Estradiol (E2), also called as estrogen, it is an steroid hormone and is a major female sex hormone. It is involved in the regulation of estrous and menstrual cycles. This hormone is responsible for the development secondary sexual characteristics of female such as widening of hips, breasts etc, it is important in the maintenance and development of reproductive tissues such as mammary glands, vagina and  uterus during puberty, adulthood and pregnancy. It also has a vital role in other tissues including bone, fat, skin, liver and brain.

Estradiol levels are much lower in males than females; the hormone has an important role in males too. In addition, this hormone is found in other mammals, in most vertebrates, insects, fishes and other animal species.

Production of estrogen in your body

It is produced within the follicles of ovaries, and also in other tissues including testicles and adrenal glands, fat, breasts, liver and brain. Estradiol is produced in the body through a series of reactions and intermediates from cholesterol. The major pathway involves formation of androstenedione which is converted by aromatase into estrone and is then converted to estradiol. 

Androstenedione can be converted into testosterone, which can be converted into estradiol. Upon menopause in females, estrogen production by ovaries stops and estradiol decreases at very low levels.

Where is this hormone used?

Estradiol is used in various preparations for the treatment of moderate to severe vasomotor symptoms and vulvar and vaginal atrophy due to menopause, for the treatment of hypoestrogenism that occurs due to hypogonadism, castration, or primary ovarian failure, and for prevention of postmenopausal osteoporosis. 

It is used for the treatment of breast cancer in individuals with metastatic disease, and also for the treatment of androgen-dependent prostate cancer.

It is used in combination with other hormones as a part of oral contraceptive pills for preventing pregnancy (most commonly as ethinylestradiol, a synthetic form of Estradiol.

How does estrogen act in the body?

Estrogen is found in the ovarian, skin, prostate breast, uterine, bone, fat, and brain tissues. The main source in women is during the reproductive age in the ovarian follicle that secretes 70 to 500 mcg of estradiol each day.

After the menopause, majority of endogenous hormone is made by transformation of androstenedione-secreted by the adrenal cortex to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form that is estrone sulphate, represents the most abundant estrogens which are found in postmenopausal women.

Estradiol is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, higher estrone concentration in postmenopausal people can cause various undesirable effects. These effects include chills, vaginal dryness, hot flashes, mood swings, and irregular menstruation in addition to sleep problems.

Toxicity

Estradiol overdose leads to breast tenderness, venous thrombosis, vaginal bleeding, nausea, and vomiting, abdominal pain. In case of overdose it is highly recommended to discontinue estradiol treatment.

There are different types of estrogen

Estrone is an estrogen hormone that is present in the body after menopause. It’s a weak form of estrogen in the body that can convert to other forms of estrogen.

Estradiol is the most common type in females during their reproductive age. Contrary to the common belief,  it is produced by both male and females. Increase amount of estradiol may result in acne, loss of sex drive, osteoporosis, and depression. Excessive levels can increase the risk of uterine and breast cancer and low levels can result in weight gain and cardiovascular disease.

Estriol levels rise during pregnancy, as it helps the uterus to grow and prepares the body for delivery. Estriol levels reach their peak just before birth.

Effects of estrogen in the female

  1. Ovaries:It stimulates the growth of egg follicle.
  2. Vagina: Estrogen promotes lubrication and maintains the thickness of the vaginal wall 
  3. Uterus: Strengthens and maintains the mucous membrane that lines the uterus. It regulates the flow and thickness of uterine mucus secretions.
  4. Breasts: It is used in the formation of breast tissue by body. After weaning estrogen helps to stop the flow of milk.

Use of estrogen in IVF cycles:

           Usually your doctor will advise you to take estrogen hormone to prepare the lining of the uterus. She suggests you to take in the form of tablets, vaginal preparations or in the form of gel for application. Normally estrogen is used in frozen embryo transfer cycles, but can be used during  stimulation as well. It is also used to prepare endometrium in surrogate mothers. It is given as a luteal support after embryo transfer in some fertility centers.

Levels of estrogen

Estrogen levels vary among male and females. They fluctuate during the menstrual cycle and over a female’s lifetime. This fluctuation can sometimes cause effects such as mood swings before menstruation or hot flashes in menopause.

Factors that can affect estrogen levels:

  1. Pregnancy, breastfeeding
  2. Puberty
  3. Menopause age
  4. Old age
  5. Overweight and obese
  6. Extreme dieting or anorexia nervosa
  7. Arduous exercise
  8. Use of medications, including steroids, estrogen-containing drugs, phenothiazines, tetracyclines, ampicillin
  9. Some congenital conditions, like Turner’s syndrome
  10. Hypertension
  11. Diabetes
  12. Primary ovarian insufficiency
  13. Underactive pituitary gland
  14. Polycystic ovary syndrome (PCOS)
  15. Tumors in the adrenal glands 

Estrogen imbalance

Imbalance of estrogen leads to-

  • Oligomenorrhea or Amenorrhea
  • Light or heavy bleeding during menstruation time
  • Severe premenstrual or menopausal symptoms
  • Hot flashes, night sweats
  • Noncancerous lumps in the breast and also uterus
  • Mood swings and improper sleep
  • Weight gain, mainly in the hips, thighs and waist region
  • Low sexual desire
  • Vaginal dryness, vaginal atrophy
  • Fatigue
  • Mood swings
  • Depression and anxiety
  • Dry skin

Hereditary and other conditions can lead to high levels of estrogen in males, which results in:

  • Infertility
  • Erectile dysfunction
  • Larger breasts also called as gynecomastia

Males with low estrogen levels have low libido and excess belly fat.

Sources and uses

Estrogen products include:

  • Synthetic estrogen
  • Bio-identical estrogen
  • Premarin, that contains estrogen from the urine of pregnant mothers.

Treatment

It manages menopause symptoms as a part of hormone therapy, usually refered to as hormone replacement therapy.

Treatment consists of estrogen (estrogen replacement therapy, or ERT), or may involve a combination of estrogen and progestin, a synthetic form of progesterone.

Hormone treatment is available in the form of a pill, vaginal cream, nasal spray, patch, skin gel, injection, or ring.

It helps to manage:

  • Hot flashes
  • Vaginal dryness
  • Painful intercourse
  • Mood swings
  • Sleep disorders
  • Anxiety
  • Decrease in sexual desire

It may also help to reduce risk of osteoporosis, which increases when females enter menopause age.

Side effects

  • Bloating
  • Breast soreness
  • Headaches
  • Leg cramps
  • Indigestion
  • Nausea
  • Vaginal bleeding
  • Fluid retention, which leads to swelling

In addition to menopause, this therapy can also help to resolve-

  • Primary ovarian insufficiency
  • Ovarian issues
  • Acne
  • Prostate cancer
  • Delayed puberty in Turner’s syndrome

Birth control

Birth control pills contain synthetic estrogen and progestin or progestin only.

Pills also make the mucus in the cervix thick so that sperm cannot reach the egg.

It decreases premenstrual symptoms and reduces the severity of hormone-related acne.

Birth control pills may increase the risk of:

  • Heart attack
  • Stroke
  • Pulmonary embolism
  • Blood clots
  • Headaches
  • Nausea and vomiting
  • Irregular bleeding
  • Weight changes
  • Breast tenderness and swelling

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