The Case Against Spironolactone

Beverly Cosgrove, 5/18/2018, Version 16

What’s wrong with Spironolactone? Lots.

Spironolactone (“Spiro”) is a potassium-sparing diuretic and steroid drug frequently prescribed in the US to assigned-male-at-birth (AMAB) trans women as part of their HRT. However, the drug has a number of mild to severe mental side effects, can lead to bodily changes which most trans women might consider disfiguring, and may interfere with breast development and other feminization.

Spiro began being prescribed to trans women in the early 90’s, when the dangers of taking estrogens in the form of Ethinyl Estradiol or Premarin became known. The use of Estradiol alone, without any kind of antiandrogen, is well known to be capable of suppressing testosterone to female levels. (Refs 2,3,4,5) However in the 90’s, the Estrogen-related dangers were known to be proportional to dose, and several studies demonstrated an elevated risk of cardiovascular disease within the first 1-2 years of HRT initiation. (Ref 6) Studies at the time unfairly lumped all estrogens together, and all progestins together, as having the same dangers, a mistake which still lingers today. (7) As a result of their unwillingness to treat trans women with high levels of estrogen, Spiro was added to many HRT regimens in the US to assist in suppressing testosterone levels and blocking testosterone effects.

Spironolactone does NOT feminize significantly, though it is known to encourage some gynecomastia in males.  It’s sole use is to reduce the effect of testosterone, and also testosterone levels, a job that estradiol would do if a suitable estradiol-only regimen were used instead.  Today, AMAB transsexuals often begin their HRT in the US with an “orthodox protocol” consisting of 2-4mg a day of estradiol in pill form plus 200mg a day of Spironolactone. Physicians favor this approach because it gives a fairly quick reduction in erectile capability which can give some fast relief to genital dysphoric transsexuals.

But there are problems associated with Spiro that your doctor may not tell you about.

Spiro doesn’t work well in reducing testosterone.  A long term study of New York clinic patients showed that Spiro was unhelpful in achieving basic HRT goals. “We unexpectedly did not find that Spironolactone aided in testosterone suppression and further found that it seemed to impair the ability to reach desired serum 17-β estradiol levels.” (26) In another recent study of patients following a Spironolactone and estradiol protocol, followed for as long as 3.5 years showed that the majority did not attain female levels of testosterone in the first couple of years, with only about half attaining it by year 3. (23)   In the chart below, taken from the same study, the yellow band shows the female normal testosterone level.  Only after 3 years of treatment did at least half of patients fall into that band.  Compare this to the profound drop in testosterone caused by even a single injection of estradiol, in as little as 36 hours. “Suppression of plasma testosterone levels from a mean of 760 ng/dl… in normal young adult men… to 123 ng/dl was noted 36 h after estradiol administration.”(25)
Spiro-ineffective-Capture

Spironolactone causes patient cortisol levels to rise. (Ref 1) Patients taking Spiro at doses as low as 25mg a day experience significantly elevated cortisol levels within a few weeks. (8) However, typical dose for trans women is 200mg per day, despite it being known that doses over 100mg have diminished effect. (9) Normally, the circulating levels of cortisol are tightly controlled by the hypothalamic-pituitary-adrenal (HPA) axis. A key feature of the HPA axis is negative feedback regulation, whereby cortisol suppresses its own secretion. Spiro activates the HPA axis.  However, chronic activation of the HPA axis may play a pathogenic role in a wide range of common metabolic and psychiatric disorders, including obesity, depression, and age-associated cognitive dysfunction. (1) In particular, depression which does not respond to common anti-depressant therapy has been noted in patients with hypercortisolism due to disruption of the HPA axis, which generally resolves itself once the cause is removed. (16,18)

Spiro-complaints-CaptureThe effects of Spiro on the brain’s mineralocorticord system are complex. The primary result as cortisol is raised is a crippling of certain thinking processes, selective attention, visuospatial memory, and mental flexibility/set shifting. There is also a modulation, both up and down, of panic and anxiety and ability to withstand stress. (10) Considering that the time of beginning of a transsexual’s hormonal transition may be one of the most stress-inducing periods of the person’s life, it is not surprising that patients receiving Spironolactone complain of “brain fog”, poor memory, irritation, anxiety and panic attacks. This also begs the question: could the start of Spiro-based HRT also explain increased incidence in the transgender community of self harm, addictive behavior, and suicide? Data to answer this question is lacking, but the risk seems rational and clear, and this complex of issues — brain fog, poor memory, lethargy, depression, anxiety and panic attack — are widely known in the transgender community. (11) [and Chart (15)] Especially worrying is the evidence that, if a patient is already depressed, adding Spironolactone greatly accelerates the level of hypercortisolism it induces, creating feedback which traps the individual in a depressive state which does not respond to antidepressants. (18)

But Spiro can actually sabotage the very physical changes that trans women seek through HRT. Increased cortisol is associated with accumulation of visceral fat — hard fatty deposits interlaced with internal organs which causes a swollen belly. It is important to discriminate between belly adipose fat, which is soft “jelly like” fat directly under the skin, and visceral fat which is behind the abdominal wall. Visceral fat requires significant effort with diet or exercise to remove and cannot be removed with any kind of ordinary plastic surgery. (20)  This visceral fat is caused by raised cortisol. The informal term “Spiro belly” arose because of the perception that those on high doses of Spiro for long term (200mg/day for over a year) seem to often have the characteristic protruding belly. Once visceral fat has accumulated, it is difficult to achieve an ideal waist-to-hip size ratio again, even if Spiro is stopped and diet and exercise is tried. Research on young girls with poor Waist/hip measurements correlate to higher cortisol levels and visceral fat, as well as mobilization of fat from elsewhere in the body to the central region — the opposite of the desired fat mobilization sought by trans women. (12) The association between hypercortisolism, major depressive illness, and deposits of visceral fat has been well established. (17)

Finally, Spiro use is associated with poor breast development in trans women. A preliminary study showed that patients using Spiro instead of another antiandrogen (such as Cyproterone) had significantly more dissatisfaction with breast development. (13) At this point, the causation is uncertain, but it is known that elevated cortisol suppresses Human Growth Hormone, resulting in smaller stature (14) and therefore possibly, reduced breast growth even in later life. Trans women are doubly penalized for Spiro use in this respect, because chest measurement to waist measurement ratio may be sabotaged at BOTH ends – the very opposite of an “hourglass figure”.

If you are taking Spironolactone now, and wish to quit, please be warned — quitting Spiro suddenly without preparation is difficult and hazardous, and your doctor is very unlikely to understand some of the problems you will encounter.  I will be writing a new article soon on the practical aspects of quitting, or if you are in a rush, you may consult materials and experiences in the Facebook HRT group for more information. Also, experience suggests that most trans women on megadoses of Spiro (200mg or higher) can successfully drop to 100mg a day without rebound effects (speak to your doctor). But, the best solution regarding Spiro is to never start.

Endocrine-Society-CapturePermit me to venture some personal opinions here. Spironolactone was made part of HRT based on standards set by The Endocrine Society (19,21) among others. By setting a standard for estradiol levels based on 90’s-era risk data about Premarin and Provera, the most dangerous forms of HRT, and ignoring the risk reduction of estradiol 17b given parenterally, they created an artificial standard based on what they did not know rather than what they knew. The risks of injected estradiol levels in the 300-500 pg/ml range are far lower than the risks of suicide or psychotic episodes or sustained mental illness due to mood disturbances from the antiandrogens the prescribers are now offering their patients to keep them below that level. The prescribers are saving their patients from a small risk by exposing them to a larger risk. It is simply a bad risk assessment. I have written more on this elsewhere. (7) It is notable that the 2009 version of The Endocrine Society guidelines even include a mention of estradiol injection (19) but still refer to Spironolactone. One final thought, this time a speculation: it seems possible based on observations that high levels of testosterone provide some protection against the cortisol-raising properties of Spironolactone, such that testing of the drug on male volunteers might not have shown such a large side effect when the drug was originally tested, leading to a situation where heavy dosing of trans women led to these oversized effects.

The medical community owes it to the transsexual community to take a second look at the overall risk/benefit ratio for the use of Spironolactone as an antiandrogen. Not only is there evidence that Spiro may be interfering with the primary goal of HRT, but Spiro may be directly responsible for patient harm by crippling the cognitive ability of patients and compromising their ability to withstand stress — a terrible burden for this highly stressed minority.


SOME ANECDOTAL EXPERIENCES

“The short term memory deficit and cognitive impairment were debilitating side effects of 25mg over a month’s time. This along with unusual bruising,dizziness/unsteadiness, and chronic exhaustion prompted me to stop taking it. I can’t imagine what might have happened with the common higher doses.”, MT, December 2016

“Was on that crap for 21 months. Lowered it from 200mg/day to 100, then 50, then 0. This was in Oct. of this year. Since then all the symptoms are going away. I also stopped using finasteride. Switched from pills and oral P4 to injectable EV and P4. 5mg EV and 20mg P4 every 3.5 days. Feeling much better.”, KA, Dec 2016.

“After taking it for about 4 years it started to just quit blocking T all together. I was on injected estradiol valerate and yet my T was at 400! Believe me that Spiro is bad shit. It cost me my job. The brain fog and short term memory loss may be permanent. Depression was increased and not to mention the long term memory I lost.”, SL, Dec 2016.

“I had a lot of emotive/cognitive issues with Spiro that noticeably improved when I dropped it after two years (my high E2 level allowed this).” BRB, Dec 2016.

“I had a bout of severe dizziness and got a very itchy rash which my housemates initially thought was a bug bite then later confirmed it was not like any bug bite they’d ever seen. The rash grew larger and more itchy over the course of a week, it disappeared completely a day or two after I stopped taking Spiro. While on Spiro I experienced greater difficulty with organizing thought, more frequent thought derailment, and more reactionary and unclear thinking. These severely impacted my job performance as I rely heavily on memorized diagnostic procedures to solve computer problems. The mental side effects of Spiro dissipated quickly for me after I stopped taking it.”, RM, Dec 2016.

“I personally can’t stand Spiro! Been on it since May…tomorrow is 7 months. I’ve had severe side effects since the beginning. Here is my list: tired, memory loss, brain fog, light headed, anxiety, poor breast development, severe depression, constipation, dehydration, and low blood pressure. I’ve been a mess since the beginning. I take the pill form. Looking into asking my doctor about moving over to injections and switching to progesterone and keeping my estradiol going.”, JMS, Dec 2016.

“I was on it for 6 months at a low dose, stopped taking and upped my. Estridol and progesterone. I don’t and didn’t want to start down the road. Had the mental side effects.”, DBS, Dec 2016.

“my endo started me on 200mg spiro daily with estradiol and i started getting spells of difficulty breathing, debilitating migraines (which i have never experienced before/not a headachey person), increased anxiety, fatigue, yadda yadda. she really didnt think it was the spiro (and theres not too much info about spiro online??) but we cut it out and i cant begin to tell you how much better i feel” DS, 1-5-18

“Started on Estradiol and Spiro pills… Wasn’t getting anywhere with my E and T levels. After 6 months, switched to EV injections and dropped the Spiro, because of this forum. Now I’m consistently in ideal range of E and T. It’s very possible with no Spiro.”, AA, 1-5-18

“I switched from spiro to cypro only a few days ago. Ok, its still an AA, but its the lesser of two evils as Beverly pointed out in a previous thread when I asked. In that few days, the brain fog has already gone, I have elevated energy levels and i’m not feeling tired constantly. I no longer pee like a race horse. Getting off spiro will only benefit your health. If my E levels are right next week when I go for my bloods, i’ll be dropping the cypro too.” EC, 1-5-18

“I have a bad reaction to antiandrogens. I’m now completely off of spironolactone, feminizing rapidly, feel very healthy, and have no brain fog or other symptoms typical to longer term exposure to anti androgens. I’m just taking injectable estradiol valerate at a normal dosage, subcutaneous twice a week to keep levels more stable, and micronized progesterone. I am pre-op and my testosterone is actually lower than the female index range without antiandrogens.”, JM, 1-6-2017

“I dropped 200mg of daily Spiro. Increased my E from 4mg to 8mg. My E increased and T dropped and got my libido back. Worked for me. In two weeks at next DR. appt, I am going to ask to switch from pills to injections.”, SK, 8-1-2018.

“I too feel 1000 times better since dropping Spiro and taking no AAs, I like the E and p only for T suppression, works way better that I had ever expected, almost too good actually.”, RS, 1-8-2018.


REFERENCES and LINKS
(1) “Combined Receptor Antagonist Stimulation of the Hypothalamic-Pituitary-Adrenal Axis Test Identifies Impaired Negative Feedback Sensitivity to Cortisol in Obese Men”, Mattsson C, The Journal of Clinical Endocrinology & Metabolism, Volume 94, Issue 4, 1 April 2009, Pages 1347–1352, https://doi.org/10.1210/jc.2008-2054
(2) “ Direct inhibition of Leydig cell function by estradiol.”, Jones TM, J Clin Endocrinol Metab. 1978 Dec;47(6):1368-73.
(3) “ The effect of oestrogen administration on plasma testosterone, FSH and LH levels in patients with Klinefelter’s syndrome and normal men.” Smals AG, Acta Endocrinol (Copenh). 1974 Dec;77(4):765-83.
(4) “In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion.”, Raven G, J Clin Endocrinol Metab. 2006 Sep;91(9):3324-8. Epub 2006 Jun 20.
(5) “Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and gonadotropin-releasing hormone-deficient men.”, Finkelstein JS, J Clin Endocrinol Metab. 1991 Sep;73(3):621-8.
(6) “Hormone Therapy Dose, Formulation, Route of Delivery, and Risk of Cardiovascular Events in Women: Findings from the WHI Observational Study”, Shufelt C, Menopause. 2014 Mar; 21(3): 260–266.
(7) “What Went Wrong With MTF Hormonal Therapy?“, Cosgrove, B.
(8) “Effect of eplerenone versus spironolactone on cortisol and hemoglobin A₁(c) levels in patients with chronic heart failure”, Yamaji M, Am Heart J. 2010 Nov;160(5):915-21
(9) “Spironolactone Dose-Response Relationships in Healthy Subjects”, McInness G, Br. J. clin. Pharmac. (1982), 13, 513-518
(10) “Blockade of the Mineralocorticoid Receptor in Healthy Men: Effects on Experimentally Induced Panic Symptoms, Stress Hormones, and Cognition”, Otte C, Neuropsychopharmacology (2007) 32, 232–238
(11) “Hormone Therapy is Lifesaving — But Why is No One Studying Its Long-Term Effects?“, Out Magazine, Tourjee D, 2016-09-20 09:38
(12) “Stress and Abdominal Fat: Preliminary Evidence of Moderation by the Cortisol Awakening Response in Hispanic Peripubertal Girls”, Donoho C, Obesity (2011) 19, 946–952
(13) “Predictive Markers for Mammoplasty and a Comparison of Side Effect Profiles in Transwomen Taking Various Hormonal Regimens”, Seal LJ, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 12, 1 December 2012, Pages 4422–4428
(14) “Cortisol and growth hormone: clinical implications of a complex, dynamic relationship”, Stratakis CA, Pediatr Endocrinol Rev. 2006 Apr;3 Suppl 2:333-8.
(15) Chart from active survey of over 200 Spironolactone patients, from Online Facebook Group, “The MTF Trans HRT Hormone Forum“, founded Dec. 2014, membership approx 9800.
(16) “Handbook of Stress and the Brain: Stress: integrative and clinical aspects”, Elsevier. pp. 440–
(17) “Increased Intra-Abdominal Fat Deposition in Patients with Major Depressive Illness as Measured by Computed Tomography”, Thakore J, BIOL PSYCHIATRY 1997;41:1140-1142
(18) “Mineralocorticoid receptor function in major depression”, Young EA, Arch Gen Psychiatry. 2003 Jan;60(1):24-8.
(19) “Endocrine Treatment of Transsexual Persons:An Endocrine Society Clinical Practice Guideline”, Hembree W, The Journal of Clinical Endocrinology & Metabolism, Volume 94, Issue 9, 1 September 2009, Pages 3132–3154
(20) “High visceral fat mass and high liver fat are associated with resistance to lifestyle intervention.”, Thamer C, Obesity (Silver Spring). 2007 Feb;15(2):531-8.
(21) “Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline”, Hembree WC, The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 11, 1 November 2017, Pages 3869–3903
(22) “The 45-year story of the development of an anti-aldosterone
more specific than spironolactone”, Menard J, Molecular and Cellular Endocrinology 217 (2004) 45–52
(23) “Testosterone Levels Achieved by Medically Treated Transgender Women in a United States Endocrinology Clinic Cohort”, Liang J, Endocrine Practice: February 2018, Vol. 24, No. 2, pp. 135-142.
(24) “The effect of oestrogen administration on plasma testosterone, FSH and LH levels in patients with Klinefelter’s syndrome and normal men.” Smals AG, Acta Endocrinol (Copenh). 1974 Dec;77(4):765-83.
(25) “Direct inhibition of Leydig cell function by estradiol.”, Jones TM, J Clin Endocrinol Metab. 1978 Dec;47(6):1368-73.

(26) “Hormonal Treatment of Transgender Women with Oral Estradiol“, Leinung M., https://doi.org/10.1089/trgh.2017.0035

25 thoughts on “The Case Against Spironolactone

  1. I been on and still on the Spironolactone 200 mg. a day. I been on the 0.1 mg. Estradiol, 3 patches a week about 33 months. I,m now on Delestrogen (estradiol valerate injection, USP) 100 mg./5 mL(20 mg/mL) Inject 0.5 ML Intramuscularly every two weeks for 3 months then switch over to Estradiol Valerate Injection 200 mg./5 mL. Inject 0.5 MLS Intramuscularly Every Two Weeks for 3 months = total of 6 months supply. I am a 64 year old 01/05/1954 single mix breed Native American Pre/Op transgender women live alone over 40 years. My breast are not really big normal size, yet I stress out a lot not being fully developed, high cost of out of pocket cost $$$$ and what my retirement Health Ins.will pay. I was approved in full vaginoplasty and breast surgeries on my Employers Cobra Health Ins.$714.40 month premiums. My Cardiology Doctor said all surgeries are to be cancelled until I get a MRI scan done first. While waiting for my appointment MRI scan two months later my Social Security Medicare plan took over where I pay about with the Extra Help $135.00 monthly premiums. After I pass the Stress Test instead of MRI scan that I call my to Health Insurance about what they will and will not cover threw their plan? Their plan said I will have to pay out of pocket about $6,500.00 for vaginoplasty surgery, $350.00 for the first 5 days in recovery room in hospital and after that will be cover in full with no extra charge. The breast surgery will not be cover. I told from Social Service I make to much money on Social Security to get Medicaid. I work over 40 years of my single life paying into Social Security, Medicare, Fed. and State Taxes and not able to get Medicaid. I am able to get about $15.00 month on Food Stamps and notable to get Heep program to help pay some my heat bills.

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    1. Rhonda, the problem with your estradiol injection routine is the two week interval. You generally cannot get reliable testosterone suppression using a two week interval — if you inject by gluteus, a 7 day interval works for most. If you inject by thigh, you should not go more than 5 day interval. Success with estradiol by injection is more a matter of avoiding dropouts than in achieving high peaks. The two week interval is probably the most common mistake made by prescribing doctors — that interval only works for women with productive ovaries. Even if you are a trans woman without testicular tissue, 14 days is too long, and may contribute to stress an depression. Doctors are usually amenable to you injecting half doses twice as often.

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  2. Thank you for writing this article! I am a 36 y/o trans woman who plans on starting HRT this year. My latest blood test showed a T level of 264. If I can successfully convince my endo to not force spiro on me, I’d rather not take it. Is it possible to only take E off the bat and avoid AAs altogether from the start? And in your opinion, should I try to get him to prescribe IM EV right away? I know a lot of docs and endos seem to prefer to prescribe sublingual E for months at first. I’ve heard it can be challenging to convince endos to think outside their normal box, and I live in a smaller city without a PP or many options at all for docs / endos willing to supervise HRT. But I’ve heard that IM is the most effective for a lot of folks, and I’d rather inject every 5-7 days than have to let pills dissolve slowly in my mouth 2-3 times a day. Anyway, thank you for any advice you can provide!

    Liked by 1 person

    1. Jocelyn, it is widely known among patients that IM estradiol gives superior results compared to any kind of oral estradiol, and trying to get prescribers to recognize this fact is a common problem. Yes, generally if one begins with an injection regimen with no antiandrogen at all, the levels of testosterone begin a slow decline and in 1-6 months reaches female normal levels. See my other article https://transhormones.wordpress.com/2017/11/19/the-top-12-myths-about-injections-for-mtf-trans-people/
      Good luck!

      Liked by 1 person

  3. “Visceral fat cannot easily be reduced with diet or exercise and cannot be removed with any kind of plastic surgery. (20) ”
    “Once visceral fat has accumulated, it is difficult or impossible to ever achieve an ideal waist-to-hip size ratio again, even if Spiro is stopped and diet and exercise is tried.”

    These statements are blatantly wrong. Ten minutes of research is enough to figure out what you’re saying is genuinely not true. Visceral fat can absolutely be lost through weight loss.
    What’s worse is that the paper you use (20, http://onlinelibrary.wiley.com/doi/10.1038/oby.2007.568/full ) to make these claim does not back up your statements. That paper discusses the success of lifestyle intervention (resulting in weight and fat loss) and its effectiveness on increasing insulin sensitivity. That paper you cited suggests that lifestyle intervention may have less effect on increasing insulin sensitivity for those who have higher BMI and visceral fat stores when starting lifestyle intervention compared to those who have lower BMI and visceral fat stores given the same amount of BMI/visceral fat loss. The paper does NOT make any claims about the ease with which visceral fat can be lost in comparison to adipose fat, nor does it remotely make any claims suggesting that an ideal waist-to-hip measurement ratio becomes “difficult or impossible to ever achieve.” The paper isn’t relevant to either of these claims.

    Please, do actual research and find good sources before making extreme statements. You’re going to scare the hell out of trans women with blatantly wrong statements like that. I spent a long time looking and I have not found any research suggesting visceral fat gain is largely irreversible. Telling people that if they gain visceral fat they’ll never be able to lose it and they’ll never be able to change their hip/waist ratio afterwards is both irresponsible and incorrect. You should not be making such dangerous statements like that without a hell of a lot of material to directly back up your argument.

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    1. Good points, and I’ve incorporated them into the article. The emphasis is that visceral fat is caused by high cortisol levels (among other things) and requires dieting combined with a fairly substantial (though not extreme) exercise regimen to get significant improvement. It’s still a scary thing to get abdominal fat that’s difficult to remove, and certainly it is not the desired result of a trans woman’s HRT. And it is also of concern that unless and until it is removed, it is associated with risks of metabolic syndrome and insulin insensitivity. And it is truly difficult to remove, and requires a significant effort – if you are a sedentary person, your chances of getting rid of it are small to none.

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      1. No-carb diet is more effective for weight loss than usually advised limited-calories, low-fat diet + exercise. As an aside, ubiquitous assertion of harm from saturated fats is a huge fraud. An example of no-carb diet: fatty joghurt with neither sugar nor starch (fermented milk with nothing added), medium-boiled eggs, chicken or any meat, sour cream, fatty curd, plain water, orange juice without sugar added diluted in about 10 times with water, canned sardines, liver – eat as much as you want of these and when you want (not when clock tells you), but nothing else. No bread, no sweets, no salt, no spices/sauces. Take a vitamins+minerals supplement (like plain Centrum) all year round. Weight loss with no hunger, no exercise.

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  4. Hi Beverly, it’s really helpful that you write these articles. This is all far better than the majority of information on hrt out there and I hope others listen to you
    I’m a 40 year old MTF with a background in bodybuilding and all that goes with that so I am a natural sceptic about doctors having all the answers to hormone protocols and their view of estrogen and testosterone .

    I have always have had the view injections are by far the best most effective delivery method and the safest, for the liver etc.

    I will be doing more research and if I do go on to use Hormones will definitely avoid Spiro and Fina, as I can’t see a good reason to use them….. Estrogen alone and maybe Progesterone make sense.

    Thanks Alexa.

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  5. Both times I used spiro (both 9 month periods)it ends up in psychotic episodes and defeminization..I cant take this drug anymore so im currently in a estrogen only regimen.. Im so sad but the psychotic episodes were horrible and I wouldnt want to go through that.

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  6. Thanks for this article. I wish I saw this years ago spiro has destroyed my life. The list of sideffects are exhaustive. It masculinized me, my face, jaw, made hair grow on my body where it never was before, made my skin horrible, made my voice deeper, and gave me terrible mental problems, anxiety, depression, just to name a few, I was even prescribed meds for it that I wont take. Even my hair started thinning. I’ve been off it for about 3 months and still don’t feel like myself. Will I ever feel like myself again? I cry as I write this. I wouldn’t wish this on my worst enemy.
    I started on estrogen first and felt unbelievable euphoria, after the spiro I was never the same. I did lots and lots of research and found out that spiro can actually activate androgen receptors wtf? Oposite of what we need. I also feel it increased dht which would account for the masculinization. I’ve never felt suicidal until I took the spiro. I never hated myself until the spiro. I was ok with every thing and was always relaxed now amost everything bothers me.
    I want my motivation back. Is there any way to undo the damage that spiro has caused? And they wonder why the suicide rate is 40% amongst trans people. Screw aas. It saddens me even more to think that they’re still prescribing it to desperate girls. Any advice would be greatly appreciated. Bless n love

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  7. I was on Spiro for 2 years, at the end of it I ended up having surgeries delayed, due to the side effects not being known to my doctor. I was put through agonizingly painful tests on my muscles and nervous system, when Spiro was causing my symptoms. My legs and most muscles would just drop out at random and sometimes for up to 2 hours I couldn’t feel the ability to even flex a muscle in my lower body, it was typically just after anything that required me to stand still. When I ended up hospitalized because I was at that point losing the ability to walk or stand upwards of 6 hours a day, it was found the cause was intense dehydration, I was at that point drinking close to 3 gallons of water a day and because of spironolactone I had no ability to retain water. My doctors had me on several regimens prior to getting off of spironolactone, due to poor blood results. The month following my switch to finasteride, all of my levels were perfect.

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  8. Androcur (cyproterone acetate) causes depression, anxiety, fatigue or other mental disorders in 30% of MtFs. Finasteride in usually prescribed dosages (1-5 mg/day) can interfere with the progesterone->allopregnanolone conversion causing same side effects in some (fewer) MtFs, but finasteride dosage decrease to 0.05 – 0.1 mg/day (1/100 – 1/50 of a 5 mg pill once a day) prevents these side effects while giving equally strong useful effects (on hair only). There is a safe antiandrogen: bicalutamide 6-100 mg/day. But I agree, injectable estradiol valerate or cypionate at least 7 mg every 5 days without antiandrogen (with finasteride 0.05-0.1 mg/day in case of male pattern baldness in the past) is a safe and effective MtF HRT regimen. Moreover, it’s so safe for MtF and doesn’t interfere with any disease that no doctor checks, no blood tests are necessary. Of course, effects on libido, potency, fertility and social consequences of transition (or no transition with breasts) are your problems.

    The most common disastrous thoughtlessness is taking hormones while postponing facial needle electrolysis.

    Liked by 1 person

    1. Hello. Thank you for your input. Do you happen to know how it’s is interfering with progesterone>Allopregnanolone conversion? I’m guessing excess dht? Is that what causes depression? Thanks

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      1. Finasteride blocks 2 of 3 types of the 5alpha-reductase enzyme which performs both conversions testosterone->DHT in hair follicles and progesterone->allopregnanolone in the brain. Allopregnanolone is anti-depressive and anti-anxiety. Dutasteride blocks all 3 types and more often causes depression, so I don’t recommend dutasteride.

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    1. Cyproterone does not interfere with feminization like Spiro does, as far as we know, but since it is an antiandrogen it is associated with low-estradiol treatment regimens, which may be generally sub-par compared to estradiol-progesterone regimens.

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    1. Or use an injectable estradiol ester (such as injectable estradiol valerate) at least 7 mg every 5 days. It’s safe and suppresses testosterone production by testicles without an antiandrogen.

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    2. The best alternative to using Spiro is to use Estradiol injections, or multiple patches, or implanted pellet, to achieve estradiol blood levels in the 350-700 pg/ml range, for at least a couple of years, which causes all testosterone production to cease in the body. No surgery is needed and this method is safe when done correctly, as proven by some studies. However, getting off Spiro if it has been used for years at megadoses (over 100mg a day) can require up to 6 months of a recovery period while your endocrine system rebalances. During that time false symptoms of testosterone may appear, even though testosterone remains low, because of the sensitized androgen receptors. However experience shows that patients taking megadoses can reduce to 100mg immediately without such problems, and then taper off slowly — as long as they are receiving estradiol as I mentioned above. Get your doctor’s approval.

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  9. Well I am 40 and presently on 200mg spiro a day and two 0.1mg patches of E for 6 or 7 months. Before that I was on 4mg oral E and 50mg of cyproterone for at least 18mths – it was definitely more effective but it ended up really screwing up my liver to the point of being admitted to hospital (AST/ALT >700). I can’t say I get brain fog or any of the bad symptoms suggested (at least anecdotally within myself without research). I am only pleased to be honest where I am at.
    But forgive me for being analytical – I have a science degree – but the list of references doesn’t inspire me. A lot of the research is offline and 30 or 40 yrs old (I am looking offline soon), one reference is your own article (thats not a reference!) and one is an OUT magazine article (a good read tho). The one that does backup some of your claims (Leinung M) is a bit flawed as it’s measuring T levels but Spiro blocks T being effective and doesn’t actually stop production. The reference concludes correctly that it’s the E that drops production.
    Do you have any other references? Happy to hear your thoughts.

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    1. The reference to my own article was linked to the statement “Studies at the time unfairly lumped all estrogens together, and all progestins together, as having the same dangers, a mistake which still lingers today.” which was NOT the main topic of the article and is intended to lead the reader into a branching path of knowledge. But I will edit the list of footnotes so it reads “References and Links” instead of just “References”. Oh, and I do have a science degree also. I didn’t expect to be graded on this one so it is done in a casual style. However I may be part of a formal paper later this year for WPATH. You can grade that one if you want. As far as the age of the references, the fundamental research on Spiro and some of the other points is of course very old. This is not a new drug by any means.

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