Estrogen is a generic term for estrus-producing compounds; the female sex hormones, which include the following:
- Estrone (E1)
- Estradiol (E2)
- Estriol (E3).
Estrogen is produced by the ovaries and in smaller amounts by the adrenal cortex (The outer segment of the adrenal gland located on top of each kidney), testes (testicles) and fetoplacental unit (the fetus and the placenta).
Estrogen is considered to be the "female" hormone, whereas testosterone is considered the "male" hormone. However, both hormones are present in both sexes.1
Estrogen hormones play an essential role in the growth and development of female secondary sexual characteristics such as breasts, pubic and armpit hair, endometrium, regulation of the menstrual cycle and the reproductive system. During the menstrual cycle, estrogen acts to produce an environment suitable for fertilization, implantation, and nutrition of the early embryo.
In males, estrogen plays a role in normal male reproductive processes. Aspects of pubertal development in boys (growth of the long bones, their mineralization and epiphyseal closure) attributed to the actions of androgens are now recognized as being mediated in part by estrogen.2 The final steps of spermatid maturation, spermiogenesis, appear to be particularly sensitive and dependent upon estrogen.3
Uses for estrogen as a drug include:
- Birth control
- Hormone replacement therapy
- Advanced prostate or postmenopausal breast carcinoma treatment
- Osteoporosis prophylaxis.
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Fast facts on estrogen
Here are some key points about estrogen. More detail and supporting information is in the main article.
- Estrogen refers to a family of hormones, including estrone, estradiol and estriol which are primarily responsible for female reproductive processes and secondary sexual characteristics in mammals.
- Estrogen is produced by the ovaries and in smaller amounts by the adrenal cortex, testes and fetoplacental unit.
- Although estrogen is considered to be the "female" hormone it is present in both sexes.
- Estrogen hormones play an essential role in the growth and development of female secondary sexual characteristics.
- At puberty, a female's ovaries begin releasing estrogen hormone in synchronization with each monthly menstrual cycle.
- In males, estrogen assists in maturation of sperm and is important for normal male reproduction.
- Estrogen is likely involved in mood disturbances such as premenstrual syndrome (PMS).
- Synthetic estrogen is commonly used in birth control pills, contraceptives and hormone replacement therapy.
- HRT helps to restore female hormone levels to premenopausal levels, which can relieve some symptoms experienced after menopause.
- Estrogen is required during pregnancy for stimulating the production of progesterone from the placenta.
What is estrogen?
At puberty, a female's ovaries begin releasing estrogen hormone in synchronization with each monthly menstrual cycle.
Estrogen is produced by the ovaries and in smaller amounts by the adrenal cortex and fetoplacental unit.
The estrogen level rises suddenly mid-cycle, which triggers the release of an egg (ovulation). The estrogen level then quickly decreases after ovulation.
Hormones are chemical messengers that tell specific tissues to behave in a certain way. Estrogen is secreted by one tissue, travels by way of fluid, usually through the bloodstream, interacts with cells in a variety of target tissues in the body and delivers a message - in the case just mentioned, the message is "ovulate."
The three related hormones that make up the family known as estrogen include estrone, estradiol and estriol.
Estrone is considered a weaker form of estrogen and is the major estrogenic form found in naturally-menopausal women who are not taking HRT. It is the only estrogen that is present in any amount in women after menopause.
Estrone has a chemical name of 3-hydroxy-estra-1,3,5(10)-trien-17-one with the chemical formula C18H22O2.5 Estrone is the least abundant of the three hormones. Small amounts of estrone are made throughout the body in most tissues, especially fat and muscle.
Estrone is the major estrogenic form found in naturally-menopausal women who are not taking HRT. It is the only estrogen that is present in any amount in women after menopause.
Estradiol is the most potent form of estrogenic steroids produced by ovaries and exerts the fullest range of estrogenic effects. When estradiol reaches the tissues it connects with estrogen receptors to trigger specific activities in those tissues and cells.
Estradiol's chemical name is estra-1,3,5(10)-triene-3,17β-diol and it has the molecular formula of C18H24O2.
In addition to being produced by ovaries, estradiol can also be produced by conversion from a number of precursors in the adrenal glands and the placenta.
Estriol is a metabolic waste product of estradiol metabolism that can still have some effects upon a limited number of estrogen receptors.
Estriol has a chemical name of estra-1,3,5(10)-triene-3,16α,17β-triol and a molecular formula of C18H24O3.
Estriol is only produced in significant quantities during pregnancy.
Estriol is made by the placenta from 16-hydroxydehydroepiandrosterone sulfate (16-OH DHEAS)4, which is an androgen steroid made in the fetal liver and adrenal glands and is 8% as potent as estradiol and 14% as potent as estrone.
How does estrogen work?
Estrogens have an effect on target tissues by binding to fractions of cells called estrogen receptors. These receptors are protein molecules found inside those cells that are targets for estrogen action. Only estrogens (or closely related molecules) are able to bind to these receptors.
The target tissues affected by estrogen molecules all contain estrogen receptors; other organs and tissues in the body do not. Therefore, when estrogen molecules circulate in the bloodstream and move throughout the body, they exert effects only on cells that contain estrogen receptors.6
Estrogen receptors exist in the cell's nucleus, together with DNA molecules.
In the absence of estrogen molecules, these estrogen receptors are inactive and have no influence on DNA (which contains the cell's genes). When an estrogen molecule enters a cell and passes into the nucleus, the estrogen binds to its receptor, in doing so causing the shape of the receptor to change. This estrogen-receptor complex then binds to specific DNA sites, called estrogen response elements, located near genes that are controlled by estrogen.
After attachment to estrogen response elements in DNA, this estrogen-receptor complex binds to coactivator proteins, which then activates genes nearby. The active genes produce molecules of messenger ribonucleic acid (RNA), which guide the synthesis of specific proteins. These proteins can then influence cell behavior in different ways, depending on the cell type involved.6
Where does estrogen come from?
The ovaries are the prime location for estrogen production. The estrogens are released from the ovarian follicles and are also secreted by the corpus luteum (the temporary endocrine structure involved in ovulation and early pregnancy) following the release of an egg from the follicle and the placenta.
Follicle-stimulating hormone (FSH) causes estrogen release and in return estrogen inhibits FSH. The pituitary gland produces FSH in the brain.
Follicle-stimulating hormone (FSH) causes the release of estrogen and estrogen inhibits FSH as part of a negative feedback loop. The pituitary gland produces FSH in the brain.
Key functions of these hormones and their interactions with each other are listed below:
- Causes an egg to mature in an ovary
- Stimulates the ovaries to release estrogen.
- Encourages the growth of the uterine lining
- Inhibits FSH production to ensure that only one egg matures in a cycle
- Stimulates the pituitary gland to release the luteinising hormone (LH)
- Inhibits LH after ovulation.
- Stimulates egg release (ovulation)
- Stimulates estrogen and progesterone production.
Other sites of estrogen production in humans include:
- Adrenal cortex
- Fat cells
What does estrogen do?
Estrogen is a crucial component that contributes to the estrus cycle, influencing female reproductive capacity. Estrogen has a range of effects on a number of areas of the body, however, and these are discussed below.
Effect of estrogen on the female reproductive system
In females, estrogen affects the following:7
- Ovaries - estrogen helps stimulate the growth of the egg follicle
- Vagina - estrogen stimulates the growth of the vagina to its adult size, the thickening of the vaginal wall, and the increase in vaginal acidity that reduces bacterial infections are also correlated to estrogen activities
- Fallopian tubes - estrogen is responsible for developing a thick muscular wall in the fallopian tubes, and for the contractions that transport the egg and sperm cells
- Uterus - estrogen enhances and maintains the endometrium, the mucous membrane that lines the uterus. The endometrium's size and weight are increased in addition to cell number, cell types, blood flow, protein content, and enzyme activity. Estrogen stimulates the muscles in the uterus to develop and contract. Contractions help during the delivery of a child and placenta, and help the uterine wall to cast off dead tissue during menstruation
- Cervix - estrogen is thought to regulate the flow and thickness of uterine mucous secretions to enhance sperm transport
- Mammary glands - estrogen forms unique complexes with other hormones in the breast and is responsible for growth of the breasts during adolescence, the pigmentation of the nipples, and the eventual cessation of the flow of milk.
Effect of estrogen on physical structure
Estrogen influences the structural differences between the male and female bodies, for example in females:7
- Bones are smaller and shorter, the pelvis is broader, and the shoulders are narrower
- Body is more curved and contoured because estrogen increases fat storage around the hips and thighs. Estrogen helps decelerate height increase in females during puberty, and increases sensitivity to insulin (which influences a person's amount of body fat and lean muscle)
- Body hair is finer and less pronounced, and the scalp hair is usually more permanent
- Voice box is smaller and the vocal cords shorter, giving a higher-pitched voice than in males
- Sebaceous (oil-producing) gland activity is suppressed by estrogens and thereby reduces the likelihood of acne in the female.
Effect of estrogen on the brain
In the brain estrogen:
- Helps maintain body temperature
- May delay memory loss
- Helps to regulate parts of the brain that prepare the body for sexual and reproductive development
- Increases serotonin and the number of serotonin receptors in the brain
- Modifies production and the effect of endorphins, the "feel-good" chemicals in the brain
- Protects nerves from damage and possibly stimulates nerve growth.
Effect of estrogen on hormones
Estrogen's effects on other hormones include:8
- An increase in cortisol and sex hormone binding globulin
- An increase in melanin and pheomelanin
- A reduction in eumelanin
- An increase in sensitivity to insulin.
In addition to increasing levels of sex hormone-binding globulin, estrogen also increases the serum concentrations of binding proteins that transport other substances, including the binding proteins for cortisol, thyroxine, and iron. The degree to which estrogen influences these hormones depends on the type of estrogen, i.e. estriol, estradiol, or estrone.
Effect of estrogen on skin
The quantity of estrogen receptors varies in different parts of the body. The highest levels are seen on the facial skin and skin over the thighs and breasts.
It is recognized that estrogen is an important factor in the maintenance of human skin, these factors include:8
- Improved collagen content and quality
- Increased skin thickness
- Improved blood supply to the skin.
Effect of estrogen on bones
Estrogen has various actions that are related to bone development and bone maintenance including:9
- Bone formation and the closure of bone epiphyses, which causes linear growth to cease at the end of puberty, maintaining bone throughout the reproductive years, and limiting bone resorption to preserve bone strength
- Preventing bone loss by working together with calcium, vitamin D and other hormones and minerals to build bones. Osteoporosis is a bone condition that results in a loss of bone density and an increase in susceptibility to fracture, especially of the hip, wrist and spinal vertebrae.
Bone is constantly being broken down and rebuilt, but the daily removal of small amounts of bone mineral, a process called resorption, must be balanced by an equal deposition of new mineral to preserve bone strength. Up until the mid to late twenties, the body typically builds more bone than it breaks down. Once estrogen levels start to decline, this process of bone-building slows, and around the age of 30-35, the breakdown of bone begins to outstrip the rate at which new bone is built.
There is a rapid increase in bone resorption in the first few years after menopause, which may result in the loss of some 20% of bone mass. It becomes more challenging after menopause to keep bones strong and healthy to prevent osteoporosis and fractures.10
Effect of estrogen on the heart and liver
Estrogen decreases serum cholesterol concentrations by helping to regulate the liver's production of cholesterol. It can also increase serum triglyceride concentrations, but the beneficial effects of estrogens on blood vessels and the mitigation of factors that contribute to plaque build-up offer an overall protective effect against atherosclerosis before menopause.11
Estrogen and the menstrual cycle
The female sex hormones control the menstrual cycle and naturally rise and fall throughout the month. The menstrual cycle is a dynamic process that repeats itself every 28 days on average and estrogen plays a leading role in this cycle.
Day 1: Period12
Estrogen and progesterone levels are at their lowest at this point in the cycle.
Day 5: Egg is selected
Inside the ovary, the egg is present within a follicle, an anatomical structure in which the egg develops - the follicle releases increasing amounts of estrogen.
Days 6-14: Preparing for ovulation
Toward the end of this stage, estrogen levels rise slowly, then more rapidly.
Around Day 14: Ovulation
The follicle surrounding the egg breaks open and the ovary releases an egg into the fallopian tube so it can be fertilized by a sperm. The follicle remains in the ovary.
Days 15-28: After ovulation
After ovulation has occurred, levels of progesterone start to increase. If the egg is released and not fertilized, estrogen and progesterone levels drop after approximately 2 weeks and the lining of the uterus gets ready to be shed. The next period begins, and the cycle starts again.
Estrogen is likely involved in mood disturbances such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Estrogen levels in women with PMS or PMDD are usually normal, however, this has led scientists to speculate that the problem may lie in the way estrogen "talks" to the parts of the brain involved in mood. Women with PMS or PMDD may also be more affected by the normal fluctuations of estrogen during the menstrual cycle.
On the next page we look at medication for estrogen levels, estrogen during pregnancy and menopause and estrogen in men. We also discuss normal estrogen levels and the link between estrogen and disease.