Fibrilação atrial crônica tratada com testosterona ou DHEA][
Testosterone as an atrial fibrillation treatment and stroke
preventative in aging men: Case histories and hypothesis
Correspondence/Medical Hypotheses 75 (2010) 269-274
1o caso: 59-year old man.
The elderly subject had an initial serum TT level of 361 ng/dl.
He received natural testosterone (20 mg in AM and 20 mg in PM)
as a % aqueous, sublingual/buccal liquid, slowly swallowed over
a 30-60 min period. He had AF daily for 1 year prior to TT treatment.
He was also taking warfarin, a beta-blocker (metoprol ER)
and a calcium channel blocker (diltiazem ER), but no rhythm
drugs. His blood pressure, cholesterol and CRP were normal. Other
than pre-atrial contractions (PACs) for the preceding 10 years, he
had no other heart conditions according to an MRI and history.
His serum TT rose to 463 ng/dl within 14 days of initiation of TT
treatment, and to 1489 ng/dl within 45 days, with each measurement
being taken mid-day. NSR and no instances of AF and only
a few instances of PACs were observed in seven weekly EKGs
and by direct observation after the second week of TT treatment.
His INR changed from 2.5 to 5.4 upon treatment with TT, requiring
substantial reduction in warfarin.
2o caso: The 59-year old subject with strongly symptomatic nocturnal
paroxysmal AF and depression received both DHEA (25 mg/day)
and natural testosterone (50 mg/day) as a gel applied to his shoulders.
His serum mid-day TT levels at initiation of TT treatment was
150 ng/dl, much lower than normal. He was also being treated
with warfarin, a rate drug (sotalol) and a rhythm drug (dofetilide).
Previously, he had congestive heart failure and persistent AF which
had been treated with ablation and cardioversion. An MRI showed
no cardiac damage. His depression and ectopics ended, and his observed
AF episodes over a 45-day period rapidly declined after initiation
of daily TT, with only two observed instances of overt AF
lasting 5 min and 1 h after the first 2 weeks.
Both subjects felt that TT was a necessary, superior and safe
natural rhythm treatment for AF. Since beta-blockers lower testosterone
in men [11], replacing TT when they are used in AF treatment
appears essential. Rhythm drugs for AF have side effects
sufficiently severe to recommend their initial administration in a
hospital, and the apparent safety of treating AF with TT should
be welcome. An increase in TT from exercise, carbohydrates, fats
and other TT boosters is also hypothesized to be helpful in AF
treatment.
Illicitly obtained anabolic steroids as testosterone ethanate
(250mg-1.5g weekly) and stanozolol (50-200 mg weekly), both
via intramuscular injections over a 12-week duration caused rapid,
highly symptomatic AF in a young male athlete/body builder [12],
and similarly, 200 mg of testosterone cypionate, 200 mg of extrabolin
decanoate, and 120mg of stanozolol 2 days per week for
5 weeks caused the same adverse symptoms in another young athlete/
body builder [13].
Dear Dr. Charlton,
Testosterone (TT) may play an important role in treating atrial
fibrillation (AF) and preventing stroke in aging men. AF increases
[1 ], while TT declines in them [2]. In 2009, TT was first shown by
Lai et al. [3] to be low in men with lone atrial fibrillation (lone
AF) compared with non-AF controls (476 ng/dl versus 514ng/dl,
p = 0.005). No significant differences were found in estradiol levels.
They suggested that low TT is associated with susceptibility to
lone AF in men. Similarly, serum dehydroepiandrosterone-sulfate
(DHEA-S) was shown to be low in lone AF in men and in a number
of other aging related illnesses as a non-specific indicator of aging
and health status [4]. Deficiency of TT promoted arrhythmia in rat
atria by mechanisms which induce calcium leakage from the
sarcoendoplasmic reticulum helping to explain the increase in AF
in association with low TT, particularly in elderly men [5]. Circulating
TT levels in men have a diurnal variation, usually reaching a
mean maximum level of 710ng/dl at approximately 6 AM and
declining gradually to a mean minimum level of 426 ng/dl at
approximately 10 PM, averaging about 610 ng/dl in mid-day and
afternoon [6j.
Stroke is a major disabling and sometimes lethal complication
of AF, with ischemic strokes occurring 2-7 times more frequently
in AF than in the general population [7]. Low testosterone
is an independent risk factor for acute ischemic stroke,
stroke severity and related death in men considering age, blood
pressure, diabetes, ischemic heart disease, smoking and atrial
fibrillation [8]. Low testosterone is also associated with coronary
artery disease and with myocardial infarction in men [9], and
all-cause mortality independent of numerous risk factors in
men [10]. Beta-blockers, commonly used rate drugs in cardiology,
lower testosterone in men [11], apparently increasing the
risk of AF and stroke.
An elderly (69-year old) paroxysmal/lone AF subject often experienced
normal sinus rhythm (NSR) early in the morning at the
same time of day when TT is highest. Considering the literature
and his experience, 1 hypothesized that low testosterone was the
cause of his AF, and that increasing TT would terminate AF. I tested
my hypothesis in this
Since both lower and higher than normal TT concentrations
are associated with AF, blood levels of TT should not be elevated
much in excess of the normal physiologic range in the treatment
ofAF.
These two cases are the first reports of TT treatment for AF and
stroke prevention in men. These observations suggest the possibility
of a safer and more effective natural rhythm treatment for AF
and stroke prevention. Since TT blood levels of the two young athlete/
body builders were not reported, 1 hypothesize that their levels
were considerably higher than the 1489 ng/dl reported for my
elderly AF-free subject. Large scale clinical trials to establish the
extent of efficacy and safety are strongly recommended.
References
[ 1 ] Wetzel U. Hindricks G, Piorkowski C. Atrial fibrillation in the elderly. Minerva
Med 2009:100:145-50.
[2] Rabijewski M, Zgliczynski W. Testosterone deficiency in elderly men. Pol
Merkur Lekarski 2009:27:517-23 (Review].
[3] Lai J, Zhou D. Xia S, et al. Reduced testosterone levels in males with lone atrial
fibrillation. Clin Cardiol 2009:32:43-6.
[4] Ravaglia G, Forti P. Maioli F, et al. Dehydroepiandrosterone-sulfate serum
levels and common age-related diseases: results from a cross-sectional Italian
study of a general elderly population. Exp Gerontol 2002:37:701-12.
[5] Tsuneda T, Yamashita T, Kato T, et al. Deficiency of testosterone associates
with the substrate of atrial fibrillation in the rat model. J Cardiovasc
Electrophysiol 2009:20:1055-60.
[6[ Winters SJ. Current status of testosterone replacement therapy in men. Arch
FamMed 1999:8:257-63.
[7] Stollberger C, Chnupa P, Abzieher C, et al. Mortality and rate of stroke or
embolism in atrial fibrillation during long-term follow-up in the embolism in
left atrial thrombi (ELAT) study. Clin Cardiol 2004:27:40-6.
J8] Jeppesen LL, Jergensen HS. Nakayama H, et al. Decreased scrum testosterone in
men with acute ischemic stroke. Arterioscler Thromb Vase Biol 1996;16:
749-54.
19] Phillips GB. Pinkernell BH, Jing TY. The association of hypotestosteronemia
with coronary artery disease in men. Arterioscler Thromb 1994:14:701-6.
[10] Haring R, Volzke H, Stevefing A, et al. Low serum testosterone levels are
associated with increased risk of mortality in a population-based cohort of
men aged 20-79. Eur Heart J 2010 [Feb. 17. PMID: 20164245].
[11] Rosen RC, Kostis JB. Jekelis AW. Beta-blocker effects on sexual function in
normal males. Arch Sex Behav 1988:17:241-53.
[12] Lau DH, Stiles MK, John B. Atrial fibrillation and anabolic steroid abuse. Int J
Cardiol 2007;! 17:e86-7.
[13] Sullivan ML, Martinez CM, Gallagher EJ. Atrial fibrillation and anabolic
steroids. J Emerg Med 1999:17:851-7.
George Eby
George Eby Research Institute,
14909-C Fitzhugh Road,
Austin, TX 78736,
United States
Tel.: +1 512 263 0805
E-mail address: [email protected]
doi:l0.lOl6/j.mehy.2010.03.023