A recent study in the journal Biomedicine & Pharmacotherapy analyzed the simultaneously indispensable and antagonizing role of estrogen in the human body.
Estrogen, often thought of as the female hormone, is, in fact, present in both men and women. Commonly known as sex hormones, estrogens play a role that extends far beyond sexual and reproductive functions. They influence many physiological processes such as cardiovascular health, bone metabolism, cognition, and skeletal growth among many others. Estrogen levels spike up during puberty and start to deplete in perimenopause. The production almost stops after menopause resulting in a woman’s susceptibility to various pathological conditions. The estrogen family mainly includes three steroid hormones: estrone, estradiol, and estriol. Estradiol, produced by the ovaries, is the most potent estrogen and therefore most significant.
Aromatase enzyme is critical in estrogen production
Estrogens are derived from androgens, the male hormone precursors, by an intricate process called aromatization, controlled by an enzyme called aromatase. The function of aromatase is critical in controlling the production of estrogens. An abnormality in aromatase activity can disrupt estrogen levels in the body and lead to ailments such as breast cancer, polycystic ovary syndrome (PCOS), endometriosis, osteoporosis, ovarian, gastric or pituitary cancer, neurodegenerative diseases, and transgender problems.
The dual and opposing nature of estrogen is intriguing. It plays significant roles in both health and ailments. Scientists have been trying to understand the widespread role of estrogen in human physiology.
A recent article published in the journal Biomedicine and Pharmacotherapy analyzed the important role of estrogen in human health and discussed various factors that are important for maintaining balance. In addition, the authors stressed the effects of inflammatory agents in everyday life that mimic estrogen and result in estrogen dominance. Furthermore, the researchers highlighted the significance of estrogen receptors, diseases associated with estrogen imbalance, and the regulation of estrogen levels.
Role of estrogen receptors
Estrogen mediates its effects through estrogen receptors (ER), which are proteins to which estrogen binds. Some of these effects are necessary for the overall health of an individual while some effects of estrogen binding to estrogen receptors lead to the progression of disease.
There are several mechanisms by which estrogens induce cellular changes in the body. Binding to estrogen receptors is the principal mechanism of action of estrogen. Estrogen receptors are found in the nucleus, cytoplasm, and mitochondria of cells. Genetic variations result in various types of estrogen receptors, the most common being ER-alpha and ER-beta.
Estrogens diffuse into the cells and bind to receptors. This estrogen-ER complex triggers a cascade of interactions with various proteins leading to increased or decreased mRNA levels and associated protein production, and finally a physiological response. Estrogen activity is considerably high in tissues where large numbers of estrogen receptors are present such as in ovaries, breasts, brain, kidneys, and bones.
Although ER-alpha and ER-beta have different biological functions, a balance between these two types of receptor activities in tissues either stimulates or inhibits estrogen signalling. Studies have shown that the relative ratio of each receptor type governs the net action of estrogens in the body.
Association between estrogen receptors and cancer
Many studies implicate the role of estrogen in the development of breast cancer. There is evidence that estrogen-ER complex stimulates proliferation of breast cells, increasing the risk of replication errors and mutations. In the ER+ type of breast cancer, the binding of estrogens to their receptors results in cancerous epithelial hyperplasia. Ovarian cancer, gastric cancer, lung cancer, hepatic cancer, prostate cancer, endometrial cancer, and pituitary cancer are among many other forms of cancer caused by a high level of estrogen.
Other diseases caused by an estrogen imbalance
It is normal for estrogen levels to vary between different days or at different times on the same day but when levels rise or fall too far for too long, it can lead to various health problems. High estrogen levels have been linked to polycystic ovary syndrome that are characterized by symptoms such as alopecia, amenorrhea, infertility, type 2 diabetes, and depression among others. Other conditions caused by high estrogen include autoimmune diseases such as systemic lupus erythromatosus (SLE) and multiple sclerosis (MS), endometriosis, the proliferation of male breast tissue, and breast hypertrophy in females.
A lower than normal level of estrogen is associated with osteoporosis, arthralgia, Alzheimer’s disease, schizophrenia, and Parkinson’s disease. A reduced level of estrogen also results in impaired glucose homeostasis leading to adiposity, insulin resistance, and an increased risk of cardiovascular disease and diabetes.
What causes estrogen imbalance?
The natural cause of low estrogen is aging. Some induced causes include ovariectomy, the use of aromatase inhibitors, the use of certain drugs such as antidepressants, opiates, antihypertensive, antimalarial, and anticancer drugs. Cigarette smoking may also be responsible for inhibiting aromatase activity. The use of certain personal care and household supplies that contain endocrine disrupting chemicals such as parabens, phthalates, benzophenones, bisphenol A (BPA), pesticides, and fire hydrants is associated with estrogenic properties. These chemicals mimic human estrogen and bind to estrogen receptors thus affecting estrogen signalling process. These deliberate or unintentional exposures result in an imbalance in estrogens and various health problems.
How can estrogen balance be regulated?
There have been numerous studies to understand the precise regulation of estrogen and associated receptors. Researchers are still working on many unanswered questions. What studies have made clear is that the estrogen is a very powerful yet delicately balanced hormone that is vital for a healthy life. Hormone replacement therapy is one way to correct estrogen levels but it is a complex task. Minimizing exposure to endocrine disrupting chemicals and inflammatory substances that lead to increased aromatase activity can help delay or prevent diseases associated with estrogen imbalance.
A delicate balance needs to be maintained
In conclusion, estrogen balance is critical for maintaining good health. Various pathological conditions are associated with both high and low levels of estrogen. Therefore, a delicate balance needs to be maintained. In addition to physiological factors, certain environmental triggers can affect estrogen levels. Toxic chemicals and pollutants in everyday use act as endocrine disruptors and perturb the estrogen balance. Making lifestyle changes to avoid exposure to these chemicals by air, water, pesticides, or cosmetics is an important step towards achieving estrogen balance. The authors suggest that authorities should act to control the exposure of the public to these harmful chemicals.
Written by Preeti Paul, MS Biochemistry
Reference: Seema Patel et al., Estrogen: the necessary evil for human health, and ways to tame it. Elsevier-Biomedicine and Pharmacotherapy 102 (2018) 403-411 https://doi.org/10.1016/j.biopha.2018.03.078