alleyoop wrote on Jan 27th, 2009 at 5:25pm:Maybe this will help explain (if it all makes it on the post):
DISCUSSION
Prior to the advent of functional neuroimaging,
cluster headache was already deemed a hypothalamic-
2
influenced syndrome based on the multitude of hypothalamic
hormonal changes noted in cluster headache
sufferers.Melatonin, cortisol, prolactin, LH, and testosterone
levels can all be altered during a cluster
headache cycle and some of the hormone levels
remain abnormal in the interictal period.7 The idea of
treating these hormonal alterations to see if they
would change the course of cluster headache is not
new with clomiphene citrate. Low testosterone levels
documented in cluster headache sufferers led Nicolodi
et al8 to give testosterone supplementation to chronic
cluster headache patients in the early 1990s. Most of
the treated patients showed no change in headache
intensity or attack frequency, but all subjects had a
dramatic increase in sexual activity. A more recent
investigation, however, did demonstrate a positive
influence of testosterone administration for treatment
resistant cluster headache with some treated patients
having a total remission of attacks.9 The conflicting
treatment response to testosterone may reflect that
testosterone levels are not always low in cluster headache
patients and in some studies testosterone levels
have been found to be normal.7 Leuprolide, a gonadotropin
releasing hormone (RH) analog, was looked at
in a single-dose study and led to a decrease in cluster
headache pain intensity and attack frequency in 26 of
30 chronic cluster headache patients studied.10Twelve
patients had complete resolution of their headaches
17 days after leuprolide administration. Prior to treatment,
all patients had normal testosterone and LH
levels,with an initial rise in serumLHand testosterone
levels (Day 1-5) after leuprolide injection, followed by
a marked reduction in both. The testosterone levels
remained low for 30 days while the duration of headache
improvement lasted 3.25 months. This study in
which testosterone levels were actually persistently
lowered rather than raised gives more credence to the
thought that altering testosterone levels alone may not
be the prime effect of hormonal manipulation therapy
for cluster headache.This investigation was the first to
suggest that giving a medication that can directly
alter the hypothalamic-pituitary-gonadal axis can suppress
cluster headache. Based on these promising
results, it is somewhat surprising that leuprolide has
not been looked at further for cluster headache
prevention.
Clomiphene citrate is a synthetic non-steroidal,
ovulatory stimulant that can raise testosterone levels
in males by competing with endogenous estrogen at
hypothalamic estrogen receptors.11 In essence, clomiphene
citrate blocks the endogenous estrogen feedback
inhibition of LH-RH, thus leading to a rise in
LH and FSH levels with subsequent leydig cell stimulation
and testosterone production. The manner by
which clomiphene citrate prevents cluster headache
can only be speculated. The ability for clomiphene
citrate to elevate testosterone levels would appear to
be its primary mechanism of action in cluster headache
modulation, but as stated previously, testosterone
supplementation alone does not always improve
cluster headache and in the case of leuprolide, cluster
headache frequency decreased after a lowering of testosterone
levels.10 In addition, the case patient had no
change in his headaches after direct testosterone
supplementation. Could an elevation of LH levels by
clomiphene citrate in some manner suppress cluster
headache? There are conflicting reports on LH levels
in cluster headache patients with some studies documenting
normal levels while in others LH levels are
reduced.7 It is unlikely that raising LH levels alone
plays a role in cluster headache prevention as LH
levels were markedly reduced in the study subjects
who responded to leuprolide. In addition to altering
testosterone and LH levels, clomiphene citrate has
been shown to reduce prostaglandin E2 levels in a rat
model of ovulation and also in human endometrial
cells.12,13 Prostaglandins are known to have vasoactive
properties and serum prostaglandin E2 levels are
elevated during cluster headache cycles.14 Recently,
prostaglandin E2 was shown to enhance the release of
calcitonin gene-related peptide (CGRP) in a capsaicin
evoked CGRP release model involving the rat
trigeminal nucleus caudalis.15 CGRP is an integral
component to cluster headache pathogenesis. There
are elevated CGRP levels in jugular venous blood
during cluster headache attacks.16 Clomiphene citrate’s
ability to block prostaglandin E2 and thus theoretically
block CGRP release may help explain its
preventive effect in cluster headache. However, there
are no studies to date looking at the direct effect of
clomiphene citrate on CGRP levels in humans or
animals.
An interesting read...who wrote this information?
Is there a link to find this online?
" Most of
the treated patients showed no change in headache
intensity or attack frequency, but all subjects had a
dramatic increase in sexual activity. A more recent
investigation, however, did demonstrate a positive
influence of testosterone administration for treatment
resistant cluster headache with some treated patients
having a total remission of attacks.9"
It would be interesting to see the credits for the information cited in the article.
Were the subjects of this report male or female?
What form of Testosterone and in what dose were they administered?
My Dr. relayed to me at today's appointment that Hormone treatment for clusters should not be attempted by anyone that has some success with traditional coping therapies, be that high flow O2 as an abortive or any of the available drugs abortive/preventers.
The only candidates that should try this treatment should be those resistant to all existing alternative options. This is exactly what Dr. Stillman used as his criteria in his study report which is available by looking back to the first post in this thread.
Hormone treatments are not to be taken lightly...there are some serious complications that can arise from this course of therapy, most notably, the increased risk of prostrate cancer in men. My Dr. has me tested (PSA) every three months when taking testosterone.
Considering the risks , this should be a last resort treatment option worth trying based on the published high rate of success for resistant CH sufferers that show low testosterone levels.
Paul