The levels of female hormones, such as estrogen and progesterone, fluctuate naturally throughout the different stages in a women’s life. They are steroid hormones that are synthesized from cholesterol which bind to receptors that are found throughout the body, including the nervous system.
The presence of these hormones has been shown to influence the development of certain pathologies such as atherosclerosis, as well as cause significant changes in mood and behavior if their levels become unstable or dysregulated.
Central to reproductive health and the biological pathways involved in hormone synthesis is the availability of several nutrients that are essential for reproductive health. Lack of nutrients such as folate affects menstrual cycle characteristics, and therefore fertility 1.
Single nucleotide polymorphisms (SNPs) in genes that code for these hormones, or the enzymes that are involved in their production or degradation, affect the circulating levels of these hormones which can affect women’s health.
Estrogen is produced largely by the ovaries and remains at relatively constant levels throughout a women’s reproductive life until menopausal transition is reached. An imbalance in estrogen levels can lead to symptoms that include, but are not limited to mood disorders, premenstrual syndrome, abdominal or pelvic pain, and water retention.
There are three primary estrogens:
Estrone (E1) – mostly found in post-menopausal women
Estradiol (E2) – potent estrogen and predominates in cycling females
Estriol (3) – weak estrogen that is present during pregnancy
Estradiol is required to be inactivated to keep circulating levels at optimum concentrations, however, research has now linked certain SNPs in the enzyme that is meant to break down estradiol, to the inability to conceive 2.
The process of estrogen metabolism is quite complex, but it can be divided into three main processes:
SNPs in genes that control these processes are associated with a high risk of hormone-dependent cancers. For example, lifetime exposure to steroid hormones, especially estrogen, is a major risk factor for breast cancer. SNPs in genes encoding estrogen metabolizing enzymes are important as they could be used as biomarkers of an individual’s susceptibility to breast cancer 3, since dysfunction may cause estrogen levels to be too high, or too low.
Folate is an essential B vitamin that is needed for the proper formation of red blood cells and DNA synthesis and is one of the 13 essential vitamins. It cannot be synthesized within the body, and must therefore be obtained either from diet or supplementation. It is also a precursor to the important amino acid, methionine.
Dietary folate is a naturally occurring nutrient found in foods such as:
Leafy green vegetables
Interestingly, in the United States, approximately 60% of the population are ‘intermediate metabolizers’ of folate or heterozygous (2 different copies of the gene)4 for a genetic polymorphism of a folate metabolizing enzyme, whereas approximately 25% of certain populations are homozygous (two copies of the gene) for these genetic variations 5. Homozygotes have about 30% enzyme activity compared to the typical form of the gene (wild type).
Demands for folate increase during pregnancy because it is essential for the growth and development of the fetus. Folate deficiency has been associated with placenta-related pregnancy complications 6, as have SNPs in genes of the folate-dependent enzymes. Further, some SNPs in folate metabolism have been linked to recurrent, spontaneous abortions 7 and migraine susceptibility 8.