MEDICAL
RESEARCH
NATURAL
PROGESTERONE
In
her book “Once a Month:
Understanding and Treating PMS”,
Katharina
Dalton advocates
treatment of PMS with progesterone (sex
hormone) during the luteal phase (last 14 days of cycle before
menstruation). She asserted that the cause of PMS in certain women was
that they didn’t produce enough progesterone during luteal phase. One
site I found said Dalton prescribed 400-1600mg progesterone daily plus
50-200mg of Vit B6. However many scientific studies have failed
to find any evidence of progesterone’s efficiacy.
Research
on progesterone:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Link&db=PubMed&dbFrom=PubMed&from_uid=11588078
http://www.psychosomaticmedicine.org/cgi/content/full/61/5/676
I
am
going to try natural progesterone over the next few months and will
report back on my experiences afterwards! 19/12/2003
You
can buy progesterone
creams on the internet. Progesterone can be synthesised from
Wild Yam extract but Wild Yam creams do not contain progesterone
unless
it has been manufactured and added separatelyto the cream. These creams
are
expensive so if you do want to try natural progesterone I would
recommend buying it from a reliable source, ie your doctor.
Further
information on
natural progesterone
28/04/2004
Well I tried progesterone pessaries, 200mg twice a day for a couple of
months. The first month I was taking them I wasn't working and seemed
ok. The second month I felt very very drowsy and confused and my moods
were quite severe so I decided to stop as they didn't seem to be
helping. I'm going to see the doctor again to ask if I can get a lower
dose as I don't think women produce more than 30mg of progesterone a
day so it seems strange they prescribe such a high dose? Also I didn't
like using pessaries as it can be uncomfortable inserting them
sometimes. Perhaps progesterone creams are better as less progesterone
would be absorbed that way. It definately has a sedative effect but
this didn't seem to prevent wild mood swings when my period came... :(
:(
NEUROTRANSMITTERS
Our impulses and
emotions are
controlled by the passing of electrical signals between neurons (nerve
cells) in the brain. Neurons are made up of a cell body, an axon
and
numerous long dendrites. Electrical signals travel along the dendrites
(which are like electrical cables), through the cell body and down the
axon. However there is a small gap between the axon of each neuron and
the dentrites of neighbouring neurons which the electrical signal needs
to cross somehow. This gap is called the synapse. Certain chemicals
called neurotransmitters act as chemical
messengers
which transport signals between the axon of one neuron and the dentrite
of another. The surfaces of the neuron cells have sites called
receptors which neurotransmitters bind to. Receptor sites can only
receive specific types
of neurotransmitters. Some
examples of neurotransmitters
are serotonin, dopamine, GABA and
noradrenaline. After the neurotransmitter has attached to a receptor
site (and passed on it's chemical message), it releases from the
receptor site and floats back into the synapse. Two things can then
happen to the neurotransmitter. Either it is broken down by enzymes
called monoamine oxidase or it may be sucked back into the synapse that
released it.
For more information about the role of specific neurotransmitters on
mood and behaviour see the following sites:
http://www.mcmanweb.com/article-235.htm
http://www.psychiatrictimes.com/p011052.html
http://www.benbest.com/science/anatmind/anatmd10.html
http://www.indstate.edu/thcme/mwking/nerves.html
SSRI
anti-depressants, such
as
Prozac/Sarafem, inhibit the reuptake of serotonin by the axons and so
serotonin levels build up in the synapse. MAOI or monoamine
oxidase inhibitors are another class
of anti-depressants which destroy the enzyme monoamine oxidase so that
levels of certain neurotransmitters build up in the synapse
without being destroyed.
Certain hormones
which are synthesised in the brain are called neurosteroids. It is
becoming clear that neurosteroids can have a profound affect on neuron
receptor function. For instance the neurosteroid allopregnanolone,
which is derived from progesterone, binds to GABA-A receptors in the
brain and enhances their function.
CURRENT RESEARCH
Some
of the latest research seems to suggest
that women with PMDD/PMS either have low levels of or have an abnormal
sensitivity to
fluctuations of the neurosteroid
allopregnanolone......
Role
of allopregnanolone in PMS
Mice
treated with
progesterone or allopregnanolone showed an increase in cortical
allopregnanolone levels
Allopregnanolone
levels and alochol
Prozac, SSRI's and allopregnanolone:
http://www.abc.net.au/science/news/stories/s65195.htm
http://www.sciencedaily.com/releases/1999/11/991110061714.htm
http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s11123.htm
Allo
supresses sexual behaviour and ovulation
Dysregulation of
the g-aminobutyric acid
A/benzodiazepine receptor complex for PMDD
Talks
about action of neurosteroids on GABA-A receptors
Very
interesting paper, see 2nd
paragraph under section with heading SSRI's in particular
Research on PMDD:
Research by Medello, M.D.
Research
by Alessandro Guidotti, M.D.
Research by T Backstrom,
M.D.
SSRI's and
depression:
5HT (serotonin) increases neurogenesis (process of generating new brain
cells) and starting this process is thought to be how anti-depressants
treat depression. This process takes several
weeks though and is clearly not the same process by which SSRI's treat
PMS symptoms therefore, and so possibly Prozac's efficiacy in treating
PMS has nothing to do with serotonin. This is further
evidence for allopregnanolone or some other neurochemicals being
involved. A doctor suggested to me that the increase in serotonin
causes an increase in allopregnanolone.
http://www.biopsychiatry.com/newbraincell/
http://www.dbsalliance.org/research/researchupdate3.html
Best paper i've read
on PMDD and
PMS
(PDF version)
Conclusion
from this paper: These data strongly
suggest that the GABAergic system is substantially modulated by
menstrual cycle phase in healthy women and those with PMDD.
Furthermore, they raise the possibility of disturbances in cortical
GABA neuronal function and modulation by neuroactive steroids as
potentially important contributors to the pathogenesis of PMDD.
MY PERSONAL
CONCLUSIONS
The occurrence of PMS is increasing in Western society, yet not much is
known
about it's causes still. Some experts think pollution may be to blame,
particularly environmental oestrogens (chemicals which mimic the female
hormone oestrogen and could also be responsible for the increase in
breast cancer cases). What can we do about environmental oestrogens?
Ban all
substances containing them? This is not likely to happen for a long
time, or help this generation of women who suffer from PMS, even if
they did
prove that these chemicals were causing PMS and ban them. Eating
plants which contain phytoestrogens is recommended to help combat the
effects of environmental oestrogens (since these block the effects of
oestrogen). Soya beans are a particularly rich source of
phytochemicals. However if a hormonal imbalance was the cause of PMS,
how come medical research has failed to prove this? Perhaps
because the researcher's test woman's blood for levels of natural
progesterone and oestrogen and not for the unnatural chemicals which
can
mimic the effect of oestrogen? Also supplementation with natural
progesterone has not been proven to help in medical studies. Perhaps
the amount of progesterone given to subjects of the studies was too
high? I was prescribed 200mg by the doctor (see section at top) and
this made me so drowsy and confused that I had to stop taking it after
2 months.Some women
swear natural progesterone creams alleviate PMS symptoms. Perhaps only
small amounts of progesterone are needed to combat effects of
environmental oestrogens? Certainly this is something researcher's
should consider
studying...
The most recent PMS research points towards the GABAergic system being
modulated by the menstrual cycle and especially by the neurosteroid
allopregnanolone which is a derivative of progesterone.
Allopregnanolone combats anxiety as it is a potent GABA-A receptor
agonist. It surprises me therefore that natural progesterone did not
cure my symptoms since taking
progesterone should increase allopregnanolone levels in the
brain. I definately felt a sedative effect from natural
progesterone. PMS has been likened to drug-withdrawal since
allopregnanolone acts like a sedative on the brain. If this is the case
though surely taking a high dose of progesterone before your period
will only aggravate the withdrawal symptoms when you stop taking it. My
moods were a lot worse the second month I took it. Perhaps it would be
better to take progesterone during period until oestrogen levels build
back up, although i'm not sure if it's safe to do this as it might
confuse your body!!
Oestrogen is a GABA-A receptor antagonist, meaning it prevents the
receptor from functioning. It is my guess(!) that PMS patients have too
many GABA-A antagonists in their brains and not enough GABA-A agonists
(chemicals which increase GABA-A receptor function). I came to this
conclusion from reading the last research paper referenced.
And finally Prozac....how does it treat PMS? It seems no-one knows, we
are but mere guineapigs.... :(
If Prozac treats pms by increasing serotonin levels then supplementing
with the amino acid (protein
constituent) L-tryptophan and eating more complex carbohydrates is a
far safer way of increasing serotonin levels, in my opinion. Prozac's
mechanism of action during PMS treatment is thought to be the increase
in allopregnanolone levels and these may be increased by the rise in
serotonin levels also. Interestingly
alcohol increases
allopregnanolone levels and many women (including myself) crave alcohol
and
drink more while they are premenstrual. Of course this could be just a
coincidence! Alcohol also increases dopamine which rewards the pleasure
centres of the brain which could explain the cravings as well.
Clearly more research needs to be done in this area, especially since
most women in Western Society now work as well as raising a family! The
question is, who is going to fund the research?
Pharmacuetical companies don't seem that interested, perhaps because
Prozac makes them a lot of money, or perhaps because they are run by
men who are uneducated about woman's issues! They are missing out on a
huge marketing opportunity though given the high percentage of women
who suffer from PMS.
ENVIRONMENTAL
OESTROGENS
It may be wise to avoid xenoestrogens: alky
phenols in detergents and methyl paraben, propyl paraben and butyl
paraben in found in skin care products as these can be absorbed by the
body.
DO NOT store food in
clingfilm or soft plastic and do not cook it in plastic containers.
SUPPLEMENTS THAT
MAY
AFFECT BRAIN NEUROTRANSMITTER LEVELS
Article which
discuss's how amino
acids and diet
can affect mood
Gaba:
" GABA
(Gamma-aminobutyric
acid) is the number one inhibitory (calming) neurotransmitter in the
brain. Its function is to decrease neuron activity and inhibit nerve
cells from overfiring. GABA supports the brain against stress-related
messages from reaching the motor centers of the brain by occupying
their receptor sites. Together with l-theanine, GABA supports
relaxation without compromising cognitive function."
"Research
with human
volunteers has demonstrated that L-theanine creates its relaxing effect
in approximately 30 to 40 minutes after ingestion. The mechanism behind
this effect is two-fold:
1) L-theanine directly
stimulates production of alpha brain waves, which creates a deep state
of relaxation while maintaining mental alertness.
2) L-theanine appears to play
a role in the formation of gamma-aminobutyric acid, better known as
GABA. GABA acts as a powerful inhibitor of neurotransmitters and helps
maintain relaxed levels of neuron activity. "
From: http://www.l-theanine.com/intro.htm
Kava Kava, L-Theanine.
Serotonin:
" Tryptophan is
still available by prescription. Oddly enough, less is more, with lower
doses (one to three gm) more effective than higher doses. Taking the
amino acid with carbohydrates helps in its absorption."
" Serotonin synthesis
is a 2-step
process, the first step of which
requires the enzyme tryptophan hydroxylase with oxygen, iron and THB as
co-factors. Neither the enzyme nor the co-factors are rate-limiting for
either step of these reactions -- virtually all brain tryptophan is
converted to serotonin. Serotonin concentration in the brain is far
more sensitive to the effects of diet than any other monoamine
neurotransmitter -- and can be increased up to 10-fold by dietary
supplementation in laboratory animals.
Consumption of a meal that is high in carbohydrate, branch-chained
amino acids and tryptophan has a particularly dramatic effect because
both glucose from carbohydrate and branch-chained amino acids
(especially leucine) increase insulin secretion. Insulin facilitates
the transport of the branch-chained amino acids into muscle cells,
thereby reducing the competition tryptophan faces for the large neutral
amino acid transporter that takes it across the blood-brain barrier.
The resultant drowsiness induced by serotonin is a common effect of a
large carbohydrate meal. "
From: http://www.mcmanweb.com/article-235.htm
L-tryptophan or 5-HTP are
pre-cursors to serotonin and will have fewer side-effects than SSRI's.
You may experience nausea or drowsiness when you first start taking
L-tryptophan but apparently this disappears after a week or so..
POSSIBLE
FUTURE TREATMENTS??!!!
Pheromone
nasal spray
"Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20-one), an
orally active synthetic analog of the neuroactive steroid
allopregnanolone, is a positive allosteric modulator of
gamma-aminobutyric acid(A) receptors with anticonvulsant properties."
I don't think Ganaxolone passed clinical trials and company who made it
(CoCensys) were taken over by Purdue. This was a dead end in my
research for PMS cure!! Do a google search on ganaxolone if you are
interested!
Other anxyiolytic drugs:
http://jpet.aspetjournals.org/cgi/content/full/295/1/337
(Co 2-67 49)
http://jpet.aspetjournals.org/cgi/content/full/293/3/1084
(THIP)
MORE (RANDOM!)
LINKS ON
NEUROSTEROIDS..........
Neurosteroids
and PMS
Neurosteroids
and tranquilisers
Allopregnanolone
affects sleep in tranquiliser-like fashion
Research
on epilepsy and allopregnanolone
Allopregnanolone
and DHEA act as anti-depressants
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