| wayne203 2005-04-27, 5:48 pm |
| http://www.medscape.com/viewarticle/473414
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Medscape Medical News
Carnitine Improves Symptoms of Male Aging CME
News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP
Complete author affiliations and disclosures, and other CME information,
are available at the end of this activity.
Release Date: April 14, 2004; Valid for credit through April 14, 2006
Credits Available
Physicians - up to 0.25 AMA PRA category 1 credit(s)
All other healthcare professionals completing continuing education
credit for this activity will be issued a certificate of participation.
Participants should claim only the number of hours actually spent in
completing the educational activity.
This activity was originally released on April 14, 2004. It was reviewed
and renewed in its original form on April 14, 2005.
April 14, 2004 — Carnitine is more active than testosterone for
improving symptoms of male aging such as sexual dysfunction, depressed
mood, and fatigue, according to the results of a randomized study
published in the April issue of Urology.
"Testosterone increases the tissue carnitine concentration," write G.
Cavallini, from the Società Italiana di Studi di Medicina della
Riproduzione in Bologna, Italy. "Propionyl-L-carnitine and
acetyl-L-carnitine proved active for diseases typical of aging."
In this trial, 120 patients were randomized to receive testosterone
undecanoate 160 mg/day, propionyl-L-carnitine 2 g/day plus
acetyl-L-carnitine 2 g/day, or placebo for six months. Mean age was 66
years (range, 60-74 years).
Compared with baseline, testosterone and carnitines significantly
improved the peak systolic velocity, end-diastolic velocity, and
resistive index of cavernosal penile arteries, as well as nocturnal
penile tumescence (NPT), International Index of Erectile Function score,
Depression Melancholia Scale score, and fatigue scale score.
Compared with testosterone, carnitines were significantly more active in
improving NPT and International Index of Erectile Function score.
Testosterone, but not carnitines, significantly increased the prostate
volume and free and total testosterone levels and significantly lowered
serum luteinizing hormone. Prostate-specific antigen (PSA) and prolactin
did not change significantly in any group.
No symptoms or physiological markers improved in the placebo group.
Adverse effects were negligible in all groups.
Carnitines and testosterone were effective for as long as they were
administered, with reversal to baseline values when treatment was
stopped. Six months after testosterone suspension, prostate volume
remained significantly greater than baseline.
"Testosterone and, especially, carnitines proved to be active drugs for
the therapy of symptoms associated with male aging," the authors write.
"At least one side effect of testosterone administration (i.e. prostate
enlargement) will be avoided by carnitine administration."
Two of the authors are patent inventors for use of carnitines in
treating symptoms of male aging.
Urology. 2004;63:641-646
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
* Describe the possible mechanisms of androgen replacement and
carnitine in improving symptoms of male aging.
* Evaluate the efficacy of these two therapies in treating symptoms
of male aging.
Clinical Context
Both testosterone and carnitine metabolism have been implicated in
contributing to the symptoms of sexual dysfunction, depressed mood, and
fatigue in older men. A decline of testosterone's effects in the
hypothalamic dopaminergic system, striated skeletal muscle, and corpus
cavernosum may explain why older men suffer from the symptoms described
above.
Both male and female sex hormones increase L-carnitine levels, in vivo
carnitine-acetyl-transferase activity, and the activities of
mitochondrial carnitine palmitoil-transferases. Carnitines act as an
antioxidant by promoting activity in the Krebs cycle, while also
decreasing apoptosis via a reduction in ceramide levels along with
insulin-like growth factor.
The authors of the current study sought to determine if the direct
administration of carnitine could improve symptoms of male aging to a
similar degree as androgen treatment. They also wanted to establish the
safety of carnitine administration.
Study Highlights
* Patients eligible for participation were men older than 60 years
with symptoms of decreased libido and erectile quality, depressed mood
and ability to concentrate, irritability, and fatigue. Patients with a
free testosterone level less than 6 pg/mL were also included.
* Patients had to be generally healthy to participate in the study.
Those with a history of obstructive urinary symptoms, alcohol or
cigarette use, or cardiovascular disease were excluded.
* Subjects were randomized to receive 1 of 3 treatments:
testosterone undecanoate 160 mg/day, propionyl-L-carnitine 2 g/day plus
acetyl-L-carnitine 2 g/day, or placebo. All treatments were administered
for 6 months.
* Participants were followed for PSA levels and prostate volume,
measurements of penile blood flow, NPT, and serum levels of
testosterone, luteinizing hormone (LH), and prolactin. They were also
assessed for sexual function, mood, and fatigue. All of these
evaluations were performed at baseline, at 3 and 6 months after
initiation of treatment, and 6 months after cessation of treatment.
Although treatment was administered by blinded personnel, the authors
did not comment whether subjects' assessment was completed in a
similarly blinded manner.
* 150 patients were randomized into the study, and 130 completed
the study protocol. The authors did not perform an intent-to-treat
analysis of their data.
* Baseline values for all study groups were similar. Mean age of
subjects was 64 years.
* The testosterone group exhibited an increase in prostate volume
as measured by ultrasonography at 3 and 6 months. The authors mention in
their discussion that this increase prompted cessation of the study
protocol at 6 months. Prostate volume in the testosterone group had
decreased 6 months after cessation of treatment but had not returned to
baseline levels.
* Carnitine administration had no effect on prostate volume.
* Neither testosterone nor carnitine treatment changed PSA levels.
* Both carnitine and testosterone treatment improved penile blood
flow at 3 and 6 months compared with placebo. There was no difference
between the carnitine and testosterone groups in this outcome.
* NPT was improved to a similar degree in both active treatment
groups at 3 months compared with placebo, and this improvement was
stable at 6 months.
* Testosterone therapy caused an increase in serum testosterone
levels and a decrease in LH levels at 3 months that remained stable at 6
months. Prolactin was unaffected by testosterone treatment. Carnitine
did not significantly change any hormonal levels measured.
* Testosterone improved erectile dysfunction and sexual desire
scores at 3 months, but it did not improve scores for orgasm or general
sexual well-being at any point.
* Carnitine improved erectile dysfunction, sexual desire, orgasm,
and general sexual well-being scores at 3 months, and these values
either remained stable or improved slightly at 6 months.
* Carnitine was superior to testosterone in the 3- and 6-month
erectile function domain, the 6-month orgasm domain, and the 6-month
general sexual well-being domain.
* Both carnitine and testosterone improved depression scores
compared with placebo, but carnitine was superior to testosterone in
this variable.
* Fatigue was improved to a similar degree in both active treatment
groups compared with placebo.
* Adverse events were similar among all treatment groups.
Pearls for Practice
* Both testosterone and carnitine can affect symptoms of male aging
through multiple biochemical pathways in different tissues.
* Carnitine appears to improve symptoms of male aging to a similar
or better degree than testosterone without causing an increase in
prostate volume.
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This article is intended for primary care physicians, urologists,
geriatricians, and other specialists who care for older men.
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News Author
Laurie Barclay, MD
Freelance writer for Medscape Medical News
Disclosure: Dr. Barclay has reported no significant financial
interests.
Clinical Reviewer
Gary Vogin, MD
Senior Medical Editor, Medscape
Disclosure: Gary Vogin, MD, has disclosed no relevant financial
relationships.
CME Author
Charles Vega, MD, FAAFP
Assistant Clinical Professor, Associate Residency Program;
Director, Department of Family Medicine, university of California, Irvine
Disclosure: Dr. Vega has disclosed that he has received grants for
educational activities from Pfizer.
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Medscape Medical News 2004. © 2004 Medscape
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