Estrogen: how does estrogen work?

Estrogen: how does estrogen work?

Estrogen is the primary female sex hormone. Among other roles, it promotes the development and maintenance of female characteristics in the human body.

Estrogen is a generic term for estrus-producing compounds; the three most common naturally occurring estrogens are: Estrone (E1), estradiol (E2), and 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.

Estrogen hormones play an essential role in the growth and development of female secondary sexual characteristics such as breasts, pubic and armpit hair, endometrium, and the regulation of the menstrual cycle and reproductive system.

During the menstrual cycle, estrogen acts to produce an environment suitable for fertilization, implantation, and nutrition of the early embryo.

Here are some key points about Estrogen. More detail and supporting information is in the main article.

  • The ovaries are the prime location for estrogen production
  • Estrogen influences the structural differences between the male and female bodies; for example, females having a wider pelvis
  • Synthetic estrogen has numerous uses in medicine, such as in birth control pills
  • Normal estrogen levels vary extensively, with differences typically seen between two women on the same day of their cycles, and in the same woman on different days
  • Estrogen is implicated in the development or progression of numerous diseases

What is estrogen?

Estrogen is a generic term for estrus-producing compounds.

Hormones are chemical messengers that tell specific tissues to behave in a certain way.

At puberty, a female's ovaries begin releasing the hormone estrogen in synchronization with each monthly menstrual cycle.

The estrogen level rises suddenly mid-cycle, which triggers the release of an egg (ovulation). The estrogen level then quickly decreases after ovulation.

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 related hormones that make up the family known as estrogen include estrone, estradiol, and estriol.

Estrone (E1)

Estrone is considered a weaker form of estrogen and is the major estrogenic form found in naturally menopausal women who are not taking hormone replacement therapy (HRT). It is the only estrogen that is present in any amount in women after menopause.

Estrone is the least abundant of the three hormones.

Estrone is made in small amounts in most tissues of the body, notably fat and muscle.

Estradiol (E2)

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.

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.

Estradiol is thought to contribute to many gynecological problems such as endometriosis, fibroids, and even female cancers, particularly endometrial cancer.

Estriol (E3)

Estriol is a metabolic waste product of estradiol metabolism that has some effects on a limited number of estrogen receptors.

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 percent as potent as estradiol and 14 percent as potent as estrone.

How does estrogen work?

Estrogens have an effect on target tissues by binding to estrogen receptors. These receptors are protein molecules found inside those cells that are targets for estrogen action. Only estrogens (or closely related molecules) can 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.

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. When an estrogen molecule enters a cell and passes into the nucleus, the estrogen binds to its receptor, 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.

After attachment to estrogen response elements in DNA, this estrogen-receptor complex binds to coactivator proteins, which then activate genes nearby. The active genes produce molecules of messenger ribonucleic acid (mRNA), which guide the synthesis of specific proteins. These proteins can then influence cell behavior in different ways, depending on the cell type involved.

Where does estrogen come from?

Estrogen is released from the ovaries, the prime location of estrogen production.

The ovaries are the prime location for estrogen production. The estrogens are released from ovarian follicles and the corpus luteum (a temporary structure involved in ovulation and early pregnancy) following the release of an egg from the follicle, and the placenta.

Follicle-stimulating hormone (FSH) causes the release of estrogen and, conversely, estrogen inhibits the release of FSH; this is called a negative feedback loop.

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 luteinizing hormone (LH)
  • Inhibits LH after ovulation


  • Stimulates egg release (ovulation)
  • Stimulates estrogen and progesterone production

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:

Effect of estrogen on the female reproductive system

In females, estrogen affects the following:

  • 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. It also plays a part in vaginal lubrication.
  • 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 the 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:

  • 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

Estrogen has multiple effects on the brain, including helping to prepare the body for sexual reproduction.

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 skin

The number 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:

  • 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:

  • Bone formation and the closure of bone epiphyses, which causes bone-lengthening to stop 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

Bone is constantly being broken down and rebuilt, but the daily removal of small amounts of bone mineral (resorption), must be balanced by an equal deposition of new mineral to preserve bone strength. Up until the mid to late 20s, 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 percent of bone mass. It becomes more challenging after menopause to keep bones strong and healthy to prevent osteoporosis and fractures.

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.

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, however the beneficial effects of estrogens on blood vessels and its reduction of plaque build-up offer an overall protective effect against atherosclerosis.

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 every 28 days on average; estrogen plays a leading role in this cycle.

Day 1: Period

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). However, estrogen levels in women with PMS or PMDD are usually normal; 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.


Synthetic estrogen has numerous uses in medicine. The most common and notable uses of estrogen are in birth control pills or contraceptives and in hormone replacement therapy.

Birth control pill (also called oral contraceptives or hormonal contraceptives)

Low-dose birth control pills contain 20-50 micrograms of estrogen.

Birth control pills are the most commonly used method of birth control in America. Estrogen is included in combination oral birth control pills alongside the hormone progestin.

Many women take low-dose birth control pills, which contain 20 to 50 micrograms of estrogen.

Estrogen in the combined pill sends negative feedback to the brain and works to:

  • Stop the pituitary gland from secreting FSH
  • Stop the production of luteinizing hormone (LH)
  • Prevent ovulation
  • Support the uterine lining to inhibit breakthrough mid-cycle bleeding.

Some doctors may prescribe oral contraceptives for alternative uses including:

  • Regulating a woman's menstrual cycle
  • Easing severe cramping and heavy bleeding
  • Reducing the risk of ovarian cancer
  • Reducing development of ovarian cysts
  • Protection against ectopic pregnancy
  • Decreasing perimenopausal symptoms
  • Helping reduce the severity of hormone-related acne

Risks associated with birth control pills that contain estrogen include:

  • Heart attack
  • Stroke
  • Blood clots
  • Pulmonary embolism
  • Nausea
  • Vomiting
  • Headaches
  • Irregular bleeding
  • Weight gain
  • Weight loss
  • Breast tenderness
  • Increased breast size

Hormone replacement therapy (HRT)

HRT aims to replicate normal levels of female hormones, which can help relieve some symptoms of menopause. The treatment can be provided as estrogen-only or as estrogen and progestin combined.

Estrogen replacement therapy (ERT)

Estrogen replacement therapy (ERT) is used to increase estrogen levels in postmenopausal women who have had a hysterectomy and are, therefore, not at risk of uterine cancer. ERT can also treat conditions such as delayed onset of puberty, symptomatic vaginal atrophy, and breast atrophy.

ERT may help:

  • Prevent perimenopausal symptoms
  • Prevent osteoporosis
  • Prevent colon cancer
  • Reduce early bone loss and osteoporosis in women who have had their ovaries removed between the ages of 20 and 40

ERT should be avoided if the patient:

  • Is pregnant
  • Has unexplained vaginal bleeding
  • Has liver disease or chronic impaired liver function
  • Has a history of breast cancer, ovarian cancer, or endometrial cancer
  • Is a smoker
  • Has a history of blood clots
  • Has had a stroke

ERT can improve sleep problems caused by hormone changes.

ERT can reverse the effects of low estrogen levels and may:

  • Control the occurrence and severity of hot flashes
  • Improve mood and sleep problems that are due to hormone changes
  • Reduce vaginal irritation by maintaining the lining and lubrication
  • Maintain skin collagen levels
  • Prevent postmenopausal osteoporosis
  • Reduce the risk of dental problems including tooth loss and gum disease

Hormone therapy (HT)/estrogen and progestin therapy

For women with a uterus, the hormone progestin is used alongside estrogen to prevent estrogen encouraging the overgrowth of the uterine lining, which can lead to endometrial cancer. HT is available as a pill, nasal spray, patch, skin gel, injection, vaginal cream, or ring.

HT may relieve symptoms of menopause such as:

  • Hot flashes
  • Vaginal dryness
  • Pain with intercourse
  • Mood swings
  • Sleep disorders
  • Anxiety
  • Decreased sexual desire

The risks of HT include:

  • Blood clots
  • Breast cancer
  • Endometrial cancer
  • Heart disease
  • Deep venous thrombosis (DVT)
  • Stroke
  • Gallbladder disease

The side effects of HT may include:

  • Bloating
  • Breast soreness
  • Headaches
  • Mood swings
  • Nausea
  • Water retention

The US Food and Drug Administration (FDA) recommend that HRT is used at the lowest doses for the shortest duration needed to achieve treatment goals.

Postmenopausal women who use or are considering using hormone therapy should discuss the possible benefits and risks to them with their physicians.

Hormone therapy is also used to help transgender people who wish to transition, with estrogen often prescribed to help trans women looking to develop female secondary sexual characteristics. Due to the risks posed by estrogen therapy, it is vital that such hormone therapy is accessible with appropriate medical supervision and monitoring.

During pregnancy

Throughout pregnancy, progesterone dominates. However, estrogen is required for many of progesterone's functions and is necessary to stimulate the production of progesterone in the placenta.

Estrogen is made and released by:

  • The corpus luteum of the ovaries
  • The fetal-placental unit

The fetal-placental unit is where the fetal liver and adrenal glands produce an estrogen called estriol, which establishes fetal well-being and is converted into other estrogens by the placenta.

Estrogen levels increase throughout pregnancy and have effects including:

  • Supporting, regulating, and stimulating the production of pregnancy hormones
  • Developing fetal organs such as the liver, kidneys, and lungs
  • Facilitating placental growth and function
  • Preparing the mother for lactation (breast-feeding) by encouraging maternal breast tissue growth.

High levels of pregnancy hormones are essential for a healthy pregnancy but often cause unwelcome side effects in the first trimester including:

Morning sickness is one of the many unwelcome side-effects of pregnancy hormones.

  • Mood swings
  • Morning sickness
  • Pelvis and lower back discomfort
  • Constipation

Estrogen and a hormone called oxytocin cause the release of a group of hormones, known as prostaglandins.

These hormones stimulate the maturation of the cervix leading to successive dilation during labor. The cervix must dilate (open) to around 10cm for the baby to pass through.

At around 4 months into the pregnancy, women would be able to breast-feed if not for high levels of progesterone and estrogen during this time preventing lactation.

After the placenta is delivered following birth, the blood levels of progesterone and estrogen fall which allows the mother to produce colostrum, a high-density milk that contains the necessary protein, minerals, and fat-soluble vitamins (specifically A and K) for a newborn.

During menopause

Menopause brings significant, permanent changes to hormone levels and hormone balance in the body. The ovaries stop producing eggs, and they also stop producing their hormones. The average age for a woman to reach the menopause is 52, with menopause marking the point at which it has been 12 months since a woman's last menstruation.

The transition to menopause, called perimenopause, can typically last 2-8 years and initiates physical and emotional changes due to erratic estrogen levels. Symptoms include:

  • Hot flashes
  • Depression
  • Irregular menstrual cycles
  • Breast tenderness
  • Migraines
  • Loss of libido
  • Mood swings

Estrogen levels may continue to fluctuate in the year after menopause. Low levels of estrogen cause the vagina to become drier and the vaginal walls thinner, which can make sex painful.

Some women treat menopausal symptoms with estrogen and estrogen-progestin therapy to prevent osteoporosis and to improve overall health. However, after the publication of results from the Women's Health Initiative (WHI) in 2002 and March 2004, the U.S. Food and Drug Administration (FDA) now advise doctors to prescribe menopausal hormone therapies at the lowest possible dose and for the shortest possible length of time to achieve treatment goals. Treatment is reserved for management of menopausal symptoms rather than prevention of chronic disease.

Young women who have their ovaries surgically removed experience a dramatic drop in estrogen, resulting in surgical menopause that may require similar treatment to that of natural menopause.

Estrogen levels

Normal estrogen levels vary extensively, with differences typically seen between two women on the same day of their cycles, and in the same woman on different days.

Why do estrogen levels fall?

Reasons for estrogen levels falling include:

  • Hypogonadism (ovarian failure)
  • Hypopituitarism (an underactive pituitary gland)
  • Pregnancy failure (estriol)
  • The perimenopause and the menopause (estradiol)
  • Polycystic ovarian syndrome (PCOS)
  • Anorexia nervosa (eating disorder)
  • Extreme exercise or training
  • Medication such as clomiphene
  • Immediately after childbirth
  • During breast-feeding

Why do estrogen levels rise?

Reasons for estrogen levels rising include:

  • Puberty
  • Overweight and obesity
  • High blood pressure
  • Diabetes
  • Healthy pregnancy
  • Tumors of the ovaries or adrenal glands
  • Medications such as steroids, ampicillin, estrogen-containing drugs, phenothiazines, and tetracyclines

Estrogen and disease

Estrogen is implicated in the development or progression of numerous diseases.

Indeed, many scientists have expressed concern over the ingestion of hormones, including estrogen, from dairy products, with research ongoing as to the effects of such consumption on the risk of a variety of estrogen-dependent cancers.

Breast cancer

Estrogen stimulates some breast cancers to grow by triggering particular proteins (receptors) in the cancer cells. If breast cancer cells have estrogen receptors, the cancer is said to be estrogen receptor-positive.

Hormone therapies that stop estrogen from stimulating the cells to divide and grow are often successful for estrogen receptor-positive breast cancers.

Endometrial cancer

Endometrial cancer is the most common uterine cancer. Increased levels of estrogen appear to play a role in the cause of endometrial cancer. Estrogen helps stimulate the buildup of the lining of the uterus.

Studies have shown that high levels of estrogen result in excessive endometrial growth and cancer.

Ovarian cancer

Most studies show that estrogen-only HRT increases ovarian cancer risk, including a study published in 2007 involving more than 1 million women aged 50 and over and a combined analysis of studies published in 2009.

Most women who take HRT take one of the types of combined HRT. Studies show that these can increase the risk of ovarian cancer if they are taken for longer than 5 years. The longer women take HRT, the more the risk increases. When women stop taking HRT, the risk goes back down over a few years to the same level as women who have never taken HRT.

Colorectal cancer

Studies have shown that combination hormone replacement therapy (HRT) that includes both estrogen and progesterone lowers the risk of invasive colorectal cancer in postmenopausal women. However, combination HRT does not lower the risk of dying from colorectal cancer.

Not all hormone replacement therapy decreases the risk of having colorectal cancer. HRT with estrogen alone does not lower the risk of having invasive colorectal cancer or the risk of dying from colorectal cancer.

Heart disease

The increase in heart disease among post-menopausal women could be due to a decline in estrogen. Estrogen appears to have a positive effect on the inner layer of the artery wall, keeping blood vessels flexible. This allows them to relax and expand to accommodate blood flow.

The American Heart Association recommend against using postmenopausal hormone therapy to reduce the risk of coronary heart disease or stroke because some studies suggest that it does not lower risk.

Estrogen may protect neuronal health.

Neurodegenerative diseases

Estrogen has been proposed to act as a neuroprotectant.

Estrogen deprivation, post-menopause, is likely to initiate or enhance degenerative changes caused by oxidative stress, and to reduce the brain's ability to maintain synaptic connectivity and cholinergic integrity, thus leading to cognitive decline.

There is sufficient evidence that estradiol is a powerful neuroprotectant which might have uses against Alzheimer's disease (AD), stroke, and Parkinson's disease, both in women and men.

Recent research found that a combination of estradiol and progesterone had benefits for cognition in women, including supporting verbal working memory and visual memory.

Alzheimer's disease

All people carry two copies of a gene called ApoE; one copy is inherited from each parent. Like genes for eye or hair color, ApoE comes in more than one version.

Some 15-20 percent of Americans carry at least one copy of ApoE4, a version that puts them at substantially increased risk for late-onset Alzheimer's disease in comparison with people who are not ApoE4 carriers.

Estrogen showed a protective effect in women carrying the ApoE4 gene. Hormone replacement therapy may help slow down cellular aging and have a protective effect on the blood vessels, which could reduce the risk of dementia, including vascular dementia.

Parkinson's disease

Increasing evidence suggests that estrogen may protect the nigrostriatal dopaminergic pathway affected in Parkinson's disease (PD). Animal studies show that estrogens influence the synthesis, release, and metabolism of dopamine and can modulate dopamine receptor expression and function.


Women are more likely to develop gallstones than men. Extra estrogen can increase cholesterol levels in bile and decrease gallbladder contractions, which may cause gallstones to form. Women may have extra estrogen due to pregnancy, hormone replacement therapy, or birth control pills.


Osteoporosis is the most common bone disease. The leading cause of osteoporosis is a drop in estrogen in women at the time of menopause. Women over 50 and men over 70 have a higher risk for osteoporosis.

Systemic lupus erythematosus (SLE)

Many studies have looked at how hormones trigger and affect SLE. From these studies, we know that estrogens enhance autoimmunity while androgens and progesterones suppress the immune response.

The body fluids and blood of patients with lupus show decreased concentrations of androgens from different parts of the body, as well as a decreased ratio of androgens to estrogens.

In addition, SLE patients have a quicker conversion of androgens to estrogens, and high estrogen concentrations have been found in the joint fluid of these patients.

Because of this hormonal connection, women with SLE need to be very careful about hormonal contraceptive use and hormone replacement therapy.

Estrogen Levels In Women | Her Body (Video Medical And Professional 2018).

Section Issues On Medicine: Medical practice