Quote from: Naomi71 on November 14, 2016, 05:15:02 PM
Ok, that's better. However, this long list isn't conclusive at all and actually consistently shows a small blood pressure reduction at best. these numbers are not good enough to actually replace beta blockers, like you suggested (i take metoprolol). It proves I would still have high blood pressure on spiro, if anything.
You wanted proof for a causal effect between spironolactone and lower blood pressure. I believe the studies I provided, taken together, strongly suggest there is indeed a causal relationship. I spent 12 yrs reading reports from transsexual women who took spironolactone and I know how much it can affect blood pressure, to what extent and that sometimes, it can even cause too much of a drop, resulting in lowering of the dose or withdrawal of the drug. Personally, I don't need further proof but should I come across more studies, I will share them with you.
QuoteHypertension. 2007;49:839-845 - nonrandomized and not placebo controlled.
Indeed, randomized double blind placebo controlled trials are the most reliable of the studies BUT do you really think blood pressure would have fallen to such an extent in a placebo group, by 21.9/9.5 mm Hg? I know your answer but it's doubtful.
QuoteThe principal results of the Prevention And Treatment of Hypertension With Algorithm based therapY (PATHWAY) - - Bingo! That's the first relevant paper you came up with. Unfortunately it only focuses on patients with resistant hypertension, which is a tiny percentage of the people suffering from high blood pressure.
Circulation. 2012 Apr 3; 125(13): 1594–1596."Using data collected from 2003 through2008, Persell estimated that the prevalence of resistant hypertension was 8.9% of all US adults with hypertension"
"Looking at trends in blood pressure control as measured by NHANES, Egan et al found that the estimated prevalence of resistant hypertension has been increasing progressively over the last several decades.4 Between 1988-1994 the estimated prevalence of resistant hypertension was 5.5% of all US hypertensive adults. Between 1999-2004, the rate was 8.5%, and most recently, between 2005-2008, the estimated prevalence was 11.8%. With an estimated 76 million adult Americans with hypertension, a prevalence rate of almost 12% would translate into an estimated 9 million Americans with resistant hypertension.5"
Not that tiny but still, I agree, a small portion of that population.
QuoteNephrology (Carlton). 2015 Aug;20( 8 ):567-71. - It's considered effective to reduce blood pressure relative to the other medicines that were part of this research. However, compared with my medication, the results reported are laughable. On spiro they went from 163 to 139, while I went from 182 to 125 in less than a week on beta blockers
What I wonder is what would happen if you took estrogen and spiro and progesterone (also shown to have antimineralocorticoid effects and hypotensive action, the latter being confirmed in small scale studies)? Would you need as much of the other medications that you took for control of your blood pressure? This is something I personally would discuss with my doctors and ask if it could be tried, gradually, under their supervision. What's the harm in just proposing this course of action to your doctors? You've never tried this particular approach. Spiro, in addition to estradiol and progesterone, would help further reduce blood pressure and exert anti-androgenic action. Double whammy!
Food for thought. Take it or leave it.
QuoteMedicine (Baltimore). 2014 Dec;93(27) In this study, spiro was used as an add-on to other medication, so it's hard to tell to what extent reduced blood pressure can be attributed to that.
It isn't because a placebo group WAS present.
"One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned
to receive (...) spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization."
"At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of -9.8, -13.0, -10.5, and -9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office. The respective DBP differences were -3.2, -6.4, -3.5, and -3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003)."
"The office SBP goal <14 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001). Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control."
QuoteMed J Aust. 1980 Feb 9;1(3):124-5. - A study consisting of 17 patients? Next.
I see this study as additional proof, additional confirmation, even if the sample was small. It's important to look at the whole picture, I think.
QuoteAm J Cardiol. 1990 Jun 19;65(23):36K-38K. - only 47% of the patients had reduced blood pressure after a whopping 45 days? ? Not good enough.
The dose was somewhat low, had it been slightly higher, perhaps the effect would have been greater/faster. I do however realize that studies found a plateau after which, further increasing dose didn't provide additional reduction in BP. But, that plateau was not fully reached in this particular study as slightly higher doses were found to be more effective in other experiments.
Blood pressure also continued to fall after 90 days. An extra 15-16 for systolic and 8-9 for diastolic.
QuoteAm J Cardiol. 1987 Oct 1;60(10):820-5. - "limitations inherent in the interpretation of data banks" next.
See how I don't cherrypick and instead mention everything. I could have quoted:
"it is concluded that spironolactone administered in daily practice reduced BP without inducing adverse metabolic adverse effects"
You don't know me. You've made quick personal judgments about me without giving me a chance, a second chance. I seek facts and I care more about that than being right. I will readily admit when I am wrong about something and reconsider after enough proof is provided. Always! These are principles that matter very much to me and that I force myself to abide by, at all times.
"
Despite limitations inherent in the interpretation of data banks,
it is concluded that spironolactone administered in daily practice reduced BP without inducing adverse metabolic adverse effects"
In addition, in full study,
"
Besides those induced by the nonrandom choice of
the therapy, the main bias of such interrogation of a
data bank when used to determine treatment efficacy
are those introduced by the
patients lost to follow-up.1°
Indeed, when a patient is not followed-up at the clinic,
it is almost impossible in such a retrospective study to
analyze the reason for his outcome: decision of the
clinic, voluntary choice of the patient or of the general
practitioner, high quality of the results, drug's side effects,
complications due to the disease or the treatment.
However, we already showed the validity of
retrospective analysis of data in the ARTEMIS system
in a study of the cost effectiveness of different methods
of investigating hypertension, which provided the
same results as a simultaneously performed randomized
trial.ll Other authors have also shown that such
pragmatic retrospective analysis could provide results
similar to those obtained in randomized trials in areas
as different as the results of aortocoronary bypass12
or the efficacy of tonsillectomy for recurrent throat
infection.13"
"The results confirm the efficacy of spironolactone
in treating moderate essential hypertension on a long
term basis. Indeed, 60% of the patients had a diastolic
BP of 90 mm Hg or less on treatment, and in only 10%
was it more than 100 mm Hg with this monotherapy."
"These results are in agreement with the reports of randomized studies that concern a small number of patients.14J5"
I know...SMALL. But it ADDS up.
QuoteEur J Clin Pharmacol. 1982;21(4):263-7. - a study consisting of nine patients? next.
But adding yet to the pool of evidence. Small samples here and there eventually become bigger and bigger sample. The whole picture.
QuoteHypertension. 1980 Sep-Oct;2(5):672-9. - "statistically significant". How much is that? a blood pressure reduction of one already is statistically significant.
Looking at the actual results from the study (full article), a difference of 16-22 for systolic between placebo and spironolactone at low and high doses AND a difference of 8-11 for diastolic between placebo and spiro, in supine position. In the upright position, 19-27 for systolic and 8-10 for diastolic. The only thing I take issue with is that results with placebo are only available before Spiro use and not after so that blood pressure was taken pre and post in all Spiro group but only pre for placebo. That is not right and objective. And you say I cherrypick. Pfff...LOL. I thank you though for for making these remarks and helping me look closer at the ways in which I report findings. I am extra careful now.
QuoteJ Endocrinol Invest (2015) 38:269–282 - A risk for hypotension (I suppose in people who dont have high blood pressure) is not the same as a reduction of high blood pressure.
If there is a risk of hypotension in people who don't have high blood pressure, then that means that a reduction in blood pressure can occur in normotensive people as well, confirming spironolactone's blood pressure lowering effects which was what you wanted proof of. In other words, even in normotensive individuals, spironolactone can potentially lower blood pressure.
You didn't mention the last study I provided for some reason which states:
J Sex Reprod Med Vol 1 No 1 Summer 2001
Towards optimal hormonal treatment of male to female
gender identity disorder"
Spironolactone's hypotensive effect
is an advantage in many cases, but in a small minority of
patients, particularly in the leaner and very physically
active individual, the hypotensive effects necessitate a
change in therapy"
So that they did notice an improvement in blood pressure in
many transsexual patients and even to the point that in a small group of people, blood pressure dropped TOO MUCH.
Really, do you need more proof for spironolactone's effects on blood pressure?
Others:
J Am Geriatr Soc. 2010 Jul;58(7):1327-32."To determine the efficacy of spironolactone (SPIRO) and hydrochlorothiazide (HCTZ) as monotherapy in older patients with hypertension in blood pressure (BP) control and measures of vascular stiffness."
"Randomized double-blind trial."
"Forty-five subjects with hypertension (24 men, 21 women, mean age 69)."
"Six months of HCTZ and SPIRO treatment was associated with significant decreases in 24-hour and nocturnal SBP and diastolic BP (DBP) (analysis of variance (ANOVA) P<.001). At 6 months, average 24-hour and nocturnal SBP were lower in the SPIRO than the HCTZ group (P<.001)."
142/81 to 126/74 for Spiro at 6 months (24 hour BP)
130/73 to 116/67 for Spiro at 6 months (nocturnal BP).
Moderate to typically prescribed amount for TS women.
(Remember, it's adding up).
Hypertension. 2010 May;55(5):1217-23. "Aldosterone receptor blockade and thiazide therapy effectively lower blood pressure in geriatric hypertension. Their impact on sympathetic nervous system function has not been evaluated. In a double-blind, randomized study, 36 patients with stage 1 hypertension underwent 6 months of therapy with either aldosterone receptor blockade (spironolactone, n=19; 68+/-1 years) or hydrochlorothiazide (n=17; 68+/-2 years)."
"Arterial blood pressure decreased significantly with both spironolactone (160+/-3 to 134+/-2 mm Hg; 77+/-2 to 68+/-2 mm Hg) and hydrochlorothiazide (161+/-4 to 145+/-4 mm Hg; 78+/-2 to 73+/-2 mm Hg) treatment."
"These findings demonstrate a beneficial effect of aldosterone receptor blockade on reducing sympathetic nervous system activity and blood pressure in hypertensive older patients."
Clin Exp Hypertens. 2009 Nov;31( 8 ):648-56."This study was performed to investigate the additional anti-hypertensive effects and safety of low-dose thiazide diuretic, trichlormethiazide (TCTZ), and a mineralocorticoid receptor blocker, spironolactone (SPI), as add-on therapy in 64 patients whose blood pressure (BP) at office were over 140/90 mmHg, while receiving anti-hypertensive medication including an angiotensin-converting enzyme inhibitor or angiotensin II type I receptor antagonist. After 6 months, we observed a decrease of office and home BP."
From full study,
"After 6 months of treatment, we observed a significant decrease of office BP (systolic BP/ diastolic BP), 140 ± 7/77 ± 10 mmHg to 122 ± 14/71 ± 9 mmHg in the SPI-treated group"
"and of home BP (systolic BP/diastolic BP), 139 ± 6/79 ± 10 mmHg to 124 ± 8/71 ± 9 mmHg in the SPI-treated group"
"In conclusion, low-dose thiazide diuretic or SPI provided a significant additional anti-hypertensive effect in patients in whom hypertension was not controlled by medication"
Clin Cardiol. 2005 Oct;28(10):484-7."The study was a prospective, double-blind, randomized, placebo-controlled trial. Thirty elderly subjects between 60 and 85 years of age with isolated diastolic dysfunction and no contraindications for spironolactone were randomized to (...)spironolactone or placebo for 4 months."
Very low dose of Spiro.
"Spironolactone may improve diastolic function in the elderly."
Hypertension. 2005 Sep;46(3):481-7."In a prospective, randomized, placebo-controlled, double-blind clinical trial, we used a 2-by-2 factorial design with 4 treatment groups: amiloride (a direct inhibitor of ENaC), spironolactone (an aldosterone receptor antagonist), the combination of both drugs, and placebo. The subjects (n=98) had an elevated blood pressure despite treatment that included a diuretic and a calcium channel blocker; the level of plasma renin activity was < or =0.56 ng/L per second."
"The reductions in systolic and diastolic blood pressures (mm Hg) were, respectively, 9.8+/-1.6 (SE) and 3.4+/-1.0 for amiloride (P<0.001) and 4.6+/-1.6 (P=0.006) and 1.8+/-1.0 for spironolactone (P=0.07)."
"In conclusion, treatment with either amiloride or spironolactone can provide an additional reduction in blood pressure in blacks already receiving conventional antihypertensive therapy."
LOW DOSE spironolactone.
Contraception. 1991 Aug;44(2):113-24."Fifty-one hirsute women were randomly treated for nine months with ethinyl estradiol (...) plus norethindrone (...) or (...) ethinyl estradiol plus (...) norethindrone acetate if they needed contraception or spironolactone (...) daily if they did not."
From full study:
"Spironolactone, unlike the two OC preparations, caused a lowering of the systolic blood pressure (Fig. 2)."
79 to 77 after 3 months to 72 after 9 months with Spiro. No real change in other groups.
Br J Clin Pharmacol. 1981 Oct;12(4):585-8."All were caucasian, fully ambulant and on an unrestricted
diet. Their ages ranged from 17.6 to 70.7
years, mean 50.3 + 13.2 years"
"
Their previous maximum
mean systolic and diastolic blood pressure was 186 +
22/119 + 12 mm Hg (mean + s.d.), with a mean
duration of hypertension 4.9 ± 4.8 years"
"At entry into the study
all patients were taking spironolactone (...).
Their mean supine systolic and diastolic blood
pressure was 153 ± 19/93 + 10 mm Hg. Three of the
patients were receiving another antihypertensive
drug (debrisoquine, propranolol and metoprolol)."
"In this admittedly small group of 13 patients with
moderate hypertension, spironolactone(...) produced effective blood
pressure control when used in once a day or divided
daily dose schedules, either alone or in combination
with other antihypertensive drugs."
Schweiz Med Wochenschr. 1977 Sep 3;107(35):1228-32."The blood pressure lowering effects of spironolactone have been studied in 40 subjects with benign essential hypertension in an attempt to determine the optimum starting dose for the drug. The trial was carried out by the double blind method. In almost all patients (...) spironolactone caused a signnificant decrease in diastolic and systolic arterial pressure."
"In conclusion, it would appear that spironolactone--in association with other antihypertensive regiments--may improve the treatment of essential hypertension, especially in patients showing a tendency to hypokalemia and uricemia, and may offer an additional possibility or alternative in the therapy of hypertensive diseases."
Am J Cardiol. 1976 Mar 31;37(4):642-9."Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (...) for 2 months, propranolol (...) for 2 months and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions."
"There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone."
"All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration."
From full study,
"During treatment with spironolactone
blood pressure decreased by 34/15 mm Hg in
the recumbent and by 38/12 mm Hg in the standing
positions (P <O.OOl for all) from pretreatment
values. At the end of the corresponding placebo period,
blood pressure again increased to almost pretreatment
values with differences of 11/6 mm Hg supine
and 7/4 mm Hg standing (P <O.Ol for difference
of supine systolic pressure, all other differences P
<0.05)."
"Spironolactone has been reported
to reduce blood pressure in patients with primary
hypertension. In addition, it has been
found especially effective in patients with primary aldosteronisms7,a8
and low renin
hypertension.ls,"s Our
study confirms that spironolactone has a clinically
useful antihypertensive effect in patients with primary
hypertension with low and normal plasma renin
activity levels."
Arch Inst Cardiol Mex. 1975 Jul-Aug;45(4):487-94."Spironolactone is a diuretic, selective aldosterone, antagonist with its own antihypertensive action which prevents body loss of potassium. Its clinical use has been documented on the treatment of essential arterial hypertension; however, there does not seem to be enough information to form a solid chemical criterion. This work is a clinical evaluation of the antihypertensive effect of the drug using double-blind technic with 41 patients with essential arterial hypertension, all external patients from the Instituto de Cardiología. They were divided in two groups, selected at random, to be able to observe their tensional range with spironolactone every two weeks, during 16 weeks; and using a placebo for the next 16 weeks. On group following this order; and the other one viceversa. After 32 weeks, the results observed show the effect of placebo, as well as spironolactone on arterial pressure and the statistic comparison, states the real antihypertensive effect of the drug on this group of patients."
"The authors suggest that this drug is useful in cases of essential hypertension although its pathway isn't deeply known. Apparently, the antihypertensive effect of spironolactone is not solely on patients with hypertension due to primary aldosteronism."
Eur J Obstet Gynecol Reprod Biol. 2007 Mar;131(1):61-7."Thirty-two women with PCOS were divided into two groups: 16 received (...) spironolactone and 16 spironolactone plus (...) licorice"
"Mean blood pressure was significantly reduced during spironolactone treatment, while it was unchanged in women receiving spironolactone plus licorice."
Full study,
"Systolic blood pressure was significantly reduced after 1 and 2 months of therapy with SP, but not during the combination therapy, while diastolic blood pressure was unchanged."
In the range of typical dose for transsexual women. 118 ± 5/82 ± 4 at baseline, 115 ± 4/80 ± 2 at day 4, 115 ± 6/78 ± 3 at day 7, 114 ± 5/75 ± 3 at 1 month (p < 0.05), 113 ± 4/72 ± 5 at month 2 (p < 0.05), with spironolactone treatment.
