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:

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... :( :(

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:

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.


      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:

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.

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.


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 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.


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.


Article which discuss's how amino acids and diet can affect mood

" 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. "

Kava Kava, L-Theanine.

" 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. "

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..


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: (Co 2-67 49) (THIP)


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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