PMS, Genetics, and Solutions

PMS, Genetics, SolutionsA LOT of us know the moodiness and inability to think that come with premenstrual syndrome (PMS).  It can range from simply feeling irritable and icky to being something that really interferes with our lives.  Is there something genetic that predisposes some women to PMS?  It has been shown in the past few years that there is a genetic component, especially for a severe form of PMS called premenstrual dysphoric disorder (PMDD).

Neurotransmitters play a role in some of the symptoms of PMS or PMDD (brain fog, anyone?).  Serotonin is an important neurotransmitter involved in mood stability.  Estrogen is a serotonin agonist, and fluctuations in estrogen levels also effect serotonin  levels.  GABA, another neurotransmitter, is also involved in PMS symptoms for some.

Genes involved in PMS:

The HTR1A gene codes for a serotonin receptor. According to one study, the G/G genotype is “associated with impaired WM [working memory] in the premenstrual phase and premenstrual decline of cognitive function.  …  As the G/G genotype of HTR1A () involves in reducing serotonin neurotransmission, our results provide insight into the serotonin mechanism of cognitive function among women with PMDD.”     [ref]

Note that on this SNP, when you look it up in SNPedia, the orientation is “minus”.  So to switch to the 23andMe plus orientation, you will need to switch the C and G.  Makes it confusing when reading through the literature!

Check your 23andMe results for rs6295 (plus orientation):

  •  GG : normal/ wildtype
  •  CC:   Impaired working memory in premenstrual phase

ESR1 (estrogen receptor 1 gene) mediates estrogen activity in the brain and has been studied with implications in diseases including breast cancer, osteoporosis, and endometriosis as well as severe PMS.  ESR1 has also been studied in relation to cognitive impairment and Alzheimer’s Disease.   [ref]   (There are lots and lots of studies on this gene – worth looking into if you are homozygous.)

Check your 23andMe results for rs9340799:

  • GG : 8x higher risk for sever PMS [ref]
  • AG:   normal risk of PMS
  • AA: normal risk of PMS

One study showed that the ESR1 polymorphisms are most associated with PMDD for those with a COMT (catechol-o-methyl transferase) polymorphism.  [ref] Also known as COMT Val158Met (rs4680), this is a well studied polymorphism that is involved in dopamine activity.  When you are reading research on this polymorphism, often it will refer to the A-allele as Met and the G-allele as Val.

Check your 23andMe results for rs4680:

  • GG : higher risk of PMDD (combined with ESR1 polymorphism) [ref]
  • AA: normal risk of PMS


While genes do seem to play a role in PMDD, for most of us, we may need to look further for solutions to our PMS woes.

PMS Remedies and Options:

Histamine intolerance is tied to PMS, especially for menstrual cramps.  You can read up on the genes involved in histamine intolerance here and here – as well as Googling histamine intolerance.   Perhaps a diet lower in histamines would help your PMS.  Food that are high in histamines (avoid for low histamine diet) include anything fermented (soy sauce, vinegar, wine, kombucha), lunch meats, tomatoes, oranges, strawberries, chocolate, and fish that is not completely fresh.  An interesting article on histamine from the Hitting on HIT blog says this about PMS:

dysmenorrhea (menstruation pain) – The uterus consists of smooth muscle, and a heightened amount of histamine can cause more severe menstruation cramps in women. As histamine also tampers with hormonal levels like progesterone and oestrogen, which in turn can influence levels of histamine. The good news is that the placenta in pregnant women produces large amounts of DAO leading to a remission of the intolerance during pregnancy.

GABA is a neurotransmitter that has been found to be low in some women with PMDD and PMS.   This may be due to low levels of allopregnanolone, a metabolite of the hormone progesterone, which modulates GABA.  [ref]  Nutrients that increase GABA levels include theanine (found in tea), magnesium, chamomile, potassium, and glycine (found in gelatin).  [ref]  When you think about it, the age old remedy of chicken soup (made with homemade chicken stock) and a cup of hot tea may be just the thing for raising your GABA levels.   Follow this with a nice soak in the bath with some Epsom salt to raise your magnesium levels.

Vitamin B6 has been studied in placebo controlled studies and was found to help decrease PMS symptoms. [ref]   The active form of B6 is pyridoxal-5-phosphate (P5P) and can be found in better quality supplements. Read your supplement labels and look for P5P instead of pyroxidine.

Interestingly, P5P is a co-factor for diamine oxidase, which is the enzyme that breaks down histamine.  P5P is also involved in many, many other enzymatic reactions.  Food sources of B6 include raw meat, cheese, and milk as well as beef liver, sunflower seeds, and pistachios.  Here is a great article on B6 helping with PMS:

Hopefully this has given you some ideas of how to be proactive with your PMS symptoms.  Keep searching for what works for your body!




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