physiological levels; high levels of testosterone will lead to inhibition of GnRH and LH production, reducing subsequent testosterone production.Manipulating the hypothalamic–pituitary–gonadal axis to achieve castrate levels of testosterone is a key therapeutic intervention in men with advanced prostate cancer. However, the testes produce only 90% of the testosterone present in the adult male. The remaining 10% is derived from adrenal steroid synthesis. The adrenal glands secrete the weak androgens dehydroepiandrosterone and androstenedione that can be converted into testosterone in peripheral tissues and the prostate gland. Newer hormone treatments have been developed to target the production of androgen precursors in the adrenal gland, and have shown to be effective in the treatment of advanced prostate cancer.Despite the undoubted benefit of lowering testosterone in men with advanced prostate cancer, there may be unwanted side effects as these hormones have other physiological roles in the body. The potential consequences of androgen deprivation therapy (ADT) are described in this review.Introduction: an historical background In 1941, Huggins et al published their historic studies, which heralded the age of hormone therapy (perhaps more correctly referred to as ADT) for human prostate cancer.1,2 In 2010, a science advisory was jointly published by the American Heart Association, the American Cancer Society, and the American Urological Association, highlighting the link between ADT for prostate cancer and cardiovascular risks.3 It seems fair to say that there is now a high level of awareness on the part of cancer physicians and surgeons of the detrimental effects of ADT in terms of cardiovascular risk, but this is now expressed as a general feeling that ADT is bad for men, and, as others have noted, patients who would benefit from ADT might be under-treated if a careful balance is not maintained.4 Before addressing the – now high-profile – complications of ADT, let us begin with a clear and unequivocal statement of its benefits. For metastatic prostate cancer ADT, usually using orchidectomy or LHRH agonists, is the mainstay of treatment. In addition, ADT is frequently used in combination with radiotherapy, and the evidence is quite unequivocal that ADT improves survival when given in addition to radiotherapy for high-risk disease.58 In addition, it might improve cancer outcomes when given in addition to radiotherapy for intermediate-risk prostate cancer.9 It is informative to look at the evolution of hormone therapy for prostate cancer when discussing cardiovascular risk with ADT. The Veterans Administration Cooperative Urologic Research Group (VACURG) carried out a series of trials in the 1960s looking at treating all stages of prostate cancer. The first, and arguably most important trial randomized patients with stage I and II prostate cancer to radical prostatectomy and either diethylstilbestrol (DES) or placebo, and stage III and IV patients to placebo, DES 5 mg, orchidectomy and DES 5 mg or orchidectomy and placebo.10 In stage III patients, there was an excess of cancer deaths in the arms treated with placebo but quite unexpectedly, an excess of cardiovascular deaths in the DES arms. A similar pattern was also seen in the stage I and II patients and importantly, there were more total deaths in the DES arms of the trial. A retrospective review of patients’ medical records suggested a history of cardiovascular disease was a predisposing factor to early death.11 Patients randomized to placebo did, however, derive significant benefit when given DES later on for symptom control. The excess of cardiovascular deaths in the first VACURG trial did not appear to be driven by androgen deprivation – patients randomized to orchidectomy did not appear to be at greater risk. One criticism of the first VACURG trial was the high dose of DES used. The second VACURG trial attempted to address this by using three doses of DES (0.2 mg, 1 mg, and 5 mg). In addition, cardiovascular data were also collected prospectively, to try and understand the surprising findings from the first trial showing excess cardiovascular deaths in the DES arms.12 The second trial showed that 0.2 mg DES was ineffective, and that the 1 mg dose was as effective as the 5 mg dose in controlling prostate cancer, but did not seem to be associated with excess risk of cardiovascular death. Tellingly, the placebo arms in stage III patients were still superior to all DES arms with regard to survival and this was thought due to excess noncancer deaths in those taking DES. Taking data from the VACURG trials into consideration, it was recommended that 1 mg DES should be used in preference to 5 mg but to withhold treatment until required.13 In the following decades, an increasing knowledge of the androgen pathway led to the development of new hormone treatments to either inhibit androgen production or block the effect of androgen on target cells.1418 LHRH agonists have been tested in a large number of randomized trials that compared the various approaches to androgen-ablative therapies (such as orchidectomy, estrogen administration, and LHRH agonists). The received wisdom from these studies is that all approaches are equally effective, reducing tumor growth in 70%–80% of symptomatic patients, though the robustness of this conclusion is debatable.19 On the basis of these studies, LHRH agonists have become the preferred method for androgen-ablative therapy. LHRH antagonists, which directly inhibit the LHRH receptor, have also been developed as prostate cancer therapeutics.20 These antagonists were initially developed for contraceptive purposes. Several of these antagonists have been tested in clinical trials as treatment for men with advanced prostate cancer. Preliminary data indicate that these agents are as effective as the LHRH agonists in lowering serum testosterone, but do not cause the testosterone flare that is synonymous with the LHRH agonists.Testosterone and cardiovascular riskTo look at the potential effects of ADT on cardiovascular risk, it is useful to look at the effects of testosterone on the cardiovascular system. Herring et al have carried out a comprehensive basic science review on this subject, and it seems that testosterone might have both beneficial and harmful effects.21 Testosterone has been shown to exhibit potential antiarrhythmic properties, and in animal models, reduces myocardial infarct size by modulating the myocardial K (adenosine triphosphate [ATP]) channel, enhancing vaso-dilation, attenuating atherosclerosis, and improving lipid metabolism. There are, however, studies that found testosterone may cause vasoconstriction, inflammation, and result in death signaling. These findings suggest a complex interaction between the cardiovascular system and testosterone.The population-based evidence on the effect of testosterone on cardiovascular risk is also very variable in its findings, and testosterone may not be the only androgen involved. In men, approximately 5% of testosterone undergoes 5α-reduction to form the more potent androgen dihydrotestosterone (DHT). This enzymatic conversion is carried out in the prostate, testes, hair follicles, and adrenal glands. DHT has two to three times greater androgen receptor (AR) affinity than testosterone, and given its potency, several studies have looked at the effect of both testosterone and DHT on cardiovascular risk. Yeap et al measured plasma total testosterone and DHT in early morning samples from 3,690 community-dwelling men aged 70–89 years.22 Higher testosterone or DHT was associated with a lower incidence of stroke, but not of myocardial infarction.In a longitudinal cohort study, Shores et al evaluated whether total testosterone, calculated free testosterone, DHT, and calculated free DHT were associated with cardiovascular disease and mortality in 1,032 men in the Cardiovascular Health Study who were free of cardiovascular disease at the time of the study.23 In models adjusted for cardiovascular risk factors, total testosterone and calculated free testosterone were not associated with incident cardiovascular disease or all-cause mortality, whereas DHT and calculated free DHT were so, in a nonlinear fashion, with the lowest incidence of stroke associated with a total DHT concentration just above the mean, at approximately 65–70 mg/mL, while free DHT had an inverse correlation with risk.Shores et al also looked at whether testosterone or DHT was associated with incident ischemic stroke in the same cohort of men.24 Total testosterone and free testosterone were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke. The lowest risk of stroke was at DHT levels of 50–75 ng/dL, with a greater risk of stroke at DHT levels >75 ng/dL or <50 ng/dL. Thus, variable results have been reported in both basic science and population-based studies on the relationship between androgens on the cardiovascular system. Further studies are needed to better define this relationship and establish whether in fact there is an optimal androgen range associated with the least risk of adverse outcomes.The metabolic syndrome is a cluster of the most dangerous risk factors for cardiovascular disease.25 Patients with metabolic syndrome have a two-fold increase in cardiovascular disease risk.26 The International Diabetes Federation defines patients as having the metabolic syndrome if they have central obesity plus two any of the following four factors:
  • raised triglycerides;
  • reduced high-density lipoprotein (HDL) cholesterol;
  • raised blood pressure;
  • raised fasting plasma glucose.
A low serum testosterone concentration predicts or is associated with the metabolic syndrome, and type 2 diabetes mellitus.27,28 As might be expected, men with the metabolic syndrome and type 2 diabetes mellitus often have low testosterone levels.29 It is worth noting though, that the mechanisms whereby a low testosterone level increases the risk of death may be complex. A prospective, population-based study of 794 men aged 50–91 years reported low testosterone was associated with an increase in mortality that was independent of the metabolic syndrome, diabetes, and prevalent cardiovascular disease.30The link between low testosterone and increased cardiovascular risk has also been reported in observational studies. Brand et al conducted an individual participant data meta-analysis of 20 observational studies.31 Mixed effects models were used to assess cross-sectional and prospective associations of total testosterone, sex hormone-binding globulin, and free testosterone with metabolic syndrome and its individual components. Men with low concentrations of total testosterone, sex hormone-binding globulin, and free testosterone were more likely to have metabolic syndrome compared to those having high sex hormone concentrations. The associations were independent of age and lifestyle factors. Interestingly, the association between total testosterone and metabolic syndrome was strongest in men with a body mass index (BMI) <25 kg/m2. The reason for this interaction is not clear, but the weaker association in overweight men suggests a dominant role for non-androgenic risk factors, or perhaps the emergence of relative androgen insensitivity with increasing BMI. In children, an inverse association between BMI and AR sensitivity has been reported, but no studies so far have explored this association in middle-aged and older men.32Several trials have shown that elevating low testosterone levels may improve features of the metabolic syndrome and glycemic control, and hence modify cardiovascular risk factors. In a single blind, 52-week randomized clinical trial, the effects of supervised diet and exercise with or without transdermal testosterone administration on components of the metabolic syndrome in hypogonadal men with the metabolic syndrome and newly diagnosed type 2 diabetes were assessed. Glycosylated hemoglobin, fasting plasma glucose, HDL cholesterol, triglyceride concentrations, and the waist circumference improved in both treatment groups after 52 weeks of treatment, but were significantly better in the testosterone-supplemented group.33In a prospective, observational, long-term study, 181 obese (BMI ≥30 kg/m2) hypogonadal men (serum testosterone <12.1 nmol/L), with and without type 2 diabetes mellitus, were treated with testosterone over 5 years.34 In the total study population, there was an improvement in all cardiovascular risk factors. Significant improvements were seen in lipid profile, blood pressure, fasting glucose, HbA1c, and liver function. In the diabetic subgroup, there were significant improvements in fasting glucose and HbA1c with comparatively greater decreases seen in the diabetic subgroup than in the general population.Testosterone has been studied as a treatment for congestive heart failure (CHF). Three randomized placebo-controlled trials showed that testosterone therapy for men with CHF improved various functional CHF outcomes, such as exercise capacity, peak oxygen consumption, and New York Heart Association heart failure class, but did not improve left ventricular function.3537 Thus, studies show that testosterone for heart failure improves patient functional status, exercise capacity, and ventilatory efficiency, with most evidence showing an absence of changes in cardiac anatomy or left ventricular function. Therefore, the benefits are likely because of peripheral effects of testosterone, perhaps relating to testosterone’s vasodilator effects, its effects on glucose metabolism, and its ability to improve skeletal muscle function. According to the muscle hypothesis, improvement in skeletal muscle function might improve cardiac function by neurohumoral, autonomic nervous system, or hemodynamic mechanisms, or because improvement in skeletal muscle physiology might result in a delay of muscle converting to anaerobic metabolism during exercise.There are, however, studies that suggest a detrimental effect of testosterone on the cardiovascular system. A retrospective national cohort study of men with low testosterone levels who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011 showed that testosterone was associated with an increased risk of adverse events (all-cause mortality, myocardial infarction, or stroke).38It is clear that there is a complex interaction between testosterone and the cardiovascular system. To complicate the picture further, ADT may result in men acquiring some but not all aspects of the metabolic syndrome, and some of the changes seen may be different. Smith et al carried out an open-label prospective study on 26 men with recurrent or locally advanced prostate cancer who were treated with leuprolide (LHRH agonist) for 12 months.39 In this trial, in contrast to the metabolic syndrome, leuprolide increased subcutaneous fat mass, HDL cholesterol, and adiponectin, and did not alter the waist-to-hip ratio or blood pressure.In summary, most animal models and population-based research strongly suggest a beneficial effect of testosterone on cardiovascular risk, but there are studies with conflicting results. Low serum testosterone is associated with the metabolic syndrome, but it is possible that the changes induced by ADT for prostate cancer are different from those seen in classical metabolic syndrome, making any estimation of cardiovascular risk from ADT more difficult. 

Formatting in this forum totally sux

Allison Wunderland's Transcend Dance
http://allisontranscend.blogspot.com/

Last Edited By: AllisonWunderland May 18 17 12:20 PM. Edited 1 time

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May 18 17 1:21 PM

Finasteride blocks the conversion of T into DHT, which is the main culprit in the masculation of older males. There are other medications that block T directly such as Spironolactone, but from what I have read, those have even more side effects. You might want to try saw palmetto, which is supposed to be a natural DHT blocker similar to Finasteride, but there is conflicting scientific evidence as to its effectiveness in that regard.

Last Edited By: April May 18 17 2:20 PM. Edited 1 time.

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May 18 17 2:17 PM

-- Or I can present as "stone butch" and deconstruct gender stereotypes. Finasteride put me in the Cardio ward. Spironolactone seems to have more adverse cardio issues than Finasteride.

It's not the meds, but rather the imbalance in the metabolism of testosterone and all the cardio related things testosterone does. Mostly, I just wish the hair would stop growing all over and instead thicken up on my head. Also, I wish I didn't need to pee a half dozen times during the night.

Stone Butch, "stealth lesbian." I don't need to be "femme" so much as I simply desire not being so testosterone driven masculine, Bilateral orchiectomy raises the same cardio issues as the meds. Thankfully, as a radical feminist lesbian, I am becoming more and more at ease with the "Stone Butch" presentation. I'm not broken and don't need the masculinist hegemony of the medical establishment to "fix" me. My gender presentation is becoming more and more resolved and situated in between the two overlapping bell curves of the hetero-normative dyad. Not male, not female, but rather a sort of militant queer.

But then this raises a whole other issue: I'm not seeking hetero-sexual relations with cis-M . . . or any form of masculine presentation. Sexually, I like females, would like to be one.

Judith Butler refers to this as "hetero-sexual melancholia" -- the foreclosure of the "other" (Lacan) and epistemological angst of the hetero-normative dyad.

And so I wonder . . . How many of us in this forum are "homo-sexual" (as in cis-M and desiring sex with males) ???

allisontranscend.blogspot.com

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May 19 17 10:34 AM

Bi lateral orchiectomy is standard Rx for prostate cancer treatment. Post operative mgmt requires monitoring calcium intake and bone density to control osteoporosis. Single orchi is often an option for testicular cancer. Finasteride is an option for mgmt of BPH benign prostate hyperplasia -- which has one peeing frequently, problems empyting the bladder, urinary urgency. The docs wanted to Rx something for BPH, and I opted for Finasteride -- as an adjunct to lower testosterone, supporess hair growth. Finasteride precipitated atrial fibrillation.

Bottom line is -- tweaking the endocrine system is fussy business.

Last Edited By: AllisonWunderland May 19 17 10:36 AM. Edited 1 time.

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Jun 15 17 11:30 AM

In other news --

My Primary Care MD, my cardio, and my psych meds docs all have opted to get me back on Finasteride, 5mg, / day.

Allison Wunderland's Transcend Dance
http://allisontranscend.blogspot.com/

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AllisonWunderland wrote:
In other news --

My Primary Care MD, my cardio, and my psych meds docs all have opted to get me back on Finasteride, 5mg, / day.

Allison Wunderland's Transcend Dance
http://allisontranscend.blogspot.com/

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Maybe you don't actually need it, if you just have ultra low-dose estradiol instead?
http://programme.exordo.com/epath2017/delegates/presentation/27/
One way to avoid the negative side effects of a drug is just not to take it at all..

What do I know, to me one of the positive side effects of the drug is growing a set of hooters, and it feels all warm and scrummy at the same time.

Last Edited By: Xora . Edited 1 time.

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Xora, Good point there. Estrogen taken over time will lower T levels. My endo was initially opposed to me taking any type of T blockers because of some health concerns, She started me out on fairly low dose of E and stepped it up every several months. My T levels slowly came down by following that protocol. It takes longer that way, but my endo believes it actually produces better long term results than slamming T levels down from the start. It gives the body and the psyche time to adjust. And yes, having boobs is way fun. My own were rather slow to progress, but my development has kicked into full gear in the last 6 months. The downside now is that I can't really hide them anymore should I choose to go butch.

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Well, my endo asked if I'd had much growth, and I said that I didn't think I had, not more than I'd already self-induced with the PM before, but that was taken over 6+ months. I have felt some stuff going on though, and I definitely like it and it's just sort of natural and what I've been waiting for for years, but to an extent I'm still kind of living in denial and dissociated from my body, which has probably kind of gradually been changing shape for years, in ways that other people have noticed far more than I have.
So other people who are looking can probably see things I can't, but having lived in total denial mode for decades it's hard not to keep thinking of yourself as a kind of a brain in a vat, rather than a body that other people are interacting with.

I mean, as a teenager I was getting the 'she is one of me' type feeling from people like this:
image,
as in, in an ideal world, that's the kind of person other people would think they were interacting with when they were interacting with me, and not what I actually look like. But I was too scared to think of myself like that, and so kept it at arms length and it's me in a parallel universe, and not in this one, so I didn't put in effort to take myself physically in that direction, and that definely wasn't what other people were seeing, so every interaction I had was kind of stilted, coz I think I'm living in some kind of plausible deniability, and if I just don't believe I'm a girl in public, then other people won't know what I'm getting up to in private, and everything will just work out. It wasn't what I wanted, but it was the best I thought I 'deserved', given my situation.

It's kind of sad, you make one big 'pragmatic' decision driven mostly by fear when you are 15, and you never get to experience all the kinds of situations that you actually want to experience in the next 20 years.

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