PMS, Genetics, and Solutions

A lot of women know the moodiness and brain fog that comes with premenstrual syndrome (PMS). The symptoms can range from simply feeling irritable and icky to being something that interferes with your normal lifestyle.

Premenstrual syndrome and premenstrual dysphoric disorder:

What role do genes play in 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).

A 2011 study of twins estimated the heritability of PMS to be around 95%.[ref]

PMS affects about 30-40% of women, while the rarer PMDD affects only 3-8%.[ref]


Is it all in your head?

In a literal way…  It turns out that neurotransmitters cause some of the symptoms of PMS and PMDD. Both conditions are linked to physically altered neurotransmitter levels.

  • Serotonin is an important neurotransmitter involved in mood stability. Estrogen is a serotonin agonist, and fluctuations in estrogen levels also affect serotonin levels.
  • GABA, another neurotransmitter, is also involved in PMS symptoms for some.[ref]

Genetic variants in these neurotransmitter genes are linked to increased susceptibility to PMS and PMDD — and they may hold the clues to what to do about PMS symptoms.

Genes Involved in PMS and PMDD

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HTR1A Serotonin Receptor Gene:

The HTR1A gene codes for a serotonin receptor found mainly in the brain. Rs6295 is a fairly common genetic variant of this serotonin receptor gene. One study found the variant (C/C for 23andMe) reduces serotonin neurotransmission and is “associated with impaired WM [working memory] in the premenstrual phase and premenstrual decline of cognitive function.” [ref]

Check your genetic data for rs6295 (23andMe v4, v5):

  • G/G: typical*
  • C/G: increased risk of PMDD
  • C/C: Impaired working memory in the premenstrual phase[ref] increased risk of PMDD[ref]

Members: Your genotype for rs6295 is .
*Given in the plus orientation to match your data.

ESR1 Estrogen Receptor 1 gene:

ESR1 mediates estrogen activity in the brain and has been studied as a risk for diseases such as 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 for the variant.)

Check your genetic data for rs9340799 (23andMe v4, v5; AncestryDNA):

  • G/G: 8x higher risk for severe PMS[ref][ref]
  • A/G: normal risk of PMS
  • A/A: normal risk of PMS

Members: Your genotype for rs9340799 is .

One study showed that the ESR1 polymorphisms are most associated with PMDD for those with a COMT (catechol-o-methyl transferase) variant.[ref] Also known as COMT Val158Met (rs4680), this well-studied polymorphism is involved in dopamine activity.

Check your genetic data for rs4680 (23andMe v4, v5; AncestryDNA):

  • G/G: higher risk of PMDD (combined with ESR1 polymorphism)[ref]
  • A/G: normal risk of PMS
  • A/A: normal risk of PMS

Members: Your genotype for rs4680 is .


Genetics seem to play a bigger role in PMDD. For many of us, though, we may need to look further for solutions to PMS woes.

Diet and Supplements:

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.  If the symptoms of histamine intolerance seem to fit you, a diet lower in histamines may help your PMS.  Foods 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.

GABA, a neurotransmitter, shows being 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 with PMS.  Follow this with a nice soak in the bathtub with some Epsom salt to raise your magnesium levels… Sounds like a good plan to me.

Zinc sulfate supplementation (50mg) decreased the symptoms of PMS in a study.[ref]

Vitex agnus castus (Chasteberry) in quite a few studies helped with premenstrual syndrome.[ref]  About half of the women who tried it in one study had a positive response.

Vitamin B6 in placebo-controlled studies helped decrease PMS symptoms.[ref]  The active form of vitamin B6, pyridoxal-5-phosphate (P5P), can be found in better quality supplements. 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 vitamin B6 include raw meat, cheese, and milk as well as beef liver, sunflower seeds, and pistachios.

A study of teenage girls with very low vitamin D levels (<10ng/mL) found supplementing with vitamin D helped their PMS irritability and anxiety.[ref] Other studies show varying results, but if you are deficient in vitamin D, a supplement or getting more sunshine may help.

What doesn’t seem to work?

Antioxidants – specifically vitamins A, E, and C – were studied and found to have no effect on PMS symptoms.[ref]

Shockingly (not!), a study found that women with PMDD tend to eat more right before their period.[ref]

Related Genes and Topics:

Estrogen: How it is made and how we get rid of it
Estrogen is usually thought of as the female hormone. While it is true women produce more estrogen than men, this applies to all of us. Estrogen – from how much is made to how it is broken down – is dependent on both genetics and lifestyle factors affecting both men and women.

9 Genetic Variants Associated with PCOS
Polycystic ovarian syndrome (PCOS) is an endocrine disorder that causes an increase in androgen hormone production in women. It affects 5 -10% of premenopausal women, and genetics plays a large role in whether you have PCOS.

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